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Migraine is a periodic disorder in which a patient experiences changes in the morphological and functional brain, leading to the abnormal processing of repeated external stimuli in the inter-ictal phase, known as the habituation deficit. This is a significant feature clinically of migraine in both two types with aura or without aura and plays an essential role in studying pathophysiological differences between these two groups. Several studies indicated that the reason for migraine aura is cortical spreading depression (CSD) but did not clarify its impact on migraine without aura and lack of habituation. In this study, 22 migraine patients (MWA, N = 13), (MWoA, N = 9), and healthy controls (HC, N = 19) were the participants. Participants were exposed to the steady state of visual evoked potentials also known as (SSVEP), which are the signals for a natural response to the visual motivation at four Hz or six Hz for 2 s followed by the inter-stimulus interval that varies between 1 and 1.5 s. The order of the temporal frequencies was randomized, and each temporal frequency was shown 100 times. We recorded from 128 customized electrode locations using high-density electroencephalography (HD-EEG) and measured amplitude and habituation for the N1-P1 and P1-N2 from the first to the sixth blocks of 100 sweep features in patients and healthy controls. Using the entropy, a decrease in amplitude and SSVEP N1-P1 habituation between the first and the sixth block appeared in both MWA and MWoA ( = 0.0001, Slope = -0.4643), ( = 0.065, Slope = 0.1483), respectively, compared to HC. For SSVEP P1-N2 between the first and sixth block, it is varied in both MWA ( = 0.0029, Slope = -0.3597) and MWoA ( = 0.027, Slope = 0.2010) compared to HC. Therefore, migraine patients appear amplitude decrease and habituation deficit but with different rates between MWA, and MWoA compared to HCs. Our findings suggest this disparity between MWoA and MWA in the lack of habituation and amplitude decrease in the inter-ictal phase has a close relationship with CSD. In light of the fact that CSD manifests during the inter-ictal phase of migraine with aura, which is when migraine seizures are most likely to occur, multiple researchers have lately reached this conclusion. This investigation led us to the conclusion that CSD during the inter-ictal phase and migraine without aura are associated. In other words, even if previous research has not demonstrated it, CSD is the main contributor to both types of migraine (those with and without aura).

Sexually transmitted infections (STIs), such as (Ct) infection, have serious consequences for sexual and reproductive health worldwide. Ct is one of the most common sexually transmitted bacterial infections in the world, with approximately 129 million new cases per year. is an obligate intracellular Gram-negative bacterium. The infection is usually asymptomatic, notwithstanding, it could also be associated with severe sequels and complications, such as chronic pain, infertility, and gynecologic cancers, and thus there is an urgent need to adequately treat these cases in a timely manner. Consequently, beyond its individual effects, the infection also impacts the economy of the countries where it is prevalent, generating a need to consider the hypothesis of implementing Chlamydia Screening Programs, a decision that, although it is expensive to execute, is a necessary investment that unequivocally will bring financial and social long-term advantages worldwide. To detect Ct infection, there are different methodologies available. Nucleic acid amplification tests, with their high sensitivity and specificity, are currently the first-line tests for the detection of Ct. When replaced by other detection methods, there are more false negative tests, leading to underreported cases and a subsequent underestimation of Ct infection's prevalence. Ct treatment is based on antibiotic prescription, which is highly associated with drug resistance. Therefore, currently, there have been efforts in line with the development of alternative strategies to effectively treat this infection, using a drug repurposing method, as well as a natural treatment approach. In addition, researchers have also made some progress in the Ct vaccine development over the years, despite the fact that it also necessitates more studies in order to finally establish a vaccination plan. In this review, we have focused on the therapeutic options for treating Ct infection, expert recommendations, and major difficulties, while also exploring the possible avenues through which to face this issue, with novel approaches beyond those proposed by the guidelines of Health Organizations.

L. essential oil (CEO), commonly known as Ceylon cinnamon or cinnamon tree, is regarded as one of the most employed essential oils in the field of aromatherapy. It is usually applied externally as astringent, antipruritic, rubefacient, and anti-septic agent. Furthermore, both in vitro and in vivo research have demonstrated its numerous pharmacological effects, including the potentiality for treating neuralgia, myalgia, headache, and migraine. Several pieces of research also corroborated its significant antiviral and antimicrobial properties. Cinnamaldehyde, eugenol, caryophyllene, cinnamyl acetate, and cinnamic acid are the most representative compounds that are generally found in greater quantities in CEO and play a pivotal role in determining its pharmacological activities. Due to the global antibiotic resistance scenario and the dwindling amount of funding dedicated to developing new antibiotics, in recent years research has concentrated on exploring specific economic approaches against microbial infections. In this context, the purpose of this study was the investigation of the synergistic antibacterial activities of commercially available and chemically characterized CEO in combination with sertraline, a selective serotonin reuptake inhibitor (SSRI), whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. In vitro effects of the titled combination were assessed toward a wide panel of both Gram-positive and Gram-negative bacteria. The antimicrobial efficacy was investigated by using the checkerboard microdilution method. The interesting preliminary results obtained suggested a synergistic effect (fractional inhibitory index, FICI < 0.5) of sertraline in combination with CEO, leading to severe growth inhibition for all bacterial species under investigation.

Honey and propolis have recently become the key target of attention for treating certain diseases and promoting overall health and well-being. A high content of flavonoids and phenolic acids found in both honey and propolis contributes to the antioxidant properties to scavenge free radicals. Honey and propolis also exhibited antibacterial effects where they act in two ways, namely the production of hydrogen peroxide (HO) and gluconic acids following the enzymatic activities of glucose oxidase, which exerts oxidative damage on the bacteria. Additionally, the anti-inflammatory effects of honey and propolis are mainly by reducing proinflammatory factors such as interleukins and tumor necrosis factor alpha (TNF-α). Their effects on pain were discovered through modulation at a peripheral nociceptive neuron or binding to an opioid receptor in the higher center. The aforementioned properties of honey have been reported to possess potential therapeutic topical application on the exterior parts of the eyes, particularly in treating conjunctivitis, keratitis, blepharitis, and corneal injury. In contrast, most of the medicinal values of propolis are beneficial in the internal ocular area, such as the retina, optic nerve, and uvea. This review aims to update the current discoveries of honey and propolis in treating various ocular diseases, including their antioxidant, anti-inflammatory, antibacterial, and anti-nociceptive properties. In conclusion, research has shown that propolis and honey have considerable therapeutic promise for treating various eye illnesses, although the present study designs are primarily animal and in vitro studies. Therefore, there is an urgent need to translate this finding into a clinical setting.

Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≤ 7 and numerical rating scale pruritus ≤ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort.

This study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of danuglipron (PF-06882961)-a novel, oral, small-molecule glucagon-like peptide-1 receptor agonist-in Japanese participants with type 2 diabetes mellitus (T2DM).

Bio-signals are being increasingly used for the assessment of pathophysiological conditions including pain, stress, fatigue, and anxiety. For some approaches, a single signal is not sufficient to provide a comprehensive diagnosis; however, there is a growing consensus that multimodal approaches allow higher sensitivity and specificity. For instance, in visceral pain subjects, the autonomic activation can be inferred using electrodermal activity (EDA) and heart rate variability derived from the electrocardiogram (ECG), but including the muscle activation detected from the surface electromyogram (sEMG) can better differentiate the disease that causes the pain. There is no wearable device commercially capable of collecting these three signals simultaneously. This paper presents the validation of a novel multimodal low profile wearable data acquisition device for the simultaneous collection of EDA, ECG, and sEMG signals. The device was validated by comparing its performance to laboratory-scale reference devices. N = 20 healthy subjects were recruited to participate in a four-stage study that exposed them to an array of cognitive, orthostatic, and muscular stimuli, ensuring the device is sensitive to a range of stressors. Time and frequency domain analyses for all three signals showed significant similarities between our device and the reference devices. Correlation of sEMG metrics ranged from 0.81 to 0.95 and EDA/ECG metrics showed few instances of significant difference in trends between our device and the references. With only minor observed differences, we demonstrated the ability of our device to collect EDA, sEMG, and ECG signals. This device will enable future practical and impactful advances in the field of chronic pain and stress measurement and can confidently be implemented in related studies.

Low back pain represents the leading cause of disability since 1990. In 90% of cases, it is classified as non-specific low back pain, being chronic in 10% of subjects. Ultrasound has proven to be an effective measurement tool to observe changes in the activity and morphology of the abdominal muscles. This article reviews which core synergies are studied with ultrasound in healthy subjects and with chronic non-specific low back pain. A systematic review was conducted on studies analyzing synergies between two or more core muscles. Publications from 2005 until July 2021 were identified by performing structured searched in Pubmed/MEDLINE, PEDro and WOS. Fifteen studies were eligible for the final systematic review. A total of 56% of the studies established synergies between the core muscles and 44% between the homo and contralateral sides of the core muscles. The most studied core synergies were transversus abdominis, internal oblique and external oblique followed by the rectus abdominis and the lumbar multifidus. No studies establishing synergies with diaphragm and pelvic floor were found. Eight studies were conducted in healthy subjects, five studies in subjects with chronic non-specific low back pain compared to healthy subjects and two studies in subjects with chronic non-specific low back pain.

(1) Background: Abnormal corneal wound healing compromises visual acuity and can lead to neuropathic pain. Conventional treatments usually fail to restore the injured corneal tissue. In this study, we evaluated the effectiveness of a synthetic heparan sulfate mimetic polymer (HSmP) in a mouse model of corneal wound healing. (2) Methods: A surgical laser ablation affecting the central cornea and subbasal nerve plexus of mice was used as a model of the wound-healing assay. Topical treatment with HSmP was contrasted to its vehicle and a negative control (BSS). Corneal repair was studied using immunofluorescence to cell proliferation (Ki67), apoptosis (TUNEL assay), myofibroblast transformation (αSMA), assembly of epithelial cells (E-cadherin) and nerve regeneration (β-tubulin III). (3) Results: At the end of the treatment, normal epithelial cytoarchitecture and corneal thickness were achieved in HSmP-treated animals. HSmP treatment reduced myofibroblast occurrence compared to eyes irrigated with vehicle ( < 0.01) or BSS ( < 0.001). The HSmP group showed 50% more intraepithelial nerves than the BSS or vehicle groups. Only HSmP-treated corneas improved the visual quality to near transparent. (4) Conclusions: These results suggest that HSmP facilitates the regeneration of the corneal epithelium and innervation, as well as restoring transparency and reducing myofibroblast scarring after laser experimental injury.