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Recently, there has been significant exploration into the utilization of food by-products as natural reservoirs of bioactive substances, particularly in the creation of functional foods naturally enriched with antioxidants. Citrus peels represent a viable option for formulating enhanced olive oils that contribute to a healthier diet, due to their bioactive compound content. This study aimed to (i) ascertain the compositional characteristics of Citrus reticulata olive oil (CrOO) and (ii) assess its nutraceutical properties in rats with metabolic disorder induced by 3 weeks of feeding with a high-fat diet (HFD). The results showed a peculiar phytochemical composition, thanks to the contribution of citrus peels, which are excellent bio-products. In addition, it demonstrated HFD-induced weight gain (18 ± 2% for HFD vs. 13 ± 0.9% for CrOO) and showed protective effects on fasting blood glucose levels (90.2 ± 3.8 mg/dL for HFD vs. 72.3 ± 2.6 for CrOO). Furthermore, a reduction in cardiovascular risk (total cholesterol/HDL cholesterol = 5.0 ± 0.3 for HFD vs. 3.8 ± 0.3 for CrOO) and an improvement in myocardial tissue function were observed, as well as a significant reduction in inflammatory mediators such as iNOS, COX-2, and mPGES-1 in aortic vessel tissues, thus preserving endothelial function at the vascular level.

Purpose: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC)., Experimental Design: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring design for toxicity was used for excessive toxicity., Results: In both the MIBC (n = 8) and mRCC (n = 8) cohorts, no toxicity events were encountered. In the MIBC cohort, one patient experienced pathologic complete response rate. In the mRCC cohort, no objective responses were reported, and the median progression-free survival was 1.5 months (95% confidence interval, 1.1-1.8 months). Immune monitoring found significant reductions in NK cells in circulation in both cohorts after treatment. In the tissue analysis, IHC found evidence of diminished CD38 presence in mRCC with treatment, whereas the baseline levels in MIBC were low., Conclusion: Treatment with daratumumab was safe. No signal of efficacy was detected in mRCC, and conclusions on the activity in MIBC were limited. Evidence of daratumumab targeting CD38 was detected in circulating immune cells and within the tumor microenvironment of mRCC and MIBC., Significance: In this prospective clinical trial of daratumumab, treatment in patients with MIBC and mRCC was safe. Limited efficacy was observed. Treatment with daratumumab resulted in CD38-expressing immune cell subsets to be targeted both in circulation and within the tumor microenvironment., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Understanding the shelf life of wine is complex and involves factors such as aroma preservation, flavour development and market acceptance. Ageing potential, crucial for flavour complexity, exposes wine to oxidation, influenced by oxygen, temperature and light, with an impact on quality. This type of oxidation is non-enzymatic, is catalyzed by metal ions and alters colour and flavour., Scope and Approach: This review examines the dynamics of wine preservation, focusing on oxidation and the impact of closure. Corks allow controlled oxygen transfer, while screw caps offer a nearly hermetic closure. Oxygen transfer rates vary, with natural corks having fluctuating rates and synthetic corks causing over-exposure. Additives such as sulphur dioxide and alternative substitute such as lysozyme and ascorbic acid are examined for their role in preventing oxidation and ensuring microbiological stability., Key Findings and Conclusions: Closure choice significantly affects wine preservation. Balancing oxygen exposure, temperature, and light is vital. Effective management, including the strategic use of preservatives and additives, is crucial for maintaining quality and extending shelf life. This review underscores the delicate equilibrium necessary for preserving wine quality from production to consumption., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ylenia Pieracci reports financial support was provided by 10.13039/501100007514University of Pisa, Department of Agriculture, Food and Environment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299., (© 2024. The Author(s).)

Virgin olive oil (VOO) is a globally esteemed product renowned for its chemical composition, nutritional value, and health benefits. Consumers seeking natural, nutritious, and healthy foods increasingly favor VOO. The optimization of the extraction system ensures the production of high-quality VOO with abundant antioxidant compounds that naturally protect it from degradation. Proper storage is crucial in maintaining the quality of VOO, prompting the exploration of novel extraction and preservation techniques. Factors such as light, temperature, and oxygen greatly influence the degradation process, resulting in reduced levels of natural antioxidants like polyphenols. Undesirable by-products and non-aromatic compounds may be formed, making the oil unacceptable over time. On the basis of all this consideration, this study aimed to evaluate the synergic use of two different gases (CO 2 and argon) during the malaxation phase to limit radical development and delay lipid autoxidation. Additionally, unconventional preservation systems, namely argon headspace, shellac, and bottle in bag, were assessed over a period of 150 days. The results evidenced that the use of CO 2 and argon during the malaxation process resulted in an improvement in the oil quality compared to the one obtained with the traditional system. However, in traditional oils, the alternative packaging systems determined interesting outcomes as they were able to positively affect different parameters, while the packaging effect was more mitigated in the test oils.

The aging process of wine is influenced by various factors, including the presence of oxygen, the temperature, and the storage conditions. While oxygen can have both positive and negative effects on wine quality, temperature fluctuations during storage can impact its chemical composition. This study has investigated the aging of Merlot and Sangiovese wines under traditional cellar conditions and underwater, exploring the influence of storage parameters on their chemical evolution. Analyzing parameters such as temperature, pressure, and chemical composition, the research revealed subtle but significant changes in the wines over time. Both wines showed a gradual reduction in total phenols, anthocyanins, non-flavonoid compounds, and total sulfur dioxide, irrespective of the storage conditions. Preliminary findings suggested that aging wine underwater does not induce significant alterations in its fundamental characteristics compared to traditional cellar aging. These results contribute to a deeper understanding of wine aging processes and highlight the importance of storage conditions in preserving wine quality. Further research is needed to fully elucidate the complexities of underwater aging and its broader implications for wine production.

The complex dynamics between oxygen exposure, sulphur dioxide (SO 2 ) utilization, and wine quality are of the utmost importance in wine sector, and this study aims to explore their fine balance in winemaking. As a common additive, SO 2 works as an antiseptic and antioxidant. However, its excessive use has raised health concerns. Regulatory guidelines, including Council Regulation (EC) N° 1493/1999 and Commission Regulation (EC) No 1622/2000, dictate SO 2 concentrations in wines. The increasing demand for natural preservatives is driving the search for alternatives, with natural plant extracts, rich in phenolic compounds, emerging as promising substitutes. In this context, Bioma Company has proposed alternative additives deriving from vineyard waste to replace SO 2 during winemaking. Thus, the aim of the present work was to compare the compositional characteristics between the product obtained with the alternative vinification and the traditional one during the winemaking, as well as the aroma compositions of the final wines. After a year of experimentation, the wines produced with Bioma products showed compositional characteristics comparable to their traditional counterparts. Notably, these wines comply with current legislation, with significantly reduced total sulphur content, allowing their designation as "without added sulphites". Bioma products emerge as potential catalysts for sustainable and health-conscious winemaking practices, reshaping the landscape of the industry.

Recent movements like #MeToo and #TimesUp have surfaced and challenged ideas about masculinity in popular conversations. In particular, these ideas have centered around "toxic masculinity"-a version of masculinity that reflects stereotyped, dated, and even dangerous expectations for manhood. This notion of masculinity can be reinforced in a number of ways, especially through pop culture, where it runs the risk of becoming commonly accepted or normalized. This study evaluates the narratives of masculinity in three different novels that are marketed toward high school-aged students in the United States: Lord of the Flies ; Gabi, A Girl in Pieces ; and Aristotle and Dante Discover the Secrets of the Universe . Using a critical literacy lens, this study considers the symbols, behaviors, expectations, and meanings given to masculinity in and through each novel and considers the implications of this analysis for adolescent readership inside and outside of schooling. The study concludes that the more contemporary novels showcase a range of masculine portrayals, including positive, affirming versions of masculinity, compared to a more singular and pessimistic one found in a novel traditionally used in schools. Thus, the study concludes that formal schooling may be an important way to address and disrupt unhealthy versions of masculinity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hernandez and Macaluso.)

The use of by-products as functional ingredients for bread recipes may open up new horizons in terms of product innovation to increase nutraceutical characteristics and/or shelf-life. In this research, the ability of residual products from important food chains ( Citrus and wine) to influence the water binding capacity of dough and bread was investigated in order to create industrial breads of high quality with prolonged shelf-life in the absence of any chemical additives (e.g., ethanol, sorbic acid, and propionic acid). The product under study is the 'Pan Bauletto bianco con olio EVO' (white bakery bread with EVO oil), an 'industrial bread' type usually treated with ethanol before being marketed, aiming to prolong its short shelf-life. The effect of the addition of different amounts of pectin ( Citrus supply chain) and grape pomace (wine supply chain), in combination or not, has shown promising results from both a technological point of view and the increasing shelf-life, allowing to obtain products with high nutraceutical value and interesting properties.

Background: With more than 103 million cases and 1.1 million deaths, the COVID-19 pandemic has had devastating consequences for the health system and the well-being of the entire US population. The Rare Diseases Clinical Research Network funded by the National Institutes of Health was strategically positioned to study the impact of the pandemic on the large, vulnerable population of people living with rare diseases (RDs)., Objective: This study was designed to describe the characteristics of COVID-19 in the RD population, determine whether patient subgroups experienced increased occurrence or severity of infection and whether the pandemic changed RD symptoms and treatment, and understand the broader impact on respondents and their families., Methods: US residents who had an RD and were <90 years old completed a web-based survey investigating self-reported COVID-19 infection, pandemic-related changes in RD symptoms and medications, access to care, and psychological impact on self and family. We estimated the incidence of self-reported COVID-19 and compared it with that in the US population; evaluated the frequency of COVID-19 symptoms according to self-reported infection; assessed infection duration, complications and need for hospitalization; assessed the influence of the COVID-19 pandemic on RD symptoms and treatment, and whether the pandemic influenced access to care, special food and nutrition, or demand for professional psychological assistance., Results: Between May 2, 2020, and December 15, 2020, in total, 3413 individuals completed the survey. Most were female (2212/3413, 64.81%), White (3038/3413, 89.01%), and aged ≥25 years (2646/3413, 77.53%). Overall, 80.6% (2751/3413) did not acquire COVID-19, 2.08% (71/3413) acquired it, and 16.58% (566/3413) did not know. Self-reported cases represented an annual incidence rate of 2.2% (95% CI 1.7%-2.8%). COVID-19 cases were more than twice the expected (71 vs 30.3; P<.001). COVID-19 was associated with specific symptoms (loss of taste: odds ratio [OR] 38.9, 95% CI 22.4-67.6, loss of smell: OR 30.6, 95% CI 17.7-53.1) and multiple symptoms (>9 symptoms vs none: OR 82.5, 95% CI 29-234 and 5-9: OR 44.8, 95% CI 18.7-107). Median symptom duration was 16 (IQR 9-30) days. Hospitalization (7/71, 10%) and ventilator support (4/71, 6%) were uncommon. Respondents who acquired COVID-19 reported increased occurrence and severity of RD symptoms and use or dosage of select medications; those who did not acquire COVID-19 reported decreased occurrence and severity of RD symptoms and use of medications; those who did not know had an intermediate pattern. The pandemic made it difficult to access care, receive treatment, get hospitalized, and caused mood changes for respondents and their families., Conclusions: Self-reported COVID-19 was more frequent than expected and was associated with increased prevalence and severity of RD symptoms and greater use of medications. The pandemic negatively affected access to care and caused mood changes in the respondents and family members. Continued surveillance is necessary., (©Maurizio Macaluso, Marc E Rothenberg, Thomas Ferkol, Pierce Kuhnell, Henry J Kaminski, David W Kimberlin, Michael Benatar, Mirna Chehade, The Principal Investigators of the Rare Diseases Clinical Research Network – Cycle 4. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.02.2024.)

Objective: This project aimed to assess the information contained on general psychiatry program websites and identify common themes that may be useful and informative for residency applicants., Methods: A survey study design was used to evaluate all US general psychiatry program websites as listed in the FREIDA database. The evaluation form included 44 binary (yes or no) items. Two reviewers rated each item on all program websites between September 2021 and January 2022. Item discrepancies were settled by a third reviewer. Fisher's exact tests evaluated differences between geographic regions and program types. Multidimensional scaling and Rasch modeling were conducted to examine clustering and the probability of items reported on program websites., Results: A total of 285 websites were identified; 13 were excluded. Internal consistency was high among reviewers, Cronbach's Alpha = 0.927; κ = 0.863. Websites varied considerably in quality. Significant inconsistent reporting was observed by region for current residents' photos and alumni careers (fellowship/jobs); p<0.001. Program types varied regarding information about program faculty, which included significant differences for faculty photo, faculty research interest, and faculty research publications; p<0.001., Conclusions: While inter-rater reliability was high, considerable variation among websites was observed. Residency programs could be improved by consistently reporting resident and faculty information. Results show that applicants may encounter issues finding pertinent information, as programs' FREIDA link did not direct the user to the residency program website two-thirds of the time., (© 2023. The Author(s), under exclusive licence to American Association of Chairs of Departments of Psychiatry, American Association of Directors of Psychiatric Residency Training, Association for Academic Psychiatry and Association of Directors of Medical Student Education in Psychiatry.)

In 2020, esketamine received a supplemental indication as a therapy for major depression with suicidal ideation (MDSI), based on protocols enrolling hospitalized patients. Given the high risk of suicide following hospital discharge and the high relapse rates following discontinuation of esketamine, the optimal long-term treatment approach remains unclear. Cognitive behavioral therapy (CBT) is highly effective in relapse prevention and has been shown to prevent suicide attempts in high-risk populations. Here we describe the study protocol for the CBT-ENDURE trial: Cognitive Behavioral Therapy Following Esketamine for Major Depression and SUicidal Ideation for RElapse Prevention. Patients with depression (N = 100) who are admitted to hospital or are outpatients with clinically significant suicidal ideation will be enrolled in the study. All patients will receive esketamine (twice weekly for four weeks) and will be randomly assigned (1:1 ratio) to receive a 16-week course of CBT plus treatment as usual (CBT group) or treatment as usual only (TAU only group). Patients are followed for a total of 6 months. Supported under a funding announcement from NIMH to conduct safety and feasibility trials for patients at high risk for suicide, the primary outcome of the CBT-ENDURE study is feasibility (as measured by recruitment and retention), with a key secondary outcome being relapse among those who experience substantial benefit following two weeks of esketamine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Generally, olive oil possesses natural protection against oxidation due to antioxidant compounds such as phenols and tocopherols. However, in the case of refined olive oil, the refining process unavoidably reduces the presence of these compounds. Considering these considerations, the objective of this study was to address the issues related to the "tightness" of the cap used for packaging oil in SALOV, aiming to extend the product's shelf life. The oil under investigation was packaged in 250 mL transparent glass bottles, each filled with either argon or air. Subsequently, the samples were divided into three groups: one group sealed with a conventional screw cap, another covered with a special protective bag, and a third one sealed with a wax cover directly on the cap. The storage period varied, during which the atmospheric conditions were monitored daily through both destructive and non-destructive analyses. The preliminary results indicate that alternative preservation techniques, such as the use of argon, sealing wax, and protective bags, can effectively enhance the shelf life of the oil and maintain its quality (reduce oxidation, preserve phenolic compounds, and reduce the degradation of pigments). Further research and development in this area could lead to the production of high-quality extra virgin olive oils with extended shelf life and improved sensory and nutritional properties.

When bottled wine is opened, a completely different scenario occurs that can accelerate the oxidation of the product. This is called the secondary shelf life (SSL), which is generally shorter and less predictable than the primary shelf life (PSL). In this context, the research aim was to evaluate the changes that occur in two types of red wine during two tests to evaluate the secondary shelf life as a function of the packaging systems. The variation of Total SO 2 and Free SO 2 and the other chemical parameters (polyphenols, anthocyanins, proanthocyanidins, color, and volatile acidity) were used to assess the oxidation rate of the packaging samples after opening during the SSL. In both tests and for the two types of stored red wine, the polymeric cap showed the best results. The other types of closure (screw cap, natural cork, crow cap, and Tetra Brik) showed a negative trend and a reduced SSL for both red wines. Finally, the sensory results confirmed that with the polymeric cap, the SSL increases considerably compared to other capping systems. These results may be due to the technical characteristics of polymeric materials, which tend to vary slightly in shape after repeated usage.

The shelf-life of bread is influenced by flour components, such as starch, composed of amylose and amylopectin. The aim was to test the effect of different balances of N (45, 90, 135 kg/ha) and P (48, 96 kg/ha) fertilizers on the flour characteristics and consequently the shelf-life of PDO Tuscan bread, stored in different modified atmosphere packaging (Ar, N 2 , Air). The amylose and phytochemical compounds were increased by N and decreased by the addition of P, but excessive doses of N (135 kg/ha) had a negative effect on flour quality. In the bread, the study highlighted the tendency of N 2 and Ar, as storage filler gases, to reduce water loss, slow down the staling process, and prolong shelf-life. However, the most significant influence on shelf-life was related to the different fertilizations of wheat. In fact, when N was present in equal dose to P (90/96 or 45/48 kg/ha) or slightly higher (90/48 kg/ha), the bread tended to last longer over time. Instead, when these ratios were unbalanced in favor of N (135/48 or 135/96 kg/ha) and in favor of P (45/96 kg/ha), the shelf-life decreased considerably.

Background: Randomized controlled trials offer the best design for eliminating bias in estimating treatment effects but can be slow and costly in rare disease research. Additionally, an equal randomization approach may not be optimal in studies in which prior evidence of superiority of one or more treatments exist. Supplementing prospectively enrolled, concurrent controls with historical controls can reduce recruitment requirements and provide patients a higher likelihood of enrolling in a new and possibly superior treatment arm. Appropriate methods need to be employed to ensure comparability of concurrent and historical controls to minimize bias and variability in the treatment effect estimates and reduce the chances of drawing incorrect conclusions regarding treatment benefit., Methods: MILES was a phase III placebo-controlled trial employing 1:1 randomization that led to US Food and Drug Administration approval of sirolimus for treating patients with lymphangioleiomyomatosis. We re-analyzed the MILES trial data to learn whether substituting concurrent controls with controls from a historical registry could have accelerated subject enrollment while leading to similar study conclusions. We used propensity score matching to identify exchangeable historical controls from a registry balancing the baseline characteristics of the two control groups. This allowed more new patients to be assigned to the sirolimus arm. We used trial data and simulations to estimate key outcomes under an array of alternative designs., Results: Borrowing information from historical controls would have allowed the trial to enroll fewer concurrent controls while leading to the same conclusion reached in the trial. Simulations showed similar statistical performance for borrowing as for the actual trial design without producing type I error inflation and preserving power for the same study size when concurrent and historical controls are comparable., Conclusion: Substituting concurrent controls with propensity score-matched historical controls can allow more prospectively enrolled patients to be assigned to the active treatment and enable the trial to be conducted with smaller overall sample size, while maintaining covariate balance and study power and minimizing bias in response estimation. This approach does not fully eliminate the concern that introducing non-randomized historical controls in a trial may lead to bias in estimating treatment effects, and should be carefully considered on a case-by-case basis. Borrowing historical controls is best suited when conducting randomized controlled trials with conventional designs is challenging, as in rare disease research. High-quality data on covariates and outcomes must be available for candidate historical controls to ensure the validity of these designs. Additional precautions are needed to maintain blinding of the treatment assignment and to ensure comparability in the assessment of treatment safety.MILES ClinicalTrials.gov Number: NCT00414648.

This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and psychiatric characteristics as potential predictors of response (≥50% reduction from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) and remission (MADRS total score ≤12) at day 28. Overall, younger age, any employment, fewer failed ADs in the current depressive episode, and reduction in Clinical Global Impression-Severity (CGI-S) score at day 8 were significant positive predictors of response and remission at day 28. Treatment assignment was an important predictor of both response and remission. Patients treated with ESK+AD had 68% and 55% increased odds of achieving response and remission, respectively, versus those treated with AD+PBO. In the ESK+AD group, attainment of response and remission was more likely in patients who were employed, without significant anxiety at baseline, and who experienced a reduction in CGI-S score at day 8. Identification of predictors of response and remission may facilitate identification of those patients with TRD most likely to benefit from ESK+AD. Trial Registration: ClinicalTrials.gov: NCT02417064 (clinicaltrials.gov/ct2/show/NCT02417064) and NCT02418585 (clinicaltrials.gov/ct2/show/NCT02418585)., Competing Interests: Declaration of Competing Interest GS is a stockholder of Johnson & Johnson, Inc. This work was conducted when GS was an employee of Janssen. SB is an employee of Janssen and a stockholder of Johnson & Johnson, Inc. ED is a stockholder of Johnson & Johnson, Inc. This work was conducted when ED was an employee of Janssen. JSh is an employee of Janssen and a stockholder of Johnson & Johnson, Inc. JSi is a stockholder of Neurocrine Biosciences. This work was conducted when JSi was an employee of Janssen and stockholder of Johnson & Johnson. IT is an employee of Janssen and a stockholder of Johnson & Johnson, Inc. DW is a stockholder of Johnson & Johnson, Inc. This work was conducted when DW was an employee of Janssen. MM has conducted clinical trials research as principal investigator for the following pharmaceutical companies over the last 12 months: Boehringer Ingelheim Liva Nova, Merck, Neurocrine, Janssen, Novartis, Otsuka. All clinical trial and study contracts were with, and payments made to, the University of Alabama at Birmingham. MM was a member of the speaker bureau for Janssen Pharmaceuticals from April 2019 through June 2020 (Spravato®/esketamine). JCN has served as an adviser or consultant to Astellas, Axsome, Biohaven, Janssen, Johnson and Johnson, Novartis, Otsuka, Sunovion. MT has received consulting fees from Allergan; Alto Neuroscience Inc.; Applied Clinical Intelligence, LLC; Axsome Therapeutics; Boehringer Ingelheim; Engage Health Media; GreenLight VitalSign6 Inc.; Janssen, Lundbeck Research USA; Merck Sharp & Dohme Corp.; Navitor Pharmaceutical, Inc.; Otsuka; Perception Neuroscience; Pharmerit International; Sage Therapeutics; and Signant Health; research support from the NIMH, NIDA, Patient-Centered Outcomes Research Institute (PCORI), Cancer Prevention Research Institute of Texas (CPRIT); and editorial compensation from the American Psychiatric Association (Deputy Editor for American Journal of Psychiatry) and Oxford University Press. STW has received contract funding from Janssen, Sage Therapeutics, and Oui Therapeutics for the conduct of clinical trials administered through Yale University. He has received consulting fees from Janssen, Biohaven, and Oui Therapeutics., (Copyright © 2023. Published by Elsevier B.V.)

"Avanzi 3-Grano 23" (G23) is an old variety of Triticum aestivum from the mountain areas of Lunigiana (north Tuscany, Italy), where traditional farming communities have contributed to its success and on-farm conservation. G23 flour, traditionally used for typical food products, is characterized by particular nutritional and sensory traits but has technological properties which limit its suitability for breadmaking. The aim of this work was to evaluate how to promote the use of G23 through the optimization of bread formulation by leveraging both flour blending and the leavening system. During the preliminary test, three different mixes of G23 flour and a strong flour (C) were tested in terms of their leavening power as a function of leavening agent (baker's yeast or sourdough). The selected M2 flour, composed of G23:C (1:1 w / w ), was used for further breadmaking trials and 100% C flour was utilized as a control. The sourdough bread obtained with the M2 flour (SB-M2) showed an improved sensory profile compared with the related control (SB-C). Furthermore, SB-M2 exhibited the best aromatic (high content in aldehydes, pyrazines and carboxylic acids) and phytochemical profile (total polyphenols and flavonoids content and antioxidant activity). In contrast, the use of baker's yeast, although optimal from the point of view of breadmaking, did not result in the same levels of aromatic complexity because it tends to standardize the product without valorizing the sensory and nutritional qualities of the flour. In conclusion, in the experimental conditions adopted, this old wheat variety appears to be suitable for the production of sourdough bakery products., Competing Interests: The authors declare no conflict of interest.

Meat production has a higher economic and ecological impact than other commodities. The reduction in meat loss and waste throughout the whole supply chain is a demanding challenge. In recent years, the interest in the food-grade polysaccharide chitosan (CH) and essential oils (EOs) employed as allies in meat protection has increased. In this work, we selected five EOs obtained from plants traditionally used as spices, and after their chemical characterisation, a trained panel of expert sensorial analysts determined that, among them, Laurus nobilis (Lauraceae) and Piper nigrum (Piperaceae) EOs were the most suitable to season meat. Therefore, the effect of CH, the L. nobilis and P. nigrum EOs, and EOs-enriched CH solutions on meat was tested to assess how they deter the oviposition behaviour of the blowfly Calliphora vomitoria (Diptera: Calliphoridae) and against water loss, lipid peroxidation, and colour changes. All the applied treatments, compared to the control, did not accelerate meat dehydration but increased colour lightness, an attractive feature for consumers, and discouraged the blowfly's oviposition. In particular, the P. nigrum EO-enriched CH was the most active in repelling C. vomitoria without negatively affecting the organoleptic qualities and shelf-life of meat., Competing Interests: The authors declare no conflict of interest.

The short shelf-life of PDO Tuscan bread limits its distribution to markets close to the production area, affecting its commercial success and the economic return by supply chain operators. While the application of MAP to store bread is widely accepted, the suitability of this technique to extend the shelf life of the PDO Tuscan bread is still to be explored. Furthermore, to the best of our knowledge no data are available in the literature about the use of argon as filling gas neither in pure atmosphere nor in combination with CO 2 . In this context, the aim of this study was to evaluate the effect of different modified packaging atmospheres on the shelf-life of sourdough bread. Slices of bread were stored individually in plastic bags at 23 °C in five different atmospheres (Ar (100%), N 2 (100%), CO 2 (100%), Mix CO 2 /N 2 (70% CO 2 , 30% N 2 ), Mix CO 2 /Ar (70% CO 2 , 30% Ar)), and Air was selected as a control. To select the best storage conditions, both chemical-physical, rheological, and organoleptic features were evaluated. Results showed that pure gases (CO 2 , N 2 , Ar) displayed good qualities as storage atmospheres compared to Air. In contrast, both Mix CO 2 /N 2 and Mix CO 2 /Ar were the best in slowing down the staling process, thus doubling the shelf-life of bread, compared to other atmospheres. In conclusion, argon, as a preservation atmosphere, seems to be the best solution to extend the shelf-life of PDO Tuscan bread.

Background: Many risk-prediction models for lung transplantation are centered on recipient characteristics and do not account for impact of donor and transplant-related factors or only examine short-term outcomes (eg, predicted 1-y survival). We sought to develop a comprehensive model guiding recipient-donor matching., Methods: We identified double lung transplant recipients (≥12 y old) in the United Network for Organ Sharing Registry (2005-2020) to develop a risk scoring tool. Cohort was divided into derivation and validation sets. A total of 42 recipient, donor, and transplant factors were included in the analysis. Lasso method was used for variable selection. Survival was estimated using Cox-proportional hazard models. An interactive web-based tool was developed for clinical use., Results: A derivation cohort (n = 10 660) informed the model with 13-recipient, 4-donor, and 2-transplant variables. Adjusted risk scores were computed for every transplant and grouped into 3 clusters. Model-estimated survival probabilities were similar to the observed in the validation cohort (n = 4464) for all clusters. The mortality increases for medium- and high-risk groups was similar in both derivation and validation cohorts (C statistics for 1-, 5-, and 10-y survival were 0.67, 0.64, and 0.72, respectively). The web-based application estimated 1-, 5-, 10-y survival and half-life for low- (92%, 73%, 52%; 10.5 y), medium- (89%, 62%, 38%; 7.3 y), and high-risk clusters (85%, 52%, 26%; 5.2 y)., Conclusions: Advanced methods incorporating machine/deep learning led to a risk scoring model (including recipient, donor, and transplant factors) and a web-based clinical tool providing short- and long-term survival probabilities for recipient-donor matches. This will enable risk-based matching that could improve utilization of and benefit from a limited donor pool., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study utilizes the two different criteria of the DSM-5 Alternative Model of Personality Disorder Assessment to evaluate the relationship between attachment style and personality pathology. One-hundred forty patients from a combined sample of psychiatric and internal medicine clinics were given a survey composed of the DSM-5 Levels of Personality Functioning Questionnaire (DLOPFQ), the Personality Inventory for DSM-5-Brief Form (PID-5-BF), and the Relationship Questionnaire (RQ). Analysis of variance indicated that attachment styles were differentiated across all four the DLOPFQ scales and the Detachment trait domain. Elastic net regression modeling with bootstrap was used to assess the strength of the level of personality functioning dimensions and trait domains in the prediction of attachment style, both independently and interactively while accounting for multicollinearity. This study offers readers insight to a novel statistical approach to model building that addresses two issues among psychiatric data: high correlation and small sample size., (© 2021 John Wiley & Sons, Ltd.)

The aim of this study was to evaluate the cytotoxic activity and the chemical composition of the tomato extracts coming from, Pomodoro Giallo and San Marzano Cirio 3, and then to evaluate the potential changes when plants were grown in soils contaminated by cadmium, chromium and lead. Extracts were investigated by UHPLC-HRMS and UV-Vis. Cell viability (CellTiter-Glo Luminescent assay), enzyme aldehyde dehydrogenase activity (ALDEFLOUR Assay), cell cycle progression (Accuri C6 Flow Cytometer), apoptosis and necrosis (Annexin V-FITC assay) were evaluated on two gastric cancer (AGS and NCI-N87) and two colorectal cancer (HT-29 and HCT 116) cell lines. Different content of polyphenol and carotenoid constituents was observed. Extracts from uncontaminated soil induced cytotoxic activity towards all selected cancer cells, while extracts coming from contaminated soils showed the aberrant phenotype increased in colorectal cancer cells. Chloroform extracts exerted the highest cytotoxic activity. AGS and HT-29 were the most sensitive to cell cycle arrest and to apoptosis. No necrotic effect was observed in HCT 116. The contrasting effects on cancer cells were observed based on tomato variety, the extract polarity, heavy metal identity, and tested cell line. The investigation of potential adverse health effects due to Cd in the fruits should be explored., (© 2022. The Author(s).)

The recent growing interest in lactose intolerance has resulted in the proliferation of lactose-free products by food manufacturing companies. Since updated papers about lactose and its uses are missing, the main purpose of this review is to investigate this sugar comprehensively. Firstly, its chemical and physical characteristics were studied, following its employment in the food and drug industries. The positive and negative health-related effects of lactose are reported, focusing on the condition of lactose intolerance, for which an adequate lactose-free diet has to be followed to avoid symptoms that impairs quality of life. Considering that EU legislation on lactose-free product labelling is still controversial, suitable options for producing and identifying lactose-free products are suggested, in order to meet lactose-intolerant people's needs.

The Mediterranean diet has, among its cornerstones, the use of olive oil for its nutraceutical and organoleptic properties. Despite the numerous merits, olive-oil mill wastewater (OMWW), which is generated by the olive-oil extraction process, is one of the most serious environmental pollutants in the Mediterranean countries. The polluting potential of OMWW is due to its high content of tannins, polyphenols, polyalcohols, pectins and lipids. In order to close the recovery cycle of a fortified citrus olive oils previously developed, we tested the ability of five microalgae of the Chlorella group (SEC&#95;LI&#95;ChL&#95;1, CL&#95;Sc, CL&#95;Ch, FB and Idr) in lowering the percentage of total phenolic compounds in vegetation water. This was obtained with three different extraction processes (conventional, and lemon and orange peels) at three concentrations each (10%, 25% and 50%). The results showed that strains Idr, FB and CL&#95;Sc from the Lake Massaciuccoli can tolerate vegetation water from conventional and lemon peel extractions up to 25%; these strains can also reduce the phenolic compounds within the tests. The application of microalgae for OMWW treatment represents an interesting opportunity as well as an eco-friendly low-cost solution to be developed within companies as a full-scale approach, which could be applied to obtain a fortified microalgal biomass to be employed in nutraceutical fields.

Among the various existing techniques, enzymatic degumming represents a process that is establishing itself as a valid alternative to the more classic chemical processes. Moreover, vegetable oils of various origins have been gaining more consideration as sustainable and affordable protectants for cereals and pulses against the attack of several insect pests. Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae) is one of the key pests of cereal crops in the field and in stored and processed cereal products. Based on these highlighted issues, the overall aim of this research was twofold: (i) firstly, the effectiveness of the enzymatic degumming process was evaluated through the use of three different enzymes in order to verify the possible industrial application within the SALOV company as an alternative to the conventional chemical process; (ii) in a second phase, the possible use of the innovative refined oils was explored for sustainable stored grain protection towards S. zeamais . The results obtained confirm the strong possibility of applying the enzymatic process, which is innovative and, in a chemical way, more sustainable than the classical one. Regarding the toxicity towards S. zeamais , the crude peanut oil and the chemically refined peanut oil had lower LC 50 values (1.836 and 1.372 g kg -1 , respectively) than the oils rectified through enzymatic degumming (LC 50 from 2.453 to 4.076 g kg -1 ), and, therefore, they can be suggested as sustainable stored grain protectants.

Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's disease and ulcerative colitis patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease patients remains unknown. Studies have linked the Th17 subset of CD4 + T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis, ischemic brain injury, and Alzheimer's disease. To better understand how CD4 + T lymphocytes contribute to brain pathology in chronic intestinal inflammation, we investigated the development of brain inflammation in the T cell transfer model of chronic colitis. Our findings demonstrate that CD4 + T cells infiltrate the brain of colitic Rag1 -/- mice in proportional levels to colitis severity. Colitic mice developed hypothalamic astrogliosis that correlated with neurobehavioral disorders. Moreover, the brain-infiltrating CD4 + T cells expressed Th17 cell transcription factor retinoic acid-related orphan receptor γt (RORγt) and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of RORγt-deficient naive CD4 + T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1 -/- recipients, with significantly less brain infiltration of CD4 + T cells. The finding is mirrored in chronic dextran sulfate sodium-induced colitis in Rorc fl/fl Cd4-Cre mice that showed lower frequency of brain-infiltrating CD4 + T cells and astrogliosis despite onset of significantly more severe colitis compared with wild-type mice. These findings suggest that pathogenic RORγt + CD4 + T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Winemaking variables and techniques are known to affect the composition of wines. To obtain a rapid and safe fermentation course, with a reduced risk of proliferation of unwanted microbial species, frequent recourse is made to the use of selected microorganisms, which can greatly simplify the complex management of the fermentation process. In particular, selected strains of lactic acid bacteria are used, which are much more sensitive than yeasts to the operating conditions of the medium. In this regard, the overall aim of this research was to verify whether the early inoculation of homolactic acid bacteria for hexoses ( Lactobacillus plantarum ) carried out after 24 h, compared with that of saccharomycetes operating alcoholic fermentation, could be advantageous compared with a traditional innoculation with a different heterolactic bacterial strain for hexoses ( Oenococcus oeni ) operated at the end of alcoholic fermentation. The grape variety chosen was Sangiovese, the protagonist of Tuscan oenology. The evaluation focused on different aspects such as the management of winery operations, and the quality and longevity of the product; was carried out in all phases of winemaking; and analysed both from a chemical and sensory point of view.

This summary provides context for the role of L-methylfolate (LMF) in treating antidepressant non-responders. Bidirectional relationships have been observed between obesity and/or inflammation and depression. Studies have shown an increased prevalence of depression among patients with elevated body mass index and/or chronic inflammation and an increased risk of becoming obese and experiencing chronic inflammation in those with depression. These relationships can negatively affect the pathophysiology of depression. Elevated cytokine levels have been found to be among the factors that correlate with poor antidepressant treatment responsiveness. Low baseline neurotransmitter levels (e.g., serotonin) can also be associated with reduced effectiveness of commonly used antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs)]. LMF is an approved nutritional adjunctive antidepressant therapy that increases central neurotransmitter levels and thereby improves the effectiveness of antidepressant therapy. LMF can increase clinical response when used adjunctively in patients with major depressive disorder (MDD) and who are SSRI-resistant. In 2 randomized controlled trials, the pooled results showed increased response rates (32.3 vs. 14.6%; P = 0.04) as measured by a ≥50% reduction or final score ≤ 7 on the Hamilton Depression Rating Scale (HAM-D) and greater mean HAM-D reductions (-5.6 vs. -3.0; P = 0.05) when LMF was added to an SSRI compared with an SSRI plus placebo. Additionally, LMF has demonstrated effectiveness in real-world studies, with 67.9% of patients responding to therapy, using the 9-item Patient Health Questionnaire ( P < 0.001). Post-hoc analyses found that patients with inflammation and/or obesity responded better to adjunctive LMF therapy compared with the overall sample (mean HAM-D reduction: -2.74 vs. +0.99)., Competing Interests: This study/publication received funding from Alfasigma USA, Inc. The funder was not involved in the interpretation of data, the writing of this article or the decision to submit it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Macaluso.)

Background: Little is known about the spatial distribution of idiopathic inflammatory myopathies (IIM) in the United States (U.S.), or their geospatial associations., Methods: We studied a national myositis patient registry, with cases diagnosed in the contiguous U.S. from 1985-2011 and comprised of dermatomyositis (DM, n = 484), polymyositis (PM, n = 358), and inclusion body myositis (IBM, n = 318) patients. To assess the association of myositis prevalence with distance from roads, we employed log-Gaussian Cox process models, offset with population density., Results: The U.S. IIM case distribution demonstrated a higher concentration in the Northest. DM, IBM, and cases with lung disease were more common in the East, whereas PM cases were more common in the Southeast. One area in the West and one area in the South had a significant excess in cases of DM relative to PM and of cases with lung disease relative to those without lung disease, respectively. IIM cases tended to cluster, with between-points interactions more intense in the Northeast and less in the South. There was a trend of a higher prevalence of IIM and its major phenotypes among people living within 50 m of a roadway relative to living beyond 200 m. Demographic characteristics, rural-urban commuting area, and female percentage were significantly associated with the prevalence of IIM and with major phenotypes., Conclusions: Using a large U.S. database to evaluate the spatial distribution of IIM and its phenotypes, this study suggests clustering in some regions of the U.S. and a possible association of proximity to roadways., Competing Interests: JW and JM were employed by DLH Holdings Corp Company. PF was a contractor with Kelly Government Solutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hossain, Wilkerson, McGrath, Farhadi, Brokamp, Khan, Goldberg, Brunner, Macaluso, Miller and Rider.)

Introduction: The Covid-19 pandemic has devastated the world and demonstrated the inadequacy of health care in the United States. To assess its impact, the Rare Disease Clinical Research Network conducted a survey to assess the pandemic on the rare disease community of patients, including those with myasthenia gravis (MG)., Methods: A cross-sectional survey was designed to target people or their care givers who live in the United States, have a rare disease, and are under 90 years of age. Respondents logged onto a dedicated web page and completed the survey online, which requested demographic, disease-specific, drug treatment, and symptom information as well as assessment of Covid-19 impact on them. The survey was open from May 2020 to December 2020., Results: Five hundred ninety-four with self-reported myasthenia gravis completed the survey, which was the largest number of respondents. Sixty percent of respondents were women with a mean age of 60 years. Eighty-nine percent identified as White. Respondents did not appreciate a worsening of symptoms after the pandemic. Only 7 respondents reported the diagnosis of Covid-19 but 11% indicated they had difficulty accessing care at the time of the survey., Discussion and Conclusion: Patients with MG complained of worse access to medical care during the early months of the pandemic, including challenges in diagnosis of suspected Covid-19 infection. A major limitation of the survey is its inability to access minority populations. Nevertheless, the results of the Rare Disease Clinical Research Network (RCDRN) survey of patients with MG provide clear evidence that the pandemic has demonstrated the deficiencies in US healthcare., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Burnout and depression are major problems facing physicians, with 300-400 physicians dying by suicide each year. In an effort to address this issue, the Accreditation Council for Graduate Medical Education (ACGME) revised the Common Program Requirements for residency and fellowship programs to include a strong emphasis on well-being, and this revision has been extended to including a subcompetency on well-being in the Milestones 2.0. The Psychiatry Milestones 2.0 Work Group was convened to draft updated psychiatry milestones. As part of the open feedback period, the American Association of Directors of Psychiatric Residency Training submitted an organizational letter outlining several points to consider regarding the original draft of the well-being subcompetency. The ACGME was receptive to this feedback and allowed the Psychiatry Milestones 2.0 Work Group to revise the subcompetency. Current research indicates that burnout is largely driven by systemic factors, but well-being literature and initiatives often focus on individual factors and responsibility for burnout rather than systemic change. Program directors tasked with assessing resident well-being can additionally encounter several professionalism concerns, including how to (1) define a subcompetency within a competency that itself has not been well defined; (2) decide the appropriate balance between individual and systemic responsibility for well-being; (3) consider mental health as a parameter of well-being; (4) balance roles as physicians, psychiatrists, and training directors in thinking about the mental health of residents without overstepping boundaries and while maintaining privacy, confidentiality, and resident safety; and (5) measure well-being in a sociocultural context. This article describes how these considerations were incorporated into the revision of the Psychiatry Milestones 2.0 version of the well-being subcompetency, which has subsequently been made available to other specialty work groups for potential use as they develop their specialty-specific Milestones 2.0., (Copyright © 2021 by the Association of American Medical Colleges.)

Pharmacogenomic testing can be used to guide medication selection in patients with major depressive disorder (MDD). Currently, there is no consensus on which gene or genes to consider in medication management. Here, we assessed the clinical validity of the combinatorial pharmacogenomic algorithm to predict sertraline blood levels in a subset of patients enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial. Patients who reported taking sertraline within ≤2 weeks of the screening blood draw were included. All patients received combinatorial pharmacogenomic testing, which included a weighted assessment of individual phenotypes for multiple pharmacokinetic genes relevant for sertraline (CYP2C19, CYP2B6, and CYP3A4). Sertraline blood levels were compared between phenotypes based on: 1) the pharmacokinetic portion of the combinatorial pharmacogenomic algorithm, and 2) individual genes. When evaluated separately, individual genes (for CYP2C19 and CYP2B6) and the combinatorial algorithm were significant predictors of sertraline blood levels. However, in multivariate analyses that included individual genes and the combinatorial pharmacogenomic algorithm, only the combinatorial pharmacogenomic algorithm remained a significant predictor of sertraline blood levels. These findings support the clinical validity of the combinatorial pharmacogenomic algorithm, in that it is a superior predictor of sertraline blood levels compared to individual genes., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding the type of immigration flow that maximises the expected economic benefits in the destination countries is one of the main debated topics both in the economic literature and in policy agendas worldwide. In recent years, governments have developed regulations of migration flows by adopting some form of selective immigration policy based on either human capital criteria or skill needs. Admission policies in the destination countries are likely to affect the direction and magnitude of selection as well as the socio-economic performance of immigrants. However, the relationship between quality-selective policy and immigrants' skill composition remains largely unexplored. This paper aims to survey the existing literature on how selective-immigration policies shape the characteristics of immigrants from the receiving-country perspective. First, it introduces the main route of admissions and the theoretical models to understand how the direction of selection works; second, it discusses the theoretical models; third, it reviews the empirical works. A final concluding section briefly points out the actual findings and future avenues of work., (© The Author(s) 2022.)

As the world becomes increasingly interconnected, psychiatrists across geographical regions and from various international organizations need to collaborate to promote global health and wellness. A necessary step is for nations of the world to develop combined teaching initiatives and curricula to ensure best practices are shared globally. In no field of medicine is this more pressing than in psychiatry - especially psychopharmacology given the recent advances in the field. This paper highlights the need to work collaboratively in developing teaching curricula in psychopharmacology in order to incorporate pedagogy and content from international partners-here from Asia and America., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ozone is widely used in the agri-food and food processing industries mainly as a sanitizing agent. However, it has recently become clear that ozone exposition leads to another important benefit: in living tissues, the induced-oxidative stress triggers the antioxidant response, and, therefore, it enhances the production of antioxidant and stress-related secondary metabolites. As such, ozone can be considered an abiotic elicitor. The goal of the present review was to critically summarize knowledge about the possibility of improving bioactive compounds and, consequently, the health-related properties of grapes and wine, by using ozone. The greatest interest has been given not only to the pre- and post-harvest treatment of table and wine grapes, but also to the explanation of the mechanisms involved in the ozone-related response and the main secondary metabolites biosynthetic pathways. From the literature available, it is clear that the effect of ozone treatment on health-related properties and secondary metabolites accumulation depends on many factors, such as the cultivar, but also the form (water or gaseous), doses, and application method of ozone. Most of the published papers report an increase in antioxidant compounds (e.g., polyphenols) and stress-related volatiles, confirming the hypothesis that ozone could be used to improve berry and wine compositional and sensory quality.

Due to the greenhouse gas increase, grapes are often exposed to high temperatures in several growing areas especially during the final developmental stages, and this is particularly true when early ripening cultivars are harvested. This may cause undesirable effects on berry metabolism and composition and wine quality, particularly concerning the aroma profile. Harvesting at night or keeping the harvested grapes in cold rooms before vinification are empirical protocols applied in specific viticultural areas. To study the effects of decreasing berry temperature after harvest, white-skinned berries (cv Vermentino) were maintained at 4 or 10°C for 24 or 48 h before processing (pre-cooling). Control grapes were kept at 22°C. Grapes cooled at 10°C for 24 and 48 h resulted richer in polyphenols and showed a significant up-regulation of genes involved in polyphenols biosynthesis (i.e., VvPAL, VvSTS2 , and VvFLS1) . Similar behavior was observed in samples kept at 4°C for 48 h. Pre-cooling induced specific changes in the volatile organic compound (VOC) profiles. In particular, higher amounts of a specific subcategory of terpenes, namely sesquiterpenes, were detected in cooled samples. The induction of the expression of key genes involved in terpenoids biosynthesis ( VvHDR, VvDX3, VvTER, VvGT14 ) was detected in cooled grapes, with variable effects depending on temperature and treatment duration. In both cooled samples, the evolution of alcoholic fermentation followed a regular trend but ended earlier. Higher phenolic content was detected in wines obtained from the 10°C-treated grapes. Higher residual concentration of malic acid at the end of fermentation was detected in wine samples from grapes pre-cooled at 4°C. Sesquiterpenes also showed a general increase in wines from cooled grapes, especially after pre-cooling at 10°C for 48 h. Different sensory profiles characterized the wine samples, with the best scores in terms of general pleasantness obtained by the wine produced from grapes pre-cooled at 4°C for 24 h. These results demonstrate that pre-cooling harvested grapes induces specific effect on the VOC profile and other quality parameters of Vermentino wine, and this appears to be the result of specific metabolic and compositional changes occurring in the berries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Modesti, Shmuleviz, Macaluso, Bianchi, Venturi, Brizzolara, Zinnai and Tonutti.)

Weight gain is a common side-effect of medications used to treat major depressive disorder (MDD). We sought to estimate the frequency of weight gain for obesogenic medications prescribed for MDD and to evaluate if bupropion mitigated risk for weight gain. We analyzed a prospective cohort of patients with weight available at baseline and 12 weeks (n = 1,032) or 24 weeks (n = 871) in a post hoc analysis of the G enomics U sed to I mprove DE pression D ecisions (GUIDED) study of patients with MDD who failed at least one medication trial. We compared weight gain between those on versus not on medications with high risk for weight gain, including a subgroup receiving combination treatment with bupropion. A second analysis evaluated weight gain across traditional medication classes, adjusting for potential confounding variables. Those on medications identified as high risk for weight gain were significantly more likely to experience clinically significant weight gain (≥3%) at 12 weeks (29.3% vs. 16.3%, p < .001) and 24 weeks (33.5% vs. 23.5%, p = .015). No protection from clinically significant weight gain was observed among patients treated with a high-risk medication concomitantly with bupropion (N = 31, 35% and 52% with clinically significant weight gain at 12 and 24 weeks). Antipsychotic medications and tricyclic antidepressants were most often associated with clinically significant weight gain. This study helps quantify the real-world risk of weight gain for patients with MDD on medications with high risk for weight gain, especially for patients taking antipsychotics. Concurrent treatment with bupropion does not appear to mitigate the weight gain risk., (Copyright © 1964–2021 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

In Italy, Chianti Classico identifies a territory located in the heart of Tuscany that was once known as Chianti. From the pedological point of view, the entire DOCG (Denomination of controlled and guaranteed origin) has some common features but also shows many specific features related to certain small areas that give rise to the presence of many "terroirs". Due to the intertwining created by the alternation of valleys and hills and the different characteristics of the territory, factors such as altitude and exposure play a very important role in the vegetative and productive expression of grapes. Some production areas were identified within the appellation where it is argued that the terroir and the grapes are quite distinct from those of other surrounding areas, albeit within the Chianti Classico appellation. On the basis of this information and considering that no data are available in the literature, the present study proposed an innovative multidisciplinary approach (analytical and statistical) that was capable of carrying out an objective evaluation of the various sub-areas investigated, using Sangiovese grapes as the variety in question. This research took into account the climatic results and the different pedological characteristics, evaluating the evolutionary phenomena that were linked to the ripening of the grapes in each phase of its formation.

Introduction: With the COVID-19 vaccine rollout is well underway now beginning in children ages 12 and over, it is unknown what percent of parents plan to vaccinate their children against COVID-19., Method: The purpose of this descriptive correlational study was to examine parents' attitudes, beliefs, and behaviors in administering a COVID-19 vaccine., Results: Only 21.93% of the subjects reported overall VH. Half of parents (49.45%) say they want the COVID vaccine for their child, and 44.17% plan to vaccinate against COVID once the vaccine becomes available to them. Concern for vaccine side effects (61.5%) and vaccine safety (48.96%) were significant factors that increased VH. In addition, there was a significant correlation between parents who were planning to vaccinate their child against the flu and being less VH about a COVID-19 vaccine for their child., Discussion: This is the first known study to describe parental perceptions' of COVID-19 VH and identify factors that increase VH for parents., (Published by Elsevier Inc.)

Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings., Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital., Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods., Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response., Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Individuals with opioid use disorder often report feelings of shame and describe feeling judged negatively. These feelings are especially true for pregnant women with opioid use disorder. The Ohio Perinatal Quality Collaborative conducted a multimodal quality improvement initiative for infants born with Neonatal Abstinence Syndrome (NAS). An important component of the project was focused on improving staff attitudes toward mothers of infants with NAS., Methods: The Ohio Perinatal Quality Collaborative implemented an education program for healthcare providers at 39 participating hospital units regarding opioid use as a chronic disease and principles of nonjudgmental, trauma-informed care. Healthcare providers partnered with the mother of infants with NAS in the care of the infant and connected with local community resources. This work was a subcomponent of an overall multimodal quality improvement project. Healthcare provider attitudes were measured with the "Attitude Measurement: Brief Scales" questionnaire anonymously, at 3 different time points throughout the project. Attitude change was measured by pretraining and posttraining scores. ANOVA methods were used to compare individual items and a summary score across the 3 surveys., Results: Summary scores improved significantly from 18.99 at baseline (January-March 2014) to 19.94 ( P < 0.0001) in February 2015 and were maintained at 20.05 in July 2016., Conclusions: A nonjudgmental attitude toward mothers of infants with NAS is an important component of compassionate care. Improving healthcare provider attitudes can benefit a mother of an infant with NAS and help preserve the mother-infant dyad., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Neuropsychologists play an important role on multidisciplinary teams with physicians from multiple specialties. The extent of residency training on the use of neuropsychological services is unclear. Medical residents across multiple specialties throughout the United States were surveyed to assess resident education, training, and understanding of neuropsychological services, along with their intent to consult neuropsychologists in the future., Methods: A survey was sent to residents in accredited psychiatry, neurology, family medicine, and internal medicine programs. After data were collected, chi-square group level analyses with post-hoc pairwise comparisons were used to analyze the data., Results: A total of 434 residents took the survey. The proportion of residents exposed to neuropsychology during residency varied significantly according to specialty (χ 2 (3, N = 419) = 51.4, p < 0.001), with more psychiatry and neurology residents reporting exposure than residents in family medicine or internal medicine. Similarly, the proportion of psychiatry and neurology residents who 'agree' or 'strongly agree' that they understand the nature of neuropsychological services differed significantly from family medicine and internal medicine residents (χ 2 (3, N = 415) = 40.4, p < 0.001). The majority of residents across all specialties (85.7%) reported they are likely to consult/order neuropsychological services in future practice., Conclusions: The majority of residents in all specialties reported exposure to neuropsychological services in some manner, but forms of exposure varied. Results indicated a need for increased education and training in neuropsychological services, especially within family medicine and internal medicine programs., (© 2021 The University of Kansas Medical Center.)

The human metabolome may vary based on age, over time, and in the presence of viral carriage and bacterial colonization-a common scenario in children. We used nuclear magnetic resonance spectroscopy to identify and quantify urinary metabolites of children without signs or symptoms of respiratory illness. A urine sample and two nasopharyngeal swabs were collected to test for respiratory viral pathogens and colonization by Streptococcus pneumoniae ( Sp ). Urine samples were collected at the initial visit, 24 h post-enrollment, and 10-14 days post-enrollment. Of the 122 children enrolled, 24% had a virus detected and 19.7% had Sp detected. Intraclass correlation coefficients demonstrated greater within-subject versus between-subject variability for all metabolites detected. In linear mixed models adjusted for age, time, history of asthma, Sp , and viruses, 1-methylnicotinamide was increased by 50% in children with Sp and decreased by 35% in children with rhinovirus/enterovirus. Children with Sp had 83% higher levels of trimethylamine-N-oxide compared with those without Sp . However, when adjusting for multiple comparisons, the association was no longer statistically significant. In conclusion, there appear to be short-term changes within the urinary metabolome of healthy children, but levels of metabolites did not statistically differ in children with viral carriage or Sp detected.

Objective: To evaluate response to esketamine nasal spray plus an oral antidepressant (ESK + AD) at day 28 in patients with major depressive disorder ( DSM-5 ) and treatment-resistant depression (TRD) who did not meet response criteria within the first week of treatment., Methods: The current study is a pooled post hoc analysis of two phase 3, double-blind, active-controlled studies, conducted between August 2015 and February 2018, comparing ESK + AD with an oral antidepressant plus placebo (AD + PBO). Early treatment response was defined as a ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale total score at day 2 or days 2 and 8. Response rates at day 28 were determined among those not meeting early response criteria., Results: 518 patients in the analysis had day 28 observations (ESK + AD, n = 310; AD + PBO, n = 208). A greater percentage of patients treated with ESK + AD versus AD + PBO met response criteria beginning at day 2 (17.3% [55/318] vs 9.4% [19/203]) and at all subsequent timepoints, including day 28 (58.7% [182/310] vs 45.2% [94/208]). In day 2 nonresponders, 54.9% vs 44.3% (ESK + AD vs AD + PBO, respectively) achieved response at day 28 ( P  < .01). Similarly, among day 2 and 8 nonresponders, 52.1% vs 42.4% achieved response by day 28 ( P  = .01). In nonresponders at day 2 and at days 2 and 8, the odds ratio for a response at day 28 was 1.61 (95% CI, 1.09-2.40) with ESK + AD versus 1.56 (95% CI, 1.04-2.35) with AD + PBO., Conclusions: Patients with TRD without a demonstrated response within the first week of treatment may still derive benefit from a full 4-week induction course of esketamine nasal spray., Trial Registration: ClinicalTrials.gov identifiers NCT02417064 and NCT02418585., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objective: To conduct a meta-analysis of studies of vortioxetine in adults with major depressive disorder (MDD)., Data Sources: Abstracts were identified using PubMed by cross-referencing vortioxetine with placebo and randomize d. No language or publication year restrictions were used., Study Selection: Randomized, double-blind, placebo-controlled clinical trials comparing oral vortioxetine monotherapy with placebo for acute treatment of MDD., Data Extraction: Data were extracted with a pre-coded form, as follows: number of patients randomized, treatment group, Montgomery-Asberg Depression Rating Scale (MADRS) response and remission rates, and mean change in scores from baseline and standard errors for the MADRS, Hamilton Anxiety Rating Scale (HARS), and Digit Symbol Substitution Test (DSST)., Results: 7,269 subjects randomized to vortioxetine (n = 3,630) or placebo (n = 3,639) from 17 studies were included. The probability of receiving placebo did not predict difference in change in MADRS scores between vortioxetine and placebo (estimate = 4.1, P  = .54). The standardized mean difference (SMD) (95% CI) for change in MADRS score for vortioxetine overall versus placebo was 0.33 (0.24 to 0.41) and was 0.24 (0.08 to 0.39), 0.33 (0.19 to 0.47), 0.26 (-0.06 to 0.58), and 0.44 (0.27 to 0.62) for 5-mg, 10-mg, 15-mg, and 20-mg doses, respectively. Greater difference in efficacy between drug and placebo was observed in studies with a low rather than a high placebo response rate., Conclusions: Vortioxetine is more effective than placebo in improving depression, anxiety, and cognition. Less informative or uninformative studies obscured the true treatment effect., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objective: The goal of this study was to examine the association between aspects of the psychosocial work environment and prevalence of musculoskeletal disorders (MSDs) and associated functional consequences among pediatric healthcare providers., Background: The psychosocial work demands make pediatric care providers susceptible to MSDs and subsequent functional consequences, but research on this at-risk group is lacking., Methods: Randomly selected pediatric registered nurses, behavioral health specialists, and patient care assistants (N = 569) completed a survey assessing psychosocial factors, MSDs, and functional consequences (e.g., missing work). Logistic regression was used to assess associations between psychosocial factors and outcomes., Results: The analysis yielded moderate-to-strong, significant associations between psychosocial environment factors and MSDs and their functional consequences. The odds of MSDs increased nearly three-fold in the highest quartile of the psychosocial summary score vs. the lowest (OR: 2.7, 95% CI: 1.6-4.5). The highest quartiles of the psychosocial environment measures were significantly associated with functional consequences of MSDs., Conclusion: Results confirm knowledge about the association between the psychosocial environment and MSDs and demonstrates the association also exists among pediatric providers. Our study highlights the importance of studying the functional consequences of MSDs, which characterize the impact of MSD burden at work and elsewhere., (Copyright © 2021 Elsevier Inc. All rights reserved.)