Rejected

Periodontitis is a chronic inflammatory disease associated with the formation of dysbiotic plaque biofilms and characterized by the progressive destruction of the alveolar bone. The transition from health to disease is characterized by a shift in periodontal immune cell composition, from mostly innate (neutrophils) to adaptive (T lymphocytes) immune responses. Resolvin E1 (RvE1) is a specialized pro-resolution mediator (SPMs), produced in response to inflammation, to enhance its resolution. Previous studies have indicated the therapeutic potential of RvE1 in periodontal disease; however, the impact of RvE1 in the microbial-elicited osteoclastogenic immune response remains uncharacterized . In the present study, we studied the impact of RvE1 on the gingival inflammatory infiltrate formation during periodontitis in a mouse model. First, we characterized the temporal-dependent changes of the main immune cells infiltrating the gingiva by flow cytometry. Then, we evaluated the impact of early or delayed RvE1 administration on the gingival immune infiltration and cervical lymph nodes composition. We observed a consistent inhibitory outcome on T cells -particularly effector T cells- and a protective effect on regulatory T cells (Tregs). Our data further demonstrated the wide range of actions of RvE1, its preventive role in the establishment of the adaptive immune response during inflammation, and bone protective capacity.

The aim of the present clinical trial is to evaluate the efficacy of kinesio taping on patients with chronic low back pain, when the exploration identifies skin/fascia mobilization as a factor that could modify the treatment effect. This study is a randomized controlled trial with intention-to-treat analysis. Sixty-two participants with chronic low back pain were therefore recruited from a tertiary referral hospital. Targeted kinesio taping, according to skin/fascia mobility exploration, was applied in the experimental group (17 female/13 male; 49.47 ± 11.15 years) once a week for four sessions. The control group (17 female/14 male; 48.87 ± 9.09 years) underwent a placebo taping application. At post-treatment time there was a statistically significant reduction both in disability (Roland-Morris Disability Questionnaire) and pain (Numeric Pain Rating Scale) in the experimental group (disability: -2.88, 95% confidence interval [CI] -4.56 to -1.21, P < .001; pain: -1.58, 95% CI -2.67 to -0.54 P = .001) and the control group (disability: -1.82, 95% CI -3.46 to -0.17 P = .025; pain: -1.30, 95% CI -2.32 to -0.28 P = .008). However, at six months, these changes only remained significant in the experimental group (disability: -2.95, 95% CI -4.72 to -1.18, P < .001; pain: -1.06, 95% CI -2.07 to -0.04, P < .05). As a conclusion, the application of targeted kinesio taping produced a significant reduction in pain and disability, at 4 weeks and at 6 moths follow-up, although there were no differences between groups at any measurement time point.

Osteoarthritis (OA) is a chronic and degenerative joint disease, which causes stiffness, pain, and decreased function. At the early stage of OA, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line treatment. However, the efficacy and utility of available drug therapies are limited. We aim to use bioinformatics to identify potential genes and drugs associated with OA.

Neuropathic pain is one of the important challenges in the clinic. Although a lot of research has been done on neuropathic pain (NP), the molecular mechanism is still elusive. We aimed to investigate whether the Wnt/-catenin pathway was involved in NP caused by sustaining dorsal root ganglion (DRG) compression with the chronic compression of dorsal root ganglion model (CCD). Our RNA sequencing results showed that several genes related to the Wnt pathway have changed in DRG and spinal cord dorsal horn (SCDH) after CCD surgery. Therefore, we detected the activation of the Wnt/-catenin pathway in DRG and SCDH and found active -catenin significantly upregulated in DRG and SCDH 1 day after CCD surgery and peaked on days 7-14. Immunofluorescence results also confirmed nuclear translocalization of active -catenin in DRG and SCDH. Additionally, rats had obvious mechanical induced pain after CCD surgery and the pain was significantly alleviated after the application of the Wnt/-catenin pathway inhibitor XAV939. Furthermore, we found that the levels of proinflammatory factors tumor necrosis factor- (TNF-) and interleukin-18 (IL-18) were significantly elevated in CCD rat serum, while the levels of them were correspondingly decreased after the Wnt/-catenin pathway being inhibited. The results of Spearman correlation coefficient analysis showed that the levels of TNF- and IL-18 were negatively correlated with the mechanical withdrawal thresholds (MWT) after CCD surgery. Collectively, our findings suggest that the Wnt/-catenin pathway plays a critical role in the pathogenesis of NP and may be an effective target for the treatment of NP.

Lactic acidosis (LA) can be categorized as type A, which occurs in the presence of tissue hypoxia, or type B, occurring in the absence of tissue hypoxia. Hematologic malignancies are an uncommon cause of type B LA.

Robust sex difference among humans regarding psychiatry- and pain-related behaviors is being researched; however, the use of female mice in preclinical research is relatively rare due to an unchecked potential behavioral variation over the estrous cycle. In the present study, a battery of psychiatry- and pain-related behaviors are examined under physiological condition in female C57BL/6J mice over different estrous cycle phases: proestrus, estrous, metestrous, diestrous. Our behavioral results reveal that there is no significant difference over different phases of the estrous cycle in social interaction test, sucrose preference test, tail suspension test, open field test, marble burying test, novelty-suppressed feeding test, Hargreaves thermal pain test, and Von Frey mechanical pain test. These findings implicate those psychiatry- and pain-related behaviors in normal female C57BL/6J mice appear to be relatively consistent throughout the estrous cycle; the estrous cycle might not be a main contributor to female C57BL/6J mice's variability of behaviors.

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.

Copper, as a salt, is toxic and has the potential to harm multiple organs. Copper intoxication causes intravascular haemolysis followed by liver and kidney failure that can be fatal. We present a case of chronic copper sulfate poisoning in a 66-year-old man with dysphagia to solids and liquids, anaemia, acute kidney injury, liver cytolysis and hypocalcaemia. The patient improved with supportive care, but chronic kidney disease was established. Anamnesis was crucial for the diagnosis, given the non-specific signs and symptoms. The history of chronic exposure to pest treatment with a blue dust cloud made us suspect copper sulfate poisoning.

Neuropathic itch occurs due to damage of neurons of the peripheral or central nervous system. Several entities, including metabolic, neurodegenerative, orthopedic, infectious, autoimmune, malignant, and iatrogenic conditions, may affect the somatosensory system and induce neuropathic itch. Due to the complex nature of neuropathic itch, particularly concerning its clinical presentation and possible etiological factors, diagnostic work-up of this condition is challenging. A detailed medical history, especially in regard to the itch, and a comprehensive physical examination are relevant to detect characteristic signs and symptoms of neuropathic itch and to rule out other possible causes for chronic itch. Complementary diagnostic exams, especially laboratory tests, determination of the intraepidermal nerve fiber density via a skin biopsy and radiological examinations may be indicated to confirm the diagnosis of neuropathic itch and to identify underlying etiological factors. Functional assessments such as quantitative sensory testing, nerve conduction studies, evoked potentials, or microneurography may be considered in particular cases. This review article provides a comprehensive overview of the diagnostic work-up recommended for patients with neuropathic itch.

The SARS-CoV-2 virus may affect both adults and children. Although COVID-19 has a lower prevalence in infancy and has been described as mild, the clinical characteristics may vary, and there is a possibility of complications. The objectives of this study were to describe the clinical and epidemiological aspects of confirmed COVID-19 pediatric cases in the state of Sinaloa, Mexico, during the first 3 months of the pandemic, and children admitted with COVID-19 to a secondary hospital.