Background
Motor neuron diseases (MND) represent a group of disorders that evolve with inexorable muscle weakness and medical management is based on symptom control. However, deeper characterization ...of non‐motor symptoms in these patients have been rarely reported.
Methods
This cross‐sectional study aimed to describe non‐motor symptoms in MND and their impact on quality of life and functional status, with a focus on pain and sensory changes. Eighty patients (31 females, 55.7 ± 12.9 years old) with MND underwent a neurological examination, pain, mood, catastrophizing and psychophysics assessments quantitative sensory testing (QST) and conditioned pain modulation (CPM), and were compared to sex‐ and age‐matched healthy controls (HC).
Results
Chronic pain was present in 46% of patients (VAS =5.18 ± 2.0). Pain of musculoskeletal origin occurred in 40.5% and was mainly located in the head/neck (51%) and lower back (35%). Neuropathic pain was not present in this sample. Compared to HC, MND patients had a lower cold detection threshold (p < 0.002), and significantly lower CPM scores (4.9 ± 0.2% vs. 22.1 ± 0.2%, p = 0.012). QST/CPM results did not differ between MND patients with and without pain. Pain intensity was statistically correlated with anxiety, depression and catastrophism, and spasticity scores were inversely correlated with CPM (ρ = −0.30, p = 0.026).
Conclusions
Pain is frequently reported by patients with MNDs. Somatosensory and CPM changes exist in MNDs and may be related to the neurodegenerative nature of the disease. Further studies should investigate the most appropriate treatment strategies for these patients.
Significance
We report a comprehensive evaluation of pain and sensory abnormalities in motor neuron disease (MND) patients. We assessed the different pain syndromes present in MND with validated tools, and described the QST and conditioned pain modulation profiles in a controlled design.
Intracellular peptides generated by limited proteolysis are likely to function inside and outside cells and could represent new possibilities for drug development. Here, we used several ...conformational-sensitive antibodies targeting G-protein coupled receptors to screen for novel pharmacological active peptides. We find that one of these peptides, DITADDEPLT activates cannabinoid type 1 receptors. Single amino acid modifications identified a novel peptide, DIIADDEPLT (Pep19), with slightly better inverse agonist activity at cannabinoid type 1 receptors. Pep19 induced uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive- and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications.
Aims
The microbial dynamics associated with the decomposition of maize (Zea mays) and coconut (Cocos nucifera) residues were investigated to assess the feasibility of using them as mulch in tropical ...soils.
Methods and Results
Phospholipid fatty‐acid (PLFA) profiling, microbial biomass (MB‐C), basal respiration, C‐cycle enzyme activities and inorganic N dynamics were monitored in a microcosm experiment incubating soil samples with plant residues for 425 days. Maize stover (MS) showed a higher decomposition, respiration rate, MB‐C, enzymes activities and shift in microbial community structure than coconut husk (CH), which was barely changed. In MS, the lower N level increased C losses and decreased N mineralization compared to the higher N level.
Conclusions
Maize stover is suitable for mulching and has a high potential of increasing soil quality if the proper N fertilization level is used, avoiding excessive C mineralization and N immobilization. Coconut husk decomposition was mostly impaired, indicating that a pre‐processing is necessary to improve the benefits of this residue.
Significance and Impact of the Study
Tropical soils are prone to degradation. Mulching can promote soil conservation, but depends on residue type and soil chemistry. Our study showed that MS managed under the recommended N fertilization level is suitable for mulching while CH is highly inaccessible for microbial degradation.
Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in ...transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.
PspA is an important pneumococcal vaccine candidate that is capable of inducing protection in different animal models. Because of its structural diversity, a PspA-based vaccine should contain at ...least one fragment from each of the two major families (1 and 2) in order to elicit broader protection. In the present work, we have tested the potential of PspA hybrids containing fused portions of family 1 and 2 (PspA1ABC-4B and PspA1ABC-3AB) PspA fragments to induce protection against pneumococci bearing distinct PspA fragments. Sera from mice immunized with these hybrid PspA fragments were able to increase C3 deposition on pneumococci bearing PspA fragments from both families, in contrast with sera made against the PspA family 1 (PspA1ABC) and PspA family 2 (PspA3ABC) fragments, which were effective only within the same family. Although PspA hybrids were able to extend protection against pneumococcal infection with strains bearing diverse PspA fragments, the immunity elicited by family 2 was clade dependent, suggesting that PspA fragments from family 2 clades 3 and 4 should both be included in a comprehensive PspA vaccine. These results indicate that PspA fusion proteins constitute an efficient immunization strategy for future PspA-based antipneumococcal vaccines since they are able to extend protection provided by a protein derived from a single transcript.
The skin redoxome Schalka, S.; Silva, M.S.; Lopes, L.F. ...
Journal of the European Academy of Dermatology and Venereology,
February 2022, 2022-Feb, 2022-02-00, 20220201, Letnik:
36, Številka:
2
Journal Article
Recenzirano
Redoxome is the network of redox reactions and redox active species (ReAS) that affect the homeostasis of cells and tissues. Due to the intense and constant interaction with external agents, the ...human skin has a robust redox signalling framework with specific pathways and magnitudes. The establishment of the skin redoxome concept is key to expanding knowledge of skin disorders and establishing better strategies for their prevention and treatment. This review starts with its definition and progress to propose how the master redox regulators are maintained and activated in the different conditions experienced by the skin and how the lack of redox regulation is involved in the accumulation of several oxidation end products that are correlated with various skin disorders.
Summary
Background
Cow's milk allergy (CMA) is one of the most common causes of food allergy in the first years of life. Fortunately, the majority of children with CMA develop clinical tolerance with ...time. However, no good individual markers exist to predict whether this will occur. Therefore, a prognosis to identify children with persistent CMA at diagnosis would be helpful.
Objective
In this study, we sought to assess whether measurement of IgE to individual allergens of cow's milk (CM) would separate patients with persistent CMA from those who became clinically tolerant to CM over time.
Methods
A total of 52 patients ranging from 3 months to 114 months of age with proven CMA by DBPCFC were followed over time. From these 52 patients, 32 (61.5%) patients became tolerant in the analysed time period. All patients were rechallenged at least once, some were rechallenged two or three times. Serum was analysed prior to each challenge for specific IgE, IgG and IgG4 binding to crude CM protein as well as to individual allergens of CM.
Results
The individual likelihood of outgrowing CMA significantly correlates with a low level of CM‐specific IgE as well as a low level of specific IgE to α‐lactalbumin, β‐lactoglobulin (Bos d5.0102), κ‐casein and αs1‐casein. No significant correlation was found for IgE levels to total casein, lactoferrin, β‐casein and β‐lactoglobulin (Bos d5.0101) as well as IgG and IgG4 levels to α‐lactalbumin, β‐lactoglobulin and total casein.
Conclusions
CM‐specific IgE is a good prognostic marker for persistence of CMA. In addition, component‐resolved diagnostic showed similar results. However, in our view, the rising laboratory costs do not justify a measurement on a daily basis. Additional determination of specific IgG or IgG4 levels was not useful in predicting tolerance development in our study population.
Respiratory manifestations of panic disorder (PD) include a greater respiratory instability and enhanced responsiveness to CO2 compared to normal individuals. Although the prevalence of PD is ...approximately three times greater in women compared to men, the origins of this sexual dimorphism remain poorly understood. Similar to PD patients, adult female rats previously subjected to neonatal maternal separation (NMS) show an increase in their ventilatory response to CO2. Because this effect of NMS is not observed in males, we hypothesised that testosterone prevents NMS‐induced hyper‐responsiveness to CO2. Pups subjected to NMS were placed in an incubator for 3 h d‐1 from postnatal days 3‐12. Control pups remained undisturbed. At adulthood (8‐10 weeks of age), rats were then subjected either to sham surgery or castration. Fourteen days later, breathing was measured at rest (room air) and during acute exposure to hypercapnia (5 and 10% CO2 for 10 minutes each) using plethysmography. To gain insight into the mechanisms involved, c‐fos expression was used as an indicator of neuronal activation. Brains were collected following air or CO2 exposure for quantification of c‐fos positive cells by immunohistochemistry in selected regions, including the paraventricular nucleus of the hypothalamus, the dorsomedial hypothalamus and the amygdalar complex. Castration produced a 100% increase of hyperventilatory response to 10% CO2 in control rats. Unexpectedly, castration had no effect on the hyperventilatory response of NMS rats. The intensity of the hypercapnic response was inversely correlated with c‐fos expression in the medial amygdala. We conclude that testosterone prevents the hyper‐responsiveness to CO2, whereas NMS attenuates sensitivity to hormone withdrawal. We propose that an inhibitory influence from the medial amygdala contributes to this effect.
Preterm birth (PTB) is a phenomenon that brings risks and challenges for the survival of the newborn child. Despite many advances in research, not all the causes of PTB are already clear. It is ...understood that PTB risk is multi-factorial and can also be associated with socioeconomic factors. Thereby, this article seeks to use unsupervised learning techniques to stratify PTB risk in Brazil using only socioeconomic data. Through the use of datasets made publicly available by the Federal Government of Brazil, a new dataset was generated with municipality-level socioeconomic data and a PTB occurrence rate. This dataset was processed using various unsupervised learning techniques, such as
-means, principal component analysis (PCA), and density-based spatial clustering of applications with noise (DBSCAN). After validation, four clusters with high levels of PTB occurrence were discovered, as well as three with low levels. The clusters with high PTB were comprised mostly of municipalities with lower levels of education, worse quality of public services-such as basic sanitation and garbage collection-and a less white population. The regional distribution of the clusters was also observed, with clusters of high PTB located mostly in the North and Northeast regions of Brazil. The results indicate a positive influence of the quality of life and the offer of public services on the reduction in PTB risk.
Introduction
Myelomeningocele (MMC) is the most frequent neural tube defect and is frequently associated (around 80% of cases) with hydrocephalus (HC). Both diseases can have severe clinical ...consequences, insomuch as they require surgical treatment whose complications are not negligible, either when performed in utero or after birth. Therefore, clinical therapies that could have an impact on the incidence and progression of MMC and HC would be certainly valuable; however, this is not the current picture, and there are no effective pharmacological treatments for such patients to this day.
Aim and Methods
Therefore, knowing that an inflammatory process comes associated with these disorders, mostly due to nervous tissue distension, the present article aimed at reviewing the role of corticosteroids in reducing inflammation and thus improving the outcome of patients with HC and MMC, considering the well-established anti-inflammatory effects of CS.
Results
The systematic review performed herein has found varying results regarding the role of steroids (even though a positive trend was observed) on the treatment and prevention of hydrocephalus, whereas for MMC.
Conclusion
There are many reports demonstrating beneficial effects of CS therapy, from a clinical and histopathological point of view.
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