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Abstract Complex disease phenotypes often span multiple molecular processes. Functional characterization of these processes can shed light on disease mechanisms and drug effects. Thermal Proteome Profiling (TPP) is a mass-spectrometry (MS) based technique assessing changes in thermal protein stability that can serve as proxies of functional protein changes. These unique insights of TPP can complement those obtained by other omics technologies. Here, we show how TPP can be integrated with phosphoproteomics and transcriptomics in a network-based approach using COSMOS, a multi-omics integration framework, to provide an integrated view of transcription factors, kinases and proteins with altered thermal stability. This allowed us to recover consequences of Poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer cells on cell cycle and DNA damage response as well as interferon and hippo signaling. We found that TPP offers a complementary perspective to other omics data modalities, and that its integration allowed us to obtain a more complete molecular overview of PARP inhibition. We anticipate that this strategy can be used to integrate functional proteomics with other omics to study molecular processes.

Lubricant oils are largely responsible for environmental contamination and surfactants can hopefully improve the bioremediation process in soils contaminated with this kind of waste. However, to date only a few studies have elucidated how different surfactants affect the bioremediation process in oil-contaminated soils using the bioaugmentation technique. Thus, this study aimed to compare the effects of surfactants on the bioremediation process of waste lubricant oil in soil in association or not with bioaugmentation. Three biostimulating agents were tested: a chemical detergent, a synthetic surfactant, and a biosurfactant (rhamnolipid). The bioaugmentation process with Pseudomonas aeruginosa showed a faster biodegradation activity with total biodegradation on 181 day after application. The biosurfactant increased the number of microbial and fungal colonies leading to high biodegradation levels and a quicker treatment with or without the bioaugmentation. Bioaugmentation associated with biosurfactant reached 30.43 mg of CO2 of production on 181 day (90% of total biodegradation of waste lubricant oil) and reduced soil toxicity to 30%. Therefore, results showed that the association of biosurfactant and bioaugmentation with P. aeruginosa represents an ecologically viable strategy for bioremediation of soils contaminated with waste lubricant oil. [ABSTRACT FROM AUTHOR]

background: We conducted a systematic review and meta-analysis to evaluate the role of High Energy Devices (HEDs) versus conventional clamp and tie technique in thyroidectomy. This work is endorsed by the Italian Society of Surgical Endoscopy (Italian Society of Endoscopic Surgery and new technologies—SICE) in the broader project on the evaluation of the role of HEDs in different surgical settings with the full health technology assessment report. Mehods: Inclusion criteria were adult patients (≥ 18 years old) undergoing Thyroidectomy/Parathyroidectomy conducted with High Energy Devices (as ultrasonic (US), radiofrequency (RF), and hybrid energy (H-US/RF)) in the setting of thyroid surgery (both partial and total) for benign and malign diseases. However, some variability was found in included studies and described in the text. This systematic review and meta-analysis were performed according to the Cochrane handbook for systematic reviews, and the recommendations of the 2020 updated Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines were pursuit. Selection of abstracts was performed in Ryyan system by 2 independent reviewers, and doubts were solved by another independent reviewer. At the end of literature research, Randomized controlled trials and observational studies were included. Risk of Bias was assessed with ROB2 for RCTs, and New Castle Ottawa Scale for Observational studies. Results: The literature search yielded 47 studies, including 29 RCTs and 18 observational studies. Meta-analysis was performed for 29 randomized clinical trials. Outcomes included in the comparison between High Energy Devise and conventional technique groups were operative time, operative blood loss, overall post-operative drainage volume, length of stay, complications, and costs. HED significantly reduced operative time (28 studies, 3097patients; MD -128.8; 95% CI -34.4 to -23.20; I2 = 96%, p < 0.00001, Random-effect), intra-operative blood loss (13 studies, 642 vs 519 patients; SMD -0.82; 95% CI -1.33 to -0.32; I2 = 93%, p < 0.00001, Random-effect), LOS (22 studies, 2808 vs 2789 patients; MD -0.38, 95% CI -0.59 to -0.17; I2 = 98%, p < 0.00001 Random-effect), and healthcare costs (8 studies, 1138 vs 1129 patients, SMD 1.05; 95% CI -0.06 to 2.16; I2 = 99%, p < 0.00001 Random-effect). The rate of overall intraoperative complications was significantly different between both groups (25 studies, 2804 vs 2775 patients; RR 0.88, 95% CI 0.80 to 0.97; I2 = 38%, p = 0.03 Random-effect), but the sensitivity analysis did not find a statistically significant difference (6 studies, 605 vs 594 patients, RR; 95% CI to; I2 = 0%, p = 0.50, Random-effect). There was no difference in the subgroup analysis for the occurrence of transient and permanent RLN palsy, nor hematoma formation and hypocalcaemia. Discussion: Though findings of our systematic review and metanalysis are limited by heterogeneous data, surgeons, hospital managers, and policymakers should note that the use of High Energy Devices compared to conventional clamp and tie technique have reduced operative times, intra-operative blood loss, length of stay, and hospital costs in patients underwent to tyroid surgery. Future work must explore issues of equity to mitigate barriers to patient access to safe thyroid surgical care and define better this initial results. [ABSTRACT FROM AUTHOR]

The hydrothermal conversion of a complex sugars solution comprising glucose, arabinose, and xylose with zirconia-based catalysts to produce lactic acid (LA) was studied. Catalysts were synthesized by a simple template-assisted sol–gel method. Alternative template removal procedures, such as refluxing ethanol extraction, were compared to the conventional direct calcination. The catalyst obtained after ethanol extraction (Z-Ex) reported the highest specific surface area (323 m2 g−1), total pore volume (0.21 cm3 g−1) and density of acid sites (1.111 µmol m−2), with a significant contribution of strong acid sites. On the other hand, template removal by thermal treatment transformed the hydrous zirconia into crystalline tetragonal phase, reducing the specific surface area and removing most of the acid sites. Catalytic tests were carried out in a stirred batch reactor, resulting Z-Ex the most selective towards LA production. A four-factor experimental design was performed for Z-Ex catalyst by varying temperature, reaction time, initial pressure, and catalyst/reactants ratio. Results were analyzed using the response surface methodology (RSM) to maximize the LA production. A molar yield of 61.2% towards LA and complete sugars conversion were reached at optimized operating conditions: 189 °C, 208 min, 0.5 g catalyst g−1 reactants, and 10 bar N2. Additionally, fitting models for main by-products molar yields (furans, glyceraldehyde, glycolic, formic, acetic, and levulinic acids) were obtained with good accuracy prediction. All responses were jointly studied to understand the reaction mechanisms involved in generation of intermediaries and undesired degradation products. [ABSTRACT FROM AUTHOR]

In this article, we consider the numerical prediction of the noise emission from a wheelset in laboratory conditions. We focus on the fluid–structure interaction leading to sound emission in the fluid domain by analyzing three different methods to account for acoustic sources. These are a discretized baffled piston using the discrete calculation method (DCM), a closed cylindrical volume using the boundary element method (BEM) and radiating elastic disks in a cubic enclosure solved with the finite element method (FEM). We provide the validation of the baffled piston and the BEM using measurements of the noise emission of a railway wheel by considering ground reflections in the numerical models. Selected space-resolved waveforms are compared with experimental results as well as with a fluid–structure interaction finite element model. The computational advantage of a discretized disk mounted on a baffle and BEM compared to FEM is highlighted, and the baffled pistons limitations caused by a lack of edge radiation effects are investigated. [ABSTRACT FROM AUTHOR]

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment. [ABSTRACT FROM AUTHOR]

The disturbance of infrastructures may affect biological communities that are exposed to them. This study assesses the impact of high-speed (highway and railway) infrastructures in a protected study site, the Natural Reserve Fontanili di Corte Valle Re (Emilia–Romagna, Italy). We compared bird diversity with sound intensity and frequency in three sampling areas, increasingly distant from the infrastructures at the border with the reserve, during the last 4 years (2019–2022), monitoring sedentary, nesting, and migratory bird species. We hypothesize a decreasing diversity closer to the source of disturbance, which is mostly attributable to noise pollution. Our findings confirmed this trend, and we show that, in particular, disturbance seems to influence species richness more than the total abundance of birds. We also discovered that highway disturbance was much higher than railway in terms of frequency and duration. In light of these results, we suggest that some species, which have a behavioral ecology strongly based on singing to communicate with each other for their reproductive and defensive strategies, may suffer more from constant acoustic disturbance. The installation of effective noise barriers to shield the sound produced by the highways should be considered a mandatory request not only in proximity to houses but also in the vicinity of protected areas. [ABSTRACT FROM AUTHOR]

Objective: The videolaryngostroboscopy parameters form (VLSP form) is a diagnostic tool for the collection of videolaryngostroboscopic basic findings through the evaluation of 12 parameters. The aim of the present study is to preliminarily investigate intra- and inter-rater reliability, validity and responsiveness of the VLSP form. Methods: A study on a total amount of 160 forms for the evaluation of VLS basic findings was carried out. 80 forms were scored through the VLSP form and 80 with the Voice Vibratory Assessment with Laryngeal Imaging (VALI) form Stroboscopy (S) by four expert phoniatricians, that blindly scored the VLS recordings of 5 subjects without voice disorders and 5 patients with organic voice disorder before and after successful phonosurgery. Intra-rater and inter-rater analysis have been performed for both forms. The scores obtained through VLSP form and VALI form S have been compared to analyse concurrent validity, while VLSP scores before and after phonosurgery have been compared to analyse responsiveness. Finally, each rater annotated the "difficulty" in rating every parameter and its "importance" for the diagnosis. Results: The VLSP form showed good inter- and intra-rater reliability. It showed a good accuracy for the documentation of changes of laryngeal anatomy and function after phonosurgery, similarly to the VALI form S. The 12 parameters of the VLSP form were judged "Slightly Important" in 28.3% of the samples, "Very Important" in 64.8% of the samples, "Not Difficult" in 73.1% of the samples. Conclusions: The results of the present study suggest that the VLSP form is comparable to the VALI form S for the evaluation of videolaryngostroboscopic parameters and is a valid, reliable and reproducible diagnostic tool. It can help voice clinicians in the evaluation of VLS examinations and it allows for a punctual assessment of modifications in laryngeal anatomy and function in pathological conditions and after phonosurgery. [ABSTRACT FROM AUTHOR]

Purpose: Emergency treatment of acute diverticulitis remains a hazy field. Despite a number of clinical studies, randomized controlled trials (RCTs), guidelines and surgical societies recommendations, the most critical hot topics have yet to be addressed. Methods: Literature research from 1963 until today was performed. Data regarding the principal RCTs and observational studies were summarized in descriptive tables. In particular we aimed to focus on the following topics: the role of laparoscopy, the acute care setting, the RCTs, guidelines, observational studies and classifications proposed by literature, the problem in case of a pandemic, and the importance of adapting treatment /place/surgeon conditions. Results: In the evaluation of these points we did not try to find any prospective evolution of the concepts achievements. On the contrary we simply report the individuals strands of research from a retrospective point of view, similarly to what Steve Jobes said: "you can't connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future". We have finally obtained what can be defined "a narrative review of the literature on diverticulitis". Conclusions: Not only evidence-based medicine but also the contextualization, as also the role of 'competent' surgeons, should guide to novel approach in acute diverticulitis management. [ABSTRACT FROM AUTHOR]

Purpose: To characterise dynamic postural stability of gait in patients with vestibular hypofunction (PwVH) using a sensor-based assessment while performing dynamic tasks and to correlate the results of this evaluation with clinical scales. Methods: This cross-sectional study involved 22 adults between 18 and 70 years old from a healthcare hospital centre. Eleven patients suffering from chronic vestibular hypofunction (PwVH) and eleven healthy controls (HC) were evaluated through a combined inertial sensor-based and clinical scale assessment. Participants were equipped with five synchronised inertial measurement units (IMUs) (128 Hz, Opal, APDM, Portland, OR, USA): three IMUs were located on the occipital cranium bone, near the lambdoid suture of the head, at the centre of the sternum, and at L4/L5 level, just above the pelvis, and were used to quantify gait quality parameters, while the other two were located slightly above lateral malleoli and used to perform stride and step segmentation. Three different motor tasks were performed in a randomized order: the 10-m Walk Test (10mWT), the Figure of Eight Walk Test (Fo8WT) and the Fukuda Stepping Test (FST). A set of gait quality parameters related to stability, symmetry and smoothness of gait were extracted from IMU data and correlated with the clinical scale scores. PwVH and HC results were compared to test for significant between-group differences. Results: Significant differences were found for the three motor tasks (10mWT, Fo8WT and FST) when comparing PwVH and HC groups. For the 10mWT and the Fo8WT, significant differences between the PwVH and HC groups were found for the stability indexes. Considering the FST, significant differences between the PwVH and HC groups were also found in the stability and symmetry of gait. A significant correlation was found between the Dizziness Handicap Inventory and gait indices during the Fo8WT. Conclusions: In this study, we characterized the dynamic postural stability alterations during linear, curved, and blindfolded walking/stepping in PwVH combining an instrumental IMU-based with traditional clinical scales approach. Combining instrumental and clinical evaluation for dynamic stability of gait alterations in PwVH is useful in thoroughly evaluating the effects of unilateral vestibular hypofunction. [ABSTRACT FROM AUTHOR]

Aim: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. Methods: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. Results: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. Conclusion: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients’ compliance and overall treatment time of the radiation course is still unclear and needs further investigation. [ABSTRACT FROM AUTHOR]

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A β-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5–7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates. Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy. [ABSTRACT FROM AUTHOR]

Different types of lasers have been applied for various proctological conditions. We discuss about published articles regarding the application of lasers, with concern about evidence-based use of these techniques and technologies. We performed a literature search about laser treatments for proctological conditions. 55 studies were included for the final revision. Meta-analysis of data was not performed because of heterogeneity of study designs and outcome measures. A scoping review was performed. Laser treatments for hemorrhoids require a shorter operative time and show less postoperative pain and bleeding compared to conventional hemorrhoidectomy, but are more expensive. Studies are heterogeneous in design, endpoints, postoperative assessment, length of follow-up and outcome measures. Only 3 RCTs are available and only three studies evaluate long-term outcomes. FiLaC (fistula laser closure) was initially described in 2011 for the treatment of anal fistula. In the published studies the reported healing rates vary between 20 and 82%, and the ideal indication is yet to be defined. Studies with long-term follow-up are lacking. SiLaT (sinus laser treatment) applied the technology used for FiLaC to the treatment of pilonidal sinus disease. This technique had less perioperative pain and shorter hospital stay, but a lower primary healing rate when compared to traditional techniques. Available data is very limited, and no randomized trials are published to date. Laser assisted techniques are a viable, minimally invasive, but expensive option for the treatment of several proctological conditions. Further researches are needed to assess if patients could benefit of their use, and for what indication. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review paper is intended to show that changes in body composition are key in the pathogenesis of bone fragility amongst patients with breast and prostate cancer receiving hormone deprivation therapies (HDTs) and that the mechanism is based on the development of alterations in bone quality rather than in bone quantity. Recent Findings: Preclinical and clinical data suggest a tight connection amongst bone, adipose and muscular tissues by means of several soluble mediators, potentially leading to (1) bone resorption and bone quality deterioration in sarcopenic obese subjects, (2) bone mineral deposition in healthy trained subjects. Cancer patients treated with HDTs frequently fall into the first condition, named osteosarcopenic obesity. Summary: Current clinical guidelines for the prevention of treatment-induced osteoporosis focus on bone mineral density (BMD) as a main predictive factor for fracture risk; however, the pathophysiology underlying HDT-induced bone fragility differs from that of primary and postmenopausal osteoporosis, suggesting a prevalent role for bone quality alterations. Focusing on available data from clinical trials, in our review we suggest osteosarcopenic obesity as a common target for the prevention and treatment of HDTs-related metabolic and skeletal complications, beyond a BMD-centred approach. [ABSTRACT FROM AUTHOR]

The authors discuss the incidence, the embryological development, the classification, the presentation and the treatment options of this rare reproductive tract abnormality. In the past, the treatment proposed almost unanimously was hysterectomy and subsequent construction, when necessary, of a neovagina. In recent decades, numerous experiences of conservative therapies have accumulated that allow the restoration of menstrual function and in some rare cases even the achievement of a pregnancy. However, complications associated with recanalization of the cervix frequently resulted in the need for repeated surgery, risk of serious and sometimes fatal ascending infection. This review aims to analyze the most recent and significant experiences of conservative surgery in this field to provide an accurate picture of the various techniques and their outcomes, especially from the point of view of fertility. Conservative surgery should now be considered as the first-line treatment option. On the other hand, it is not possible to draw conclusions on the superiority of one technique over another among the various conservative options. This would require large series with adequate follow-up, which unfortunately are not available. [ABSTRACT FROM AUTHOR]

Hepcidin, the hepatic iron hormone, is the central regulator of iron homeostasis. Cyclic AMP-Responsive Element-Binding protein 3-like 3 (CREB3L3/CREB-H) is a liver homeostatic regulator of essential nutrients (i.e. glucose and lipids) and has been previously involved in hepcidin response to pathologic stress signals. Here, we asked whether CREB-H has also a physiologic role in iron homeostasis through hepcidin. To this end, we analyzed hepcidin gene expression and regulation in the liver of wild type and Creb3l3 knockout mice during early postnatal development, as a model of "physiologic" stressful condition. The effect of iron challenge in vivo and BMP6 stimulation in vitro have been also addressed. In addition, we investigated the BMP signaling pathway and hepcidin promoter activity following CREB3L3 silencing and hepcidin promoter mutation in HepG2 cells. Creb3l3 knockout suckling and young-adult mice showed a prominent serum and hepatic iron accumulation, respectively, due to impaired hepcidin mRNA expression which progressively returned to normal level in adult mice. Interestingly, upon iron challenge, while the upstream BMP/SMAD signaling pathway controlling hepcidin was equally responsive in both strains, hepcidin gene expression was impaired in knockout mice and more iron accumulated in the liver. Accordingly, hepcidin gene response to BMP6 was blunted in primary CREB-H knockout hepatocytes and in HepG2 cells transfected with CREB-H siRNA or carrying a hepcidin promoter mutated in the CREB-H binding site. In conclusion, CREB-H has a role in maintaining the homeostatic balance of iron traffic through hepcidin during the critical postnatal period and in response to iron challenge. Key messages: CREB-H KO mice develop liver iron overload shortly after weaning that normalizes in adulthood. CHEB-H is involved in hepcidin gene response to oral iron in vivo. CREB-H loss hampers hepcidin promoter response to BMP6. CREB-H is a key stress-sensor controlling hepcidin gene transcription in physiologic and pathophysiologic states. [ABSTRACT FROM AUTHOR]

The objective of this research was to produce an activated carbon (AC) from exhausted coffee grounds (ECG) and chemically activate it with natural lye from eucalyptus ash to subsequently evaluate the fluoride adsorption process in an aqueous medium. The thermal analysis of ECG was determined as well as solubilized extraction, alkalinity and calcium content of eucalyptus ashes. AC was characterized by elemental analysis, scanning electron microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), analysis of textural properties, pH and point of zero charge (PZC). The AC presented macroporosity and XRD confirmed the amorphous characteristic of cellulose-containing materials. Carboxylic acid functional group was identified in the AC surface, which can contribute to the adsorption of fluoride. The specific surface area of ECG and AC were 189.01 and 21.74 m2/g. The adsorption kinetics of fluoride revealed that equilibrium is reached around 800 min and the data followed the pseudo-second order model. The Freundlich model fitted the experimental data with the best quality and Freundlich's constant n allowed inferring that the adsorption is favorable and the isotherm appears to be L-type, with an initial downward curvature, which suggests less availability of active sites when increasing the adsorbent concentration. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases are those caused by infectious agents or parasites and are considered endemic in low-income populations. These diseases also have unacceptable indicators and low investment in research, drug production, and control. Tropical diseases such as leishmaniasis are some of the main causes of morbidity and mortality around the globe. Electrochemical immunosensors are promising tools for diagnostics against these diseases. One such benefit is the possibility of assisting diagnosis in isolated regions, where laboratory infrastructure is lacking. In this work, different peptides were investigated to detect antibodies against Leishmania in human and canine serum samples. The peptides evaluated (395-KKG and 395-G) have the same recognition site but differ on their solid-binding domains, which ensure affinity to spontaneously bind to either graphene oxide (GO) or graphene quantum dots (GQD). Cyclic voltammetry and differential pulse voltammetry were employed to investigate the electrochemical behavior of each assembly step and the role of each solid-binding domain coupled to its anchoring material. The graphene affinity peptide (395-G) showed better reproducibility and selectivity when coupled to GQD. Under the optimized set of experimental conditions, negative and positive human serum samples responses were distinguished based on a cut-off value of 82.5% at a 95% confidence level. The immunosensor showed selective behavior to antibodies against Mycobacterium leprae and Mycobacterium tuberculosis, which are similar antibodies and potentially sources of false positive tests. Therefore, the use of the graphene affinity peptide as a recognition site achieved outstanding performance for the detection of Leishmania antibodies. [ABSTRACT FROM AUTHOR]

In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. 1,2) do not provide enough ionizing photons to drive this cosmic reionization. Fainter galaxies are thought to dominate the photon budget; however, they are surrounded by neutral gas that prevents the escape of the Lyman-α photons, which has been the dominant way to identify them so far. JD1 was previously identified as a triply-imaged galaxy with a magnification factor of 13 provided by the foreground cluster Abell 2744 (ref. 3), and a photometric redshift of z ≈ 10. Here we report the spectroscopic confirmation of this very low luminosity (≈0.05 L*) galaxy at z = 9.79, observed 480 Myr after the Big Bang, by means of the identification of the Lyman break and redward continuum, as well as multiple ≳4σ emission lines, with the Near-InfraRed Spectrograph (NIRSpec) and Near-InfraRed Camera (NIRCam) instruments. The combination of the James Webb Space Telescope (JWST) and gravitational lensing shows that this ultra-faint galaxy (MUV = −17.35)—with a luminosity typical of the sources responsible for cosmic reionization—has a compact (≈150 pc) and complex morphology, low stellar mass (107.19 M⊙) and subsolar (≈0.6 Z⊙) gas-phase metallicity.The JWST, with the aid of gravitational lensing, confirms the extreme distance of an ultra-faint galaxy at a redshift of 9.79, showing it to have a luminosity typical of the sources responsible for cosmic reionization and highly compact and complex morphology. [ABSTRACT FROM AUTHOR]

Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress. In adult male mice, the effects of chronic social stress on discriminative reward learning and reward effort are shown to be mediated by reward-encoding and aversion-encoding neurons, respectively, in amygdala-nucleus accumbens circuitry [ABSTRACT FROM AUTHOR]

Forest school is a form of outdoor learning that takes children into regular and repeated learning experiences in natural settings. Being based on a comprehensive experience with nature, it is assumed to be beneficial for learning and to promote restorative effects on cognitive and emotional function in preschool children. This review aimed to examine the available evidence on the benefits of forest school compared to indoor school activities in children aged 3 to 6 years. We searched for studies on forest school for preschool children in PsycInfo, JSTOR, and Scopus, with no restriction on publication year. The risk of bias was assessed using Joanna Briggs’s criteria for quasi-experimental design. Of the 190 articles identified, 16 studies were reviewed (N = 1560). Higher benefits were found in children attending forest school compared to those attending indoor school in various areas of child development: cognitive function, motor coordination and balance, connectedness to nature, and health and well-being outcomes. There is, however, still a shortage of empirical evidence, and the methodological quality of most studies was limited. The literature on forest schools for preschool children in general supports positive effects in a wide range of variables that promote child health and development, but more evidence is needed to assess their effectiveness. Due to the methodological weaknesses of the reviewed studies, one should interpret their findings with caution. [ABSTRACT FROM AUTHOR]

Purpose: Adrenocortical carcinoma (A.C.C.) is a rare tumour, often discovered at an advanced stage and associated with a poor prognosis. Surgery is the treatment of choice. We aimed to review the different surgical approaches trying to compare their outcome. Methods: This comprehensive review has been carried out according to the PRISMA statement. The literature search was performed in PubMed, Scopus, the Cochrane Library and Google Scholar. Results: Among all studies identified, 18 were selected for the review. A total of 14,600 patients were included in the studies, of whom 4421 were treated by mini-invasive surgery (M.I.S.). Ten studies reported 531 conversions from M.I.S. to an open approach (OA) (12%). Differences were reported for operative times as well as for postoperative complications more often in favour of OA, whereas differences for hospitalization time in favour of M.I.S. Some studies showed an R0 resection rate from 77 to 89% for A.C.C. treated by OA and 67 to 85% for tumours treated by M.I.S. The overall recurrence rate ranged from 24 to 29% for A.C.C. treated by OA and from 26 to 36% for tumours treated by M.I.S. Conclusions: OA should still be considered the standard surgical management of A.C.C. Laparoscopic adrenalectomy has shown shorter hospital stays and faster recovery compared to open surgery. However, the laparoscopic approach resulted in the worst recurrence rate, time to recurrence and cancer-specific mortality in stages I–III ACC. The robotic approach had similar complications rate and hospital stays, but there are still scarce results about oncologic follow-up. [ABSTRACT FROM AUTHOR]

Purpose: This review aims at investigating pathophysiological mechanisms in spondyloarthritis (SpA). Analysis of genetic factors, immunological pathways, and abnormalities of bone metabolism lay the foundations for a better understanding of development of the axial clinical manifestations in patients, allowing physician to choose the most appropriate therapeutic strategy in a more targeted manner. Recent Findings: In addition to the contribution of MHC system, findings emerged about the role of non-HLA genes (as ERAP1 and 2, whose inhibition could represent a new therapeutic approach) and of epigenetic mechanisms that regulate the expression of genes involved in SpA pathogenesis. Increasing evidence of bone metabolism abnormalities secondary to the activation of immunological pathways suggests the development of various bone anomalies that are present in axSpA patients. Summary: SpA are a group of inflammatory diseases with a multifactorial origin, whose pathogenesis is linked to the genetic predisposition, the action of environmental risk factors, and the activation of immune response. It is now well known how bone metabolism leads to long-term structural damage via increased bone turnover, bone loss and osteoporosis, osteitis, erosions, osteosclerosis, and osteoproliferation. These effects can exist in the same patient over time or even simultaneously. Evidence suggests a cross relationship among innate immunity, autoimmunity, and bone remodeling in SpA, making treatment approach a challenge for rheumatologists. Specifically, treatment targets are consistently increasing as new drugs are upcoming. Both biological and targeted synthetic drugs are promising in terms of their efficacy and safety profile in patients affected by SpA. [ABSTRACT FROM AUTHOR]

Purpose: Whether or not androgen receptor (AR) axis could still be targetable in castration resistant prostate cancer (CRPC) patients with disease progression to next generation hormonal agents (NGHAs) is a controversial issue. Results: Serum testosterone in CRPC patients has a positive prognostic role and increasing testosterone levels after androgen deprivation therapy (ADT) withdrawal or testosterone supplementation, as part of a bipolar androgen therapy (BAT) strategy, has been shown to potentially restore sensitivity to previous lines of NGHAs. Conclusion: These data suggest that maintenance of ADT in CRPC patients receiving further lines of treatment, as recommended by current international guidelines, could be questionable. Conversely, testosterone supplementation aimed to re-sensitize CRPC to further hormonal manipulation is a strategy worth to be explored in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy negatively affects gonadal function, often resulting in premature ovarian failure (POF) due to ovarian reserve depletion. Mechanisms of gonadotoxicity, such as primordial follicle overactivation and "burnout", remain to be established. Ovarian tissue cryopreservation (OTC) before treatment plays an important role in safeguarding fertility.Methods: This is a prospective observational study that aims to evaluate the feasibility of OTC after chemotherapeutic treatment initiation. Patients were divided into 2 groups depending on whether they received chemotherapy before the harvesting procedure (Group 1) or not (Group 2). The main outcomes of this study are serum anti-Mullerian hormone (AMH) levels and histological follicular counts on ovarian tissue biopsies.Results: Between 2012 and 2020, 79 patients underwent OTC at our Hospital. Follicular counts from the ovarian biopsies of 30 post-pubertal patients and respective serum AMH levels were included in the analysis. AMH levels did not significantly differ between the 2 groups (P = 0.70) as well as the number of primordial follicles (P = 0.73). Ovarian biopsies of patients from Group 1 showed a higher number of primary follicles (P = 0.04) and atretic follicles (P = 0.05) with respect to Group 2.Conclusions: In conclusion, OTC appears to be feasible even after the start of chemotherapeutic treatment, since in treated patients, the main ovarian reserve indicators (number of primordial follicles and serum AMH levels) were not significantly reduced compared to untreated patients. The "burnout" theory of chemotherapeutic damage to the ovary seems to be supported by the higher number of primary follicles found in the ovaries of patients who received chemotherapy before OTC. [ABSTRACT FROM AUTHOR]

Governments are updating national strategies to meet global goals on biodiversity, climate change and food systems proposed in the Convention on Biological Diversity post-2020 framework and agreed at the United Nation's Climate Change Conference (COP26) and Food Systems Summit (UNFSS). This represents a unique and crucial opportunity to integrate and accelerate food system actions to tackle interconnected global challenges. In this context, agroecology is a game-changing approach that can provide the world's growing population with nutritious, healthy affordable food, ensure fair incomes to farmers and halt and reverse the degradation of the natural environment. Here, we explore agroecological transition pathways in four case studies from low- and middle- income countries and identify catalysts for change. We find that enabling policy and market environments, participatory action research and local socio-technical support each plays a critical role in stimulating transitions towards agroecology. We propose strategies and priorities for research to better support agroecological transitions using these catalysts of change as entry points. Engagement of governments, private sector, civil society, farmers and farm workers in this research agenda is essential. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to investigate the socio-demographic, clinical, and psychological variables predictive of a greater functioning and quality of life in patients with gynecological cancer after their first cycle of carboplatin and taxol-based chemotherapy.Methods: The sample of the present research consisted of 104 patients. The European Organization on Research and Treatment of Cancer QLQ-C30, the State-Trait Anxiety Inventory-Form Y, and the Multidimensional Scale of Perceived Social Support were administered to each participant.Results: The analyses showed that higher state anxiety levels predicted a lower role, emotional, and social functioning and a lower general quality of life. Higher trait anxiety levels and social support perceived from one's friends predicted a greater role functioning. Similarly, having a relationship predicted a greater physical, cognitive, and social functioning. On the contrary, the presence of relapsed cancer was negatively associated with these patients' quality of life.Conclusions: The present study highlighted the importance of identifying patients at higher risk of experiencing lower levels of functioning and worse general quality of life to implement tailored interventions from the beginning of treatment, thus improving the quality of life of these patients throughout the chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Purpose: To propose an algorithm of the major and minor diagnostic criteria for macular myopic choroidal neovascularization (mCNV). Methods: This single-center, retrospective, cross-sectional study was based in Istituto Auxologico Italiano, Milan, Italy. Two authors evaluated the clinical and imaging parameters of eyes with high myopia (spherical equivalent of -6D or less) and suspected to have naïve, recurrent, or inactive mCNV. Recordings of the eyes that met the inclusion criteria were then independently evaluated by two other senior retinal specialists. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and OCT angiography were used for multimodal imaging. Results: One-hundred and twenty-two eyes (n = 107; 39 men, 68 women) were included in the study. The mean patient age was 66 years (range, 22–89 years). There were 83 and 39 eyes in the active mCNV and control groups, respectively. The best diagnostic algorithm had positive- and negative-predictive values of 89% and 85%, respectively, and was based on four criteria: leakage/staining on FA, retinal thickening, fuzzy area on SD-OCT, and recent metamorphopsia. When excluding FA-derived findings, retinal pigment epithelium (RPE) features played a diagnostic role in 33 eyes (27%). Twenty-seven eyes with active mCNV (32%) did not have the fuzzy area. Taken singularly, no clinical or imaging parameter had both sensitivity and specificity greater than 78%. Matching of 2 or 3 biomarkers did not yield a sensitivity or specificity greater than 79%. Sensitivities and specificities ≥ 90% were found in ten criteria combinations that included four to five biomarkers. The most frequent were metamorphopsia, fuzzy area, retinal thickening, and leakage. Less frequently, they included hemorrhage, staining, and RPE features such as elevation, flattening, and focal interruption. For all the parameters, the agreement between the investigators was good (Cohen k ≥ 0.66), being the lowest when detecting the ELM interruption within the lesion. Conclusions: A combination of at least four clinical and biological markers yielded the highest positive- and negative-predictive values. More ("major") and less ("minor") frequent diagnostic criteria are proposed. [ABSTRACT FROM AUTHOR]

Intestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation. Pseudomonas aeruginosa (PA) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis. PA infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance. Inhibition of the quorum-sensing transcriptional regulator MvfR(PqsR) is a desirable anti-PA anti-virulence strategy as MvfR controls multiple acute and chronic virulence functions. Here we show that MvfR promotes intestinal permeability and report potent anti-MvfR compounds, the N-Aryl Malonamides (NAMs), resulting from extensive structure-activity-relationship studies and thorough assessment of the inhibition of MvfR-controlled virulence functions. This class of anti-virulence non-native ligand-based agents has a half-maximal inhibitory concentration in the nanomolar range and strong target engagement. Using a NAM lead in monotherapy protects murine intestinal barrier function, abolishes MvfR-regulated small molecules, ameliorates bacterial dissemination, and lowers inflammatory cytokines. This study demonstrates the importance of MvfR in PA-driven intestinal permeability. It underscores the utility of anti-MvfR agents in maintaining gut mucosal integrity, which should be part of any successful strategy to prevent/treat PA infections and associated gut-derived sepsis in critical illness settings. NAMs provide for the development of crucial preventive/therapeutic monotherapy options against untreatable MDR PA infections. Pseudomonas aeruginosa infections are increasingly difficult to treat due to the development of antimicrobial resistance. Here, the authors describe the synthesis, characterisation and efficacy of a quorum sensing inhibitor. [ABSTRACT FROM AUTHOR]

To compare whether the diagnostic evaluation of metabolic acidosis can be improved by using a modified Story method compared to the traditional evaluation in a population of critically ill patients with shock. This prospective cohort study included shock patients admitted to the ICU of a tertiary hospital in Brazil between May 2018 and November 2019. We collected laboratory data necessary for traditional evaluation and the simplified Stewart's method. During the study period, 149 patients were included in the final analysis. Of the 17 patients with a normal SBE and AGcorrected, 13 (76.5%) presented with metabolic acidosis according to the modified Story assessment. Therefore, of the 149 patients included in the study, the traditional approach failed to identify metabolic acidosis that was identified by the modified Story assessment in 13 (8.7%) patients. In addition, the determination of the severity of metabolic acidosis also differed between the two methods by a mean of − 7.8 mEq/L. We found that a modified Story method can identify and quantify metabolic acidosis in patients with disorders that were not revealed by the traditional approach. [ABSTRACT FROM AUTHOR]

Habitat loss and fragmentation in the human‐modified landscape affect bee assemblages by reducing the available natural resources. The life history features and adaptations of bees to environmental conditions affect how they perceive and interact with landscape structure. Therefore, it is crucial to quantify the magnitude of the effects of the landscape structure on this group at multiscale. We address the relative contribution of landscape structure in explaining the abundance of orchid bees, richness, and diversity in landscapes of Brazilian Cerrado. We mapped the surrounding landscape around 18 focal patches and sampled male orchid bees attracted by chemical baits. We used VIF and generalized linear models (GLM) to evaluate the effects of landscape structure (composition and configuration) at different spatial scales. We sampled 658 euglossine bees from five genera and 12 species. The savanna cover, forest cover, and fragmentation per se (i.e., the number of patches) were the best predictors of the richness of euglossine bees. The abundance of bees was explained by the savanna cover. The increase in natural habitat area and the reduction in landscape fragmentation favoring the assemblages of orchid bees are supported by our results. Savanna cover also modulates the abundance of euglossine bees, confirming that the habitat amount is essential for maintaining the populations of these bees. Our results reinforce the importance of habitat loss and fragmentation effects on the richness, abundance, and composition of euglossine bees, particularly in the naturally heterogeneous landscapes. [ABSTRACT FROM AUTHOR]

Maintenance of postural control is a complex task that requires the integration of different sensory-motor processes. To improve postural control, balance training is often implemented using unstable surfaces. Little is known, however, about how different surfaces compare in terms of postural control strategy. Non-linear dynamical system analysis, like recurrent quantification analysis (RQA) applied to the center of pressure (CoP) trajectory, represents a useful tool in this respect. The aim of this study is to investigate the effects of different unstable supports on the CoP trajectory through a complementary approach based on linear and non-linear analyses. Seventeen healthy adults performed barefoot single-leg balance trials on a force plate and on three different balance training devices (soft disc, foam pad, and pillow). Sets of parameters were extracted from the CoP trajectories using classical stabilometric analysis (sway path, mean velocity, root mean square) and RQA (percent recurrence and determinism, maximum line length, entropy). Both classical and RQA analyses highlighted significant differences between stable (force plate) and unstable conditions (p < 0.001). Conversely, only classical stabilometric parameters showed significant differences among the considered balance training devices, indicating that the different characteristics of the devices do not influence the dynamic/temporal structure of the CoP trajectory. Analysis of the center of pressure trajectory during single-leg standing on three different balance training devices and on a rigid surface using both linear and non-linear techniques. [ABSTRACT FROM AUTHOR]

Purpose: Acute mesenteric ischemia with non-occlusive mechanism (NOMI) is a possible complication after cardiac surgery in patients admitted to Intensive Care Unit (ICU). Since the diagnosis is often difficult with CT-scan, some authors have evaluated the role of bed-side diagnostic laparoscopy (DL). We aimed to contribute to this topic with a personal series. Methods: We retrospectively evaluated patients admitted to ICU after cardiac surgery since 2009 up to 2019, successively operated on for a suspected NOMI of recent onset with non-conclusive CT. They were divided into laparoscopic (Ls) and laparotomic (Lt) group, depending on whether or not they had a DL. They were compared for the CT false-positive (FP) and true-positive (TP) rate and the surgical outcome. Results: Seventy-three patients were enrolled. Lt included 30 patients (41%), Ls 43 (59%). The overall FP were 38 (52%), with a higher incidence in Ls. There was no difference in the mortality rate. The morbidity rate was higher in Lt, and especially in Lt-FP. The TP were 35 (47.9%). The mean operating time (OT) in the Lt-TP group was similar to the sum of the mean OT of the laparotomies plus that of the laparoscopies in the Ls-TP group. Conversely, when considering only laparotomic procedures, the Lt-TP had higher mean OT, such as an increased blood loss Conclusions: Post-cardiosurgical patients admitted to ICU have a relatively high rate of NOMI, in which CT-scan is often initially non-conclusive. Our data and those from the literature seem to show that in such cases bed-side DL may be an advantageous and safe procedure to avoid needless laparotomy and enables a more tailored open surgery. [ABSTRACT FROM AUTHOR]

Objective: To assess the serum and salivary levels of biomarkers related to bone metabolism in cirrhotic patients as well as the evidence of osteoporotic changes on panoramic radiographs. Materials and methods: Thirty-eight cirrhotic patients underwent anamnesis and physical examination. Specimens of blood and saliva were collected for evaluation by using Luminex™ xMAP technology to quantify RANKL, OPG, IL-1β, IL-6 and TNF-α. Panoramic radiographs were evaluated based on the mandibular cortical index (MCI) and the resulting data were compared to the expression of biomarkers in serum and saliva. Descriptive data analysis was performed and the Mann–Whitney's test and Spearman's correlation were used. Results: Most of the sample consisted of males (68.4%) who had cirrhosis mostly resulting from alcoholism (28.9%). Median concentration values of RANKL (74.44 pg/mL), IL-1 β (45.91 pg/mL), IL-6 (67.69 pg/mL) and TNF-α (5.97 pg/mL) in saliva were higher than those observed in serum. In 72.7% of the panoramic radiographs, MCI was found to be suggestive of osteoporotic changes. No statistically significant correlation was observed between salivary and serum expressions of biomarkers or between biomarkers and MCI. Conclusion: RANKL, OPG, IL-1β, IL-6 and TNF-α are expressed differently in serum and saliva and the concentration of these biomarkers is not related to MCI. Clinical relevance: This study contributes to the study of the mechanisms of osteoporosis in cirrhotic individuals. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. Methods: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. Results: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22–4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23–3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23–3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49–79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69–38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38–22.09). Conclusion: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. Trial registration: Clinical trial registration number: NCT03354793. [ABSTRACT FROM AUTHOR]

To assess to what extent left atrial (LA) structure and function are associated with non-specific heart failure symptoms, so that patients were classified as HF stage A and B. Mechanisms underlying the transition to overt HF in patients with stage A and B HF are unclear. Consecutive outpatients undergoing echocardiography and clinical evaluation and classified as HF stage A and B with preserved left ventricular ejection fraction (LVEF) were included. The association between LA measures [volume (LAVi), peak longitudinal-(PALS), contraction-(PACS) and conduit-strain] and non-specific HF symptoms was assessed using adjusted logistic regression analyses. The incremental value of atrial myopathy in symptoms prediction on top of clinical or echocardiographic confounders was assessed through ROC curves analyses. The cohort comprehended 185 patients (63 ± 16 years, 47% women) of whom 133 (72%) were asymptomatic, and 52 (28%) reported non-specific HF symptoms. After adjustment for clinical and echocardiographic confounders for HF symptoms, LAVi, PALS and PACS were associated with symptoms (p < 0.05). Among echocardiographic variables, only LA parameters were significantly associated with symptoms on top of clinical confounders (for LAVi OR [95% CI] 1.56 [1.21–2.00], p < 0.0001; for PALS 1.45 (1.10–1.91), p = 0.0009; for PACS 2.10 [1.33–3.30], p = 0.002). After adjustment for age, hypertension and COPD or E/E′, LV mass-i and mitral ERO, atrial myopathy added predictive value for symptoms presence compared to the clinical variables or echocardiographic parameters described (AUC increase 0.80 to 0.88, p = 0.004, and 0.79 to 0.84, p = 0.06, respectively). In patients with HF stages A–B and preserved LVEF, measures of LA structure and function were associated with non-specific HF symptoms. A comprehensive LA remodeling evaluation may help clinicians in the appropriate identification of overt HF. [ABSTRACT FROM AUTHOR]

Surgery remains the cardinal treatment in colorectal cancers but changes in bowel habits after rectal cancer surgery are common and disabling conditions that affect patients' quality of life. Low anterior resection syndrome is a disorder of bowel function after rectal resection resulting in a lowering of the QoL and recently has been defined by an international working group not only by specified symptoms but also by their consequences. This review aims to explore an extensive bibliographic research on preventive strategies for LARS. All "modifiable variables," quantified by the LARS Score, such as type of anastomosis, neoadjuvant therapy, surgical strategy, and diverting stoma, were evaluated, while "non-modifiable variables" such as age, sex, BMI, ASA, preoperative TMN, tumor height, and type of mesorectal excision were excluded from the comparative analysis. The role of defunctioning stoma, local excision, neoadjuvant radiotherapy, and non operative management seems to significantly affect risk of LARS, while type of anastomosis and surgical TME approach do not impact on LARS incidence or gravity in the long term period. Although it is established that some variables are associated with a greater onset of LARS, in clinical practice, technical difficulties and oncological limits often make difficult the application of some prevention plans. Transtomal irrigations, intraoperative neuromonitoring, pelvic floor rehabilitation before stoma closure, and early transanal irrigation represent new arguments of study in preventive strategies which could, if not eliminate the symptoms, at least mitigate them. [ABSTRACT FROM AUTHOR]

The waste and by-products of the soybean industry could be an economic source of nutrients to satisfy the high nutritional demands for the cultivation of lactic acid bacteria. The aims of this work were to maximize the biomass production of Lacticaseibacillus paracasei 90 (L90) in three culture media formulated from an effluent derived from soy protein concentrate production and to assess the effects these media have on the enzymatic activity of L90, together with their influence on its fermentation profile in milk. The presence of essential minerals and fermentable carbohydrates (sucrose, raffinose, and stachyose) in the effluent was verified. L90 reached high levels of microbiological counts (∼ 9 log cfu mL−1) and dry weight (> 1 g L−1) on the three optimized media. Enzymatic activities (lactate dehydrogenase and β-galactosidase) of L90, and its metabolism of lactose and citric acid, as well as lactic acid and pyruvic acid production in milk, were modified depending on the growth media. The ability of the L90 to produce the key flavour compounds (diacetyl and acetoin) was maintained or improved by growing in the optimized media in comparison with MRS. [ABSTRACT FROM AUTHOR]

Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the traditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a beneficial effect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research program aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efficacious doses. By specific binding to both orexin receptors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side effects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacology studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can benefit daytime functioning. [ABSTRACT FROM AUTHOR]

The kinematics of the body center of mass (bCoM) may provide crucial information supporting the rehabilitation process of people with transfemoral amputation. The use of magneto-inertial measurement units (MIMUs) is promising as it may allow in-the-field bCoM motion monitoring. Indeed, bCoM acceleration might be obtained by fusing the estimated accelerations of body segments' centers of mass (sCoM), the formers being computed from the measured accelerations by segment-mounted MIMUs and the known relative position between each pair of MIMU and underlying sCoM. This paper investigates how erroneous identifications of MIMUs positions impact the accuracy of estimated 3D sCoM and bCoM accelerations in transfemoral amputee gait. Using an experimental design approach, 215 simulations of erroneous identifications of MIMUs positions (up to 0.02 m in each direction) were simulated over seven recorded gait cycles of one participant. MIMUs located on the trunk and sound lower limbs were shown to explain up to 77% of the variance in the accuracy of the estimated bCoM acceleration, presumably due to the higher mass and/or angular velocity of these segments during gait of lower-limb amputees. Therefore, a special attention should be paid when identifying the positions of MIMUs located on segments contributing the most to the investigated motion. Sensitivity of the estimated vertical body center of mass acceleration to erroneous identifications of MIMU positions in the anteroposterior (AP), mediolateral (ML), and vertical (V) directions, expressed in percentage of the total variance of the estimation accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described. Methods: From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan–Meier method and compared with log-rank test. Results: Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963–1.065; p = 0.62). Conclusion: Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition. [ABSTRACT FROM AUTHOR]

Ultrasound cyclo plasty (UCP) is a recently developed surgical technique for glaucoma allowing a selective and controlled coagulation of the ciliary body. We herein investigated the long-term efficacy and safety of UCP for the treatment of glaucoma. This prospective study included patients with primary and secondary glaucoma. All surgeries were performed using the EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France). Sixty-six patients were included, and 60 completed regularly the 2-year follow-up. Preoperative IOP was 28.5 ± 9.6 mmHg and significantly decreased to 17.0 ± 5.4 at 2 years (p < 0.001). The daily number of both hypotensive eye drops and acetazolamide tablets decreased significantly (respectively, from 2.6 ± 1.1 to 1.7 ± 1.2 and from 0.7 ± 0.8 to 0.2 ± 0.5; both p < 0.001). At 2 years, 68.1% of patients met the definition of qualified success (IOP < 21 mmHg regardless of glaucoma medications) and 10.3% of patients met the definition of complete success (IOP < 21 mmHg without glaucoma medications). No major intra- or postoperative complications occurred; however, 15 eyes required additional glaucoma surgery. These results suggest that UCP is an effective and safe procedure to reduce IOP in glaucoma patients through a 2-year follow-up period. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to describe the surgical outcomes of a retrospective series of consecutive patients treated with laparoscopic and robotic approach for adrenal masses in two tertiary referral centers. Methods: We retrospectively gathered data of 477 patients submitted to adrenalectomy performed at two Institutions from March 2008 to February 2018 by six highly experienced surgeons. We excluded from the analysis 43 patients that had an open approach for tumors or for anesthetic contraindications to minimally invasive surgery (MIS). Patients were selected for surgery after a radiologic and an endocrinology work up. Preoperative, perioperative and postoperative data were recorded. Results: Overall, 477 patients were included in the study. The robotic and the laparoscopic group included 110 and 367 patients, respectively. The preoperative characteristics were similar in both groups except for ASA score with a median (IQR) of 3 and 2 in the robotic and in the laparoscopic group, respectively (p = 0.03). Tumor size of adrenal tumors treated robotically (4, IQR 2.6–6 cm) was significantly larger than those treated laparoscopically (3, IQR 2.3–4.1 cm) (p = 0.01). The intraoperative complication rates were similar between robotic and laparoscopic groups (6.3% and 6%, respectively). The postoperative complication rate was 5.4% for robotic group and similarly 3.5% for laparoscopic adrenalectomy strategy. We analyzed the tumor ≥ 6 cm, with 29 patients in the robotic group and 43 in the laparoscopic one, with an overall complication rate of 19.5%. At multivariable analyses tumor size (OR 1.287; CI 1.128–1.468; p < 0.001) was the only independent predictor of overall complication. Conclusion: Adrenal tumors can be safely treated either by robotic or laparoscopic strategy. MIS seems to be feasible also in larger adrenal masses (≥ 6 cm). Tumor size represents the only predictive factors for overall complication. [ABSTRACT FROM AUTHOR]

Background: Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. Methods: Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. Results: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student's t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). Conclusion: Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment. [ABSTRACT FROM AUTHOR]

The combination of early trans-mitral inflow and mitral annular tissue Doppler velocities (E/e′ ratio) is widely applied to noninvasively estimate left ventricular (LV) filling pressures. However, when E/e′ is between 8 and 14 its accuracy decreases substantially. Left atrial (LA) deformation analysis by speckle tracking echocardiography was recently proposed as an alternative approach to estimate LV filling pressures, but its role when E/e′ is between 8 and 14 has been under-investigated. We aimed to assess whether LA strain could help to identify elevated filling pressures in patients with E/e′ between 8 and 14. Among consecutive non-selected patients who underwent a comprehensive echocardiographic evaluation, we enrolled those with E/e′ ratio > 8 and ≤ 14. Exclusion criteria were: organic mitral valve disease or mitral surgery; presence of mitral regurgitation greater than moderate in severity; diseases associated with pre-capillary pulmonary hypertension; and undetectable systolic pulmonary artery pressure (PAP-S). Peak LA longitudinal (PALS) and contraction strain (PACS) values was obtained by averaging all segments, and by separately averaging segments measured in the 4-chamber and 2-chamber views. Seventy-six patients had E/e′ > 8 and ≤ 14 and formed the study cohort. Mean age 69 ± 12 years, LV ejection fraction (LVEF) 54.5 ± 11.2%, mean E/e′ 11.2 ± 1.9, PAP-S 33 ± 7 mmHg, PALS 31.6 ± 11.7%. PALS was significantly associated to PAP-S after adjustment for LVEF, E/e′, septal LV longitudinal shortening velocity (s′), LA volume indexed (p = 0.002) and also for ASE/EACVI diastolic dysfunction classification (p = 0.0002). Furthermore, PALS but not ASE/EACVI diastolic dysfunction grading, resulted independently associated to New York Heart Association (NYHA) class (p = 0.0004). PALS is able to predict increased intra-cardiac pressure and NYHA class in patients characterized by E/e′ between 8 and 14. Therefore, we propose that PALS might be incorporated in a simplified diagnostic algorithm based on E/e′ classes. [ABSTRACT FROM AUTHOR]