Partial Relief Research Articles

Oleocanthal Protects C2C12 Myotubes against the Pro-Catabolic and Anti-Myogenic Action of Stimuli Able to Induce Muscle Wasting In Vivo.

Oleocanthal (OC) is a monophenol of extra-virgin olive oil (EVOO) endowed with antibiotic, cardioprotective and anticancer effects, among others, mainly in view of its antioxidant and anti-inflammatory properties. OC has been largely investigated in terms of its anticancer activity, in Alzheimer disease and in collagen-induced arthritis; however, the possibility that it can also affect muscle biology has been totally overlooked so far. This study is the first to describe that OC modulates alterations induced in C2C12 myotubes by stimuli known to induce muscle wasting in vivo, namely TNF-α, or in the medium conditioned by the C26 cachexia-inducing tumor (CM-C26). C2C12 myotubes were exposed to CM-C26 or TNF-α in the presence or absence of OC for 24 and 48 h and analyzed by immunofluorescence and Western blotting. In combination with TNF-α or CM-C26, OC was revealed to be able to restore both the myotube's original size and morphology and normal levels of both atrogin-1 and MuRF1. OC seems unable to impinge on the autophagic-lysosomal proteolytic system or protein synthesis. Modulations towards normal levels of the expression of molecules involved in myogenesis, such as Pax7, myogenin and MyHC, were also observed in the myotube cultures exposed to OC and TNF-α or CM-C26. In conclusion, the data presented here show that OC exerts a protective action in C2C12 myotubes exposed to TNF-α or CM-C26, with mechanisms likely involving the downregulation of ubiquitin-proteasome-dependent proteolysis and the partial relief of myogenic differentiation impairment.

P075 What has parenteral iron got to do with rheumatology?

Abstract Background/Aims A 39 year-old female had been experiencing a six-month history of insidious onset migratory joint and bone pain, stiffness, malaise and over the last four months proximal muscle weakness. There had been partial relief with the use of non-steroidal anti-inflammatory medication. Past medical history included severe menorrhagia secondary to fibroids with a haemoglobin of 50g/dl on a handful of occasions, requiring x3 iron infusions (Ferric Carboxymaltose (FCM)1000mg) over a two year period. The last two infusions were provided three months apart. After each infusion, profound fatigue ensued. A blood test demonstrated an elevated ALP 301 (RR 30-130 U/L), reduced phosphate 0.48 (RR 0.8-1.5mmol/L) and mildly reduced 25OH vitamin D 44 (RR 50-140nmol/L). Corrected calcium was low-normal 2.29 (RR 2.2-2.6mmol/L) as was PTH 4.62 (RR 1.6-6.9pmol/L). A CTCAP excluded malignancy. Methods The patient had been treated with Cholecalciferol 1000iu and Dipyridamole 100mg daily with weekly blood test monitoring for six weeks prior to review in the metabolic bone clinic. Dipyridamole aided biochemical and symptomatic improvement. Further tests returned with an elevated FGF23 252 (RR 0-100 RU/ml), a normal Urine phosphate/Creatinine 1.6 and TmP/GFR ratio (suggesting the FGF23 effect on the kidney was not severe or its effects inhibited by Dipyridamole). ALP had reduced slightly to 269, PTH was elevated at 10.81 (RR 1.95-8.49micromol/L) and 1,25 Dihydroxy Vit D 182 (RR43-144 pmol/L). Results The patient was diagnosed with Parenteral iron triggered hypophosphatemia osteomalacia (6H-syndrome). A delayed diagnosis and referral resulted from unfamiliarity of side-effects of parenteral iron, especially Ferric Carboxymaltose, which has an alert on the GOV.UK website. The patient discontinued IV iron and was placed on oral Ferrous Gluconate 300mg daily. In retrospect, bone and joint pain was likely the result of enthesial pain and pseudofractures. In patients with diagnostic uncertainty, an isotope bone scan would be beneficial in assessing the extent of such pseudofractures. Hypophosphatemia is common following FCM (≥1/100 to < 1/10), and often self-limiting and asymptomatic. However, sustained hypophosphatemia (from recurrent infusions) can result in osteomalacia. Both anaemia and certain iron preparations can cause an elevation in FGF23 leading to increased urinary phosphate excretion. Dipyridamole has anti-phosphaturic effects by inhibiting FGF23. Conclusion It is advised in such patients to monitor serum phosphate levels at two- and five-weeks post infusion and to re-evaluate therapy with FCM in patients with persistent hypophosphatemia. It is common for symptoms, imaging, and biochemistry (FGF23 and ALP) to remain elevated/positive several months after diagnosis. This case highlights the need to ask about iron infusions in the drug history in patients presenting with hypophosphatemia and to be aware that musculoskeletal pain following iron infusions can be a sign of osteomalacia which will need investigating. Rarely, proximal muscle weakness can occur following the above iron preparation. Disclosure K.M. Achilleos: None. V. Rajagopal: None. C. Adams: None. G. Clunie: None.

Epidemiology and clinical characteristics of headache among COVID-19 patients in Lebanon: a retrospective cohort study

BackgroundWith the spread and rise in the number of infections of COVID-19 globally, patients experienced neurologic manifestations such as headache and dizziness, along with other serious medical conditions such as stroke and seizures. Many reported cases highlighted headache to be one of the most common COVID-19-related neurological symptoms. With the evolution of the pandemic, broad studies are needed to better understand the mechanism of headache with COVID-19. The aim of this study is to recognize the epidemiology, characteristic and progression of headache among patients with COVID-19 in Lebanon.MethodsA retrospective cohort study was done to assess 439 patients for headache during the course of COVID-19. The Statistical Package for Social Sciences (SPSS) version 26 was used for descriptive analysis.ResultsA confirmed COVID-19 Infection by PCR test was confirmed among 86% of the participants. Tension-like headache was the most common type of headache experienced by participants during COVID-19. Pain was mainly diffuse (48.7%), and compressing in nature (77.0%). Moreover, about 29% required a physician consultation and 7.7% had emergency visits. Partial relief by analgesics was reported in 54.9%, and mainly by paracetamol (64.6%). Those who reported having a history of primary headache before contracting COVID-19 were 46.7%. Among them, 36.7% patients reported a change in the type of headache and about 49.6% reported increased severity.ConclusionHeadache accompanied with COVID-19 is a common symptom during the early stages of illness. COVID-19 related headache was characterized as mainly involving the whole head region, pressuring, and partially relieved by analgesics. Thus, headache should raise early concern for the probability of being infected by COVID-19.

Normalization of urination parameters in a boy with cerebral palsy after rehabilitation using an “ExoAtlet” exoskeleton

Lower urinary tract dysfunction occurs in 30%–55.5% of patients with cerebral palsy. The article presents a clinical example of medical rehabilitation of a child with cerebral palsy and dysfunctional urination using the verticalization method and ExoAtlet exoskeleton. Description of observation. A 15-year-old boy had urinary disorders in the form of urine leakage after urination, incomplete emptying of the bladder, episodes of enuresis, and frequent urination while sitting. The gait was unsteady and aided with crutches supported by the elbow. Examinations included uroflowmetry and electromyography. The results indicated a decrease in contractility and impaired evacuation function of the detrusor. In total, 15 rehabilitation sessions were performed using the ExoAtlet exoskeleton, after which the patient gained an independent gait supported by a cane, and the child was taught to urinate in a standing position. A repeat urological examination revealed a positive change in urination parameters with partial relief of pollakiuria and complete relief of the residual bladder volume. Verticalization and activation of striated muscles, obtained following the use of an exoskeleton in a child with cerebral palsy and dysfunctional urination, in combination with restored posture, helped normalize lower urinary tract function.

Comparative Analysis of Stereotactic Radiation Therapy and Conventional Radiation Therapy in Cancer Pain Control: A Systematic Review and Meta-Analysis

AimsApproximately 55% of patients diagnosed with primary or metastatic cancer endure pain directly attributable to the disease. Consequently, it becomes imperative to address pain management through a comparative analysis of stereotactic radiotherapy (SRT) and conventional radiation therapy (CRT), especially in light of the less efficacious improvement achieved solely through pharmacological interventions. Materials and methodsA systematic exploration was undertaken on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies that compare Stereotactic Radiotherapy to Conventional radiation therapy for pain management in individuals with metastatic bone cancer. The analyses were executed utilizing the random-effects model. ResultsA cohort of 1152 participants with metastatic bone cancer was analyzed, demonstrating significantly higher complete pain relief in the Stereotactic Radiotherapy group during both early and late follow-up (RR: 1.61; 95% CI: 1.17, 2.23, p-value: 0.004; I2: 0%). Stereotactic Radiotherapy also showed a non-significant increase in the incidence of partial pain relief (RR: 1.07; 95% CI: 0.85, 1.34, p-value: 0.56; I2: 18%). Furthermore, Stereotactic Radiotherapy was associated with a significantly reduced risk of stationary pain throughout follow-up (RR: 0.61; 95%CI: 0.48, 0.76, p-value: <0.0001; I2: 0. The incidence of progressive pain was non-significantly reduced with Stereotactic Radiotherapy during both early and late follow-up (RR: 0.77; 95% CI: 0.50, 1.17, p-value: 0.22; I2: 0%). Secondary outcomes exhibited a non-significant trend favoring Stereotactic Radiotherapy for dysphagia, esophagitis, pain, and radiodermatitis, while a non-significant increase was observed for nausea, fatigue, and vertebral compression fracture. ConclusionIn summary, stereotactic radiation therapy (SRT) has improved in achieving complete pain relief while exhibiting a decreased probability of delivering stationary pain compared to conventional radiation therapy (CRT). Nevertheless, it is crucial in future research to address a noteworthy limitation, specifically, the risk of vertebral compression fracture.

Dip eyes in water technique (Akshi Nimanjjana): Efficacy of a simple technique in the management of meibomian gland dysfunction

Abstract Background: Dip eyes in water (DEW) is an ancient technique to improve eye hygiene. Conventionally, the eyes are cleaned by splashing water on them. However, splashing is not very effective as the eyes get closed reflexly when the water is splashed onto the eyes. On the other hand, in the DEW technique, it is conveniently possible to keep eyes fully open when dipped inside the water in the eye cup. Meibomian gland dysfunction (MGD) is a chronic, frustrating disease for which there is no gold standard, and eye hygiene is presumed to play an important role. Aim: The present study was tested in a cohort of MGD patients using the DEW technique. Materials and methods: DEW was prescribed to seven patients who were symptomatic for a period ranging from 6 months to 2 years. The main four symptoms were irritation in the eyes, persistent watering of the eyes, burning sensation, and foreign-body sensation. The scale of assessment of these four symptoms was severe (+++), moderate (++), mild (+), and no symptoms (−). The outcome assessment criteria were complete relief in these four symptoms and were assessed after 1 year of starting treatment. The DEW technique was performed 3–4 times per day. It was added to the ongoing conservative treatment. Once complete relief was obtained, other conservative management measures were stopped, and only the DEW treatment continued. It was advised that the DEW treatment be continued as a part of the regular eye hygiene daily routine. Results: Five out of seven patients reported complete relief in outcome criteria (four symptoms), one had partial relief, and there was no relief in one of the patients. After a follow-up of 1 year, one patient (the one with partial relief) was lost to follow-up. Five out of seven patients had significant relief, and 5/6 patients had sustained relief on long-term follow-up. No adverse effects were reported by any of the patients. Conclusion: The DEW technique is promising in providing significant relief in patients with MGD. The encouraging results of DEW in this series can help prescribe and extend the indications of DEW in managing MGD and other eye disorders, in which eye hygiene plays a therapeutic role and as a daily routine eye-care practice to prevent various eye disorders.

Long-term outcome of microvascular decompression for typical trigeminal neuralgia with autologous muscle: an analysis of 1025 patients from a developing country.

The objective was to evaluate the long-term outcome of microvascular decompression (MVD) utilizing autologous muscle for trigeminal neuralgia (TGN). A retrospective review was performed of all first-time MVD patients for typical classic TGN without prior surgical intervention who were treated between 2000 and 2019 at a tertiary supraregional neurosurgery practice. Demographic characteristics, surgical findings, operative results, complications, and recurrence rates at 1 year, 5 years, and last follow-up were collected. Pain outcome was assessed using the Barrow Neurological Institute (BNI) pain score. The chi-square test with continuity correction was used to compare categorical variables, and Kaplan-Meier curves and Cox regression were used to identify factors associated with recurrence. In total, 1025 patients were studied with a median (interquartile range [IQR]) (range) follow-up of 8 (5-13) (3-20) years. In the immediate postoperative period, 889 patients (86.7%) had complete pain relief and 106 (10.3%) had partial pain relief; neither group required medication, and 30 patients (2.9%) had no relief. One hundred forty-one recurrences (13.8%) occurred over a median (IQR) of 3 (2-6) years after surgery. The proportion of patients without recurrence was 97% at 1 year, 90% at 5 years, 85% at 10 years, 82% at 15 years, and 81% at 20 years. There was no significant difference in the probability of recurrence between patients with complete (114/907 [12.6%] recurrences) or partial (19/106 [17.9%] recurrences) postoperative pain relief (p = 0.124, log-rank test). Patients with venous compression (n = 322) had a significantly higher rate of MVD failure (n = 16 [5%]) compared to those with arterial compression (14/703 [2%]) (p = 0.015, chi-square test). In the Cox proportional hazards model, venous compression and lack of immediate postoperative pain relief had hazard ratios of 1.62 (95% CI 1.16-2.27) and 2.65 (95% CI 1.45-4.82) for recurrence, respectively. One hundred twenty-four (12.1%) complications were documented, including facial numbness (44 [4.3%]), facial nerve palsy (37 [3.6%]), CSF leak (13 [1.3%]), and diplopia (5 [0.5%]), which resolved in all patients. MVD with autologous muscle provides long-lasting pain relief in TGN patients with vascular compression with minimum morbidity and is a viable alternative to synthetic materials.

450 Inflammatory Brachial Plexitis Mimics Postoperative Iatrogenic Neurological Deficits

INTRODUCTION: A common cause of neurosurgical malpractice cases is the misrepresentation of idiopathic brachial neuritis (incidence: 1/1000) as an iatrogenic neurological insult caused by a surgeon. METHODS: Confirmed postprocedural brachial neuritis patients from a single quaternary care institution were identified and analyzed. RESULTS: We identified 6 (3 female) postprocedural brachial neuritis patients with mean age 63.7 (range 50-75) years. Procedures included 5 cervical spine surgeries (3 multilevel ACDFs, 2 multilevel posterior fusions with laminectomies, 1 multilevel disc arthroplasty) and 1 intrajugular central venous catheter placement. Average time to symptom onset was 1 week post-procedure (range 1 day-2.5 weeks). Initial symptom was moderate-to-severe shoulder (5), arm (4), and/or neck (1) pain. Subsequently, all developed axillary/shoulder weakness; 3 distal arm/hand weakness, 2 winged scapula, and 2 dyspnea/orthopnea. For diagnosis, two patients had confirmatory EMG, 1 had MR neurography confirming plexus inflammation, and 3 had both (positive EMG findings and inflammation on MR Neurography). Average time to accurate diagnosis was 3.1 (range 1.5-5) months. Average number of clinicians seen prior to accurate diagnosis: 5. Treatments included opioids (5), steroids (1), and/or physical therapy (6). All experienced partial pain relief by 1-8 weeks; 2 had persistent pain requiring gabapentin past 6 months. All patients continued to experience motor deficits past 6 months: (4 patients had atrophy and 2-4/5 motor strength in proximal the proximal arm, 1 had distal arm 3/5 motor strength, and 1 had scapular winging). CONCLUSIONS: Postoperative idiopathic brachial plexitis mimics iatrogenic nerve damage following neurosurgical procedures. Recognition of this entity is difficult, and 6 patients at our institution saw on average 5 providers over 3 months prior to accurate diagnosis. Brachial plexitis has a prolonged course with typically only partial recovery at 6 months.

International double taxation: Interpretation in the Indian context and general mitigation Measures

International Double Taxation poses a complex challenge with diverse interpretations, especially in the Indian context. This paper investigates the nuances of double taxation, focusing on legal principles, double taxation avoidance agreements (DTAAs), and their implications for residents and permanent establishments. It analyzes India's engagement in double taxation treaties, considering monistic and dualistic principles, legislative processes, and recent judicial developments. Case studies from French and Indian courts offer insights into treaty interpretation. The paper examines relief methods such as Exemption, Credit, Tax-sparing, and Expense Deduction, emphasizing their application within Indian tax treaties. Notably, Permanent Establishment (PE) significance in international taxation is explored through relevant case law. Conclusively, the paper underscores the importance of addressing international double taxation in the globalized era. It argues that while various relief methods exist, the Exemption method is most effective in mitigating double taxation, contrasting with the partial relief provided by the Credit method. The choice of relief method varies across nations based on financial considerations. This comprehensive exploration contributes to understanding international double taxation in the Indian context, highlighting legal interpretations, treaty dynamics, and mitigation measures. It advocates for harmonizing global approaches to achieve more effective and equitable solutions in international taxation.

First reported case of &lt;i&gt;Phoma multirostrata&lt;/i&gt; from central India

A 50-year-old male patient, resident of Gondia, Maharashtra, India, presented with chief complaints of swelling and raw areas over left foot for 3 months. Patient was apparently alright 3 months prior when he had a traumatic injury with a piece of wood which went across his whole foot, which was removed by patient himself, and then he visited a private hospital where he was given various medications, which gave him partial relief. After a few days, the patient developed a painful swelling over the left foot, up to the ankle, which was associated with difficulty in walking and local rise of temperature, and not with fever or other symptoms. Following this, after a month, the patient developed a single raised lesion, which progressed to involve the whole left foot over a period of 5 days. The lesions then burst spontaneously, which was associated with bloody discharge. For these complaints, the patient visited a nearby hospital, where he was admitted and given various medications, including tablet amoxycillinpotassium clavulanate 625 mg, tablet pantoprazole 40 mg, tablet paracetamol 500 mg and fusidic acid cream application, which gave him partial relief. After a few days, the patient developed a burning sensation over these lesions, for which he was then referred to GMC, Nagpur, Maharashtra, India, from same hospital.

Safety and Efficacy of Percutaneous Morton Neuroma Cryoneurolysis Under Ultrasound Guidance.

To assess the technical success, safety and early efficacy of Morton neuroma (MN) cryoneurolysis. Retrospective review of 54 consecutive patients with MN treated with cryoneurolysis after failure of conservative treatment, from September 2022 to June 2023. Outcomes measurements included technical success (defined a successful ultrasound-guided placement of the cryoprobe), procedural safety according to Cirse classification and change in 6months post-procedure by pain numeric rating scale (pNRS). A total of 59 MN were treated during 55 procedures. Mean procedure duration was 47min, all patients were discharged 2h after the intervention. Technical success was 98.1%. No Cirse grade 3, 4 or 5 complication was reported. Three grade 2 complication occurred, including two chilblain-type lesions and one bone insufficiency fracture. At 6months post-procedure, pNRS score was significantly decreased (2.7 ± 2.2 vs 7.1 ± 1.1) (p < 0.0001), with a mean score decrease of 4.1points. Thirty-two patients (60.4%) reported a complete pain relief, 15 (28.3%) a partial pain relief and 6 (11.3%) no pain relief, or increased pain. Cryoneurolysis seems to be safe for the treatment of Morton neuroma. Six-month pain relief is promising and needs to be confirmed at long term.

Clinical efficacy of EUS-guided celiac plexus neurolysis versus EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.

To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

Adapting to sea level rise: migration decisions and disaster mitigation strategies in small-scale fishing communities

This study explores the adaptation process of small-scale fishing families in Demak, Java, in response to sea level rise and tidal floods. Qualitative research methods are used to investigate the factors influencing families’ decisions to relocate. Findings indicate that families employ home elevation as a short-term adaptation measure, but severe floods eventually lead to the challenging decision of permanent migration. The study highlights the interplay of physical, social, and economic factors in shaping migration decisions. While short-term strategies provide partial relief, migration emerges as a vital long-term resilience strategy. Mitigation efforts involve coastal protection, wetland restoration, land use planning, and climate change adaptation measures. The study emphasises the need for tailored, context-specific strategies and integration of sea level rise considerations into broader climate change mitigation efforts. Overall, understanding migration decisions and implementing targeted disaster mitigation strategies are crucial for enhancing the resilience of coastal communities facing sea level rise.

Radiological characteristics predicting early poor drug response in patients with hemifacial spasm.

Patients with hemifacial spasm (HFS) often resort to botulinum toxin injections or microvascular decompression surgery when medication exhibits limited effectiveness. This study aimed to identify MRI and demographic factors associated with poor drug response at an early stage in patients with HFS. We retrospectively included patients with HFS who underwent pre-therapeutic MRI examination. The presence, location, severity, and the offending vessels of neurovascular compression were blindly evaluated using MRI. Drug responses and clinical data were obtained from the medical notes or phone follow-ups. Logistic regression analysis was performed to identify potential factors. A total of 116 patients were included, with an average age at the time of first examination of 50.4years and a median duration of onset of 18months. Forty-nine (42.2%) patients reported no symptom relief. Thirty-seven (31.9%) patients reported poor symptom relief. Twenty-two (19.0%) patients reported partial symptom relief. Eight (6.9%) patients achieved complete symptom relief. The factors that were statistically significant associated with poor drug responses were contact in the attach segment of the facial nerve and aged 70 and above, with an odds ratio of 7.772 (p = 0.002) and 0.160 (p = 0.028), respectively. This study revealed that mild compression in the attach segment of the facial nerve in pre-therapeutic MRI increases the risk of poor drug responses in patients with HFS, while patients aged 70 and above showed a decreased risk. These findings may assist clinician to choose optimal treatment at an early stage.

Basal ABA signaling balances transpiration and photosynthesis.

The balance between the CO2 entry for photosynthesis and transpiration water loss is crucial for plant growth, and ABA signaling can affect this equilibrium. To test how ABA balances plant growth and environmental adaptation, we performed molecular genetics studies in the biotech crop Nicotiana benthamiana under well-watered or drought conditions. Studies on ABA signaling in crops are complicated by the multigenic nature of the PYR/PYL/RCAR ABA receptor family and its functional redundancy, which is particularly challenging in polyploid plants. We have generated a pentuple pyl mutant in the allotetraploid Nicotiana benthamiana through CRISPR/Cas9 gene editing. The pentuple mutant is impaired in 2 NbPYL1-like and 3 NbPYL8-like receptors, affecting the regulation of transpiration and several ABA-dependent transcriptional processes. RNA-seq and metabolite analysis revealed that the synthesis of galactinol, an essential precursor for the osmoprotective raffinose family of oligosaccharides, is ABA-dependent and impaired in the mutant under osmotic stress. In contrast, our results show that, under well-watered conditions, partial inactivation of ABA signaling leads to higher CO2 entry and photosynthesis in the mutant than in WT. Photosynthesis analyses revealed an increased CO2 diffusion capacity mediated by higher stomatal and mesophyll conductances, and higher substomatal CO2 concentration in the pentuple mutant. RNA-seq analyses revealed that genes associated with cell wall loosening (e.g., expansins) and porosity were strongly downregulated by ABA in WT. In summary, a partial relief of the ABA control on transpiration mediated by ABA receptors positively affects photosynthesis when water is not limited, at the expense of reduced water use efficiency.

Effects of Repeated Treatment with the Monoacylglycerol Lipase Inhibitor MJN110 on Pain-Related Depression of Nesting and Cannabinoid 1 Receptor Function in Male and Female Mice.

MJN110 inhibits the enzyme monoacylglycerol lipase (MAGL) to increase levels of the endocannabinoid 2-arachidonoylglycerol , an endogenous high-efficacy agonist of cannabinoid 1 and 2 receptors (CB1/2R). MAGL inhibitors are under consideration as candidate analgesics, and we reported previously that acute MJN110 produced partial antinociception in an assay of pain-related behavioral depression in mice. Given the need for repeated analgesic administration in many pain patients and the potential for analgesic tolerance during repeated treatment, this study examined antinociceptive effects of repeated MJN110 on pain-related behavioral depression and CB1R-mediated G-protein function. Male and female ICR mice were treated daily for 7 days in a 2 × 2 design with (a) 1.0 mg/kg/d MJN110 or its vehicle followed by (b) intraperitoneal injection of dilute lactic acid (IP acid) or its vehicle as a visceral noxious stimulus to depress nesting behavior. After behavioral testing, G-protein activity was assessed in lumbar spinal cord (LSC) and five brain regions using an assay of CP55,940-stimulated [35S]GTPɣS activation. As reported previously, acute MJN110 produced partial but significant relief of IP acid-induced nesting depression on day 1. After 7 days, MJN110 continued to produce significant but partial antinociception in males, while antinociceptive tolerance developed in females. Repeated MJN110 also produced modest decreases in maximum levels of CP55,940-induced [35S]GTPɣS binding in spinal cord and most brain regions. These results indicate that repeated treatment with a relatively low antinociceptive MJN110 dose produces only partial and sex-dependent transient antinociception associated with the emergence of CB1R desensitization in this model of IP acid-induced nesting depression. SIGNIFICANCE STATEMENT: The drug MJN110 inhibits monoacylglycerol lipase (MAGL) to increase levels of the endogenous cannabinoid 2-arachidonoylglycerol and produce potentially useful therapeutic effects including analgesia. This study used an assay of pain-related behavioral depression in mice to show that repeated MJN110 treatment produced (1) weak but sustained antinociception in male mice, (2) antinociceptive tolerance in females, and (3) modest cannabinoid-receptor desensitization that varied by region and sex. Antinociceptive tolerance may limit the utility of MJN110 for treatment of pain.

Factors influencing short-term prognosis after botulinum toxin type A treatment for hemifacial spasm：A retrospective study

BackgroundIt is widely acknowledged that botulinum toxin type A (BTX-A) has been widely used in the treatment of hemifacial spasm (HFS). However, there is currently a lack of systematic analysis of the factors affecting its therapeutic effect. Therefore, this study aims to explore the influencing factors of BTX-A in the treatment of HFS and to identify risk factors for poor prognosis. MethodsRetrospective study including 118 patients with HFS treated with BTX-A from 2019 January to 2023 April. Demographic and etiological variables as well as doses, number of sessions of BTX-A, infiltrated muscles, therapeutic response according to the Cohen evaluation scale, and side effects were analyzed. Logistic regression analysis was performed to identify the factors that are associated with the short-term prognosis of BTX-A for the treatment of HFS. ResultsAmong the 118 patients with HFS included in this study, 57 achieved complete relief, 51 had significant relief, 7 had partial relief, and no improvement was observed in 3. The overall effective rate was 91.53 %. Results from the univariate analysis indicated that male, drinking, diabetes, and hypertension were all associated with poor short-term prognosis of BTX-A in the treatment of HFS. Multivariable logistic regression analysis further revealed that hypertension was an independent risk factor for poor short-term prognosis following BTX-A treatment for HFS (OR=5.847, P<0.05). ConclusionBTX-A was effective in treating HFS and had minimal adverse effects. Hypertension was an independent risk factor for poor short-term prognosis following BTX-A treatment of HFS.

A novel anti-pruritic: Topical co-administration of high molecular weight hyaluronan (HMWH) with protamine, a transdermal transport enhancer.

Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.

Unusual Presentation of Trigeminal Neuralgia and its Surgical Management

Trigeminal neuralgia (TN) is a debilitating neuropathic condition characterized by excruciating, lancinating pain attacks. The standard first-line treatment of TN is carbamazepine medication, but some patients do not experience relief from this drug. For cases that do not respond to medication, surgical procedures that cut or remove portions of the peripheral nerves, such as the inferior alveolar and mental nerves, can be attempted. However, these neurectomysurgeries often have high rates of severe facial pain recurring over time. A 40-year-old man suffered from chronic, debilitating trigeminal neuralgia. He underwent multiple tooth extractions and took carbamazepine, but neither provided improvement in his agonizing facial pain. He then had surgical neurectomies of the mental and inferior alveolar nerves, which provided only partial pain relief. The patient was not relieved, so he underwent a surgical neurectomy of the lingual nerve. This third procedure successfully provided a significant reduction in his trigeminal neuralgia pain. Lingual neurectomy emerges as a potentially definitive treatment modality for trigeminal neuralgia refractory to medication or alternative neurectomy procedures. This minimally invasive surgical approach offers a valuable option for patients seeking sustained pain relief, particularly those who are not suitable candidates for or desire to avoid, more extensive or resource-intensive interventions.

Tunneled Percutaneous Transesophageal Gastrostomy for Treatment of Malignant Bowel Obstruction

ABSTRACT Introduction Malignant bowel obstruction is a common complication in patients with end-stage cancer. Gastric decompression can reduce symptoms; however, percutaneous gastrostomy tube placement may not always be feasible. A percutaneous transesophageal gastrostomy (PTEG) is an alternative for nasogastric decompression. This study describes a technical modification of PTEG tube placement for patient comfort. Methods: A single-center retrospective review was performed to compare outcomes from tunneled versus nontunneled PTEGs. Similar to previous descriptions, an esophageal balloon was percutaneously punctured with a needle for placement of a tube entering the neck and tracked through the esophagus into the stomach. Rather than suturing to the neck, the tube was navigated through a subcutaneous tunnel to create a tunneled transesophageal gastrostomy. Results: Between Dec 2017 and Oct 2023, 27 patients underwent attempted PTEG tube placement, 10 of which were tunneled. Median time to death was 24 days after the procedure. Adverse events occurred in 10 of 27 patients (37.0%) and included cellulitis, tube retraction requiring tube repositioning and replacement, tube clogging, failed placement, postprocedure extended intubation, postprocedure hypotension, and aspiration. More infections were noted in the tunneled PTEGs than in the nontunneled PTEGs. Twenty-four patients reported partial or complete symptom relief. Seventeen patients were able to tolerate a liquid, low-fiber, or soft regular diet with a PTEG. Conclusion: Using established techniques of tunneling central venous catheters and the process of placing PTEG tubes, a simple modification to the procedure can have the gastrostomy exit along the chest wall rather than the neck. However, this may cause increased infectious complications.