Rejected

Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132), an organogermanium, is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP) in aqueous solutions, and reduces inflammation, pain and cancer, whereas the underlying mechanisms remain unknown. Sulfides including HS, a gasotransmitter, generated from l-cysteine by some enzymes including cystathionine-γ-lyase (CSE), are pro-nociceptive, since they enhance Ca3.2 T-type Ca channel activity expressed in the primary afferents, most probably by canceling the channel inhibition by Zn linked via coordinate bonding to His of Ca3.2. Given that germanium is reactive to sulfur, we tested whether THGP would directly trap sulfide, and inhibit sulfide-induced enhancement of Ca3.2 activity and sulfide-dependent pain in mice. Using mass spectrometry and H NMR techniques, we demonstrated that THGP directly reacted with sulfides including NaS and NaSH, and formed a sulfur-containing reaction product, which decreased in the presence of ZnCl. In Ca3.2-transfected HEK293 cells, THGP inhibited the sulfide-induced enhancement of T-type Ca channel-dependent membrane currents. In mice, THGP, administered systemically or locally, inhibited the mechanical allodynia caused by intraplantar NaS. In the mice with cyclophosphamide-induced cystitis and cerulein-induced pancreatitis, which exhibited upregulation of CSE in the bladder and pancreas, respectively, systemic administration of THGP as well as a selective T-type Ca channel inhibitor suppressed the cystitis-related and pancreatitis-related visceral pain. These data suggest that THGP traps sulfide and inhibits sulfide-induced enhancement of Ca3.2 activity, leading to suppression of Ca3.2-dependent pain caused by sulfide applied exogenously and generated endogenously.

Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage.

To investigate safety, feasibility, and effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of COVID-19 patients with persistent olfactory dysfunction (OD).

Medicinal plants have great prominence in research into the development of new medicines. L. (Myrtaceae) is an edible and medicinal plant with economic value in the northeast region of Brazil. Several preparations from leaves and its fruits are employed as a source of nutrients and bioactive compounds. In this study we evaluated the preclinical toxicology of crude extract and vaginal gel obtained from the leaves of (5%, 10%, and 15%) aiming to provide safety for its use in the treatment of vulvovaginitis. Both formulations were applied to the vaginal cavity for 14 days. Detailed observations of the vaginal region, including pruritus, swelling, irritation, burning, pain, and vaginal secretion, as well as the estrous cycle were evaluated. On the fifth day, blood samples were obtained from the supraorbital plexus for biochemical and hematological analyses. The animals were subsequently euthanized. All animals underwent necropsy and macroscopic examination of the vaginal mucosa and reproductive system. A histological examination was also performed. No clinically significant changes were detected during the entire experimental period. All biochemical, hematological, or histopathological parameters were within the normal range for the species. The data obtained allow us to suggest that the vaginal formulations are safe in this experimental model.

To assess the differential item functioning (DIF) of the Jaw Functional Limitation Scale (JFLS) due to gender, age, and language (English vs Spanish).

Pilocytic astrocytoma is mostly a pediatric tumor with the majority of patients under age 20. Although tumors can occur throughout neuraxis, most tumors are in the cerebellum and optic chiasm. Pilocytic astrocytoma in unusual locations is often associated with different genetic alterations than the classic KIAA1549::BRAF fusion. We report a rare adult pilocytic astrocytoma of the septum pellucidum that presented with progressive headache. A detailed genomic evaluation found a fusion between BRAF and a novel partner RIN2, a gene overexpressed in both low-grade glioma and glioblastoma. The RIN2::BRAF transcript encodes a chimeric protein containing a dimerization domain SH2 and an intact kinase domain, consistent with a prototypic oncogenic kinase rearrangement. In addition, we discuss the potential oncogenic mechanisms of BRAF signaling and its implication in targeted therapy with kinase inhibitors.

is one of the first medicinal plants used by humans. Its medical use remains controversial because it is a psychotropic drug whose use has been banned. Recently, however, some countries have approved its use, including for recreational and medical purposes, and have allowed the scientific study of its compounds. is characterized by the production of special types of natural products called phytocannabinoids that are synthesized exclusively by this genus. Phytocannabinoids and endocannabinoids are chemically different, but both pharmacologically modulate CB1, CB2, GRP55, GRP119 and TRPV1 receptor activities, involving activities such as memory, sleep, mood, appetite and motor regulation, pain sensation, neuroinflammation, neurogenesis and apoptosis. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids with greater pharmacological potential, including anti-inflammatory, neuroprotective and anticonvulsant activities. Cannabidiol is showing promising results for the treatment of COVID-19, due to its capability of acting on the unleashed cytokine storm, on the proteins necessary for both virus entry and replication and on the neurological consequences of patients who have been infected by the virus. Here, we summarize the latest knowledge regarding the advantages of using cannabinoids in the treatment of COVID-19.

To review the evidence of the existing literature on the impact of guided self-determination across methodologies in different healthcare settings.

Hiccups are a rare but potentially debilitating side effect of opioid treatment, with only a handful of reported cases in the medical literature. The pathophysiological mechanism linking opioids and hiccups is unknown, and a lack of evidence exists concerning the optimal management of the condition. We report on a 64-year-old man diagnosed with advanced renal cancer and painful osteolytic metastases, presenting persistent hiccups while on opioid treatment. Hiccups recurred after multiple challenges with codeine, morphine and hydromorphone on separate occasions. Hiccups ceased only after opioid discontinuation, although various pharmacological treatments were tried to shorten the duration of hiccups. Eventually, fentanyl was introduced and was well tolerated by the patient, without any recurrence of hiccups. The chronological correlation between opioid initiation and the onset of hiccups, as well as opioid discontinuation and the termination of hiccups leads to the conclusion that a causal role of codeine, morphine and hydromorphone in this occurrence is likely. Individual susceptibility probably plays a central role in the development of opioid-related hiccups. Opioid rotation is a promising strategy in the management of opioid-related hiccups, particularly when the mere discontinuation of the opioid is not a viable option, such as in the oncology and palliative care field.

Peyronie's disease (PD) is a chronic inflammatory condition affecting adult males, involving the tunica albuginea of the corpora cavernosa of the penis. PD is frequently associated with penile pain, erectile dysfunction, and a secondary anxious-depressive state. The etiology of PD has not yet been completely elucidated, but local injury is generally recognized to be a triggering factor. It has also been widely proven that oxidative stress is an essential, decisive component in all inflammatory processes, whether acute or chronic. Current conservative medical treatment comprises oral substances, penile injections, and physical therapy.