N-Methyl D-Aspartic Acid (NMDA) Receptors and Depression

The monoaminergic hypothesis of depression has provided the basis for extensive research into the pathophysiology of mood disorders and has been of great significance for the development of effective antidepressants. Current antidepressant treatments not only increase serotonin and/or noradrenaline bioavailability but also originate adaptive changes increasing synaptic plasticity. Novel approaches to depression and to antidepressant therapy are now focused on intracellular targets that regulate neuroplasticity and cell survival. Accumulating evidence indicates that there is an anatomical substrate for such a devastating neuropsychiatric disease as major depression. Loss of synaptic plasticity and hippocampal atrophy appear to be prominent features of this highly prevalent disorder. A combination of genetic susceptibility and environmental factors make hippocampal neurons more vulnerable to stress. Abundant experimental evidence indicates that stress causes neuronal damage in brain regions, notably in hippocampal subfields. Stress-induced activation of glutamatergic transmission may induce neuronal cell death through excessive stimulation of N-methyl-D-aspartic acid (NMDA) receptors. Recent studies mention that the increase of nitric oxide synthesis and inflammation in major depression may contribute to neurotoxicity through NMDA receptor. Both standard antidepressants and NMDA receptor antagonists are able to prevent stress-induced neuronal damage. NMDA antagonists are effective in widely used animal models of depression and some of them appear to be effective also in the few clinical trials performed to date. We are still far from understanding the complex cellular and molecular events involved in mood disorders. There appears to be an emerging role for glutamate neurotransmission in the search for the pathogenesis of major depression. Attenuation of NMDA receptor function mechanism appears to be a promising target in the search for a more effective antidepressant therapy

Are the helminth communities from unisexual and bisexual lizards different?

Specimens of three species of parthenogenetic lizards (Darevskia uzzelli, D. bendimahiensis, and D. sapphirina) from northeastern Turkey were examined for gastrointestinal parasites. Only one species, the nematode Spauligodon saxicolae (Pharyngodonidae), was found. The extremely low infection and diversity parameters, falling among the lowest within the Palaearctic saurians, support depauperate helminth communities for these parthenogenetic lacertid lizards. Our results suggest that parthenogenetic Darevskia follow a pattern of parasitism similar to other unisexual lizards (i.e. Aspidocelis). The low rates of infection and diversity may be explained by the decreasing opportunities for interchanging helminths rather than factors of susceptibility of unisexual hosts

A skeletochronological study of parthenogenetic lizards of genus Darevskia from Turkey

The skeletochronological method has been used to assess age distribution and age-related differences in body size among populations of the parthenogenetic lizards Darevskia sapphirina, D. uzzelli, D. armeniaca and D. unisexualis from Turkey and Armenia. The age distribution between D. armeniaca and D. unisexualis did not significantly differ and ranged from 1 to 8 years. Maximum age for both D. uzzelli and D. sapphirina was 6 years, and 8 years for both D. unisexualis and D. armeniaca. In all the studied species, individuals reached sexual maturity after third hibernation. According to patterns of growth marks resorption, D. sapphirina is distinguished from all other rock lizards of genus Darevskia by a narrowest periosteal bone as result of high rate of endosteal resorption resulting in complete destruction of hatchling line and line of the first hibernation

Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study

Objective. The ACT-MOVE study assessed the real-world efficacy and safety of s.c. tocilizumab (TCZSC), provided as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 1 year, in patients with RA and an inadequate response to csDMARD therapy and/or first TNF inhibitor. Methods. In this UK multicentre, open-label phase IIIb study, patients received TCZ-SC 162 mg once weekly for 52 weeks as monotherapy or with csDMARDs. Efficacy and safety were evaluated at baseline, weeks 2 and 4 and every 4 weeks thereafter up to week 52. Results. Of 161 patients who received at least one dose of TCZ-SC, 21 (13.0%) received TCZ-SC alone and 140 (87.0%) TCZ-SC with a csDMARD(s). From baseline to week 52, there was a mean decrease in DAS28-ESR score among all patients (!3.68), and within monotherapy (!3.75) and combination therapy (!3.67) groups. The proportion of patients who achieved DAS28 clinical remission (DAS28-ESR <2.6) at week 52 was 75.4% (95% CI 66.8, 82.8). At the same time point, "80% of patients who remained on TCZ-SC achieved DAS28 clinical remission or had low disease activity (DAS28-ESR "2.6 and #3.2). Overall, 6.2% of patients had at least one serious adverse event (10.2/ 100 patient-years), and there was one death; 11.2% of patients discontinued owing to adverse events. Conclusion. TCZ-SC was effective and tolerated in a real-world setting over 1 year. The efficacy of TCZ-SC was similar whether given as monotherapy or with csDMARDs; its safety profile was consistent with that previously establishe

COVID-19 vaccinations: summary guidance for Cancer patients in 28Languages: breaking barriers to Cancer patient Information

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.info:eu-repo/semantics/publishedVersio

Management and valorisation of wastes through use in producing alkali-activated cement materials

There is a growing global interest in maximising the re-use and recycling of waste, to minimise the environmental impacts associated with waste treatment and disposal. Use of high-volume wastes in the production of blended or novel cements (including alkali-activated cements) is well known as a key pathway by which these wastes can be re-used. This paper presents a critical overview of the urban, agricultural, mining and industrial wastes that have been identified as potential precursors for the production of alkali-activated cement materials, or that can be effectively stabilised/solidified via alkali activation, to assure their safe disposal. The central aim of this review is to elucidate the potential advantages and pitfalls associated with the application of alkali-activation technology to a wide variety of wastes that have been claimed to be suitable for the production of construction materials. A brief overview of the generation and characteristics of each waste is reported, accompanied by identification of opportunities for the use of alkali-activation technology for their valorisation and/or management

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised