Rejected

Paclitaxel (PTX) chemotherapy treatment often leads to neuropathic pain, which is resistant to available analgesic treatments. Death of cells and neuroinflammatory response are associated with PTX-induced peripheral neuropathy (PIPN). Necroptosis is a form of regulated necrotic cell death that accompanies strong inflammatory response. It is mediated by receptor-interacting protein kinase 3 (RIP3) and mixed-lineage kinase domain-like protein (MLKL), which contribute to the pathogenesis of several neurodegenerative diseases. Nevertheless, the role of necroptosis in PIPN remains unexplored. The aim of this study was to investigate the role of necroptosis in PIPN using its antagonists (necrostatin-1 and Nec-1). The quartic PTX administration (accumulated dose: 8 mg/kg, ip) in rats induced robust hyperalgesia and allodynia with significant cell necrosis and an increase in proinflammatory cytokines in the dorsal root ganglion (DRG). PTX application also increased RIP3 and MLKL protein levels in DRG, which were primarily in neurons. Moreover, it also promoted satellite glial cells (SGCs) activation, as assayed by glial fibrillary acidic protein (GFAP) upregulation. All these PTX-induced changes were prevented by the Nec-1 treatment. When taken together, the present study indicated that RIP3/MLKL pathway-regulated neuronal necroptosis, which promoted an inflammatory cascade reaction in DRG, might be a new mechanism of PIPN.

Real-world disease management of atopic dermatitis (AD) is hampered by a lack of consistency between providers that treat AD regarding assessment of severity, disease activity, and quality of life. Variability and inconsistency in documentation makes it difficult to understand the impact of AD. This study summarizes AD-related symptoms and concerns captured in unstructured qualitative provider notes by healthcare providers during visits with patients with AD.

Inflammatory bowel disease (IBD) is a common and debilitating disease of the gastrointestinal tract. Psychological distress is highly comorbid to IBD, especially during periods of active disease. However, a controversy exists on how to best manage its symptoms in the IBD population.

Few studies have evaluated the relation of quality of life (QoL) with symptoms and disease activity in primary Sjögren's syndrome (pSS). There is also scant information on the predictors of QoL in this population. The aim of this study was to assess QoL in patients with pSS and to investigate their possible predictors.

This study was carried out to determine the prevalence of leptospirosis among febrile patients with a suspicious clinical diagnosis of dengue fever in northern Peru.

In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder.

The long-term effects of behavioural medical rehabilitation (BMR), as a type of multidisciplinary rehabilitation, in the treatment of chronic non-specific low back pain (CLBP) have been shown. However, the specific effects of behavioural exercise therapy (BET) compared to standard exercise therapy (SET) within BMR are not well understood. The aim of the study was to assess the effectiveness of BMR + BET compared to BMR + SET in individuals with CLBP in a two-armed, pre-registered, multicentre, parallel, randomised controlled trial (RCT).

Osteoarthritis (OA) is a leading cause of disability and pain especially among older adults, but it is also known to affect working age individuals, often leading to reduced productivity and increased healthcare usage. The aim of this study was to determine the burden of hip and knee OA in Finnish occupational healthcare.

Epidermolysis bullosa is a severe hereditary disease caused by mutations in genes encoding cutaneous basement membrane proteins. These mutations lead to dermal-epidermal junction failure and, as a result, to disturbances in the morphological integrity of the skin. Clinically, it manifests in the formation of blisters on the skin or mucosa that in some cases can turn into non-healing chronic wounds, which not only impairs patient's quality of life, but also is a live-threatening condition. Now, the main approaches in the treatment of epidermolysis bullosa are symptomatic therapy and palliative care, though they are little effective and are aimed at reducing the pain, but not to complete recovery. In light of this, the development of new treatment approaches aimed at correction of genetic defects is in progress. Various methods based on genetic engineering technologies, transplantation of autologous skin cells, progenitor skin cells, as well as hematopoietic and mesenchymal stem cells are studied. This review analyzes the pathogenetic methods developed for epidermolysis bullosa treatment based on the latest achievements of molecular genetics and cellular technologies, and discusses the prospects for the use of these technologies for the therapy of epidermolysis bullosa.

Ketamine is a dissociative anesthetic used in veterinary and human medicine since the 1970s. Its clinical use has expanded to control of seizures, pre-hospital emergency medical services (EMS), and is finding new purpose as an analgesic alternative and antidepressant. Ketamine brings hope for effective management of chronic pain in the absence of opioids, and decreasing suicidal ideations, however, its persistence as a recreational drug for its hallucinogenic properties remains. In the wake of expanding medicinal purposes, the diversity of New York City's population was explored to better understand its misuse. This retrospective study looks at the prevalence of ketamine in driver fatalities over a period of 18 years (2003-2020) and cases involving suspected driving under the influence of drugs (DUID) over a period of 6 years (2015-2020). Ketamine was identified in 6 driver fatalities and in 47 DUID cases. None of the driver fatalities were suspected of ketamine misuse, due to administration either in hospital or EMS administration. In the DUID cases, an increasing trend was observed over the 6-year study period with 100% (N = 47) of the cases confirmed as non-hospital/non-EMS administered ketamine. Of the DUID cases, 94% were male, with the majority between the age of 21-39 years (85%) and were predominantly Hispanic (36%) and Asian (34%). Blood concentrations of ketamine ranged from 27 to > 2000 ng/mL with polydrug use prevalent. The most common drug classes detected in addition to ketamine were cannabinoids (38%), ethanol (32%), benzodiazepines (26%), cocaine (19%), and amphetamines/MDMA (15%). In 2019, 2-fluoro-deschloroketamine (2F-DCK) was identified in two cases for the first time. Despite its increased acceptance for mental health disorders, ketamine's persistence and misuse as a recreational drug remains and should continue to be monitored by relevant toxicological, clinical, and law enforcement communities along with emerging illicit ketamine analogs.