Rejected

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. it enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors.

The management of ruptured, large and giant wide-necked aneurysms of the anterior circulation is challenging. Treatment options include balloon-assisted coiling versus flow-diverter-assisted coiling. In this technical video, https://drive.google.com/file/d/1EtyrJv3e5Z0XM2pYBNNBHVUdYwavlTFh/view?usp = sharing we demonstrate a case of a right-sided paraclinoid aneurysm in a young man who presented with post-coital sudden-onset headache. The computed tomography scan showed a Fisher grade IV subarachnoid hemorrhage. An external ventricular drain was placed, and the patient was intubated for prompt treatment. Balloon-assisted coiling of the aneurysm was attempted but abandoned because the balloon failed to provide adequate coverage of the aneurysm neck. A loading dose of aspirin and ticagrelor (Brilinta, Astra Zeneca, Cambridge, United Kingdom) was administered, and Pipeline embolization device (Medtronic, Dublin, Ireland)-assisted coiling was then performed for adequate occlusion of the aneurysm sac. The 6-month follow-up angiogram showed complete obliteration of the aneurysm. The technical video succinctly demonstrates the technical nuances of the procedure.

Shoulder dislocations are a common presenting injury to the emergency department (ED), with anterior dislocations comprising the majority of these cases. Some patients may tolerate gentle manipulation and reduction, but many require analgesia of some type. Oral or parenteral pain medication is often used alone or in combination with procedural sedation if gentle manipulation fails to achieve reduction. Recently, this treatment algorithm has grown to include regional anesthesia as a mode of analgesia for reduction of shoulder dislocations in the form of brachial plexus blocks. It has been well described that the interscalene and supraclavicular approach to the brachial plexus can be used to assist in reduction of anterior shoulder dislocations; however, there has yet to be any published literature regarding the use of ultrasound-guided retroclavicular approach to the infraclavicular region (RAPTIR) brachial plexus blocks for shoulder reduction.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p < 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p < 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p < 0.001), z-drugs (p = 0.012), antidepressants (p < 0.001), and melatonin-prolonged release (p < 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.

Epidural-related maternal fever has consequences for the mother and neonate. There has been no systematic review of preventive strategies.

Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage in which inflammatory mechanisms play a major role in the pathogenesis. Interleukin-6 (IL6), a multifunctional cytokine, can trigger osteoclast differentiation and bone resorption. Our purpose in this study was to evaluate the association of -174 G/C (rs1800795) and -572 G/C (rs1800796) variants with the susceptibility to OA. One hundred fifty OA patients and 150 healthy individuals were enrolled in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the gene variants. The results of analyses were evaluated for statistical significance. The pain intensity was assessed using the Visual Analogue Scale (VAS). There was a statistically significant difference in the genotype and allele frequencies of the -174 G/C variant between patients with OA and control groups ( respectively). -174 G/C GG genotype and G allele were more prevalent in patients with OA. We found that the -572 G/C variant was not different between patients and controls in either genotype distribution and allele frequency. 174 G/C and -572 G/C loci GG-GG combined genotype was significantly higher in OA patients (). Our study suggests that there was a strong association between the -174 G/C variant and OA in the Turkish population. Further studies on populations of different ethnic background are necessary to prove the association of variants with OA.

Primary sclerosing cholangitis (PSC) is a major unmet medical need in clinical hepatology. Cilofexor is a non-steroidal FXR agonist being evaluated for the treatment of PSC. Here, we describe the safety and preliminary efficacy of cilofexor in a 96-week, open-label extension (OLE) of a phase 2 trial.

It is debatable whether or not previous high tibial osteotomy (HTO) has negative effects on the results of subsequent medial unicompartmental knee replacement (UKR). The purpose of this study is to report, through a systematic review of the literature, the outcomes of medial UKR after failed HTO. It was hypothesized that this procedure would be safe and effective in providing satisfactory postoperative functional outcomes.

To describe the clinical characteristics of patients suffering from chronic dry eye (DE) and pain after refractive surgery (RS).

The aim of this study was to evaluate the psychometric properties of the Danish version of the Fibromyalgia Impact Questionnaire – Revised (FIQR), when used to quantify the severity of disease burden in a Danish population of patients with chronic widespread pain (CWP), including fibromyalgia (FM).