Short-term Trials Research Articles

Preface

International Conference on World Technological Trends in Agribusiness (WTTA 2021) was held at Omsk State Agrarian University, Omsk, Russia on 29-30 March 2021. WTTA 2021 aimed to develop scientific cooperation between Russian and international researchers in the field of agrotechnologies.The conference has become an agriculture forum for researchers, practitioners, and scholars to discuss the most recent developments in agro engineering, agriculture, and melioration. The participants have presented innovative engineering solutions for automated crop production and cattle breeding. A range of technological advances for the treatment, processing, and storage of vegetal raw materials and livestock products has been presented. Environmentally friendly agricultural solutions turned out to be quite a topical issue to explore.Due to the CoViD-19 pandemic, the conference was held in a mixed format. The majority of the local participants deliver their reports at the venue. At the same time, almost all non-local authors made presentations via videoconferencing.There were about 170 papers submitted for the conference. After the reviewing process, 121 of them were selected and approved for the meetings. Unfortunately, not all the authors managed to attend the venue or join the meetings virtually. Only 108 out of 121 accepted reports were delivered. In the course of the discussion, the authors of two dozen reports got a recommendation for the revision to be applied prior to publication. After the final editorial check, only 100 manuscripts were considered ready to be published in WTTA 2021 proceedings.This year virtual participation was organized using the Zoom platform. Remote technologies made it possible to make presentations for participants from Stavropol State Agrarian University, Federal Research Centre of Biological Systems and Agrotechnologies (RAS, Orenburg), Altai State University, Mari State University, Krasnoyarsk Research Center (RAS, Krasnoyarsk), Ingush Agricultural Research Institute, etc.At the time of the conference, Omsk State Agrarian University did not use the Zoom platform as the main tool for organizing distance education. In this regard, Zoom was used as a short-term trial period, which determined the tight timing of the main conference meetings.During the conference, five conference rooms equipped for videoconferencing were used. A special group of volunteer moderators was created to ensure the integrity of discussion and involvement of both local and virtual participants. The main task for the moderators was to repeat the audience’s questions to the virtual participants. Besides, they provided the right to a voice question to registered participants and read questions from listeners sent to the chat.Holding the conference in such a format has become a new and valuable experience for the entire team of organizers. This experience was successful thanks to the participation of the university administration, student volunteers, and assistance from the client department of the Zoom platform. At last, we would like to express our gratitude to the editorial team and reviewers as well as to the conference organizers. We are glad that, despite all the challenges associated with the coronavirus pandemic, we were able to collect and review the papers and prepare the WTTA 2021 proceedings.On behalf of the committee Olga Stepanova Secretary of the conference Assoc. Prof. of Omsk State Agrarian University PROGRAM COMMITTEE, ORGANIZING COMMITTEE are available in this pdf.

Ulotaront, a novel TAAR1 agonist with 5-HT1A agonist activity, lacks abuse liability and attenuates cocaine cue-induced relapse in rats

BackgroundUlotaront (SEP-363856) is a trace amine-associated receptor 1 (TAAR1) agonist with 5-hydroxytryptamine type 1A (5-HT1A) agonist activity that is currently in Phase 3 clinical development for the treatment of schizophrenia. Unlike available antipsychotics, the efficacy of ulotaront is not mediated by blockade of dopamine D2 or serotonin 5-HT2A receptors. In a short-term randomized clinical trial, ulotaront has demonstrated significant efficacy in the treatment of adults with an acute exacerbation of schizophrenia. Given ulotaront’s novel mechanism of action a series of preclinical studies were performed to evaluate its potential abuse liability. MethodsA battery of studies were conducted in male and female rats to evaluate whether ulotaront produces behavioral changes suggestive of human abuse potential. In addition, studies were undertaken to probe the potential for ulotaront to block reinstatement of cocaine-seeking behavior in male rats. ResultsUlotaront was not self-administered by rats trained to self-administer amphetamine, cocaine, or heroin. The subjective qualities of ulotaront were distinct from those produced by amphetamine in a drug discrimination procedure. Ulotaront, and buspirone, a non-scheduled anxiolytic with 5-HT1A agonism, partially generalized to the interoceptive cue elicited by 3, 4-methylenedioxymethamphetamine (MDMA). In addition, ulotaront demonstrated a trend to reduce cocaine-primed induced reinstatement, and dose-dependently reduced cue-reinstated responding. ConclusionThe current results suggest that the TAAR1/5-HT1A agonist ulotaront is not likely to pose a risk for recreational abuse in humans and may have potential therapeutic utility as a treatment of substance use disorders.

Solid-State Hydrolysis (SSH) Improves the Nutritional Value of Plant Ingredients in the Diet of Mugil cephalus

The possibility of improving the nutritional quality of plant byproducts (brewers’ spent grain and rice bran) through an enzyme treatment was tested in a formulated feed for grey mullet (Mugil cephalus). The enzyme treatment was carried out by Solid-State Hydrolysis (SSH) using a commercial preparation including carbohydrases and phytase. A feed prepared without the treatment and a commercial feed for carp were used as controls. In a preliminary short-term trial carried out at laboratory facilities, fish receiving the enzyme-treated feed showed significant improvement in both FCR and SGR when compared to those obtained with the untreated diet, although both experimental diets presented worse values than those obtained with the commercial feed. Different metabolic indicators including higher values of muscle glycogen and plasmatic triglycerides supported the positive effect of the enzyme treatment on the nutritional condition of the fish over those fed on the diet containing non-treated ingredients. Results of growth and feed efficiency that were obtained in a second long-term trial developed for 148 days under real production conditions evidenced the equivalence among the experimental and commercial diets and confirmed that enzyme pretreatment of plant ingredients by SSH may be a useful procedure to improve the nutritive value of high fiber plant byproducts when included in practical diets for this species and others with similar nutritional features.

Effect of Multiple-Nutrient Supplement on Muscle Damage, Liver, and Kidney Function After Exercising Under Heat: Based on a Pilot Study and a Randomised Controlled Trial.

Objective: This study explored the effect of multiple-nutrient supplementation on muscle damage and liver and kidney function after vigorous exercise under heat.Methods: After an initial pilot trial comprising 89 male participants, 85 participants were recruited and assigned into three groups: a multiple-nutrient (M) group, a glucose (G) group, and a water (W) group. Multiple-nutrient supplements contain glucose, fructose, maltose, sodium, potassium, vitamin B1, vitamin B2, vitamin C, vitamin K, and taurine. Participants were organised to take a 3-km running test (wet-bulb globe temperature 32°C) after a short-term (7 days) supplement. Blood samples were obtained to detect biochemical parameters [glucose (GLU), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid], inflammation factors [interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)], and oxidative stress biomarkers [superoxide dismutase (SOD) and 8-iso-prostaglandin F (2alpha) (8-iso-PGF2α)].Results: In the pilot trial, BUN decreased significantly in the M and G groups immediately after the running test. AST, Cr, and UA were significantly reduced 24 h after the running test with single-shot multiple-nutrient supplementation. In the short-term trial, multiple nutrients further prevented the elevation of CK (p = 0.045) and LDH (p = 0.033) levels 24 h after strenuous exercise. Moreover, we found that multiple nutrients significantly reduced IL-6 (p = 0.001) and TNF-α (p = 0.015) elevation immediately after exercise. Simultaneously, SOD elevation was significantly higher in the M group immediately after exercising than in the other two groups (p = 0.033). 8-iso-PGF2α was reduced in the M group 24 h after exercise (p = 0.036).Conclusions: This study found that multiple-nutrient supplementation promoted the recovery of muscle damage and decreased liver and kidney function caused by strenuous exercise in a hot environment, probably through the inhibition of secondary damage induced by increased inflammatory reactions and oxidative stress. In this respect, the current study has important implications for the strategy of nutritional support to accelerate recovery and potentially prevent heat-related illness. This study was prospectively registered on clinicaltrials.gov on June 21, 2019 (ID: ChiCTR1900023988).

Safety concerns on the abuse potential of esketamine: Multidimensional analysis of a new anti-depressive drug on the market.

Prominent features of esketamine (e.g., similar mechanism of action as ketamine and target population) require to be vigilant regarding its benefits/risks balance and its risks of abuse in real-life settings. The aim of this study was to review all available pharmacological and clinical data to assess the abuse potential of esketamine shortly after its marketing. This multidimensional study is a quantitative and qualitative analysis of complementary data sources, ranging from preauthorization data (i.e., fundamental pharmacology and clinical trials) to real-life settings data (i.e., pharmacovigilance databases and web forums). According to esketamine pharmacology, its psychoactive effects play a role both in its therapeutic effect and its abuse potential. Only one out of the three short-term efficacy trials found a significant difference between esketamine and placebo in treatment-resistant depression. Beside adverse events that may be sought for abuse purpose (e.g., dissociation, sedation, euphoric mood, hallucination, feeling drunk, and derealization), clinical signs related to substance use disorder (e.g., tolerance, withdrawal syndrome, and drug dependence) and misuse (e.g., off-label use) were also identified in pharmacovigilance databases. Analysis of pharmacovigilance narratives and web forums showed that esketamine psychoactive effects are appreciated by some patients, while they are badly experienced by others. Strict compliance with the market authorization, close monitoring of patients by psychiatrists, and surveillance of any signs of misuse, abuse, or dependence must be part of any treatment course.

Modification of High-Density Lipoprotein Functions by Diet and Other Lifestyle Changes: A Systematic Review of Randomized Controlled Trials.

High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.

Sodium-glucose cotransporter 2 inhibitors and anemia among diabetes patients in real clinical practice.

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) were reported to increase hemoglobin levels in short‐term clinical trials. Whether it is also true in real clinical practice is unknown.Materials and MethodsThis is a retrospective cohort study. Inclusion criterion was diabetes patients who visited our outpatient clinic from January 2019 to August 2020. Exposure of interest was the use of SGLT2i. Outcomes were hemoglobin levels. For the cross‐sectional analyses, non‐linear regression models were fitted with restricted cubic splines to investigate the association between hemoglobin levels and estimated glomerular filtration rate (eGFR) for users and non‐users of SGLT2i. For the case–control study, cases (anemia defined as hemoglobin <120 g/L for men, <110 g/L for women or the use of erythropoiesis stimulating agents) and controls were matched by age, sex and eGFR.ResultsAmong 2,063 diabetes patients, 723 were taking SGLT2i. In the cross‐sectional analyses, hemoglobin levels were higher among SGLT2i users compared with non‐users at eGFR >15 mL/min/1.73 m2. For the case–control study, 197 cases and controls were matched. Conditional logistic regression showed that the use of SGLT2i was associated with significantly lower prevalence of anemia (odd ratio 0.35, 95% confidence interval 0.21–0.58). Adjusted mean differences in hemoglobin levels between users and propensity score‐matched non‐users of SGLT2i were 7.0 g/L (95% confidence interval 3.0–10.0 g/L) at 6 months. Among SGLT2i users, the odds of an increase in 6‐month hemoglobin were similar across eGFR categories, except for eGFR <15 mL/min/1.73 m2.ConclusionsThe use of SGLT2i was associated with higher hemoglobin levels and lower prevalence of anemia in real clinical practice.

Opinion on the (Hemo)dialysate Sodium Prescription: Dialysate Sodium Prescription Should Not Be Considered in Isolation

With advances in hemodialysis technology and the desire to achieve cardiovascular stability during dialysis, prescribed dialysate sodium concentration has gradually increased over the years. Short-term trials suggest low dialysate sodium (&lt;138 mEq/L) is beneficial in reducing interdialytic weight gain, pre- and post-dialysis BP, and predialysis serum sodium; but it increases intradialytic hypotensive episodes. We believe dialysate sodium prescription cannot be considered in isolation. Our approach is to use patient symptoms, meticulous fluid volume management and low temperature dialysate in conjunction with neutral dialysate sodium in managing our dialysis patients. Long-term trials are needed to inform optimum dialysate sodium prescription.

Effects of ocean acidification on the biochemistry, physiology and parental transfer of Ampelisca brevicornis (Costa, 1853)

Ocean acidification (OA) has received more attention in the marine research community in recent years than any other topic. Excess carbon dioxide makes the ocean more acidic, threatening marine ecosystems. There has been little research on the impact of OA on crustaceans, particularly on their physiological and potential ecosystem-level consequences. Thus, we investigated the impacts of OA on the physiological and biochemical characteristics of the estuarine amphipod Ampelisca brevicornis. Ovigerous amphipods were harvested from nature and maintained in the laboratory to produce juveniles, which were then further reared to obtain the mature adults (F0) and successive offspring (F1). For this study, four pH treatments (pH 8.1, 7.5, 7.0, and 6.5) mimicking future OA were evaluated to understand the physiological and biochemical effects on the organisms. The findings of this study suggest that A. brevicornis is more vulnerable to OA than was previously established in short-term trials. The survival was significantly reduced as pH decreased over time and a significant interaction between pH and time was observed. Survival was higher in F1 than in F0 juveniles and vice versa in terms of growth. Animal's physiological responses such as growth, burrowing behavior, locomotor activity, swimming speed, ventilation rate and reproductive performance were negatively influenced by acidification. These physiological characteristics can be linked to the oxidative stress induced by global change conditions because excess of free radicals degrade cell functioning, affecting species' biochemical and physiological performance. These alterations may have long-term negative impacts, with ecological consequences. The results of this study provide baseline information regarding the effect of OA on this keystone crustacean that may be useful in simulating the impacts of OA to develop different conceptual models for a better understanding of the consequences and implications of climate change in the future for managing marine ecosystems.

Titanium Nitride Coated Implant Abutments: From Technical Aspects And Soft tissue Biocompatibility to Clinical Applications. A Literature Review.

To review the most up to date scientific evidence concerning the technical implications, soft tissue biocompatibility, and clinical applications derived from the use of titanium nitride hard thin film coatings on titanium alloy implant abutments. A review was performed to answer the following focused question: "What is the clinical reliability of nitride coated titanium alloy abutments?". A MEDLINE search between 1980 and 2021 was performed for investigations pertaining to the clinical use of nitride coated titanium alloy implant abutments (TiN) in case reports, case series, and short- and long-term non/randomized controlled clinical trials. Literature analysis led to addition evaluation of research related to the technical and biological aspects, as well as the physicochemical characteristics of TiN hard thin film coatings and their impact on titanium abutment biocompatibility, mechanical properties, macroscopic surface topography, and optical properties. Therefore, preclinical data from biomechanical and in vitro investigations were also considered as inclusion criteria. The limited number of clinical investigations published made a systematic review and meta-analysis not possible, therefore a narrative review was conducted. TiN coatings have been applied to dental materials and instruments to improve their clinical longevity. Implant abutments are coated with titanium nitride to mask the titanium oxide surface and enhance its surface characteristics providing the TiN abutment surface with a low friction coefficient and a very high chemical inertness. TiN coating is suggested to reduce early bacterial colonization and biofilm formation and enhance fibroblast cell proliferation, attachment and adhesion when compared to Ti controls. Additionally, studies indicate that hard thin film coatings enhance the mechanical properties (hardness and wear resistance) of titanium alloy and appears as a yellow color when deposited on the titanium alloy substrate. To date, clinical investigations show that nitride coated titanium abutments provide promising short-term clinical outcomes. Published research on nitride-coated abutments is still limited, however, the available biomedical research, mechanical engineering tests, in vitro investigations, and short-term clinical trials have, to date, reported promising mechanical, biological, and esthetic outcomes.

Pioglitazone transiently stimulates paraoxonase-2 expression in male nonhuman primate brain: Implications for sex-specific therapeutics in neurodegenerative disorders

Paraoxonase-2 (PON2) enhances mitochondria function and protects against oxidative stress. Stimulating its expression has therapeutic potential for diseases where oxidative stress plays a significant role in the pathology, such as Parkinson's disease. Clinical and preclinical evidence suggest that the anti-diabetic drug pioglitazone may provide neuroprotection in Parkinson's disease, Alzheimer's disease, and stroke, but the biochemical pathway(s) responsible has not been fully elucidated. To determine the effect of pioglitazone on PON2 expression we treated male African green monkeys with oral pioglitazone (5 mg/kg/day) for 1 and 3 weeks. We found that pioglitazone increased PON2 mRNA and protein expression in brain following 1 week of treatment, however, by 3 weeks of treatment PON2 expression had returned to baseline. This transient increase was detected in substantia nigra, striatum, hippocampus, and dorsolateral prefrontal cortex The short-term impact of pioglitazone on PON2 expression in striatum may contribute to the discrepancy in the potency of the drug between short-term animal models and clinical trials for Parkinson's disease. Both PON2 and pioglitazone's receptor, peroxisome proliferator-activated receptor gamma (PPARγ), possess sex- and brain region-dependent expression, which may play a role in the short-term effect of pioglitazone and provide clues to extending the beneficial effects of PON2 activation.

COVID-19 Breakthrough Infections and Transmission Risk: Real-World Data Analyses from Germany's Largest Public Health Department (Cologne).

Background and Methods: Vaccination is currently considered the most successful strategy for combating the SARS-CoV-2 virus. According to short-term clinical trials, protection against infection is estimated to reach up to 95% after complete vaccination (≥14 days after receipt of all recommended COVID-19 vaccine doses). Nevertheless, infections despite vaccination, so-called breakthrough infections, are documented. Even though they are more likely to have a milder or even asymptomatic course, the assessment of further transmission is highly relevant for successful containment. Therefore, we calculated the real-world transmission risk from fully vaccinated patients (vaccination group, VG) to their close contacts (CP) compared with the risk from unvaccinated reference persons matched according to age, sex, and virus type (control group = CG) utilizing data from Cologne’s health department. Results: A total of 357 breakthrough infections occurred among Cologne residents between 27 December 2020 (the date of the first vaccination in Cologne) and 6 August 2021. Of the 979 CPs in VG, 99 (10.1%) became infected. In CG, 303 of 802 CPs (37.8%) became infected. Factors promoting transmission included non-vaccinated status (β = 0.237; p < 0.001), male sex (β = 0.079; p = 0.049), the presence of symptoms (β = −0.125; p = 0.005), and lower cycle threshold value (β = −0.125; p = 0.032). This model explained 14.0% of the variance (corr. R2). Conclusion: The number of transmissions from unvaccinated controls was three times higher than from fully vaccinated patients. These real-world data underscore the importance of vaccination in enabling the relaxation of stringent and restrictive general pandemic control measures.

Effects of l-arginine and l-ornithine supplementations on the treatment of chronic periodontitis: A preliminary randomized short-term clinical trial

The growing interest in the possibilities of modulating macrophages in inflammatory diseases with therapeutic purpose has prompted the development of new approaches for the treatment of periodontitis. This randomized add-on open preliminary clinical study evaluated the short-term effects of L-arginine or L-ornithine as an adjuvant to scaling and root planing (SRP) in patients with chronic periodontitis. Materials and methodsSeventy-five periodontitis patients were recruited and monitored clinically and immunologically at baseline (before SRP) and 30 ± 5 days after SRP. All patients were assigned by stratified randomization to SRP (SRP only, n = 25), Arg (SRP + L-arginine, n = 25) or Control (SRP + L-ornithine, n = 25) Group. The medicines were used according to available instructions for 10 and 15 days, respectively. During the study, all patients were on a stable diet, without changing their rations and regiments. As immunological monitoring immunohistochemical study of CD68+ and CD163 + single positive gingival macrophages for 5 patients per group in the same time-point was conducted. The data were statistically analyzed. ResultsReduction of periodontal pocket depth (PPD) and bleeding on probing (BoP) was observed in all groups, with significant between-group differences for BoP in the Arg Group (p < 0.0001) at 30 days. The SRP and Arg groups demonstrated nonsignificantly increased density of CD68+ and CD163 + cells. The Orn Group showed an increase in the density of CD68+ and CD163 + macrophages at intragroup (p = 0.0066 and p < 0.0001) and between-group levels (p = 0.001 and p < 0.0001), and these changes corresponded to clinical PPD and BoP reduction. In the Arg and Orn groups at 30 days, CD163 + macrophages significantly predominated over CD68+ (p = 0.013, p < 0.0001). ConclusionThe use of L-arginine and L-ornithine as an adjunct to SRP promotes additional limited immunological benefit in the treatment of periodontitis. Metabolic stimulation with L-ornithine, but not L-arginine, is preferable for CD163+ Mφs subpopulation in periodontitis-affected gingiva.

Facing the Challenges of Understanding and Managing Behavior and Psychiatric Issues

Facing the Challenges of Understanding and Managing Behavior and Psychiatric Issues

Associations between fatty acid composition in serum cholesteryl esters and liver fat, basal fat oxidation, and resting energy expenditure: a population-based study

ABSTRACTBackgroundWe have repeatedly shown in short-term feeding trials that a high intake of dietary n–6 PUFAs, i.e. linoleic acid, prevents liver fat accumulation compared with saturated fat. However, population-based data is lacking and the mechanisms behind such effects are unclear.ObjectiveTo investigate associations between serum cholesteryl ester (CE) fatty acids and liver fat, basal fat oxidation [respiratory quotient (RQ)], and resting energy expenditure (REE). We hypothesized that PUFA in particular is inversely associated with liver fat and that such a relation is partly explained by a PUFA-induced increase in basal fat oxidation or REE.MethodsCross-sectional analyses using linear regression models in a population-based cohort with data on serum CE fatty acid composition and liver fat (n = 308).ResultsLinoleic acid (18:2n–6) (β = −0.03, 95% CI: −0.06, −0.001) and Δ5 desaturase index were inversely associated, whereas, γ-linolenic acid (18:3n–6) (β = 0.59, 95% CI: 0.28, 0.90), dihomo-γ-linolenic acid (20:3n–6) (β = 1.20, 95% CI: 0.65, 1.75), arachidonic acid (20:4n–6) (β = 0.08, 95% CI: 0.002, 0.16), palmitoleic acid (16:1n–7) (β = 0.37, 95% CI: 0.04, 0.70), Δ6 desaturase, and stearoyl CoA desaturase-1 (SCD-1) index were directly associated with liver fat after adjustment for confounders. Several serum CE fatty acids were correlated with both liver fat and REE, but only the association between DHA (22:6n–3) and liver fat was clearly attenuated after adjustment for REE (from β = −0.63 95% CI: −1.24, −0.02 to β = −0.34, 95% CI: −0.95, 0.27). Palmitoleic acid and SCD-1 were weakly inversely correlated with RQ but could not explain a lower liver fat content.ConclusionsSeveral serum CE fatty acids are associated with liver fat, among them linoleic acid. Although we identified novel associations between individual fatty acids and RQ and REE, our findings imply that PUFAs might prevent liver fat accumulation through mechanisms other than enhanced whole-body energy metabolism.

Preface

International conference “Agricultural Science and Engineering (ASAE 2021)” was successfully held at Michurinsk State Agrarian University, Michurinsk, Russia on 14-16 April 2021. ASAE 2021 aimed to develop the scientific cooperation in the field of agricultural engineering, crop farming technologies, and food preservation and storage.Topical issues of agroengineering, crop science and agricultural machinery were discussed. The speakers presented innovative solutions for automated crop production, cattle breeding, and environmental engineering. A range of technological advances for treatment, processing, and storage of vegetal raw materials and livestock products has been presented. Environmentally-friendly agricultural solutions were quite a pressing issue to discuss.More than 200 papers were submitted for reviewing, of which 150 were selected and approved for publication in the ASAE 2021 proceedings. Because of the COVID-19 pandemic, the conference was held in a mixed format. Most of the participants took part in presentia and about 50 people made presentations via videoconferencing.Virtual participation was organized on the Zoom platform. Zoom was used as a short-term trial period, which determined the tight timing of the conference meetings. Distance technologies made it possible to make presentations for participants from Belgorod State Agricultural University, Voronezh State Agrarian University, Kurgan State Agricultural Academy, Samara State Agrarian University and other higher institutions of Russia.Links for participation in virtual meetings were sent by the speakers freely. Speakers were encouraged to invite their colleagues as listeners. Registration of listeners was not carried out, so it is not possible to accurately estimate their number. Four conference rooms equipped for videoconferencing were used. A group of volunteer moderators was created to navigate the speakers and the listeners. Moderators helped the audience to ask questions and get full answers to them.We would like to express our gratitude to the editorial team and reviewers as well as to the conference organizers. We are glad that we were able to prepare the ASAE 2021 proceedings, despite all the challenges caused by the coronavirus pandemic.List of Program Committee are available in the pdf

The effects of drug safety warnings on drug sales and share prices.

Current regulations require that when seeking approval for new drugs, pharmaceutical companies must demonstrate their short- but not long-term safety and efficacy. Instead, post-approval, clinicians report adverse reactions to regulators, who may issue additional safety warnings. We investigate the incentives this creates for pharmaceutical companies to seek approval for new drugs with unknown long-term effects. We first construct models predicting that (1) long-run effects can be reasonably approximated from observational follow-up of short-term randomized control trials, and (2) companies will trade-off short-term sales against possible later adverse demand effects. We then test whether regulator warnings over diabetic, analgesic, analeptic, or psychoanaleptic drugs sold in the US and UK hospital and retail sectors affect the sales of individual drugs or the share prices of companies that sell them. With some exceptions, we find that pharmaceutical companies generally face no adverse market reaction in sales or share price from newly issued warnings in these four drug categories.

The use of Real-World Data (RWD) by Health Technology Assessment (HTA) agencies

Abstract Issue There are divergent views between HTA bodies and pharmaceutical industry on the potential for RWD to inform determination of added benefit or value for money of new medicines. However, exploration of use of RWD is now essential as more high-cost innovative therapies come to market with short-term uncontrolled trials. Description of problem Payers are increasingly seeing use of RWD to fill evidence gaps in clinical development programmes, including external control arms or collection of RWD after initial assessment to determine real-life effectiveness or duration of benefit. An international multi-stakeholder initiative, RWE4Decisions, led by the Belgian Payer - RIZIV/INAMI - has explored these issues over the past few years. They have proposed that all stakeholders including industry, clinicians, regulators, patients and methodologists need to be involved to determine what questions can be answered by RWD and ensuring data is of sufficient quality to generate robust real-world evidence (RWE). Alongside this, the IMPACT HTA Project has reviewed use of RWD in specific rare disease case studies. Results Several HTA/Payers have implemented RWD collection schemes, but few have been successful in delivering sufficient evidence to enable re-assessment of treatment value. Italy is an exception, with a national web-based registry system. Other countries prefer to rely on secondary use of health system data and links to clinical registries, but curating and analysing these data can be complex. The case studies show how more recently some countries are overcoming these challenges by entering into more formal agreements with stakeholders to ensure purposive data collection. Lessons There is a need to publish protocols and reports related to RWD collection in an international portal. If possible, dialogues among bodies should happen in advance to align RWD collection requirements and facilitate data analysis.

Effect of drops containing Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) on plaque acidogenicity and other caries-related variables in orthodontic patients

BackgroundThe purpose of the study was to investigate the effect of probiotics on biofilm acidogenicity and on the number of salivary Streptococcus mutans and lactobacilli in orthodontic patients.MethodsThis RCT was conducted on 28 young adults who were undergoing orthodontic treatment. The short-term prospective clinical trial lasted for three weeks. The test group rinsed daily with drops containing two Lactobacillus reuteri strains diluted in water, while the placebo group used drops without probiotics. The subjects were enrolled eight months since the beginning of orthodontic treatment. Plaque-pH, saliva and dental biofilm samples were obtained at baseline, one week and three weeks post intervention.ResultsTwenty-seven subjects successfully completed the trial period, only one drop out in the test group. No side effects were reported. A statistically significant increase in plaque pH at three weeks post-intervention was found for the test group (p < 0.05), while insignificant changes in the pH value were found for the placebo group in comparison to baseline (p > 0.05). In addition, the AUC7.0 showed a significant difference at three weeks between the test and placebo (p = 0.00002). The three-week samples of stimulated whole saliva showed a statistically insignificant difference in the number of S. mutans and lactobacilli between the two groups (p > 0.05). The qPCR analysis showed the ability of the two strains to get colonized in the dental biofilm without a significant effect on the microbial counts.Conclusion/clinical implicationsA mixture of Lactobacillus reuteri has the ability to reduce the pH fall at the three-week follow-up. However, the short-term use of probiotics does not appear to have an effect on the number of salivary Streptococcus mutans and lactobacilli in saliva and on the dental biofilm.Trial registrationClinicaltrial.gov (Identifier: NCT04593017/ (19/10/2020)).

The Effect of Alcohol on Blood Pressure and Hypertension.

To examine the acute and chronic effects of alcohol on blood pressure (BP) and the incidence of hypertension. We discuss the most current understanding of the mechanisms underlining these effects and their associations with the putative cardioprotective effects of consumption of low-to-moderate amounts of alcoholic beverages. A recent meta-analysis confirmed findings of experimental studies, demonstrating an acute biphasic effect of ethanol on BP, decreasing up to 12h of ingestion and increasing after that. This effect is mediated by vagal inhibition and sympathetic activation. A meta-analysis found that chronic consumption of alcoholic beverages was associated with a high incidence of hypertension in men and women; it also found that, in women, the risk begins at moderate alcohol consumption. The risks of alcohol consumption are higher in Blacks than in Asians or Caucasians. The mechanism underlying the chronic effects of alcohol on BP, and particularly the differential effect on Blacks, is still unknown. Short-term trials showed that alcohol withdrawal promotes BP reduction; however, the long-term effectiveness of interventions that aim to lower BP through the restriction of alcohol consumption has not been demonstrated. The harmful effects of alcohol on BP do not support the putative cardioprotective effect of low-to-moderate consumption of alcoholic beverages. The absence of a tangible mechanism of protection, and the possibility that this beneficial effect is biased by socioeconomic and other characteristics of drinkers and abstainers, calls into question the hypothesis that consuming low amounts of alcoholic beverages improves cardiovascular health. The evidence from investigations with various designs converge regarding the acute biphasic effect of ethanol on BP and the risk of chronic consumption on the incidence of hypertension, particularly for Blacks. These effects do not support the putative cardioprotective effect of consumption of low-to-moderate amounts of alcoholic beverages. Mechanisms of chronic BP increase and the demonstration of long-term benefits of reducing alcohol intake as a means to treat hypertension remain open questions.