Cannabinoids for Behavioral Symptoms in Dementia: An Overview.

Dementia, with loss of memory, cognitive abilities, and independent daily functioning, is increasing worldwide, related to an aging population. Currently, there is no curative treatment for dementia. Treatment of the frequently occurring behavioral and psychological symptoms of dementia (BPSD) is partially effective and associated with significant side effects. Cannabinoids are lipophilic molecules acting on the CB1 end CB2 receptors, essential for main biological processes such as sleep, appetite, memory, and pain. Cannabinoids might have a positive impact on amyloid formation in Alzheimer's disease, the main form of dementia, and on BPSD symptoms. Most knowledge currently concerns delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In the context of dementia and BPSD, THC might be beneficial for associated spasticity and possible pain or lack of appetite and CBD probably works better on sleep, agitation, and anxiety. This overview of prospective clinical studies and randomized clinical trials, published between 2005 and April 2023, using cannabinoids for BPSD suggests that older studies using low-dose oral synthetic THC showed no positive results. Still, more recent studies using THC/CBD-based oral medication at higher doses show promising results and are feasible and safe in this elderly polymedicated population. Several RCTs are ongoing and planned worldwide, and we hope other trials will follow to establish clinical efficiency and optimal dosing, as well as other outcomes such as deprescribing other medications and facilitation of care. We suggest that researchers also address the more sociological aspects of prescribing cannabinoids for dementia and BPSD in their specific context.

Contamination Profile of Different Formulations of Silicone Oil Tamponade Before and After Intraocular Permanence for Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to search for contaminants in silicone oil tamponades removed from eyes treated for retinal detachment, and to correlate chemical results with some clinical/functional parameters of the considered eyes. Methods: We examined a sequential cohort of eyes grouped according to the tamponade received: (1) Siluron2000 (S2), (2) RS-OIL ECS5000 (S5), and (3) Densiron Xtra (DX). Samples were collected at the beginning of the scheduled removal and analyzed by untargeted headspace gas-chromatography mass spectrometry (HS-GC-MS). Visual acuity and optic coherence tomography assessments were obtained before and after the tamponade removal. Results: Forty-one samples were analyzed: 22 belonging to the DX group, 13 to the S2 group, and 6 to the S5 group. For each group, a mixture of uninjected commercial preparation was analyzed as the reference. Different siloxanes and fluorinated compounds including perfluorodecalin (PFCL) were the most prevalent chemicals, found in 55% to 100% of the intraocular samples of the 3 groups. Some siloxanes were present also in the control matrices, whereas PFCL was only in the extracted tamponades. In the DX group, the concentration of hexamethylcyclotrisiloxane showed an inverse correlation trend with the duration of its permanence inside the eye (P = 0.054). Different alkanes, propanol, and acetaldehyde were identified only in the control matrices. Conclusions: Several contaminants including siloxanes were identified in the intraocular samples and in the control matrices. A time-related ocular uptake of some of these is conceivable. PFCL was also highly present but only in intraocular samples. Translational Relevance: After intraocular permanence silicone oils (SOs) have various unlabeled contaminants with some relevant differences with the commercial formulation chemical profile.

The seasonal distribution of plasticizers in estuarine system: Controlling factors, storage and impact on the ecosystem.

Plasticizers such as phthalate esters (PAEs) are commonly used in various consumer and industrial products. This widespread use raises valid concerns regarding their ubiquity in the environment and potential negative impacts. The present study investigates the distribution of eight common plasticizers in the largest European lagoon (Curonian Lagoon) located in the SE Baltic Sea. The concentration levels of plasticizers in the water column, containing both the dissolved and particulate-bound phases, and in sediments were evaluated to reveal seasonal patterns in distribution and potential effects on the lagoon ecosystem. A total of 24 water samples and 48 sediment samples were collected across all four seasons from the two dominant sedimentary areas within the lagoon. The average concentration of total PAEs in the water column ranged from 1 to 21 µg L-1, whereas sediment concentration varied from 5.0 to 250 ng g-1. The distribution of plasticizers was influenced by the patterns in hydrodynamics and water circulation within the lagoon. The confined south-central area contained a higher amount of PAEs in sediments, accounting for most of the lagoon's plasticizer accumulation. More than 7 tons of plasticizers are stored in the 5 upper centimetres of sediment, with over 3 tons persisting for more than five years. Di(2-ethylhexyl) phthalate (DEHP), Diisobutyl phthalate (DiBP), and Dibutyl phthalate (DnBP) were the most abundant PAE congeners, with DEHP posing the highest risk quotient to algae, based on water column concentration. Several other congeners demonstrated medium to high-risk levels for organisms living in the lagoon.

Microbial consortia and biochar as sustainable biofertilisers: Analysis of their impact on wheat growth and production.

The European Union is among the top wheat producers in the world, but its productivity relies on adequate soil fertilisation. Biofertilisers, either alone or in combination with biochar, can be a preferable alternative to chemical fertilisers. However, the addition of biofertilisers, specifically plant growth promoting microbes (PGPM), could modify grain composition, and/or deteriorate the soil composition. In this study, the two wheat cultivars Triticum aestivum (Bramante) and T. durum (Svevo) were cultivated in open fields for two consecutive years in the presence of a commercial PGPM mix supplied alone or in combination with biochar. An in-depth analysis was conducted by collecting physiological and agronomic data throughout the growth period. The effects of PGPM and biochar were investigated in detail; specifically, soil chemistry and rhizosphere microbial composition were characterized, along with the treatment effects on seed storage proteins. The results demonstrated that the addition of commercial microbial consortia and biochar, alone or in combination, did not modify the rhizospheric microbial community; however, it increased grain yield, especially in the cultivar Svevo (increase of 6.8 %-13.6 %), even though the factors driving the most variations were associated with both climate and cultivar. The total gluten content of the flours was not affected, whereas the main effect of the treatments was a variation in gliadins and low-molecular-weight-glutenin subunits in both cultivars when treated with PGPM and biochar. This suggested improved grain quality, especially regarding the viscoelastic properties of the dough, when the filling period occurred in a dry climate. The results indicate that the application of biofertilisers and biochar may aid the effective management of sustainable wheat cultivation, to support environmental health without altering the biodiversity of the resident microbiome.

Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study.

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence.

Himen imperforat en el diagnòstic diferencial de la massa vaginal / Himen imperforado en el diagnóstico diferencial de la masa vaginal / Imperforate hymen in the differential diagnosis of a vaginal mass

Introducció. L’himen és una membrana que envolta i cobreix parcialment l’introit vaginal. La presència d’un himen imperforat pot passar desapercebuda, donar símptomes obstructius de l’aparell genital i del tracte urinari en el període neonatal o presentar-se com a dolor abdominal amb amenorrea en l’adolescència, com a clínica més freqüent. Cas clínic. Presentem el cas d’una pacient de dos mesos amb diagnòstic d’himen imperforat, amb una fístula preauricular esquerra i una hèrnia umbilical concomitant. Davant de la manca de simptomatologia, s’adopta una conducta expectant fins als quatre anys; amb la persistència de l’hèrnia umbilical, s’indica la cirurgia correctora dels tres defectes, que es duu a terme sense incidències. Posteriorment, la pacient presenta una evolució correcta sense recidives. Comentari. L’obstrucció vaginal congènita sol detectar-se clínicament en la pubertat i és diagnosticada de forma poc freqüent durant el període de lactant. L’himen imperforat és la malformació congènita vaginal i l’anomalia obstructiva de l’aparell reproductor femení més freqüent, però no és l’única; per aquest motiu, és important fer un correcte diagnòstic diferencial de les masses vaginals, per donar el millor tractament dirigit i evitar una morbimortalitat més alta dels pacients. (AU)

Introducción. El himen es una membrana que rodea y cubre parcialmente el introito vaginal. La presencia de un himen imperforado puede pasar desapercibida, dar síntomas obstructivos del aparato genital y del tracto urinario en el período neonatal o presentarse como dolor abdominal con amenorrea en la adolescencia, como clínica más frecuente. Caso clínico. Presentamos el caso de una paciente de dos meses con diagnóstico de himen imperforado, con una fístula preauricular izquierda y una hernia umbilical concomitante. Ante la ausencia de sintomatología, se adopta una conducta expectante hasta los cuatro años; con la persistencia de la hernia umbilical se indica la cirugía correctora de los tres defectos, que se lleva a cabo sin incidencias. Posteriormente, la paciente presenta una correcta evolución sin recidivas. Comentario. La obstrucción vaginal congénita suele detectarse clínicamente en la pubertad y es diagnosticada de forma poco frecuente durante el período de lactante. El himen imperforado es la malformación congénita vaginal y la anomalía obstructiva del aparato reproductor femenino más frecuente, pero no es la única; por este motivo, es importante la realización de un correcto diagnóstico diferencial de las masas vaginales para dar el mejor tratamiento dirigido y evitar una mayor morbimortalidad en los pacientes. (AU)

Introduction. The hymen is a membrane that surrounds and partially covers the vaginal entrance. The presence of an imperforate hymen may go unnoticed, give obstructive symptoms of the genital tract and urinary tract in the neonatal period, or most commonly present as abdominal pain with amenorrhea in adolescence. Case report. We present a two-month-old girl diagnosed with imperforate hymen, with a left preauricular fistula and a concomitant umbilical hernia. In the absence of symptoms, conservative management was followed until four years of age, when with the persistence of the umbilical hernia corrective surgery of the three defects was performed without complications. Comments. Congenital vaginal obstruction usually occurs clinically during puberty and is rarely diagnosed during infancy. Imperforate hymen is the most common congenital vaginal malformation and obstructive anomaly of the female reproductive tract, although not the only one; for this reason, it is important to make a correct differential diagnosis of a vaginal mass in children to optimize management. (AU)

Ultra-high Performance Liquid Chromatography-Ion Mobility-High-Resolution Mass Spectrometry to Evaluate the Metabolomic Response of Durum Wheat to Sustainable Treatments.

Sustainable agriculture aims at achieving a healthy food production while reducing the use of fertilizers and greenhouse gas emissions using biostimulants and soil amendments. Untargeted metabolomics by ultra-high performance liquid chromatography-ion mobility-high-resolution mass spectrometry, operating in a high-definition MSE mode, was applied to investigate the metabolome of durum wheat in response to sustainable treatments, i.e., the addition of biochar, commercial plant growth promoting microbes, and their combination. Partial least squares-discriminant analysis provided a good discrimination among treatments with sensitivity, specificity, and a non-error rate close to 1. A total of 88 and 45 discriminant compounds having biological, nutritional, and technological implications were tentatively identified in samples grown in 2020 and 2021. The addition of biochar-biostimulants produced the highest up-regulation of lipids and flavonoids, with the glycolipid desaturation being the most impacted pathway, whereas carbohydrates were mostly down-regulated. The findings achieved suggest the safe use of the combined biochar-biostimulant treatment for sustainable wheat cultivation.

Coexistència de la malaltia de Wilkie i la síndrome del trencanous / Coexistencia de enfermedad de Wilkie y síndrome del cascanueces / Simultaneous occurrence of Wilkie and nutcracker syndromes

Introducció. La síndrome de l’artèria mesentèrica superior,o malaltia de Wilkie, i la síndrome de compressió de lavena renal esquerra, o síndrome del trencanous, són pocfreqüents. Normalment estan provocades per una compressió extrínseca del duodè o de la vena renal esquerra, respectivament, a causa d’una disminució de l’angle entrel’artèria mesentèrica superior i l’aorta.Cas clínic. Adolescent de 15 anys que va consultar a urgències per dolor abdominal de cinc mesos d’evolució localitzata l’epigastri, acompanyat de vòmits, proteïnúria i pèrdua depes. La pacient havia consultat prèviament en altres centresi s’havien descartat patologies urgents quirúrgiques. Es vacompletar l’estudi amb una tomografia computada abdominal amb diagnòstic de síndrome de l’artèria mesentèricasuperior i síndrome del trencanous. La pacient va ingressara la planta d’hospitalització i es va tractar de forma conservadora amb una dieta hipercalòrica; el trànsit intestinal i laproteïnúria van millorar, i va poder ser remesa a domicili icontrolada ambulatòriament de forma multidisciplinària.Comentari. Els problemes secundaris a la compressió aortomesentèrica poden donar quadres compatibles amb la síndrome de l’artèria mesentèrica superior i la síndrome deltrencanous. El diagnòstic d’aquests quadres pot resultarcomplex per la incidència baixa i per la simptomatologiainespecífica que els caracteritza. El tractament conservador representa la primera línia de tractament, però en alguns casos pot no ser suficient. Per tot això és necessarifer un maneig multidisciplinari d’aquests pacients. (AU)

Introducción. El síndrome de la arteria mesentérica superior o deWilkie y el síndrome del cascanueces son poco frecuentes. Normalmente están producidos por una compresión extrínseca delduodeno o de la vena renal izquierda, respectivamente, debido a una disminución del ángulo entre la arteria mesentérica superior yla aorta.Caso clínico. Adolescente de 15 años que consultó a urgencias pordolor abdominal de cinco meses de evolución localizado en epigastrio, acompañado de vómitos, proteinuria y pérdida de peso. Lapaciente había consultado previamente en otros centros descartando patologías urgentes quirúrgicas. Se completó el estudio conuna tomografía computarizada abdominal con diagnóstico de síndrome de la arteria mesentérica superior o de Wilkie y síndrome delcascanueces. La paciente ingresó en planta de hospitalización y setrató de forma conservadora con una dieta hipercalórica con mejoría del tránsito intestinal y de la proteinuria, y pudo ser remitida adomicilio y controlada ambulatoriamente de forma multidisciplinar.Comentario. Los problemas secundarios a la compresión aortomesentérica pueden dar cuadros compatibles con el síndrome de laarteria mesentérica superior o de Wilkie y el síndrome del cascanueces. El diagnóstico de estos cuadros puede resultar complejo por subaja incidencia y por la sintomatología inespecífica que los caracteriza. El tratamiento conservador representa la primera línea de tratamiento, pero en algunos casos puede no ser suficiente. Por estosmotivos es necesario un manejo multidisciplinar de estos pacientes. (AU)

Introduction. The superior mesenteric artery syndrome or Wilkiesyndrome and the nutcracker syndrome are rare. They are normallycaused by extrinsic compression of the duodenum or the left renalvein respectively, due to a narrowing of the angle between the superior mesenteric artery and the aorta.Case report. A 15-year-old girl presented to the emergency roomwith a five-month history of abdominal pain located in the epigastrium, accompanied by vomiting, proteinuria, and weight loss. Thepatient had previously consulted in other centers, and urgent surgical conditions were ruled out. The study was completed with anabdominal computed tomography scan, which led to the diagnosisof superior mesenteric artery or Wilkie syndrome, and nutcrackersyndrome. The patient was admitted to the hospital and treatedconservatively with a hypercaloric diet with improvement in intestinal transit and proteinuria. She was discharged to continue thefollow-up with a multidisciplinary team. Comment. Problems secondary to aortomesenteric compression cangive symptoms like superior mesenteric artery or Wilkie syndromeand nutcracker syndrome. The diagnosis of these conditions canbe complex due to their low incidence and the non-specific symptomatology that characterizes them. Conservative treatment represents the first line of treatment, but in some cases it may not beenough. For these reasons, multidisciplinary management of thesepatients is necessary. (AU)

Phthalate esters delivery to the largest European lagoon: Sources, partitioning and seasonal variations.

Phthalate esters (PAEs) due to their ability to leach from plastics, widely used in our daily life, are intensely accumulating in wastewater water treatment plants (WWTP) and rivers, before being exported to downstream situated estuarine systems. This study aimed to investigate the external sources of eight plasticizers to the largest European lagoon (the Curonian Lagoon, south-east Baltic Sea), focusing on their seasonal variation and transport behaviour through the partitioning between dissolved and particulate phases. The obtained results were later combined with hydrological inputs at the inlet and outlet of the lagoon to estimate system role in regulating the transport of pollutants to the sea. Plasticizers were detected during all sampling events with a total concentration ranging from 0.01 to 6.17 µg L-1. Di(2-ethylhexyl) phthalate (DEHP) was the most abundant PAEs and was mainly found attached to particulate matter, highlighting the importance of this matrix in the transport of such contaminant. Dibutyl phthalate (DnBP) and diisobutyl phthalate (DiBP) were the other two dominant PAEs found in the area, mainly detected in dissolved phase. Meteorological conditions appeared to be an important factor regulating the distribution of PAEs in environment. During the river ice-covered season, PAEs concentration showed the highest value suggesting the importance of ice in the retention of PAEs. While heavy rainfall impacts the amount of water delivered to WWTP, there is an increase of PAEs concentration supporting the hypothesis of their transport via soil leaching and infiltration into wastewater networks. Rainfall could also be a direct source of PAEs to the lagoon resulting in net surplus export of PAEs to the Baltic Sea.

Ultra-high performance liquid chromatography high-resolution mass spectrometry for metabolomic analysis of dental calculus from Duke Alessandro Farnese and Maria D'Aviz.

Dental calculus is a valuable resource for the reconstruction of dietary habits and oral microbiome of past populations. In 2020 the remains of Duke Alessandro Farnese and his wife Maria D'Aviz were exhumed to get novel insights into the causes of death. This study aimed to investigate the dental calculus metabolome of the noble couple by untargeted metabolomics. The pulverized samples were decalcified in a water-formic acid mixture, extracted using methanol/acetonitrile and analyzed by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) using a reversed-phase separation followed by electrospray ionization and full scan in positive and negative ion mode. Waters Synapt-G2-Si High-Definition hybrid quadrupole time-of-flight mass spectrometer was used. Significant features were then identified using MSE acquisition mode, recording information on exact mass precursor and fragment ions within the same run. This approach, together with data pre-treatment and multivariate statistical analysis allowed for the identification of compounds able to differentiate between the investigated samples. More than 200 metabolites were identified, being fatty acids, alcohols, aldehydes, phosphatidylcholines, phosphatidylglycerols, ceramides and phosphatidylserines the most abundant classes. Metabolites deriving from food, bacteria and fungi were also determined, providing information on the habits and oral health status of the couple.

From Ties to Events in the Analysis of Interorganizational Exchange Relations.

Relational event models expand the analytical possibilities of existing statistical models for interorganizational networks by: (i) making efficient use of information contained in the sequential ordering of observed events connecting sending and receiving units; (ii) accounting for the intensity of the relation between exchange partners, and (iii) distinguishing between short- and long-term network effects. We introduce a recently developed relational event model (REM) for the analysis of continuously observed interorganizational exchange relations. The combination of efficient sampling algorithms and sender-based stratification makes the models that we present particularly useful for the analysis of very large samples of relational event data generated by interaction among heterogeneous actors. We demonstrate the empirical value of event-oriented network models in two different settings for interorganizational exchange relations-that is, high-frequency overnight transactions among European banks and patient-sharing relations within a community of Italian hospitals. We focus on patterns of direct and generalized reciprocity while accounting for more complex forms of dependence present in the data. Empirical results suggest that distinguishing between degree- and intensity-based network effects, and between short- and long-term effects is crucial to our understanding of the dynamics of interorganizational dependence and exchange relations. We discuss the general implications of these results for the analysis of social interaction data routinely collected in organizational research to examine the evolutionary dynamics of social networks within and between organizations.

Medical cannabinoids for painful symptoms in patients with severe dementia: a randomized, double-blind cross-over placebo-controlled trial protocol.

Background: In an observational study in Geneva (Switzerland), we found that administering a standardized THC/CBD oil was feasible, safe, and beneficial in an elderly polymedicated population with severe dementia, behavioral troubles, and pain. Those findings need to be confirmed in a randomized clinical trial. Objectives: The MedCanDem trial is a randomized, double-blind cross-over placebo-controlled trial to study the efficacy of cannabinoids in improving painful symptoms during severe dementia disorders in patients living in long-term care facilities in Geneva. This manuscript describes the MedCanDem trial protocol. Materials and methods: Participants will be patients suffering from severe dementia associated with pain and behavioral troubles and living in long-term care facilities. We selected five facilities specialized in caring for severely demented patients in Geneva (Switzerland). A total of 24 subjects will be randomized 1:1 to the sequence study intervention/placebo or the sequence placebo/study intervention. Patients will receive study intervention treatment or placebo for eight weeks, and then after a one-week wash-out, treatments will be inversed for another eight weeks. The intervention will be a standardized THC/CBD 1:2 oil extract, and the placebo will be a hemp seed oil. The primary outcome is the reduction from the baseline of the Cohen-Mansfield score; secondary outcomes include the reduction in the Doloplus scale, the reduction of rigidity, the monitoring of concomitant drugs prescription and de-prescription, the safety assessment, and a pharmacokinetic evaluation. The primary and secondary outcomes will be assessed at the baseline, after 28 days, and at the end of both study periods. In addition, safety laboratory analysis, pharmacokinetic evaluation, and therapeutic drug monitoring for the cannabinoids will be evaluated through a blood sample analysis conducted at the beginning and the end of both study periods. Discussion and conclusion: This study will allow us to confirm the clinical results observed during the observational study. It represents one of the few studies aiming to prove natural medical cannabis efficacy in a population of non-communicating patients with severe dementia, experimenting with behavioral troubles, pain, and rigidity. Trial registration: The trial has Swissethics authorization (BASEC 2022-00999), and it is registered on clinicaltrials.gov (NCT05432206) and the SNCTP (000005168).

Drivers of the decrease of patent similarities from 1976 to 2021.

The citation network of patents citing prior art arises from the legal obligation of patent applicants to properly disclose their invention. One way to study the relationship between current patents and their antecedents is by analyzing the similarity between the textual elements of patents. Many patent similarity indicators have shown a constant decrease since the mid-70s. Although several explanations have been proposed, more comprehensive analyses of this phenomenon have been rare. In this paper, we use a computationally efficient measure of patent similarity scores that leverages state-of-the-art Natural Language Processing tools, to investigate potential drivers of this apparent similarity decrease. This is achieved by modeling patent similarity scores by means of generalized additive models. We found that non-linear modeling specifications are able to distinguish between distinct, temporally varying drivers of the patent similarity levels that explain more variation in the data (R2 ∼ 18%) compared to previous methods. Moreover, the model reveals an underlying trend in similarity scores that is fundamentally different from the one presented previously.

Single port surgery in pediatric age: report of first 300 cases.

BACKGROUND: In recent years, evolution of surgery has led to laparoscopy and then to single port surgery. In pediatric age, few papers have been published about single port procedures; in particular, no one has described the use of the Octoport device (Frankenman International Ltd., Suzhou, China). We present our experience using a new device. METHODS: A retrospective analysis of first 300 cases was performed collecting the data of all patients treated with Octoport device from October 2017 to September 2021. Epidemiological data, diagnosis, operative times, and complications were analyzed. Postoperative pain was compared with standard laparoscopy. RESULTS: A total of 300 procedures were performed during the study period. The age range was 1-17 years. The conversion rate was 3.6% (11 patients) including both conversion to traditional laparoscopy and to laparotomy. Pain management was comparable to traditional laparoscopy. The complication rate was 3.6%, in one case leading to re-do surgery. All the cases in our Unit were successfully completed, with complications mainly related to the original pathology rather than to the technique itself. CONCLUSIONS: The learning curve for Octoport use proved to be functional as for standard laparoscopy. In this study, surgical indications for the use of single port laparoscopy were defined, discerning favorable and unfavorable procedures. A proven superiority of this technique over traditional laparoscopy is yet to be defined, but Octoport has proved to be a safe and easy tool to reduce invasiveness of procedures in pediatric surgery with better cosmetic results.

Evaluation of the Benefits of Bilateral Fitting in Bone-Anchored Hearing System Users: Spatial Resolution and Memory for Speech.

OBJECTIVES: The purpose of this study was to evaluate the benefits of bilateral implantation for bone-anchored hearing system (BAHS) users in terms of spatial resolution abilities and auditory memory for speech. DESIGN: This is a prospective, single-center, comparative, single-blinded study where the listeners served as their own control. Twenty-four experienced bone-anchored users with a bilateral conductive or mixed hearing loss participated in the study. After fitting the listeners unilaterally and bilaterally with BAHS sound processor(s) (Ponto 3 SuperPower), spatial resolution was estimated by measuring the minimum audible angle (MAA) to achieve an 80% correct response via a two-alternative-forced choice task (right-left discrimination of noise bursts) in two conditions: both sound processors active (bilateral condition) and only one sound processor active (unilateral condition). In addition, a memory recall test, the Sentence-final Word Identification and Recall (SWIR) test was performed with five lists of seven sentences for each of the two conditions (unilateral and bilateral). Self-reported performance in everyday life with the listener's own sound processors was also evaluated via a questionnaire (the abbreviated version of the Speech, Spatial and Qualities of Hearing scale). RESULTS: The MAA to discriminate noise bursts improved significantly from 75.04° in the unilateral condition to 3.61° in the bilateral condition ( p < 0.0001). The average improvement in performance was 54.28°. The SWIR test results showed that the listeners could recall, on average, 55.03% of the last words in a list of seven sentences in the unilateral condition and 57.23% in the bilateral condition. While the main effect of condition was not significant, there was a significant interaction between condition and repetition (list), revealing a significantly higher recall performance in the bilateral condition than in the unilateral condition for the second repetition/list out of five (10.2% difference; p = 0.022). Self-reported performance with bilateral BAHS obtained via the Speech, Spatial and Qualities of Hearing scale questionnaire was, on average, 4.4 for speech, 3.7 for spatial, and 5.1 for qualities of hearing. There was no correlation between self-reported performance in everyday life and bilateral performance in the MAA test, while significant correlations were obtained between self-reported performance and recall performance in the SWIR test. CONCLUSIONS: These results showed a large benefit in spatial resolution for users with symmetric BC thresholds when being fitted with two BAHS, although their self-reported performance with bilateral BAHS in everyday life was rather low. In addition, there was no overall benefit of bilateral fitting on memory for speech, despite observing a benefit in one out of five repetitions of the SWIR test. Performance in the SWIR test was correlated with the users' self-reported performance in everyday life, such that users with higher recall ability reported to achieve better performance in real life. These findings highlight the advantages of bilateral fitting on spatial resolution, although bilaterally fitted BAHS users continue to experience some difficulties in their daily lives, especially when locating sounds, judging distance and movement. More research is needed to support a higher penetration of bilateral BAHS treatment for bilateral conductive and mixed hearing losses.

Metrological traceability in process analytical technologies and point-of-need technologies for food safety and quality control: not a straightforward issue.

Traditional techniques for food analysis are based on off-line laboratory methods that are expensive and time-consuming and often require qualified personnel. Despite the high standards of accuracy and metrological traceability, these well-established methods do not facilitate real-time process monitoring and timely on-site decision-making as required for food safety and quality control. The future of food testing includes rapid, cost-effective, portable, and simple methods for both qualitative screening and quantification of food contaminants, as well as continuous, real-time measurement in production lines. Process automatization through process analytical technologies (PAT) is an increasing trend in the food industry as a way to achieve improved product quality, safety, and consistency, reduced production cycle times, minimal product waste or reworks, and the possibility for real-time product release. Novel methods of analysis for point-of-need (PON) screening could greatly improve food testing by allowing non-experts, such as consumers, to test in situ food products using portable instruments, smartphones, or even visual naked-eye inspections, or farmers and small producers to monitor products in the field. This requires the attention of the research community and devices manufacturers to ensure reliability of measurement results from PAT strategy and PON tests through the demonstration and critical evaluation of performance characteristics. The fitness for purpose of methods in real-life conditions is a priority that should not be overlooked in order to maintain an effective and harmonized food safety policy.

An Efficient Solid-Phase Microextraction-Gas Chromatography-Mass Spectrometry Method for the Analysis of Methyl Farnesoate Released in Growth Medium by Daphnia pulex.

Methyl farnesoate (MF), a juvenile hormone, can influence phenotypic traits and stimulates male production in daphnids. MF is produced endogenously in response to stressful conditions, but it is not known whether this hormone can also be released into the environment to mediate stress signaling. In the present study, for the first time, a reliable solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method was developed and validated for the ultra-trace analysis of MF released in growth medium by Daphnia pulex maintained in presence of crowding w/o MK801, a putative upstream inhibitor of MF endogenous production. Two different clonal lineages, I and S clones, which differ in the sensitivity to the stimuli leading to male production, were also compared. A detection limit of 1.3 ng/L was achieved, along with good precision and trueness, thus enabling the quantitation of MF at ultra-trace level. The achieved results demonstrated the release of MF by both clones at the 20 ng/L level in control conditions, whereas a significant decrease in the presence of crowding was assessed. As expected, a further reduction was obtained in the presence of MK801. These findings strengthen the link between environmental stimuli and the MF signaling pathway. Daphnia pulex, by releasing the juvenile hormone MF in the medium, could regulate population dynamics by means of an autoregulatory feedback loop that controls the intra- and extra-individual-level release of MF produced by endogenous biosynthesis.

Cannabinoids for behavioral symptoms in severe dementia: Safety and feasibility in a long-term pilot observational study in nineteen patients.

Context: The management of behavioral symptoms and rigidity in patients with dementia constitutes a significant challenge. Short-term studies suggest an interest in the use of medical cannabis, but long-term data are lacking. Objectives: The objective of this study was to investigate the feasibility and long-term safety of administering tetrahydrocannabinol/cannabidiol (THC/CBD) treatment as an additional drug to a poly medicated population with severe dementia, evaluate clinical improvements, and collect information on the pharmacokinetics of cannabinoids and possible drug-drug interactions. Methods: A prospective observational study of patients with severe dementia living in a long-term care home to whom the physicians had prescribed a medical cannabis treatment. Data were collected over 2 years. We assessed the changes in medical cannabis dosages, safety parameters, variations in neuropsychiatric problems, agitation, rigidity, the most invalidating daily activity, and disabling behavior trouble scores. We evaluated the pharmacokinetics of cannabinoids by measuring plasma levels and analyzing the enzymatic activity. Results: We assessed 19 patients (81.4 years-17 women and two men) receiving an average of 12.4 mg THC/24.8 mg CBD per day for up to 13 months, with no reported problems related to the treatment and limited adverse drug reactions. Clinical scores showed a marked improvement that was stable over time, deprescription of other medications, and care facilitated. The pharmacokinetic evaluation showed an expected slight reduction in the enzymatic activity of CYP1A2 and CYP2C19. Conclusion: A long-term THC/CBD (1:2) medication can be administered safely and with overall positive clinical improvement to poly medicated older adults with severe dementia and associated problems. The results must be confirmed in a randomized trial.

How do turbidite systems behave from the hydrogeological point of view? New insights and open questions coming from an interdisciplinary work in southern Italy.

Turbidite successions can behave either as aquitards or aquifers depending on their lithological and hydraulic features. In particular, post-depositional processes can increase rock permeability due to fracture development in the competent layers. Thus, at a local scale, turbidite systems warrant further detailed investigations, aimed at reconstructing reliable hydrogeological models. The objective of this work was to investigate from the hydrogeological perspective a turbiditic aquifer located in southern Italy, where several perennial and seasonal springs were detected. Considering the complex hydrodynamics of these systems at the catchment scale, to reach an optimal characterization, a multidisciplinary approach was adopted. The conceptual framework employed microbial communities as groundwater tracers, together with the physicochemical features and isotopic signature of springs and streams from water samples. Meanwhile, geophysical investigations coupled with the geological survey provided the contextualization of the hydrogeological data into the detailed geological reconstruction of the study area. This modus operandi allowed us to typify several differences among the samples, allowing identification of sources and paths of surface water and groundwater, along with diffuse groundwater outflow along streams. As a final result, a hydrogeological conceptual model was reconstructed, underlining how at a very local scale the lithologic, hydraulic, and geomorphological heterogeneity of the studied relief can lead to an improved hydrogeological conceptual model compared to that of other turbidite systems. These results open new questions about the hydrogeological behavior of turbiditic aquifers, which could be pivotal in future research. In fact, these systems could support relevant ecosystems and anthropic activities, especially where climate change will force the research of new (and probably less hydrogeologically efficient) water sources.