Rejected

Hemophilia is the most common X-linked bleeding diathesis caused by the genetic deficiency of coagulation factors VIII or IX. Despite treatment advances and improvements in clinical management to prevent bleeding, management of acute and chronic pain remains to be established. Repeated bleeding of the joints leads to arthropathy, causing pain in hemophilia. However, mechanisms underlying the pathogenesis of pain in hemophilia remain underexamined. Herein, we describe the novel perspectives on the role for oxidative stress in the periphery and the central nervous system that may contribute to pain in hemophilia. Specifically, we cross examine preclinical and clinical studies that address the contribution of oxidative stress in hemophilia and related diseases that affect synovial tissue to induce acute and potentially chronic pain. This understanding would help provide potential treatable targets using antioxidants to ameliorate pain in hemophilia.

Osteoarthritis is a source of chronic pain and disability. Dietary supplements have been shown to be a more secure option than NSAIDS. Particularly, the eggshell membrane has demonstrated efficacy in relieving joint pain and stiffness. A clinical trial was designed in which three groups were assigned to two different doses of this supplement and compared to a placebo control group. The primary outcome variable was knee pain, which was assessed using a visual analogue scale. Secondary outcome variables were knee functional ability, quadriceps muscle strength (assessed by isometric and isokinetic trials), and quality of sleep. All groups showed a significant decrease in pain perception, although maximum values were obtained in the high-dose group. Isokinetic and isometric trials showed a significant increase in strength in the high-dose group. Eggshell membrane showed the potential to reduce pain and stiffness symptomatology. Here, for the first time, two quantitative variables (mobility and strength of knee joint) were used to accurately evaluate changes in the quality of life of subjects affected by knee joint pain. The results of this study indicate a dose-dependent response, which should be taken into account for later use in therapeutics to establish the correct dosage.

The objectives of this study were to investigate the current attitudes of veterinarians towards the use of locoregional anaesthesia in non-conventional animal species and to identify areas for future useful research on this topic. A questionnaire was circulated online. A total of 417 veterinarians, including American and European specialists/specialists-in-training in both zoological medicine and anaesthesia/analgesia (ACZM/ECZM and ACVAA/ECVAA), participated in the study. Fifty-nine percent of respondents performed locoregional anaesthesia in rabbits, with intratesticular injections and local infiltration being the most commonly-reported techniques. ACZM/ECZM specialists reportedly performed dental blocks in rabbits more frequently than ACVAA/ECVAA specialists ( = 0.030). Forty percent of respondents performed locoregional anaesthesia in rodents, with intratesticular injections, topical/splash blocks and local infiltration being the most commonly reported techniques. The proportions of respondents who reportedly used locoregional anaesthesia in ferrets, birds and reptiles were 37.9%, 34.5% and 31.2%, respectively. The use of Tuohy ( < 0.001) and spinal needles ( < 0.001), as well as of ultrasonography ( = 0.009) and nerve-stimulators ( < 0.001), was more common among ACVAA/ECVAA compared to ACZM/ECZM specialists. Major topic areas for future research were identified as dental block techniques for rabbits and rodents and blocks for the wings of birds.

This study assessed sleep, distress and quality of life (QoL) in parents of children with acute lymphoblastic leukemia (ALL) from diagnosis to three years after, and the impact of sleep and distress on QoL. Additionally, this study explored determinants of sleep and distress. Parents completed the MOS Sleep, Distress Thermometer for Parents and SF-12 at four-five months (T0), one year (T1), two years (T2), and three years (T3) after diagnosis. The course of outcomes and longitudinal impact of clinically relevant sleep problems (>1SD above reference's mean) and clinical distress (score ≥ 4) on QoL Z-scores were assessed with linear mixed-models. Determinants of sleep and distress were assessed with multinomial mixed-models. Parents (81% mothers) of 139 patients (60% males; 76% medium-risk (MR)) participated. Distress and QoL gradually restored from T0 to T3. Sleep problems improved, but were still elevated at T3: 33% reported clinically relevant sleep problems, of which 48% in concurrence with distress. Over time, presence of sleep problems or distress led to lower mental QoL Z-scores (SD-score -0.2 and -0.5, respectively). Presence of both led to a cumulatively lower Z-score (SD-score -1.3). Parents in the latter group were more likely to report insufficient social support, parenting problems, a chronic illness, pain for their child, having a child with MR-ALL, and being closer to diagnosis. In conclusion, parental well-being improves over time, yet sleep problems persist. In combination with ongoing distress, they cumulatively affect QoL. Special attention should be given to parents who are vulnerable to worse outcomes.

This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements.

Many people with HIV report both distress and pain. The relationship between distress and pain is bidirectional, but the mechanisms by which distress exacerbates pain are unclear. The inflammatory response to challenge (inflammatory reactivity, IR) may be a partial mediator, given that neuroimmune interactions provide a substrate for IR to also influence neurological reactivity and, thus, pain-related neural signalling. This prospective, observational, case-control study will characterise the relationships between distress, IR, pain-related signalling as captured by induced secondary hyperalgesia (SH), and pain, in people with HIV who report persistent pain (PP) (cases) or no pain (controls).

The entrapment of peripheral nerves is associated with chronic neuroinflammation and neuropathic pain, and perineural injection therapy with glucose is emerging as an effective treatment for peripheral entrapment neuropathy. However, the mechanism underlying the pharmacological effect of glucose on nerves remains unclear. One of the hypothesized mechanisms is that glucose reduces neurogenic inflammation. Therefore, we investigated the effects of high glucose concentrations on cytokine-induced neuroinflammation in vitro. Human SH-SY5Y neuronal cells were challenged with 10 ng/mL TNF-α for 16 h and subsequently treated with different glucose concentrations (0-25 mM) for 24 h. Cell viability was evaluated using the diphenyltetrazolium bromide assay, and proinflammatory cytokine levels were assessed using ELISA and quantitative PCR. In addition, mRNA levels of NF-κB and cyclooxygenase-2 were analyzed using quantitative PCR. Exposure to 10 ng/mL TNF-α resulted in decreased viability of SH-SY5Y cells and significant upregulation of IL-6, IL-1β, NF-κB, and cyclooxygenase-2. Subsequent exposure to high glucose levels (25 mM) markedly reduced the upregulation of IL-6, IL-1β, cyclooxygenase-2, and NF-κB, and restored the functional metabolism of SH-SY5Y cells, compared with that of the normal glucose control. Our findings suggest that high glucose concentrations can mitigate TNF-α-induced NF-κB activation, upregulation of proinflammatory cytokines, and metabolic dysfunction.

To synthesise the best available evidence regarding the effectiveness of using topical haemoglobin spray to promote healing in hard-to-heal wounds in adults.

To evaluate the clinical efficacy of a hypericum and neem oil dressing, Primary Wound Dressing [ONE] (1PWD) (Kerecis AG, Switzerland), in a patient population with dehiscence of surgical wounds with critical colonisation/infection. Efficacy was defined as resolution of inflammatory/infective symptoms.

Automatic extraction of cerebral vessels and cranial nerves has important clinical value in the treatment of trigeminal neuralgia (TGN) and hemifacial spasm (HFS). However, because of the great similarity between different cerebral vessels and between different cranial nerves, it is challenging to segment cerebral vessels and cranial nerves in real time on the basis of true-color microvascular decompression (MVD) images. In this paper, we propose a lightweight, fast semantic segmentation Microvascular Decompression Network (MVDNet) for MVD scenarios which achieves a good trade-off between segmentation accuracy and speed. Specifically, we designed a Light Asymmetric Bottleneck (LAB) module in the encoder to encode context features. A Feature Fusion Module (FFM) was introduced into the decoder to effectively combine high-level semantic features and underlying spatial details. The proposed network has no pretrained model, fewer parameters, and a fast inference speed. Specifically, MVDNet achieved 76.59% mIoU on the MVD test set, has 0.72 M parameters, and has a 137 FPS speed using a single GTX 2080Ti card.