Notes

Healthful Action of Nanoparticles.
Dual inhibition of the enzymatic pathways of cyclooxygenases (COX-1/COX-2) and lipoxygenase (LOX) is a rational approach for developing more efficient and safe anti-inflammatory agents. Herein, dual inhibitors of COX and LOX for the management of inflammation are reported. The structural modifications of starting pyrrolidine-2,5-dione aldehyde derivatives resulted in two structurally diverse families (Family A & B). Synthesized derivatives from both Families displayed preferential COX-2 affinity in submicromolar to nanomolar ranges. Disubstitution pattern of the most active series of compounds having N-(benzyl(4-methoxyphenyl)amino moiety presents a new template that is mimic to the diaryl pattern of traditional COX-2 inhibitors. Compound 78 with IC50 value of 0.051 ± 0.001 μM emerged as the most active compound. Highly potent COX-2/5-LOX inhibitors have also demonstrated appreciable in-vivo anti-inflammatory activity through carrageenan induced paw edema test. Moreover, the involvement of histamine, bradykinin, prostaglandin, and leukotriene mediators to adjust the inflammatory response were also studied. Apart from COX inhibition, sulfonamide is considered an important template for carbonic anhydrase inhibition. Hence, we also evaluated six sulfonamide derivatives for off-target in-vitro bovine carbonic anhydrase-II inhibition. Biological results were finally rationalized by docking simulations. Typically, most active COX-2 inhibitors interact with the amino acid residues responsible for the COX-2 selectivity.Staphylococcus pseudintermedius is a common cause of skin and soft tissue infections in dogs but can also cause infections in cats and humans. The frequency of methicillin-resistant S. pseudintermedius (MRSP) strains is increasing worldwide. Here, we obtained 43 MRSP isolates from dogs (n = 41), one cat (n = 1) and the small animal clinic environment (n = 1) in Slovenia from the period 2008-2018, which underwent whole-genome sequencing (WGS) and antimicrobial susceptibility testing. Five sequence types (STs) were identified, with ST71 (32/43) and ST551 (8/43) being the predominant. In Slovenia, ST551 was first detected in 2016, whereas a decrease in the frequency of ST71 was observed after 2015. All isolates were multidrug-resistant and most antimicrobial-resistant phenotypes could be linked to acquisition of the corresponding resistance genes or gene mutations. Core-genome multilocus sequence typing (cgMLST) revealed several potential MRSP transmission routes (i) between two veterinary clinics by a single MRSP-positive dog, (ii) between the environment of a veterinary clinic and a dog, and (iii) between a canine and a feline patient through the contaminated environment of a veterinary clinic. Of the six dogs that were additionally sampled from 14 days to five months after the initial sampling, each harbored the same MRSP strain, suggesting a limited within-host diversity of MRSP in symptomatic dogs. The present results highlight the importance of MRSP-positive dogs in the spread of veterinary care-associated MRSP infections and call for the implementation of strict control measures to reduce MRSP contamination in veterinary clinic environments originating from animal-contact surfaces.Infections with Mycoplasma hyopneumoniae (Mhyo), Mycoplasma hyorhinis (Mhr) and Mycoplasma flocculare (Mfloc) are common in swine. However, the degree of co-infections and the correlations between these mycoplasma co-infection and the severity of macroscopic lung consolidation lesions (MLCL) have not yet been explored in Brazil.The objectives were to quantify Mhyo, Mhr, and Mfloc in MLCL of slaughter pigs in Brazil, and to assess correlations with the degree of MLCL in slaughter pigs. To this end, five groups of lungs were made based on severity of lung lesions, and 80 lungs were collected for each group (400 lungs in total). The Mycoplasmas were quantified using a multiplex qPCR. Statistical differences and comparison between the groups were evaluated, respectively, by the Kruskal-Wallis test (p  less then  0.05) and Dunn's test (p  less then  0.05), and the correlation between the data was performed by Spearman's method (p  less then  0.05). The results revealed that the extent of MLCL showed a positive correlation with the Mhyo estimate (rho = 0.26; p  less then  0.05), a negative correlation with the Mfloc estimate (rho= -0.15; p  less then  0.05), and no significant correlation with the Mhr estimate (p = 0, 12). The extension of MLCL showed a positive correlation with the co-infection by Mfloc and Mhr (rho = 0.17; p  less then  0.05), and no significant correlation with Mhyo and Mhr (p = 0.87), and a negative correlation with Mhyo and Mfloc (rho= -0.28; p  less then  0.05). This study allowed to infer that, regarding the extension of MLCL, Mhr and Mfloc did not present opportunistic activity in relation to primary infection by Mhyo, but revealed some potential aggravation of these lesions. In addition, Mhyo expressed inhibitory behavior towards Mfloc, suggesting that one can compete with the other's presence.Cognitive psychology had a profound impact on psychopathology research. Nevertheless, the fact that cognition cannot be observed or manipulated directly complicates debates about the nature of the mental mechanisms that mediate psychopathology. This is less troublesome for psychopathology researchers who adopt an explicitly pragmatic approach that aims to use cognitive theories as tools for improving psychotherapy than for psychopathology researchers who seek to establish whether those theories are 'correct.' A pragmatic cognitive approach fosters progress by encouraging (a) reality-checks aimed at ending unproductive theoretical debates between cognitive theories, (b) a separation between to-be-explained psychological phenomena and explanatory mental constructs, (c) theoretical diversity, and (d) interactions with behavior analysis.Autonomic dysfunction in epilepsy is well-described. Heart rate variability (HRV) is a useful method to evaluate autonomic cardiac tone. Cardiac dysfunction may be involved in sudden unexpected death in epilepsy (SUDEP). HRV is a promising biomarker to enlighten the heart-brain axis role in SUDEP, but the required duration for a proper HRV recording in clinical routine remains unknown. This study aimed to verify the reliability of ultra-short HRV indices to evaluate cardiac autonomic tone in patients with epilepsy (PWE). Thirty-nine patients with mesial temporal lobe epilepsy (MTLE) had electrocardiogram recordings during the first day of video-EEG. Pearson's correlations were performed to evaluate the association between ultra-short HRV indices (five 1-min and five 30-s epochs) with standard time recording (5-min) and ANOVA compared the differences between mean HRV indices across epochs. Time domain (TD) indices showed higher mean r values when compared to frequency domain (FD) indices in 1-min (TD r 0.80-0.99, FD r 0.61-0.95) and 30-s epochs (TD r 0.69-0.99, only high frequency mean r values of 0.96). ANOVA evidenced that standard deviation of RR intervals and very low frequency means had at least 3 epochs significantly different for 1-min and 30-s epochs. Root mean square of the successive differences of RR intervals (rMSSD) presented higher Pearson's coefficient values and lower percentage of variation at 1-min or 30-s epochs in comparison to other HRV indices. In conclusion, rMSSD is the most reliable ultra-short HRV index for cardiac autonomic tone assessment in MTLE. The prognostic value of ultra-short HRV for cardiovascular risk evaluation in epilepsy remains to be determined in future studies.
We assessed in extremely preterm born (EPB) children whether secondary somatosensory cortex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children.

39 EPB children underwent MEG with tactile stimulation at TEA. At age 6years, 32 EPB and 26TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6years.

Unilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p=0.03). At age 6years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p=0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p=0.02).

Unilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children.

Neurophysiological methods may provide new means for outcome prognostication in EPB children.
Neurophysiological methods may provide new means for outcome prognostication in EPB children.
This study examined neurophysiological (NI), split-hand (SI) and split-leg (SLI) index in patients with amyotrophic lateral sclerosis (ALS), and their correlation with functional status, disease duration, staging and survival.

Eighty-two patients underwent nerve conduction study to analyze NI, SI and SLI. Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), disease progression rate (ΔFS), Milano-Torino (MiToS) and King's staging systems, Forced Vital Capacity (FVC), and survival data were collected.

Both NI and SI indices were significantly associated with ALSFRS-R, MiToS, King's and FVC. Phycocyanobilin cost Slow progressor patients (ΔFS < 0.5) reported a significantly higher NI and SI values compared to both normal (0.5 ≤ ΔFS < 1.00) and fast progressors (ΔFS ≥ 1.0). After dichotomizing patients in slow progressors (ΔFS < 0.5) and not-slow progressors (ΔFS ≥ 0.5), a combination of SI index and disease duration revealed to be the best prediction model to discriminate patients in accordance with their disease progression (c-index 0.92), leading to a new prognostic index the 'Split-Hand prognostic index' (SHpi).

SI and NI are correlated with functional status and FVC. SHpi index could represent an useful tool to discriminate patients in accordance with their disease progression.

These data provide novel evidence of neurophysiological indices as promising biomarkers in ALS.
These data provide novel evidence of neurophysiological indices as promising biomarkers in ALS.
Changes in baroreflex sensitivity have been reported in patients with idiopathic Parkinson's disease (PD). We sought to investigate the hypothesis that patients with isolated rapid eye movement (REM)-sleep behavior disorder (iRBD), known to be a prodromal stage for PD, will show abnormalities in baroreflex control.

Ten iRBD patients were compared to 10 sex- and age-matched healthy controls. Their cardiovascular parameters and muscle sympathetic nerve activity (MSNA) were evaluated at rest and during baroreflex stimulation.

MSNA at rest was higher in iRBD patients (burst frequency [BF] 44±3 bursts/min; burst incidence [BI] 60±8 bursts/100 heartbeats) as compared to the controls (BF 29±3 bursts/min, p<0.001; BI 43±9 bursts/100 heartbeats, p<0.001). During baroreflex stimulation, iRBD patients showed increased absolute values of MSNA (BF F=62.728; p<0.001; BI F=16.277; p<0.001) as compared to the controls. The iRBD patients had decreased diastolic blood pressure at baseline and during lower body negative pressure, but the level of significance was not met.
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