Genetic testing improves identification of transthyretin amyloid (ATTR) subtype in cardiac amyloidosis

Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC–MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC–MS/MS has not been evaluated. A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR amyloidosis, and 56 of these patients underwent both genetic testing and LC–MS/MS. LC–MS/MS and proteomics correctly reported the mutant peptide and heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who were homozygous for the ATTRV122I mutation and failed to detect the following mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and ATTRV122I. Therefore, LC–MS/MS is not sufficient to rule out a pathogenic mutation in cases of ATTR amyloid, and genetic testing should be performed in most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR amyloidosis is important for estimating prognosis, proper familial counselling and guiding use of therapies, such as liver transplantation.     

In Vitro Antiplasmodial Activity of Phospholipases A2 and a Phospholipase Homologue Isolated from the Venom of the Snake Bothrops asper

The antimicrobial and antiparasite activity of phospholipase A₂ (PLA₂) from snakes and bees has been extensively explored. We studied the antiplasmodial effect of the whole venom of the snake Bothrops asper and of two fractions purified by ion-exchange chromatography: one containing catalytically-active phospholipases A₂ (PLA₂) (fraction V) and another containing a PLA₂ homologue devoid of enzymatic activity (fraction VI). The antiplasmodial effect was assessed on in vitro cultures of Plasmodium falciparum. The whole venom of B. asper, as well as its fractions V and VI, were active against the parasite at 0.13 ± 0.01 µg/mL, 1.42 ± 0.56 µg/mL and 22.89 ± 1.22 µg/mL, respectively. Differences in the cytotoxic activity on peripheral blood mononuclear cells between the whole venom and fractions V and VI were observed, fraction V showing higher toxicity than total venom and fraction VI. Regarding toxicity in mice, the whole venom showed the highest lethal effect in comparison to fractions V and VI. These results suggest that B. asper PLA₂ and its homologue have antiplasmodial potential.     

Sertraline and Citalopram Actions on Gut Barrier Function

Introduction

Disruption of intestinal barrier is a key component to various diseases. Whether barrier dysfunction is the cause or effect in these situations is still unknown, although it is believed that translocation of luminal content may initiate gastrointestinal or systemic inflammatory disorders. Since trauma- or infection-driven epithelial permeability depends on Toll-like receptor (TLR) activity, inhibition of TLR signaling has been proposed as a strategy to protect intestinal barrier integrity after infection or other pathological conditions. Recently, selective serotonin recapture inhibitors including sertraline and citalopram were shown to inhibit TLR-3 activity, but the direct effects of these antidepressant drugs on the gut mucosa barrier remain largely unexplored.

Materials and methods

To investigate this, two approaches were used: first, ex vivo studies were performed to evaluate sertraline and citalopram-driven changes in permeability in isolated intestinal tissue. Second, both compounds were tested for their preventive effects in a rat model of disrupted gut barrier, induced by a low protein (LP) diet.

Results

Only sertraline was able to increase transepithelial electrical resistance in the rat colon both when used in an ex vivo (0.8 μg/mL, 180 min) or in vivo (30 mg/kg p.o., 20 days) fashion. However, citalopram (20 mg/kg p.o., 20 days), but not sertraline, prevented the increase in phospho–IRF3 protein, a marker of TLR-3 activation, in LP-rat ileum. Neither antidepressant affected locomotion, anxiety-like behaviours or stress-induced defecation.

Conclusion

Our data provides evidence to support the investigation of sertraline as therapeutic strategy to protect intestinal barrier function under life-threatening situations or chronic conditions associated with gut epithelial disruption.

     

Screening of in vitro antimicrobial activity of plants used in traditional Indonesian medicine

Context: In many regions of Indonesia, there are numerous traditional herbal preparations for treatment of infectious diseases. However, their antimicrobial potential has been poorly studied by modern laboratory methods.

Objective: This study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37 plant species used in Indonesian traditional medicine for treatment against Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

Materials and methods: The plants were collected from the Biopharmaca collection garden, Bogor, Indonesia. The plant material was dried, finely grounded, extracted using ethanol, concentrated, and the dried residue was dissolved in 100% DMSO. Antimicrobial activity was determined in terms of a minimum inhibitory concentration (MIC) using a broth microdilution method in 96-well microplates.

Results: The extract of Orthosiphon aristatus (Blume) Miq. (Lamiaceae) leaf produced the strongest antimicrobial effect, inhibiting the growth of C. albicans (MIC 128?μg/mL), S. aureus (MIC 256?μg/mL), E. faecalis (MIC 256?μg/mL) and P. aeruginosa (MIC 256?μg/mL). The leaf extract of Woodfordia floribunda Salisb. (Lythraceae) also exhibited significant effect against C. albicans (MIC 128?μg/mL), S. aureus (MIC 256?μg/mL) and E. faecalis (MIC 256?μg/mL). Rotheca serrata (L.) Steane &; Mabb. (Lamiaceae) leaf extract inhibited the growth of S. aureus (MIC 256 µg/mL) and C. albicans (MIC 256 µg/mL).

Discussion and conclusions: The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect. Therefore, both of these plants can serve as prospective source materials for the development of new anti-candidal agents.     

Physical fitness components in relation to attention capacity in Latin American youth with overweight and obesity

The aim of the study was twofold: (a) to examine the association between health-related physical fitness and attention capacity in Latin American children and adolescents with overweight and obesity and (b) to test whether body composition outcomes are moderators of this association. A cross-sectional design was used to study 201 overweight/obese participants (12.1 ± 2.1 years of age; 34.3% girls) from Chile (Active-Start study) and Colombia (HEPAFIT study). Body composition, muscular fitness, speed-agility, and cardiorespiratory fitness were evaluated using two similar test batteries (ALPHA and FUPRECOL). Attention capacity was measured by the d2 Test. Linear regression and moderation analyses were conducted. Linear regression analysis revealed an association between muscular fitness (β = 0.245, P = .015), speed-agility (β = −0.16, P = .027), cardiorespiratory fitness (β = 0.331, P < .001) and overall fitness score (β = 0.210; P = .004) and attention capacity (all analyses were controlled for age, sex, peak height velocity, maternal education, and study setting). Moderation analysis using the Johnson-Neyman technique revealed that the effect of the relationship between muscular fitness score and speed-agility and attention capacity was stronger as fat mass and fat mass index increased. In conclusion, physical fitness components are associated with higher attention capacity in youth with overweight/obesity, but body composition seems to moderate these relationships. Randomized controlled trials in this population would help to better understand whether improvements in different components of physical fitness lead to better attention capacity, especially in youth with excess adiposity.     

Ageusia and anosmia,a common sign of COVID-19? A case series from four countries

Journal of NeuroVirology - Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the...     

Grouping of body areas affected in traffic accidents. A cohort study

Background

Traffic accidents are considered a public health problem and, according to the World Health Organization, currently is the eighth cause of death in the world. Specifically, pedestrians, cyclists and motorcyclists contribute half of the fatalities. Adequate clinical management in accordance with aggregation patterns of the body areas involved, as well as the characteristics of the accident, will help to reduce mortality and disability in this population.

The Body Image Avoidance Questionnaire: Assessment of its Construct Validity in a Community Sample of French Adolescents

Background

Among the few instruments used to measure the behavioral component of body image disturbances, the Body Image Avoidance Questionnaire (BIAQ) is the most widely used. Despite the wide utilization of this instrument, it is currently unknown whether it is appropriate for male and female adolescents from middle and junior high schools.

Purpose

The main objective of the present series of studies was to test the construct validity of the BIAQ in a community sample of French adolescents.

Method

The content, factor, and convergent validity of the BIAQ were verified in the context of four independent studies conducted on a total sample of 945 adolescents.

Results

The first study showed that the content and formulation of the French BIAQ items were adequate for children and adolescents. The following three studies provided support for the factor validity, measurement invariance (across sex), reliability, and convergent validity of the French BIAQ. Regarding the measurement invariance tests, the results revealed that the models were invariant up to the levels of the latent means structures. Post hoc probing of these differences showed a significant higher latent mean score of the global BIAQ scale in females (in samples 2 and 3).

Discussion

The present results provide preliminary evidence regarding the construct validity of the BIAQ in a community sample of French adolescents.