A Large Follicular Dentigerous Cyst: A New Multi-portal Access: Intraoral and Endoscopic Technique.

Background: The standard treatment for a dentigerous cyst of maxilla is a surgical enucleation, the extraction of the tooth. In the case of cysts involving the maxillary sinus, a Caldwell-Luc approach is used. In case of large cysts, its marsupialization is carried out in order to reduce the bone defect, followed by enucleation and extraction of the tooth. Methods: This is a case of a large follicular dentigerous cyst of upper jaw with 18 ectopic tooth within the maxillary sinus, treated in our Unit. Results: We decided to perform a multi-portal access, the intraoral endoscopic-assisted technique; an intraoral approach has been performed, but less demolishing than the routine intraoral approach, through the anterior wall of the maxillary sinus, already eroded by the lesion. The lesion was very large, occupying the entire maxillary cavity. For this reason, by means of the intraoral approach alone, it was extremely difficult to remove the lesion in its entirety. The endoscopic-assisted technique was combined with intraoral approach. The lesion extended to the maxillary ostium. This did not allow to reach the ostium through the classic endoscopic approach. Endonasal endoscopic access was used both to enucleate the cyst, that was adherent to the orbital floor and soft tissues of the OMC (osteomeatal complex), and to restore the physiological drainage of the maxillary sinus. Conclusions: We decided to perform a combined intraoral and endoscopic approach to allow a complete excision of the cystic lesion, without being very demolishing and taking advantage of the bone erosion already caused by the large cyst.

Local production of 17ß-oestradiol in the endometrium during the implantation window: a pilot study.

Abstract: Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17ß-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17ß-oestradiol (oxidative 17ß-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17ß-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups. Lay summary: Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.

Ineffective hematopoiesis is a hallmark of myelodysplastic syndromes (MDS). Hematopoietic alterations in MDS patients strictly correlate with microenvironment dysfunctions, eventually affecting also the mesenchymal stromal cell (MSC) compartment. Stromal cells are indeed epigenetically reprogrammed to cooperate with leukemic cells and propagate the disease as "tumor unit"; therefore, changes in MSC epigenetic profile might contribute to the hematopoietic perturbations typical of MDS. Here, we unveil that the histone variant macroH2A1 (mH2A1) regulates the crosstalk between epigenetics and inflammation in MDS-MSCs, potentially affecting their hematopoietic support ability. We show that the mH2A1 splicing isoform mH2A1.1 accumulates in MDS-MSCs, correlating with the expression of the Toll-like receptor 4 (TLR4), an important pro-tumor activator of MSC phenotype associated to a pro-inflammatory behavior. MH2A1.1-TLR4 axis was further investigated in HS-5 stromal cells after ectopic mH2A1.1 overexpression (mH2A1.1-OE). Proteomic data confirmed the activation of a pro-inflammatory signature associated to TLR4 and nuclear factor kappa B (NFkB) activation. Moreover, mH2A1.1-OE proteomic profile identified several upregulated proteins associated to DNA and histones hypermethylation, including S-adenosylhomocysteine hydrolase, a strong inhibitor of DNA methyltransferase and of the methyl donor S-adenosyl-methionine (SAM). HPLC analysis confirmed higher SAM/SAH ratio along with a metabolic reprogramming. Interestingly, an increased LDHA nuclear localization was detected both in mH2A1.1-OE cells and MDS-MSCs, probably depending on MSC inflammatory phenotype. Finally, coculturing healthy mH2A1.1-OE MSCs with CD34+ cells, we found a significant reduction in the number of CD34+ cells, which was reflected in a decreased number of colony forming units (CFU-Cs). These results suggest a key role of mH2A1.1 in driving the crosstalk between epigenetic signaling, inflammation, and cell metabolism networks in MDS-MSCs.

The effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis - A systematic review with meta-analysis.

This systematic review aimed to systematically investigate the literature on the effectiveness of exercise and physical activity programs on fatigue and sleep in people with arthritis. For that, seven databases were searched for relevant randomized controlled trials. After the searches, 36 studies investigating 2281 participants were included. Risk of bias assessments were done by two independent reviewers using the Cochrane Risk of Bias tool 2. Random-effects meta-analyses were performed, and the Grading of Recommendations Assessment, Development and Evaluation framework was used to judge the certainty of evidence. The evidence on benefits of exercise and physical activity programs on fatigue and sleep parameters in people with osteoarthritis and psoriatic arthritis was either lacking or inconclusive. There was very low to low certainty evidence for a slight benefit of exercise and physical activity programs on fatigue at short-term in people with ankylosing spondylitis and rheumatoid arthritis. However, the evidence was very uncertain for the medium- and long-term as well as for any sleep parameters. The results indicate that exercise and physical activity programs may offer some benefits on fatigue for people with arthritis in the short-term, although the best type of exercise remains uncertain. The available evidence on improvements in sleep was insufficient to draw strong conclusions.

Central nervous system involvement in two siblings affected by hereditary transthyretin amyloidosis 30 years after liver transplantation: a model for gene-silencing therapies.

Hereditary transthyretin amyloidosis (ATTRv) is a genetic, autosomal dominant, severe disease characterized by progressive sensory-motor polyneuropathy, cardiomyopathy, dysautonomia, renal and eyes involvement, provoked by the deposition of the mutated and unstable transthyretin protein. In past decades, liver transplant, avoiding the synthesis of the pathologic protein, has been a good, even if not resolutive, treatment. In this report we describe two siblings affected with ATTRv, who developed first symptoms of disease at a young age and underwent a liver transplant with prompt resolution of clinical manifestations. After several years, central nervous system and eyes symptoms relapsed despite treatment, considering that the synthesis of mutated protein continues in choroid plexus, a locum where current therapies are unable to act. In our opinion, these cases represent a long-term prognostic model for the novel gene-silencers approved for ATTRv, because they share a similar therapeutic effect with liver transplant: the block of mutated protein synthesis limited only in the main transthyretin (TTR) production organ is able to prevent the progression of disease only for some years, but not to avoid long-term clinical worsening due to extra-hepatic production of TTR. Novel future therapeutic strategies are demanded to guarantee a better long-term stabilization of symptomatology.

Staphylococcus aureus adlb gene is associated with high prevalence of intramammary infection in dairy herds of northern Italy: A cross-sectional study.

Staphylococcus aureus is a major mastitis pathogen in dairy cattle worldwide, responsible for substantial economic losses. Environmental factors, milking routine, and good maintenance of milking equipment have been described as important factors to prevent intramammary infections (IMI). Staphylococcus aureus IMI can be widespread within the farm or the infection can be limited to few animals. Several studies have reported that Staph. aureus genotypes differ in their ability to spread within a herd. In particular, Staph. aureus belonging to ribosomal spacer PCR genotype B (GTB)/clonal complex 8 (CC8) is associated with high within-herd prevalence of IMI, whereas other genotypes are generally associated with individual cow disease. The adlb gene seems to be strictly related to Staph. aureus GTB/CC8, and is a potential marker of contagiousness. We investigated Staph. aureus IMI prevalence in 60 herds in northern Italy. In the same farms, we assessed specific indicators linked to milking management (e.g., teat condition score and udder hygiene score) and additional milking risk factors for IMI spread. Ribosomal spacer-PCR and adlb-targeted PCR were performed on 262 Staph. aureus isolates, of which 77 underwent multilocus sequence typing. In most of the herds (90%), a predominant genotype was identified, especially Staph. aureus CC8 (30%). In 19 of 60 herds, the predominant circulating Staph. aureus was adlb-positive and the observed IMI prevalence was relevant. Moreover, the adlb gene was detected only in genotypes of CC8 and CC97. Statistical analysis showed a strong association between the prevalence of Staph. aureus IMI, the specific CCs, and carriage of adlb, with the predominant circulating CC and presence of the gene alone explaining the total variation. Interestingly, the difference in the odds ratio obtained in the models for CC8 and CC97 suggests that it is carriage of the adlb gene, rather than the circulation of these CCs per se, that leads to higher within-herd prevalence of Staph. aureus. In addition, the model showed that environmental and milking management factors had no or minimal effect on Staph. aureus IMI prevalence. In conclusion, the circulation of adlb-positive Staph. aureus strains within a herd has a strong effect on the prevalence of IMI. Thus, adlb can be proposed as a genetic marker of contagiousness for Staph. aureus IMI in cattle. However, further analyses using whole-genome sequencing are required to understand the role of genes other than adlb that may be involved in the mechanisms of contagiousness of Staph. aureus strains associated with high prevalence of IMI.

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Probing cellulose-solvent interactions with self-diffusion NMR: Onium hydroxide concentration and co-solvent effects.

The molecular self-diffusion coefficients were accessed, for the first time, in solutions of microcrystalline cellulose, dissolved in 30 wt% and 55 wt% aqueous tetrabutylammonium hydroxide, TBAH (aq), and in mixtures of 40 wt% TBAH (aq) with an organic co-solvent, dimethylsulfoxide (DMSO), through pulsed field gradient stimulated echo NMR measurements. A two-state model was applied to estimate α (i.e., average number of ions that "bind" to each anhydroglucose unit) and Pb (i.e., fraction of "bound" molecules of DMSO, TBAH or H2O to cellulose) parameters. The α values suggest that TBA+ ions can bind to cellulose within 0.5 TBA+ to 2.3 TBA+/AGU. On the other hand, the Pb parameter increases when raising cellulose concentration for TBA+, DMSO and water in all solvent systems. Data suggests that TBAH interacts with the ionized OH groups from cellulose forming a sheath of bulky TBA+ counterions which consequently leads to steric hindrance between cellulose chains.

Penicillin resistance in bovine Staphylococcus aureus: Genomic evaluation of the discrepancy between phenotypic and molecular test methods.

Staphylococcus aureus is a major pathogen in humans and animals. In cattle, it is one of the most important agents of mastitis, causing serious costs in the dairy industry. Early diagnosis and adequate therapy are therefore 2 key factors to deal with the problems caused by this bacterium, and benzylpenicillin (penicillin) is usually the first choice to treat these infections. Unfortunately, penicillin resistance testing in bovine S. aureus strains shows discrepant results depending on the test used; consequently, the best method for assessing penicillin resistance is still unknown. The aim of this study was therefore to find a method that assesses penicillin resistance in S. aureus and to elucidate the mechanisms leading to the observed discrepancies. A total of 146 methicillin-sensitive S. aureus strains isolated from bovine mastitis were tested for penicillin resistance using a broth microdilution [minimum inhibitory concentration (MIC)] and 2 different disk diffusion protocols. Furthermore, the strains were analyzed for the presence of the bla operon genes (blaI, blaR1, blaZ) by PCR, and a subset of 45 strains was also subjected to whole genome sequencing (WGS). Discrepant results were obtained when penicillin resistance of bovine S. aureus was evaluated by disk diffusion, MIC, and PCR methods. The discrepancies, however, could be fully explained by WGS analysis. In fact, it turned out that penicillin resistance is highly dependent on the completeness of the bla operon promotor: when the bla operon was complete based on WGS analysis, all strains showed MIC ≥1 µg/mL, whereas when the bla operon was mutated (31-nucleotide deletion), they were penicillin sensitive except in those strains where an additional, bla operon-independent resistance mechanism was observed. Further, WGS analyses showed that penicillin resistance is truly assessed by the MIC assay. In contrast, caution is required when interpreting disk diffusion and PCR results.

The role of fat distribution and inflammation in the origin of endometrial cancer, study protocol of the ENDOCRINE study.

BACKGROUND: Obesity is a growing problem worldwide, especially in countries with improved socioeconomic circumstances. Also, in the Netherlands the incidence of overweight and obesity is rising. There is increasing evidence on the association between obesity and tumorigenesis. Of all cancer types, endometrial cancer (EC) has the strongest positive correlation with obesity. Obesity is generally defined as a body mass index (BMI) >30, yet does not cover the differences in fat distribution in visceral and subcutaneous compartments. Visceral fat is assumed to be relatively more metabolically active and likely negative prognostic biomarker in non-endometrioid EC. Whereas subcutaneous fat is mainly responsible for oestrogen production through increased aromatase activity. OBJECTIVE: The aim of this study is to compare hormone levels and inflammatory markers after bilateral salpingo-oophorectomy (BSO) in obese and non-obese patients. Secondary objectives are to compare the effect of fat distribution and diagnosis (benign vs. EC) on the observed changes in hormone levels and inflammatory markers, and to compare the effect of BSO on menopausal complaints. METHODS: Prospective multicentre observational cohort study. A total of 160 patients will be included, of which 80 patients with a normal BMI (18-25 kg/m2) and 80 patients with an obese BMI >32-35 kg/m2. Preoperative abdominal CT will be performed and fasting venous blood samples are obtained for hormone levels and inflammation markers analysis. During surgery, adipose tissue biopsies of subcutaneous and visceral (omental and intestinal epiploic fat) compartments will be collected and stored fresh frozen. In addition a fasting blood draw six weeks after surgery will be obtained. All subjects will fill in two questionnaires before surgery and one after surgery. DISCUSSION: We hypothesize that BMI, the type of fat distribution, and possibly the underlying pathology significantly influence in hormone levels, and systemic inflammation changes after BSO. Previous studies have found several clues for a relationship between obesity and endometrial cancer. We expect that our study will contribute to pinpoint the exact differences between 'healthy obesity' and 'unhealthy obesity' and will help to identify patients that are more at risk of developing cancer (or possibly suffer from other related problems such as cardiovascular problems e.g.).

Diabetes might not be a risk factor for worse prognosis among hospitalized patients due to COVID-19 in a Mediterranean area / La presencia de diabetes entre los pacientes ingresados por COVID-19 podría no ser un factor de peor pronóstico

Aim: type-2 diabetes (T2DM) seems to worsen the prognosis of patients admitted for COVID-19, although most studies included Asiatic patients. We aimed to assess whether this condition applies for Mediterranean patients. Methods: a total of 90 patients admitted for COVID-19 with T2DM were retrospectively compared with 50 patients without T2DM. Results: subjects with T2DM were older than their counterparts (73.3 ± 12.4 vs 53 ± 15.7 years; p < 0.0001). Either absolute lymphocyte count (1.1 ± 0.6 vs 1.3 ± 0.7 x 109/L; p = 0.005) or hemoglobin (11.9 ± 1.6 vs 13.1 ± 2.1 g/dL; p < 0.0001) were lower among subjects with T2DM. CRP and procalcitonin were higher among subjects with T2DM (91.9 ± 71.2 vs 70.1 ± 63.3 mg/L; p = 0.002 and 0.8 ± 0.3 vs 0.4 ± 0.1 ng/mL; p < 0.0001, respectively). Albumin was lower among patients with T2DM (3.4 ± 0.5 vs 3.8 ± 0.5 g/L: p < 0.001). Length of stay was longer among subjects with T2DM (11.7 ± 7.7 vs 9.7 ± 8.6 days; p = 0.01). However, both groups were comparable regarding both the proportion of subjects who were admitted to the ICU (16.5 % vs 8 %; p = 0.1) and mortality (11 % vs 4 %; p = 0.2). Conclusions: in a Mediterranean sample, despite of age, comorbidities, nutritional status, and inflammatory markers, subjects with T2DM with a proper glycemic control admitted for COVID-19 had similar prognostic outcomes than patients without this metabolic condition (AU)

Objetivo: la diabetes de tipo 2 (DM2) parece empeorar el pronóstico de los pacientes ingresados por COVID-19, aunque la mayoría de los estudios incluyeron pacientes asiáticos. Nuestro objetivo fue evaluar si esto se aplica a los pacientes de una población Mediterránea. Métodos: un total de 90 pacientes ingresados por COVID-19 con DM2 se compararon retrospectivamente con 50 pacientes sin DM2. Resultados: los sujetos con DM2 eran mayores que sus contrapartes (73,3 ± 12,4 frente a 53 ± 15,7 años; p < 0,0001). El recuento absoluto de linfocitos (1,1 ± 0,6 vs. 1,3 ± 0,7 x 109/L; p = 0,005) o la hemoglobina (11,9 ± 1,6 vs. 13,1 ± 2,1 g/dL; p < 0,0001) fueron menores entre los sujetos con DM2. La PCR y la procalcitonina fueron mayores entre los sujetos con DM2 (91,9 ± 71,2 frente a 70,1 ± 63,3 mg/L; p = 0,002 y 0,8 ± 0,3 frente a 0,4 ± 0,1 ng/ml; p < 0,0001, respectivamente). La albúmina fue menor entre los pacientes con DM2 (3,4 ± 0,5 vs. 3,8 ± 0,5 g/L: p < 0,001). La estancia hospitalaria fue mayor entre los sujetos con DM2 (11,7 ± 7,7 frente a 9,7 ± 8,6 días; p = 0,01). Sin embargo, ambos grupos fueron comparables en cuanto a la proporción de sujetos con ingreso en la UCI (16,5 % vs. 8 %; p = 0,1) y la mortalidad (11 % vs. 4 %; p = 0,2). Conclusiones: en una muestra mediterránea, a pesar de la edad, las comorbilidades, el estado nutricional y los marcadores inflamatorios, los sujetos con DM2 con un adecuado control glucémico ingresados por COVID-19 tuvieron resultados pronósticos similares a los de los pacientes sin esta condición metabólica (AU)

When your MR linac is down: Can an automated pipeline bail you out of trouble?

PURPOSE: The unique treatment delivery technique provided by magnetic resonance guided radiotherapy (MRgRT) can represent a significant drawback when system fail occurs. This retrospective study proposes and evaluates a pipeline to completely automate the workflow necessary to shift a MRgRT treatment to a traditional radiotherapy linac. MATERIAL AND METHODS: Patients undergoing treatment during the last MRgRT system failure were retrospectively included in this study. The core of the proposed pipeline was based on a tool able to mimic the original MR linac dose distribution. The so obtained dose distribution (AUTO) has been compared with the distribution obtained in the conventional radiotherapy linac (MAN). Plan comparison has been performed in terms of time required to obtain the final dose distribution, DVH parameters, dosimetric indices and visual analogue scales scoring by radiation oncologists. RESULTS: AUTO plans generation has been obtained within 10 min for all the considered cases. All AUTO plans were found to be within clinical tolerance, showing a mean target coverage variation of 1.7% with a maximum value of 4.3% and a minimum of 0.6% when compared with MAN plans. The highest OARs mean variation has been found for rectum V60 (6.7%). Dosimetric indices showed no relevant differences, with smaller gradient measure in favour of AUTO plans. Visual analogue scales scoring has confirmed comparable plan quality for AUTO plans. CONCLUSION: The proposed workflow allows a fast and accurate generation of automatic treatment plans. AUTO plans can be considered equivalent to MAN ones, with limited clinical impact in the worst-case scenario.

Unveiling unconventional magnetism at the surface of Sr2RuO4.

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.

Reputation and socio-ecology in humans.

Reputation is a fundamental feature of human sociality as it sustains cooperative relationships among unrelated individuals. Research from various disciplines provides insights on how individuals form impressions of others, condition their behaviours based on the reputation of their interacting partners and spread or learn such reputations. However, past research has often neglected the socio-ecological conditions that can shape reputation systems and their effect on cooperation. Here, we outline how social environments, cultural values and institutions come to play a crucial role in how people navigate reputation systems. Moreover, we illustrate how these socio-ecological dimensions affect the interdependence underlying social interactions (e.g. potential recipients of reputational benefits, degree of dependence) and the extent to which reputation systems promote cooperation. To do so, we review the interdisciplinary literature that illustrates how reputation systems are shaped by the variation of prominent ecological features. Finally, we discuss the implications of a socio-ecological approach to the study of reputation and outline potential avenues for future research. This article is part of the theme issue 'The language of cooperation: reputation and honest signalling'.

Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.

VMAT-like plans for magnetic resonance guided radiotherapy: Addressing unmet needs.

PURPOSE: VMAT delivery technique is currently not applicable to Magnetic Resonance-guided radiotherapy (MRgRT) hybrid systems. Aim of this study is to evaluate an innovative VMAT-like (VML) delivery technique. MATERIAL AND METHODS: First, planning and dosimetric evaluation of the MRgRT VML treatment have been performed on 10 different disease sites and the results have been compared with the corresponding IMRT plans. Then, in the second phase, 10 of the most dosimetrically challenging locally advanced pancreas treatment plans have been retrospectively re-planned using the VML approach to explore the potentiality of this new delivery technique. Finally, VML robustness was evaluated and compared with the IMRT plans, considering a lateral positioning error of ± 5 mm. RESULTS: In phase one, all VML plans were within constraint for all OARs. When PTV coverage is considered, in the 50% of the cases VML PTV coverage is equal or higher than in IMRT plan. In the remaining 50%, the highest target under coverage difference in comparison with IMRT plan is -1.71%. The mean and maximum treatment time differences (VML-IMRT) is 0.2 min and 3.1 min respectively. In phase two, the treatment time variation (VML-IMRT), shows a mean, maximum and minimum variations of 1.3, 4.6 and -0.6 min respectively. All VML plans have a better target coverage if compared with IMRT plans, keeping in any case the OARs constraints within tolerance. VML doesn't increase plan robustness. CONCLUSION: VMAT-like treatment approach appeared to be an efficient planning solution and it was decided to clinically implement it in daily practice, especially in the frame of hypo fractionated treatments.

The nature, severity and causes of medication incidents from an Australian community pharmacy incident reporting system: The QUMwatch study.

AIMS: Most research into medication safety has been conducted in hospital settings with less known about primary care. The aim of this study was to characterise the nature and causes of medication incidents (MIs) in the community using a pharmacy incident reporting programme. METHODS: Thirty community pharmacies participated in an anonymous or confidential MI spontaneous reporting programme in Sydney, Australia. The Advanced Incident Management System was used to record and classify incident characteristics, contributing factors, severity and frequency ratings. RESULTS: In total, 1013 incidents were reported over 30 months, 831 of which were near misses while 165 reports involved patient harm. The largest proportion of cases pertained to patients aged >65 years (35.7%). Most incidents involved errors during the prescribing stage (61.1%), followed by dispensing (25.7%) and administration (23.5%), while some errors occurred at multiple stages (17.9%). Systemic antibacterials (12.2%), analgesics (11.8%) and renin-angiotensin medicines (11.7%) formed the majority of implicated classes. Participants identified diverse and interrelating contributing factors: those concerning healthcare providers included violations to procedures/guidelines (75.6%), rule-based mistakes (55.6%) and communication (50.6%); those concerning patients included cognitive factors (31.9%), communication (25.5%) and behaviour (6.1%). Organisational safety culture and inadequate risk management processes were rated as suboptimal. CONCLUSION: An MI reporting programme can capture and characterise medication safety problems in the community and identify the human and system factors that contribute to errors. Since medicine use is ubiquitous in the community, morbidity and mortality from MIs may be reduced by addressing the prioritised risks and contributing factors identified in this study.