Rejected

Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6α (K6α) and inhibition of β-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of β-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of β-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.

The aim of this study was to assess pre- and postoperative cognitive functions in patients who underwent surgery for benign intracranial lesions. In total, 58 patients (21 men, 37 women, mean age 51.6 years [range 24-76 years]) with benign intracranial lesions (including benign tumors and vascular lesions) and neuralgia of the trigeminal nerve were included in this prospective study. Extensive cognitive testing was used to categorize attention, memory, and executive functions. Mood and pain were assessed preoperatively (t, mean 3.7 days before surgery), immediately after surgery/during inpatient stay (t, mean 7.6 days after surgery), and at first outpatient check-up (t, mean 99.5 days after surgery). All 58 patients were tested at t and t, but at t only 24 patients were available at t. The data were categorized as improvement/stable condition or deterioration and shown as percentages. The pre- and postoperative values of BDI-II and mood were compared by the Wilcoxon test for paired samples. Binary logistic regression analyses were performed to identify parameters influencing cognition in the subgroup of meningioma patients. Immediately after surgery (t), the percentage of patients with improvement/stable condition was > 50% in all categories in the majority of subtests (attention: 12/14 subtests, memory: 11/13 subtests, executive functions: 6/9 subtests). Similar results were shown at t. Mood and pain did not change significantly after surgery. Factors like age, Karnofsky performance status, and tumor volume were not shown as significant influencing factors for cognitive functions in meningioma patients. The results of this study suggest that-in contrast to neuroepithelial tumors-cognitive functions do not deteriorate after surgery of benign intracranial lesions. Further studies are necessary to evaluate the results of this study.

Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement.

Persistent pain following treatment for breast cancer (PPBCT) is a prevalent and complex clinical issue. Education together with physiotherapy have been shown to lessen pain and disability in chronic pain. Although the evaluation of the patient's competences is a major part of the educational program, the published educational programs rarely describe the tools used to assess competences, especially regarding those related to decision-making and problem-solving. The aim of this study was to provide two competences assessment tools: the cross-cultural adaptation and validation of the Spanish version of the Revised Neurophysiology of Pain Questionnaire (R-NPQ) and practical cases of women with PPBCT. The Spanish cross-cultural adaptation was conducted following recognized criteria. Measurement properties testing included an analysis of construct validity (known-groups approach), reliability (internal consistency and test-retest reliability), responsiveness, interpretability, and feasibility. To promote a tool that would allow evaluation of the educational program competences, a group of experts developed three cases extracted from real contexts by means of an iterative process. A total of 80 women with PPBCT (mean age 56 years) and 81 physiotherapy students (mean age 20 years) participated in the measurement properties analysis. The three developed cases were presented to the same 80 women with PPBCT before and after the educational program. As we expected, students showed a significantly higher score ( < 0.001) than did women with PPBCT in the R-NPQ questionnaire, with a large effect size (d = 2.49), demonstrating good construct validity. The Cronbach alpha was 0.90 (95% CI, 0.87-0.92) and the intraclass correlation coefficient was 0.82 (95% CI, 0.73-0.88). A large effect size (5.2) was found, as we expected, between baseline and post-treatment scores, suggesting adequate responsiveness. In addition, identifying and analyzing, decision making, communicating needs, knowing how to manage, and problem-solving skills were evaluated through the three practical cases. Most women (88.75%) reached the highest level in the assessment rubric of the proposed practical cases. The Spanish R-NPQ is a comprehensible, valid, reliable, and responsive tool for Spanish women with PPBCT. The practical cases are a useful competence assessment tool and were well accepted by women with PPBCT. Further studies are needed to investigate more competence assessment tools and to investigate whether the achievement of different levels of competences has an effect on health behaviors.

The middle meningeal artery (MMA) has been implicated in chronic headaches, but no studies have examined the relationship between MMA embolization and headaches.

Volume recruitment from the splanchnic compartment is an important physiological response to stressors such as physical activity and blood loss. In the setting of heart failure (HF), excess fluid redistribution from this compartment leads to increased cardiac filling pressures with limitation in exercise capacity. Recent evidence suggests that blocking neural activity of the greater splanchnic nerve (GSN) could have significant benefits in some patients with heart failure (HF) by reducing cardiac filling pressures and improvement in exercise capacity. However, to date the long-term safety of splanchnic nerve modulation (SNM) in the setting of HF is unknown. SNM is currently used in clinical practice to alleviate some forms of chronic abdominal pain. A systematic review of series where permanent SNM was used as a treatment for chronic abdominal pain indicates that permanent SNM is well tolerated, with side-effects limited to transient diarrhea or abdominal colic and transient hypotension. The pathophysiological role of the GSN in volume redistribution, the encouraging findings of acute and chronic pilot SNM studies and the safety profile from permanent SNM for pain provides a strong basis for continued efforts to study this therapeutic target in HF.

Visual disturbances are commonly reported in patients with neck pain. Smooth pursuit neck torsion (SPNT) test performed in neutral position and with trunk rotated under the stationary head has been used to discriminate between those with cervical component and those without. However, no studies investigated the reliability of the SPNT-test in patients with chronic neck pain and healthy controls. The aim of this study was to assess inter-visit reliability of the SPNT-test while applying different amplitudes and velocities of target movement. Thirty-two controls and thirty-one patients were enrolled in the study. The SPNT-test was performed in neutral position and through 45° torsion positions. The test was performed at 20°/s, 30°/s and 40°/s velocities and at 30°, 40° and 50° amplitudes of cyclic sinusoidal target movements. Interclass correlation coefficient and smallest detectable change were calculated for parameters of gain and SPNT-differences. In patients, moderate to good reliability was observed for gain at 40° and 50° amplitudes and for 20°/s and 30°/s velocities, while moderate to excellent reliability for gain was observed in controls. Both groups presented with moderate to good reliability for SPNT-difference. Our findings imply that amplitudes of 40° and 50° and velocities of 20°/s and 30°/s are the most reliable and should be applied in future studies assessing oculomotor functions during the SPNT test.

This case demonstrates pneumatosis intestinalis and small bowel perforation in a paediatric patient with multisystem inflammatory syndrome in children (MIS-C). Our patient presented with fever, abdominal pain and shortness of breath. She progressed to haemodynamic failure and small bowel perforation approximately 1 week after admission. Patients with suspected or confirmed MIS-C should be monitored closely for abdominal catastrophe, especially when critically ill in the intensive care unit.

There is no consensus on the optimal surgical treatment for high-grade spondylolisthesis (HGS) in adolescents. The purpose of this study was to assess the radiographic and clinical outcomes of a novel surgical approach to HGS consisting of a single-level anterior reduction, placement of a lordotic cage, and circumferential fixation without decompression.

The absorption of non-steroidal anti-inflammatory drugs (NSAIDs) through the nasal epithelium offers an innovative opportunity in the field of pain therapy. Thanks to the bonding of chitosan to the nasal mucosa and its permeability-enhancing effect, it is an excellent choice to formulate microspheres for the increase of drug bioavailability. The aim of our work includes the preparation of spray-dried cross-linked and non-cross-linked chitosan-based drug delivery systems for intranasal application, the optimization of spray-drying process parameters (inlet air temperature, pump rate), and the composition of samples. Cross-linked products were prepared by using different amounts of sodium tripolyphosphate. On top of these, the micrometric properties, the structural characteristics, the in vitro drug release, and the in vitro permeability of the products were studied. Spray-drying resulted in micronized chitosan particles (2-4 μm) regardless of the process parameters. The meloxicam (MEL)-containing microspheres showed nearly spherical habit, while MEL was present in a molecularly dispersed state. The highest dissolved (>90%) and permeated (~45 µg/cm) MEL amount was detected from the non-cross-linked sample. Our results indicate that spray-dried MEL-containing chitosan microparticles may be recommended for the development of a novel drug delivery system to decrease acute pain or enhance analgesia by intranasal application.