Tartaric Acid Synthetic Derivatives for Multi-Drug Resistant Phytopathogen Pseudomonas and Xanthomonas Combating

The resistance to antimicrobial preparations, according the WHO reports of recent years, is becoming the one of the most actual healthcare problems of this century. Nevertheless, the key role of antibiotics diversity increase, as well as the increase of their application scopes, the initial origin of antimicrobial resistance problem is the versatility of adaptation mechanisms potential of all microorganisms, including intraspecific gene horizontal transfer and quorum sensing. Thus, the actuality of search of new, ecologically safe and harmless for human health antimicrobial agents, among the natural and semisynthetic compounds, is being significantly increased. One of the prospective directions in these research is the derivatization of aldaric acids, isolated from plants different species, as the native antibacterial active substances, such as like: citric, acetic, tartaric, lactic.   In current research, 7 new derivatives of natural tartaric acid (TA): cyclohexylimide, benzylimide, phenylimide, benzyl mono amino salt, cyclohexyl mono amino salt, phenyl amino salt and mono ethanol amino salt of TA were tested on different strains from 6 subtypes of 3 species of phytopathogenic multi-drug resistant Xanthomonas and Pseudomonas. During the research it was detected the significant antimicrobial effect of studied compounds against the range of phytopathogens which are resistant to antibiotics from different classes and generations (ciprofloxacin, chloramphenicol, ceftriaxone, azithromycin, etc.). It was detected the higher efficiency of cyclohexyl- derivatives in comparison with mono ethanol-, phenyl- and benzyl- derivatives

The Benefit of Detecting Reduced Intracellular B12 Activity through Newborn Screening Remains Unclear

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable

‘I felt like a human being’ : An exploratory, multi‐method study of refugee involvement in the development of mental health intervention research

Background: Great advancements have been made in patient and public involvement (PPI), including the development of guidance on how to conduct, report and evaluate PPI. Despite these efforts, the evidence base remains relatively weak. A substantive methodological development is required. This is particularly important for vulnerable groups within society, for whom PPI can be challenging but has the potential to play a transformative role in shaping research. Objectives: To describe the group dynamic characteristics and immediate impact of PPI from the user representatives’ perspective in a case study of refugee involvement in the development of mental health intervention research. To pilot and methodologically appraise the Active Involvement of Users in Research Observation Schedule and Questionnaire. Design: The Active Involvement of Users in Research Observation Schedule and Questionnaire were administered together with a focus group discussion. Setting: ‘Refugee Advisors’ were involved in the development of a randomized con‐ trolled trial protocol evaluating a brief group intervention for refugee children expe‐ riencing symptoms of post‐traumatic stress in Sweden. Results: The multi‐method approach demonstrated good feasibility. There were clear examples of how the advisors influenced research development. The advisors described a perceived impact on the research, equality and acceptance, and knowledge gain. A sense of appreciation and empowerment was also interpreted. However, potential issues relating to the relevance of contributions and use of an interpreter were identified. Discussion and conclusion: The methodological approach piloted in this study offers a promising, rigorous way to evaluate PPI. The research tools require further refinement and validation

Neuroprotective and cerebrovascular effects of endogenous N-Arachidonoyl-GABA and its putative Cox-2 metabolite – GABA conjugate with Prostaglandin E2

Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAO model, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABA and its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions. Graphical abstract

Thulium laser versus cold steel tonsillectomy: a prospective pilot study in adult patients

Abstract Background The aim of this pilot study was to compare the operation time, intraoperative and postoperative bleeding, postoperative pain, and wound healing of the thulium RevoLix laser tonsillectomy method over the more commonly practiced cold steel tonsillectomy. Methods A prospective, single-blinded randomized pilot trial was conducted. Twenty-four adult patients with a mean age of 28.7 years with chronic recurrent tonsillitis were observed and underwent tonsillectomy. The patients were randomly assigned to have one tonsil removed with a thulium RevoLix laser 200, and the conventional cold steel tonsillectomy method was used for the other side. Results The tonsillectomy time from incision to hemostasis was 12.08 ± 0.77 (SE) min with the laser method and 10.92 ± 1.31(SE) min with the cold dissection method, with no statistically significant difference (P < 0.121). Intraoperative blood loss in the cold dissection method was 10.92 ± 1.31 ml, and 2.04 ± 1.62 ml was observed during laser treatment (P < 0.000, t = 8.363). In the cold steel tonsillectomy group, the pain score was significantly higher than that in the laser tonsillectomy group on the 7th and 12th postoperative days. Conclusion The use of the thulium RevoLix 200 laser for tonsillectomy in the present pilot study of 24 patients showed significantly better outcomes than those in conventional cold dissection methods in terms of intraoperative bleeding and postoperative pain; however, there was no statistically significant difference in other parameters, such as operational time and late postoperative bleeding. A large full-scale prospective study is needed to increase the generalizability and reliability of the results. Clinical trial registration ISRCTN16280803, registered on 25 March 2020, https://www.isrctn.com/ISRCTN16280803

Evaluation of the teaching recovery techniques community-based intervention for accompanied refugee children experiencing post-traumatic stress symptoms (Accompanied refugeeS In Sweden Trial; ASsIST) : study protocol for a cluster randomised controlled trial

Background Refugee children have often experienced traumas and are at significant risk of developing mental health problems, such as symptoms of post-traumatic stress disorder (PTSD), depression and anxiety, which can continue for years after resettlement. The Accompanied refugeeS In Sweden Trial (ASsIST) aims to evaluate a community-based intervention, called ‘Teaching Recovery Techniques’ (TRT), for accompanied refugee minors experiencing PTSD symptoms. Methods/design A cluster randomised controlled trial will be conducted in which participants will be randomly allocated to one of the two possible arms: the intervention arm (n=113) will be offered the TRT programme and the waitlist-control arm (n=113) will receive services as usual, followed by the TRT programme around 20 weeks later. Outcome data will be collected at three points: pre-intervention (T1), post-intervention (T2; c.8 weeks after randomisation) and follow-up (T3; c.20 weeks after randomisation). Ethics and dissemination Ethical approval was granted by the Regional Ethical Review Board in Uppsala (Ref. 2018/382) (24th February 2019). Results will be published in scientific journals. Trial registration details ISRCTN17754931. Prospectively registered on 4th June 2019

Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO⁻₃ output

Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. The nuclear farnesoid X receptor (FXR) and the membrane G protein-coupled receptor, TGR5, regulate bile acid (BA) homeostasis and inflammation. Therefore, we hypothesized that activation of FXR and/or TGR5 could ameliorate liver injury in Mdr2(-/-) (Abcb4(-/-)) mice, a model of chronic cholangiopathy. Hepatic inflammation, fibrosis, as well as bile secretion and key genes of BA homeostasis were addressed in Mdr2(-/-) mice fed either a chow diet or a diet supplemented with the FXR agonist, INT-747, the TGR5 agonist, INT-777, or the dual FXR/TGR5 agonist, INT-767 (0.03% w/w). Only the dual FXR/TGR5 agonist, INT-767, significantly improved serum liver enzymes, hepatic inflammation, and biliary fibrosis in Mdr2(-/-) mice, whereas INT-747 and INT-777 had no hepatoprotective effects. In line with this, INT-767 significantly induced bile flow and biliary HCO 3- output, as well as gene expression of carbonic anhydrase 14, an important enzyme able to enhance HCO 3- transport, in an Fxr-dependent manner. In addition, INT-767 dramatically reduced bile acid synthesis via the induction of ileal Fgf15 and hepatic Shp gene expression, thus resulting in significantly reduced biliary bile acid output in Mdr2(-/-) mice. CONCLUSION: This study shows that FXR activation improves liver injury in a mouse model of chronic cholangiopathy by reduction of biliary BA output and promotion of HCO 3--rich bile secretion

Evaluation of the Teaching Recovery Techniques community-based intervention for unaccompanied refugee youth experiencing post-traumatic stress symptoms (Swedish UnaccomPanied yOuth Refugee Trial; SUPpORT) : study protocol for a randomised controlled trial

BACKGROUND: In 2015, 162,877 persons sought asylum in Sweden, 35,369 of whom were unaccompanied refugee minors (URMs). Refugee children, especially URMs, have often experienced traumas and are at significant risk of developing mental health problems, such as symptoms of post-traumatic stress disorder (PTSD), depression and anxiety, which can continue years after resettlement. The Swedish UnaccomPanied yOuth Refugee Trial (SUPpORT) aims to evaluate a community-based intervention, called Teaching Recovery Techniques (TRT), for refugee youth experiencing PTSD symptoms. METHODS/DESIGN: A randomised controlled trial will be conducted in which participants will be randomly allocated to one of two possible arms: the intervention arm (n = 109) will be offered the TRT programme, and the waitlist-control arm (n = 109) will receive services as usual, followed by the TRT programme around 20 weeks later. Outcome data will be collected at three points: pre-intervention (T1), post-intervention (T2; about 8 weeks after randomisation) and follow-up (T3; about 20 weeks after randomisation). DISCUSSION: This study will provide knowledge about the effect and efficiency of a group intervention for URMs reporting symptoms of PTSD in Sweden. TRIAL REGISTRATION: ISRCTN, ISRCTN47820795. Prospectively registered on 20 December 2018.This article is distributed under the terms of the Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ </p