Rejected

Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-β-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal β-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal β-glucan a new possibility for complementary treating acute and chronic inflammation.

Chronic abdominal and pelvic visceral pain is an oftentimes difficult to treat pain condition that requires a multidisciplinary approach. This article specifically reviews the interventional treatment options for pain resulting from visceral abdominal and pelvic pain.

Approximately 10% (190 million) of women worldwide are affected by endometriosis, ectopic deposits of endometrial tissue that create a major source of pain that affects lifestyle and reproductive function. The pathogenesis of endometriosis is an estrogen-dependent inflammatory process, influenced/catalyzed by oxidative stress and consequently defective methylation, with biochemical features centered around the folate and one-carbon cycles. We aimed to determine whether a link could be found between the two major methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR SNPs), c.677C>T and c.1298A>C, involved in methylation process/epigenetic marking failures, and endometriosis. We studied a population of 158 patients in a group of >1500 referred for treatment of infertility. All the patients had experienced >2 failed assisted reproductive technology cycles and/or >2 miscarriages, a classical cohort for investigation in our group. Patients with endometriosis had at least stage 2+ disease confirmed by laparoscopy. The prevalence of the homozygous c.677C>T isoform is doubled in the endometriosis group, 21.5% versus 10.2% in the non-endometriosis group ( > 0.01). Symmetrically, the percentage of patients in the endometriosis group with the wild type MTHFR significantly decreased by one-half (8.2%-17.2%) in the non-endometriosis group ( < 0.001). Determination of MTHFR c.677C>T should not be overlooked in patients with harmful endometriosis affecting their fertility. As folates metabolism is impaired in these MTHFR SNPs carrier patients, co-treatment with 5-methyl folate may constitute a successful (co)-treatment modality.

Acute pancreatitis (AP) presenting as an initial manifestation of primary hyperparathyroidism (PHPT) is uncommon, and its timely diagnosis is crucial in preventing recurrent attacks of pancreatitis.

The I-gel is a second-generation supraglottic airway device that is built with a noninflatable elliptical gel material cuff and has a wide semirigid stem. The I-gel supralaryngeal seal has shown promising efficacy for both spontaneous and controlled ventilation under general anesthesia. The recommended, standard I-gel insertion technique is relatively challenging due to its shape and cuff size. Usually, the I-gel becomes entrapped at the oral cavity and requires excessive force to negotiate across the oropharynx, resulting in insertion resistance, tongue obstruction, insertion failure, and intraoral trauma. This case series evaluated a modified jaw thrust I-gel insertion technique because it is claimed to allow smooth and atraumatic I-gel placement in adults.

Considering the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids for treating osteoarthritis (OA), development of drugs that are more effective and better tolerated than existing treatments is urgently needed. This systematic review aimed to evaluate the efficacy and safety of anti-nerve growth factor (NGF) monoclonal antibodies vs active comparator therapy, such as NSAIDs and oxycodone, in treating hip or knee OA.

Nusinersen is an antisense oligonucleotide for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who received intrathecal nusinersen in real-world clinical settings. We report the interim analysis results of safety and effectiveness. This interim analysis was conducted using data collected from 401 patients whose case report forms were obtained at least once by May 30, 2020. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness. All 401 patients were diagnosed with SMA and were included in the safety and effectiveness analysis (infantile-onset SMA [n = 126, 31.4%], later-onset SMA [n = 275, 68.6%]). The median duration of treatment was 330 days (range 1-823 days). The incidence proportion of AEs was 31.7% (37.3% in infantile-onset SMA and 29.1% in later-onset SMA). The most common AEs were headache (4.5%), pyrexia (4.2%), and pneumonia (3.7%). The incidence proportion of serious AEs was 11.5%. Nusinersen improved motor function scores and was assessed as "effective" based on CGI-I in 99.7-100% of patients. This interim analysis of the PMS in Japanese patients treated with nusinersen found no new safety concerns, with the type of AEs consistent with the expected safety profile. The benefit-risk balance of nusinersen treatment remains favorable.

Angiostrongylus cantonensis is an emerging parasite that is the most common cause of eosinophilic meningitis worldwide. Human infection typically presents with headache, neck stiffness, and paresthesia. We report a case of a woman with PCR positive A. cantonensis infection who presented with symptoms of small fiber neuropathy (SFN) but no headache. SFN was confirmed by skin biopsy. After failing standard medications for neuropathy, she was treated with intravenous lidocaine with considerable improvement. However, she required medications for 1 year to treat her chronic neuropathy. Infection by A. cantonensis should be added to the list of causes of SFN, and its potential to cause chronic sequelae should be appreciated.

Itch is a common symptom of atopic dermatitis (AD), however, there is limited evidence of the frequency and association of skin pain alongside itch. This study assessed the incremental dual burden and impact of itch and skin pain on satisfaction, quality of life and work productivity in patients with AD in Japan.

Idiopathic hypertrophic pachymeningitis (IHP) is a rare inflammatory disease that causes focal or diffuse thickening of the dura mater. However, longitudinal follow up studies are still lacking for these patients.