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Novel therapeutic approach to slow down the inflammatory cascade in acute/subacute spinal cord injury: Early immune therapy with lipopolysaccharide enhanced neuroprotective effect of combinational therapy of granulocyte colony-stimulating factor and bone-

Bone-marrow mesenchymal stem cells (BM-MSCs) have not yet proven any significant therapeutic efficacy in spinal cord injury (SCI) clinical trials, due to the hostile microenvironment of the injured spinal cord at the acute phase. This study aims to modulate the inflammatory milieu by lipopolysaccharide (LPS) and granulocyte colony-stimulating factor (G-CSF) to improve the BM-MSCs therapy. For this purpose, we determined the optimum injection time and sub-toxic dosage of LPS following a T10 contusion injury. Medium-dose LPS administration may result in a local anti-inflammatory beneficial role. This regulatory role is associated with an increase in NF-200-positive cells, significant tissue sparing, and improvement in functional recovery compared to the SCI control group. The second aim was to examine the potential ability of LPS and LPS + G-CSF combination therapy to modulate the lesion site before BM-MSC (1 × 105 cells) intra-spinal injection. Our results demonstrated combination therapy increased potency to enhance the anti-inflammatory response (IL-10 and Arg-1) and decrease inflammatory markers (TNF-α and CD86) and caspase-3 compared to BM-MSC monotherapy. Histological analysis revealed that combination groups displayed better structural remodeling than BM-MSC monotherapy. In addition, Basso-Beattie-Bresnahan (BBB) scores show an increase in motor recovery in all treatment groups. Moreover, drug therapy shows faster recovery than BM-MSC monotherapy. Our results suggest that a sub-toxic dose of LPS provides neuroprotection to SCI and can promote the beneficial effect of BM-MSC in SCI. These findings suggest that a combination of LPS or LPS + G-CSF prior BM-MSC transplantation is a promising approach for optimizing BM-MSC-based strategies to treat SCI. However, because of the lack of some methodological limitations to examine the survival rate and ultimate fate of transplanted BM-MSCs followed by LPS administration in this study, further research needs to be done in this area. The presence of only one-time point for evaluating the inflammatory response (1 week) after SCI can be considered as one of the limitations of this study. We believed that the inclusion of additional time points would provide more information about the effect of our combination therapy on the microglia/macrophage polarization dynamic at the injured spinal cord.

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A comparison of anesthetic efficacy between dorsal penile nerve block (DPNB) with lidocaine and eutectic mixture of local anesthetics (EMLA) cream during neonatal circumcision.

Circumcision is often performed in neonates and is associated with significant pain. This study was conducted to compare the anesthetic efficacy of two methods of local anaesthesia for neonatal circumcision: topical eutectic mixture of local anesthetics (EMLA) cream and dorsal penile nerve block (DPNB) with lidocaine.

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Evaluation of unsulfated biotechnological chondroitin in a knee osteoarthritis mouse model as a potential novel functional ingredient in nutraceuticals and pharmaceuticals.

Osteoarthritis is a very disabling disease that can be treated with both non-pharmacological and pharmacological approaches. In the last years, pharmaceutical-grade chondroitin sulfate (CS) and glucosamine emerged as symptomatic slow-acting molecules, effective in pain reduction and improved function in patients affected by osteoarthritis. CS is a sulfated glycosaminoglycan that is currently produced mainly by extraction from animal tissues, and it is commercialized as a pharmaceutical-grade ingredient and/or food supplement. However, public concern on animal product derivatives has prompted the search for alternative non-extractive production routes. Thus, different approaches were established to obtain animal-free natural identical CS. On the other hand, the unsulfated chondroitin, which can be obtained biotechnological processes, demonstrated promising anti-inflammatory properties , in chondrocytes isolated from osteoarthritic patients. Therefore, the aim of this study was to explore the potential of chondroitin, with respect to the better-known CS, in an mouse model of knee osteoarthritis. Results indicate that the treatment with biotechnological chondroitin (BC), similarly to CS, significantly reduced the severity of mechanical allodynia in an MIA-induced osteoarthritic mouse model. Decreased cartilage damage and a reduction of inflammation- and pain-related biochemical markers were also observed. Overall, our data support a beneficial activity of biotechnological unsulfated chondroitin in the osteoarthritis model tested, thus suggesting BC as a potential functional ingredient in pharmaceuticals and nutraceuticals with the advantage of avoiding animal tissue extraction.

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Extension for Community Healthcare Outcomes (ECHO) Chronic Pain & Opioid Stewardship in Northwestern Ontario: A Thematic Analysis of Patient Cases.

Chronic pain (CP) is a debilitating disease that reduces quality of life, decreases productivity, and has become a primary cause of health care resource consumption. Despite this, many Canadian family physicians have received little formal education in managing CP, making it one of the most challenging areas of practice in primary care. Project Extension for Community Healthcare Outcomes Chronic Pain & Opioid Stewardship St. Joseph's Care Group (Project ECHO-SJCG) is an evidence-based educational program connecting community-based health care providers (HCPs) with an interprofessional team by videoconference to learn about management of CP in rural, remote, and underserved areas.

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Alteration of gut microbiota in migraine patients with irritable bowel syndrome in a Chinese Han population.

Migraine is frequently reported in patients with irritable bowel syndrome (IBS), and emerging evidence suggests that gut microbiota plays a role in migraine and IBS. However, alterations in the gut microbiome in migraine patients with IBS remain unknown. This study aimed to explore the compositions of gut microbiota in migraine patients with IBS in a Chinese Han population.

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Peutz-Jeghers syndrome in pediatric patients: experience in a tertiary care institution in Mexico.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by the development of polyps in the gastrointestinal tract, mucocutaneous pigmentation, and the risk of developing malignant neoplasms. This study aimed to analyze the epidemiological, clinical, and histopathological data of patients with PJS treated in a tertiary pediatric hospital.

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Gut microbiota alterations may increase the risk of prescription opioid use, but not vice versa: A two-sample bi-directional Mendelian randomization study.

Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.

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Prevalence of post-concussion syndrome and associated factors among patients with traumatic brain injury at Debre Tabor Comprehensive Hospital, North Central Ethiopia.

The occurrence of three or more of the following signs and symptoms, such as headache, dizziness, exhaustion, irritability, sleeplessness, difficulties in concentrating, or memory problems, following a head injury is referred to as post-concussion syndrome (PCS). Even though post-concussion syndrome has not been studied in Ethiopia, the productive age group is frequently affected by health issues related to head trauma, which either directly or indirectly affect the growth of the nation.

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Correlation between the severity of COVID-19 vaccine-related adverse events and the blood group of the vaccinees in Saudi Arabia: A web-based survey.

Recent epidemiological studies have reported an association between the ABO blood group and the acquisition, symptom severity, and mortality rate of coronavirus disease 2019 (COVID-19). However, the association between the ABO blood group antigens and the type and severity of COVID-19 vaccine-related adverse reactions has not been elucidated. We conducted a cross-sectional, questionnaire-based study in Saudi Arabia from February to April 2022. The study cohort included adults who had received or were willing to receive at least two doses of a COVID-19 vaccine of any type. We used Chi-square test to assess the association between the ABO blood groups and vaccine-related adverse reactions. values of <0.05 were considered significant. Of the 1180 participants, approximately half were aged 18-30 years old, 69.2% were female, and 41.6% reported their blood group as O. The most frequent COVID-19 vaccine-related adverse reactions were fatigue (65%), pain at the injection site (56%), and headache (45.9%). These adverse reactions demonstrated significant correlations with the education level ( = 0.003) and nationality ( = 0.018) of the participants following the first dose, with gender ( < 0.001) following the second dose, and with the general health status ( < 0.001) after all the doses. Remarkably, no correlation was observed between the severity of the vaccine-related adverse reactions and ABO blood groups. Our findings do not support a correlation between the severity of COVID-19 vaccine-related adverse reactions and the ABO blood groups of the vaccinees. The creation of a national database is necessary to account for population differences.

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[FIP1L1::PDGFRA-positive chronic eosinophilic leukemia presenting with multiple ulcers of oral cavity and gastrointestinal tract].

A 66-year-old man developed multiple erosions and pain in the lips and mouth, fever, and black stools. There was persistent bleeding from the lip erosions. When he was admitted to our hospital, his white blood cell count increased to 53,420/µl with 3% eosinophils, and hemoglobin decreased to 3.1 g/dl. Bone marrow biopsy revealed an elevated eosinophil level (24.0%) with markedly toxic granules. Gastrointestinal endoscopy revealed multiple ulcers and erosions in the pharynx, esophagus, stomach, and colon. Histopathological diagnosis indicated nonspecific inflammation with poor infiltration of eosinophils. Bone marrow FISH test was positive for 4q12 deletion (FIP1L1::PDGFRA), leading to the diagnosis of FIP1L1::PDGFRA-positive chronic eosinophilic leukemia. Following initiation of oral administration of imatinib 100 mg/day, the number of eosinophils decreased rapidly, and normalized 2 days after the start of imatinib. The mucosal lesions showed significant improvement and were diagnosed as leukemia-associated lesions. Based on the clinical course of our patient, multiple oral cavity and gastrointestinal ulcers could be the initial presentation in this leukemia.

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