Survivors of war in the Northern Kosovo (II): baseline clinical and functional assessment and lasting effects on the health of a vulnerable population

<p>Abstract</p> <p>Background</p> <p>This study documents torture and injury experience and investigates emotional well-being of victims of massive violence identified during a household survey in Mitrovicë district in Kosovo. Their physical health indicators such as body mass index (BMI), handgrip strength and standing balance were also measured. A further aim is to suggest approaches for developing and monitoring rehabilitation programmes.</p> <p>Methods</p> <p>A detailed assessment was carried out on 63 male and 62 female victims. Interviews and physical examination provided information about traumatic exposure, injuries, and intensity and frequency of pain. Emotional well-being was assessed using the "WHO-5 Well-Being" score. Height, weight, handgrip strength and standing balance performance were measured.</p> <p>Results</p> <p>Around 50% of victims had experienced at least two types of torture methods and reported at least two injury locations; 70% had moderate or severe pain and 92% reported constant or periodic pain within the previous two weeks. Only 10% of the victims were in paid employment. Nearly 90% of victims had experienced at least four types of emotional disturbances within the previous two weeks, and many had low scores for emotional well-being. This was found to be associated with severe pain, higher exposure to violence and human rights violations and with a low educational level, unemployment and the absence of political or social involvement.</p> <p>Over two thirds of victims were overweight or obese. They showed marked decline in handgrip strength and only 19 victims managed to maintain standing balance. Those who were employed or had a higher education level, who did not take anti-depressant or anxiety drugs and had better emotional well-being or no pain complaints showed better handgrip strength and standing balance.</p> <p>Conclusions</p> <p>The victims reported a high prevalence of severe pain and emotional disturbance. They showed high BMI and a reduced level of physical fitness. Education, employment, political and social participation were associated with emotional well-being. Interventions to promote physical activity and social participation are recommended. The results indicate that the rapid assessment procedure used here offers an adequate tool for collecting data for the monitoring of health interventions among the most vulnerable groups of a population exposed to violence.</p

SBI-fungicides : fungicidal effectiveness and resistance in «Botrytis cinerea»

In vitro fungitoxicity tests with 14 sterol biosynthesis inhibitors (SBIs) showed that the SBIs pyrifenox, flusilazol, propiconazole, triflumizole and fenpropimorph applied at the low concentration of 1 µg ml-1 inhibited the mycelial growth of wild-type and mutant strains of Botrytis cinerea that were resistant to the benzimidazoles, to the dicarboximides and to a mixture of benzimidazole+phenylcarbamate (carbendazim+diethofencarb). The SBIs tested exhibited higher effectiveness against the wild-type and mutant strains of B. cinerea compared with some widely used botryticides, such as the dicarboximides iprodione, procymidone and chlozolinate, the aromatic hydrocarbons quintozene, chloroneb and tolclofos-methyl, and the relatively new fungicides cyprodinil and fenhexamid. Only benomyl and fludioxonil presented higher effectiveness than the SBIs. In planta pot experiments with preventive applications of the commercial products Dorado 20 EC (pyrifenox), Punch 40 EC (flusilazol), Tilt 25 EC (propiconazole), Corbel 75 EC (fenpropimorph) and Trifmine 30 EC (triflumizole) showed that lesions of cucumber seedlings by all the abovementioned strains of B. cinerea were completely inhibited at low SBI concentrations of 0.05–0.1 g a.i. l-1. After chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (MNNG), only strains with low resistance (Rf 6–9, based on MIC values) to triadimefon were isolated at a mutation frequency of 3.9 10-5. Cross-resistance studies with other SBIs showed that these triadimefon-resistant strains exhibited positive cross-resistance (Rf 2–10) to the other C-14 demethylase inhibitors (DMIs), but not to the morpholine fungicides fenpropimorph or tridemorph. Study of fitness of DMI-resistant strains showed that these mutation(s) were pleiotropic, with significant adverse effects on characteristics determining phytopathogenic fitness such as rate of mycelial growth, sporulation, conidial germination and pathogenicity on cucumber seedlings. The results indicate that some SBI-fungicides are suitable for use in resistance management programmes against grey mould

Psycho-neuro-endocrino-immunologic issues in multiple sclerosis: a critical review of clinical and therapeutic implications

Multiple sclerosis (MS) is a multifactorial, chronic, immune-mediated, and neurodegenerative disease, having a well-known hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Several hormones have a great impact in the immune dysregulation, psychology, and cognitive status of patients with MS, as also in the fertility and response to treatment. In this comprehensive review, as an introduction, we mention basic data concerning MS: epidemiology, genetics, immunogenetics, epigenetics, pathophysiology, and neuroimmunology. Hormonal components of the disease cascade, mainly glucocorticoids (stress-related hormone), estrogens, prolactin and dehydroepiandrosterone (sex-related hormones), melatonin, and vitamin D, are discussed, aiming at focusing on core data regarding the impact of these hormones in MS pathophysiology, severity of the disease, correlation with comorbid mental disorders, and fertility. A great focus is given in the pre- and post-pregnancy period of MS patients, in the context of the disease-modifying treatments (DMTs) and HPA status, having in mind that there are only very limited knowledge and few papers on this specific life period of these women, having MS. All this data are presented in the main text and also in the workable tables, for the first time, suggesting targeted topics that need to be addressed in the near future. © 2020, Hellenic Endocrine Society

Differential Effect of <i>Sdh</i>B Gene Mutations on the Sensitivity to SDHI Fungicides in <i>Botrytis cinerea</i>

Succinate dehydrogenase inhibiting (SDHI) fungicides constitute a relatively novel fungicide group used for gray mold control caused mainly by Botrytis cinerea. Shortly after registration, resistance was observed in fungal populations that correlated with several mutations in the succinate dehydrogenase complex (complex II). In the current study, 30 B. cinerea isolates possessing five different mutations at three different codons of SdhB (P225F, N230I, and H272L/R/Y) were characterized for their sensitivities to eight SDHI fungicides. The results show different sensitivities and cross-resistance patterns between structurally different SDHIs. P225F mutants were resistant in vitro to all SDHIs tested. Similarly, isolates possessing the H272L mutation were highly resistant to boscalid but showed low to moderate levels of resistance to other SDHIs. The N230I mutants were moderately resistant to boscalid, fluopyram, and fluxapyroxad and showed low resistance levels to isopyrazam, bixafen, fenfuram, benodanil, and carboxin. The H272R mutants showed moderate levels of resistance to boscalid and low resistance levels to isopyrazam, fenfuram, and carboxin but remained sensitive to fluopyram, bixafen, fluxapyroxad, and benodanil. Similarly, the H272Y showed moderate levels of resistance to boscalid and very low resistance levels to isopyrazam, bixafen, fenfuram, and carboxin but showed increased sensitivity to benodanil and fluopyram. Boscalid provided moderate to high control of H272R/Y and N230I mutants in detached fruit assays but provided little control against the H272L and P225F mutants. In contrast, fluopyram controlled H272R/Y mutants and provided moderate levels of control toward H272L, N230I, and P225F mutants. Our findings suggest that sensitivity to SDHIs may vary greatly, dependent on the point mutation in the sdhb subunit. </jats:p

Fitness and Competitive Ability of <i>Botrytis cinerea</i> Field Isolates with Dual Resistance to SDHI and QoI Fungicides, Associated with Several <i>sdh</i>B and the <i>cyt</i>b G143A Mutations

Respiration inhibitors such as the succinate dehydrogenase inhibitors (SDHIs) and the quinone outside inhibitors (QoIs) are fungicide classes with increasing relevance in gray mold control. However, recent studies have shown that dual resistance to both fungicide classes is a common trait in Botrytis cinerea populations from several hosts throughout the world. Resistance of B. cinerea to SDHIs is associated with several mutations in the sdhB, sdhC, and sdhD genes, while resistance to QoIs, in most cases, is associated with the G143A mutation in the cytb gene. The objective of the current study was to investigate the fitness and the competitive ability of B. cinerea field strains possessing one of the H272Y/R/L, N230I, or P225F sdhB substitutions and the G143A mutation of cytb. Fitness parameters measured were (i) mycelial growth and conidia germination in vitro, (ii) aggressiveness and sporulation capacity in vivo, (iii) sclerotia production in vitro and sclerotia viability under different storage conditions, and (iv) sensitivity to oxidative stress imposed by diquat treatments. The competitive ability of the resistant isolates was measured in the absence and presence of the SDHI fungicides boscalid and fluopyram selection pressure. The measurements of individual fitness components showed that the H272R/G143A isolates had the lower differences compared with the sensitive isolates. In contrast, the groups of H272Y/L/G143A, N230I/G143A, and P225F/G143A isolates showed reduced fitness values compared with the sensitive isolates. Isolates possessing only the cytb G143A substitution did not show any fitness cost. The competition experiments showed that, in the absence of fungicide selection pressure, after four disease cycles on apple fruit, the sensitive isolates dominated in the population in all the mixtures tested. In contrast, when the competition experiment was conducted under the selection pressure of boscalid, a gradual decrease in the frequency of sensitive isolates was observed, whereas the frequency of H272L and P225F isolates was increased. When the competition experiment was conducted in the presence of fluopyram, the sensitive isolates were eliminated even after the first disease cycle and the P225F mutants dominated in the population. Such results suggest that the sdhB mutations may have adverse effects on the mutants. The observed dominance of sensitive isolates in the competition experiments conducted in the absence of fungicides suggest that the application of SDHIs in alternation schemes may delay the selection or reduce the frequency of SDHI-resistant mutants. </jats:p

Determination of Benzoylurea Insecticide Residues in Tomatoes by High-Performance Liquid Chromatography with Ultraviolet-Diode Array and Atmospheric Pressure Chemical Ionization-Mass Spectrometry Detection

Abstract A simple and sensitive method using high-performance liquid chromatography/mass spectrometry (LC/MS) was developed and validated for simultaneous determination of 5 benzoylurea insecticidesdiflubenzuron, triflumuron, teflubenzuron, lufenuron, and flufenoxuronin tomatoes. Residues were successfully separated on a C18 column by methanolwater isocratic elution. Detection was carried out by an ultraviolet diode array detector (UV-DAD) coupled with a quadrupole mass spectrometer, using atmospheric pressure chemical ionization (APCI) in negative-ion mode. The main ions were the deprotonated molecules [MH]&amp;lt;sup/&amp;gt; for triflumuron, and the anions formed by elimination of hydrofluoric acid [MHHF]&amp;lt;sup/&amp;gt; for diflubenzuron and flufenoxuron, and [M2HHF] for lufenuron and teflubenzuron. The calibration plots were linear for both detectors over the range 0.05 to 10 g/mL, and the method presented good quality parameters. The limits of detection for standard solutions were 0.0080.01 mg/L (equivalent to 0.080.1 ng injected) for both detectors, and the limits of quantification (LOQs) were approximately 10 times lower than national maximum residue levels (MRLs). Depending on the compound and the detector, the LOQ values ranged from 0.2 to 0.4 ng injected. The optimum LC-UV-DAD/APCI-MS conditions were applied to the analysis of benzoylureas in tomatoes. The obtained recoveries from fortified tomato samples (50 g), extracted with ethyl acetate and purified by solid-phase extraction on silica sorbent, were 88100 and 92.9105 for the UV-DAD and MS detectors, respectively, with precision values (relative standard deviations) of 2.911 and 3.714, respectively. The method was applied to 12 tomato samples from local markets, and diflubenzuron and lufenuron were detected in only one sample at concentrations lower than the MRLs. The results indicate that the developed LC/MS method is accurate, precise, and sensitive for quantitative and qualitative analysis at low levels of benzoylureas required by legislation.</jats:p