Rejected

Increased physical activity is an effective treatment for knee osteoarthritis that causes knee pain. However, due to the coronavirus disease 2019, noncontact and non-face-to-face interventions have increased, but the quality of evidence supporting their effectiveness remains unclear. The purpose of the study was to assess the quality of evidence of the effects of non-face-to-face and noncontact interventions on knee pain and physical activity in older adults with knee osteoarthritis. A meta-analysis was conducted to determine the effects of different intervention methods (education and exercise). The Cochrane Central Register of Controlled Trials, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Physiotherapy Evidence Database were systematically searched. Four randomized controlled trials were included in the analysis. The meta-analysis demonstrated that the educational intervention group was significantly effective, although supportive evidence was low quality. Educational intervention may be effective, but the effects need to be confirmed by higher quality clinical trials.

Cardiac arrest due to thyroid storm is a very rare clinical feature with high mortality that presents as multiorgan dysfunction. The mortality rate under this condition is close to 30%, even with appropriate treatment. Most thyroid storms occur in patients with long-standing untreated hyperthyroidism.

To assess the long-term patient outcomes, including the resolution of symptoms and need for subsequent procedures, after vaginal mesh removals (VMR) we evaluate our 14-year experience with VMR from a tertiary center with three FPMRS-trained surgeons. Although the use of transvaginal mesh (TVM) had decreased significantly before its ban in 2019, surgeons are still treating TVM complications and performing vaginal or open/robotic VMR for mesh-related complications.

Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered, and lacks diagnostic and therapeutic consensus.

Despite much research efforts being devoted to design alternative pharmacological interventions, chronic pain remains to be an unresolved clinical problem. Quercetin, a compound that belongs to the flavonoids family, is abundantly found in fruits and vegetables. Emerging evidence indicates that quercetin possesses anti-nociceptive effects in different rodent models of chronic pain including inflammatory pain, neuropathic pain, and cancer pain. In this review, we summarize the mechanisms underlying the analgesic effect of quercetin in preclinical studies. These studies showed that quercetin exerts potent analgesic effects against chronic pain via suppressing neuroinflammation and oxidative stress as well as modulation of synaptic plasticity, GABAergic system, and opioidergic system. Considering that the safety of quercetin is well established, it has great potential for clinical use in pain treatment.

Gerberae Piloselloidis Herba (GPH), a commonly used traditional medicine in China, is derived from Gerbera piloselloides (Linn.) Cass. It is featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial, anti-tumor, uterine analgesia, and immunity-enhancing. With a long history of medication in ethnic minority areas in China, it is often used as an effective treatment for cough and sore throat as well as allergic asthma. Although our previous investigation also has discovered GPH performed effective treatment on allergic asthma, its underlying mechanism remains unclear.

ConspectusScientific excursions into the unknown are often characterized by unanticipated twists and turns that may lead in directions that never could have been predicted. Decisions made during the course of these explorations determine what we discover. This Account chronicles one such journey that began with a challenge encountered during the synthesis of a natural product and then unfolded over more than 30 years to focus on unmet needs in neuroscience. Specifically, while developing a concise approach to tetrahydroalstonine, a heteroyohimboid alkaloid having α-adrenergic activity, we faced the predicament of assembling a key intermediate. Solving this problem resulted in the serendipitous discovery of the vinylogous Mannich reaction and a productive program wherein we used this powerful construction as a key step in the syntheses of numerous alkaloids. However, we also realized that lessons learned from the synthesis of tetrahydroalstonine could be generalized to invent a new strategy for preparing diverse collections of substituted nitrogen heterocycles that could be screened against biological targets. The approach featured the combination of several reactants in a multicomponent assembly process to give a functionalized intermediate that could be elaborated by various ring-forming reactions to give heterocyclic scaffolds that could be further diversified. Screening these compound sets against a broad range of biological targets revealed some intriguing hits, but none of them led to a productive collaboration in translational research. Notwithstanding this setback, we screened curated members of our collections against proteins in the central nervous system and discovered some substituted B-norbenzomorphans that were selective for the enigmatic sigma-2 receptor (σR), an understudied protein that had been primarily associated with cancer. With scant knowledge of its role in neuroscience, we posited that small molecules that bind to σR might be neuroprotective, thus launching a new venture. In parallel investigations we prepared analogues of the initial hits, explored their effects in animal models of neurodegenerative and neurological conditions, and identified σR as transmembrane protein 97 (TMEM97). After first establishing the neuroprotective effects of several σR/TMEM97 ligands in a transgenic model of neurodegeneration, we showed that one of these has procognitive effects and reduces levels of proinflammatory cytokines in a transgenic mouse model of Alzheimer's disease. We then identified a closely related σR/TMEM97 ligand that mitigates hippocampal-dependent memory deficits, prevents axon degeneration, and protects neurons and oligodendrocytes after traumatic brain injury. In a recent study, this compound was shown to protect retinal ganglion cells from retinal ischemia/reperfusion injury. In other collaborative investigations, we have shown that related, but structurally distinct, σR/TMEM97 ligands alleviate neuropathic pain, while a σR/TMEM97 ligand representing yet another chemotype reduces impairments associated with alcohol withdrawal. More recently, we have shown that σR/TMEM97 ligands enhance survival of cortical neurons in a neuronal model of Huntington's disease. Translational and mechanistic studies in these and other areas are in progress. Solving a problem we faced in natural product synthesis thus served as an unexpected gateway to discoveries that could lead to entirely new approaches to treat neurodegenerative and neurological conditions by targeting σR/TMEM97, a protein that has never been associated with these afflictions.

To investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D).

Functional Popliteal Artery Entrapment Syndrome (fPAES) is an under-diagnosed and under-treated etiology of atypical claudication. Symptoms of fPAES include deep posterior muscle cramping and pain with exercise and unlike anatomic PAES, there are seldom vascular complications. Common non-invasive diagnostic modalities include Ankle Brachial Index (ABI), Arterial Duplex Ultrasound (DUS), and cross-sectional imaging such as Magnetic Resonance Angiography (MRA). Entrapment can be difficult to reproduce during diagnostic testing, requiring provocative maneuvers. Because we believed different provocative maneuvers provide different diagnostic efficacy, we sought to optimize our diagnostic approach to fPAES.