Physiological and structural modifications in snail medic (Medicago scutellata L.) plants exposed to salinity

Seeds of snail medic (Medicago scutellata L.) were assessed for their response to salt at the germination and seedling stages. NaCl at concentrations 86 and 170 mM decreased the final germination percentage. Embryonic axis length, water content and dry weight of embryonic axis and cotyledons were also reduced by salt treatment. Furthermore, 28-d-old plants were grown hydroponically with different NaCl concentrations (0, 86 and 170 mM). After 7 days of treatment, growth, water content and development of the different organs of M. scutellata plant were affected especially at the highest NaCl concentration (170 mM). However, NaCl did not affect root length and the number of stem shoots but reduced stem length and total leaf area. Salt treatment increased markedly the concentration of Na+ in leaf and root tissues while reduced that of K+ only in root and stem tissues. Lipid peroxidation revealed the damage of the membranes of roots and leaves. Moreover, showed a more intense suberization and lignification at the cambial zone of roots of M. scutellata, were observed under the effect of NaCl

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Cefepime-induced neurotoxicity: a systematic review

Abstract Background Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood–brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations. We aimed to characterize the clinical course of cefepime neurotoxicity and response to interventions. Methods A librarian-assisted search identified publications describing cefepime-associated neurotoxicity from January 1980 to February 2016 using the CINAHL and MEDLINE databases. Search terms included cefepime, neurotoxicity, encephalopathy, seizures, delirium, coma, non-convulsive status epilepticus, myoclonus, confusion, aphasia, agitation, and death. Two reviewers independently assessed identified articles for eligibility and used the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) for data reporting. Results Of the 123 citations identified, 37 (representing 135 patient cases) were included. Patients had a median age of 69 years, commonly had renal dysfunction (80%) and required intensive care (81% of patients with a reported location). All patients exhibited altered mental status, with reduced consciousness (47%), myoclonus (42%), and confusion (42%) being the most common symptoms. All 98 patients (73% of cohort) with electroencephalography had abnormalities, including non-convulsive status epilepticus (25%), myoclonic status epilepticus (7%), triphasic waves (40%), and focal sharp waves (39%). As per Food and Drug Administration (FDA)-approved dosing guidance, 48% of patients were overdosed; however, 26% experienced neurotoxicity despite appropriate dosing. Median cefepime serum and cerebrospinal fluid (CSF) concentrations were 45 mg/L (n = 21) and 13 mg/L (n = 4), respectively. Symptom improvement occurred in 89% of patients, and 87% survived to hospital discharge. The median delay from starting the drug to symptom onset was 4 days, and resolution occurred a median of 2 days after the intervention, which included cefepime discontinuation, antiepileptic administration, or hemodialysis. Conclusions Cefepime-induced neurotoxicity is challenging to recognize in the critically ill due to widely varying symptoms that are common in ICU patients. This adverse reaction can occur despite appropriate dosing, usually resolves with drug interruption, but may require additional interventions such as antiepileptic drug administration or dialysis

Positive effects of salicylic acid pretreatment on the composition of flax plastidial membrane lipids under cadmium stress

Interest in use of flax (Linum usitatissimum L.) as cadmium (Cd)-accumulating plant for phytoextraction of contaminated soils opened up a new and promising avenue toward improving tolerance of its varieties and cultivars to Cd stress. The aim of this study is to get insights into the mechanisms of Cd detoxification in cell membranes, by exploring the effects of salicylic acid (SA)-induced priming on fatty acids and lipid composition of flax plantlets, grown for 10 days with 50 and 100 μM Cd. At leaf level, levels of monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), phosphatidylglycerol (PG), and neutral lipids (NL) have shifted significantly in flax plantlets exposed to toxic CdCl2 concentrations, as compared to that of the control. At 100 μM Cd, the linoleic acid (C18:2) decreases mainly in digalactosyldiacylglycerol (DGDG) and all phospholipid species, while linolenic acid (C18:3) declines mostly in MGDG and NL. Conversely, at the highest concentration of the metal, SA significantly enhances the levels of MGDG, PG and phosphatidic acid (PA), and polyunsaturated fatty acids mainly C18:2 and C18:3. Furthermore, SA pretreatment seems to reduce the Cd-induced alterations in both plastidial and extraplastidial lipid classes, but preferentially preserves the plastidial lipids by acquiring higher levels of polyunsaturated fatty acids. These results suggest that flax plantlets pretreated with SA exhibits more stability of their membranes under Cd-stress conditions.This research was supported by the Ministry of Higher Education, Scientific Research and Technology in TunisiaPeer reviewe

Treatment of Elderly Patients with Head and Neck Cancer.

In our aging society, the proportion of cancer cases in the elderly (65 years) is steadily rising. In the developed countries, the majority of head and neck squamous cell cancer affect senior people. Despite that, elderly-specific prospective trials are lacking, and these patients represent a particularly challenging population to manage. They often have decreased physiologic reserves and suffer from chronic diseases. In addition to fluctuations in social support and economic resources, older age is also associated with enhanced susceptibility to stress and altered pharmacokinetics and pharmacodynamics. Consequently, owing to concerns about excessive toxicity and insufficient efficacy, multimodality treatment is frequently withheld in these patients compared with their younger counterparts. However, chronological age is not a reliable predictor of life expectancy or the risk of adverse events. It has repeatedly been shown that fit elderly individuals may, indeed, benefit from intensive therapies like reconstructive surgery with microvascular free tissue transfer, concurrent chemoradiotherapy in locoregionally advanced setting, and even from the standard first- and second-line palliative systemic therapies, being the PFE regimen (platinum/5-fluorouracil/cetuximab) and immune oncology drugs, respectively. In this respect, geriatric assessment tools have been developed to differentiate between fit and frail senior persons and guide treatment decisions. A comprehensive geriatric assessment (CGA), evaluating functional status, comorbidities, and some other parameters, requires skilled professionals, is time-consuming and not necessary in every case. Thus, geriatric screening tools (e.g. G8 and Flemish version of the Triage Risk Screening Tool) have been introduced to clinical practice enabling to decide who will need a full evaluation (CGA), who will benefit from a specific examination, and who needs no further testing. With the advent of immune checkpoint inhibitors, new questions have emerged as to whether immunotherapy is feasible and effective in the elderly. These issues including the changing portfolio of anti-cancer agents and integration of clinical practice-oriented assessment tools should be, therefore, further explored