Abnormalities in hippocampal functioning with persistent pain

Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice compared with Sham animals exhibited hippocampal (1) reduced extracellular signal-regulated kinase expression and phosphorylation, (2) decreased neurogenesis, and (3) altered short-term synaptic plasticity. To relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared with controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.     

Bariatric Surgery and Effects on Calcium and Bone Metabolism

With the increasing epidemic of obesity in the United States as well as abroad, bariatric surgery has emerged as the most effective and sustained treatment for reduction. This treatment modality has been well recognized to diminish the risk of cardiovascular morbidity and mortality and ameliorate diabetes mellitus. However, with time, derangement in mineral metabolism has emerged as a major complication in this population. Population-based study has shown increased prevalence of bone fractures and kidney stone formation following bariatric surgery. The risk appears to be more specific after Roux-en-Y gastric bypass procedures, the most common surgical approach among this population. Over the past decade, there have been advances in the understanding of pathophysiologic mechanisms of both bone loss and kidney stone disease in these patients. The understanding of these underlying pathophysiologic mechanisms may lead to the development of drug therapies that ameliorate this complication. Unfortunately, at the present time, there is no hard data on any specific treatment showing decreased incidence of fragility fractures or kidney stone passage. However, some studies suggest that calcium and vitamin D supplementation may decrease bone loss and bone turnover, and as a result, increase bone mineral density in this population. However, there is concern with the development of kidney stone formation following such an approach. A novel treatment approach would be the use of effervescent potassium calcium citrate that not only prevents complications of bone loss but may diminish the risk of kidney stone formation. Despite preliminary results showing the effectiveness of this drug in the reduction in the parathyroid hormone, bone turnover, and improvement in the urinary saturation marker showing effectiveness against calcium oxalate and uric acid stones, there is no hard data available to support the effectiveness of this treatment in the reduction in fragility fractures or kidney stone incidence. Such studies to explore this effect must be considered in the future.     

Platelet-rich plasma versus corticosteroid injections in the management of patients with rotator cuff disease: A systematic review and meta-analysis

Platelet-rich plasma (PRP) is an alternative to corticosteroid (CS) injections in managing rotator cuff disease. This meta-analysis investigated differences between PRP and CS for function and pain scores in significance and minimal clinical important difference (MCID). A literature search of Ovid Cochrane Library, Medline, Embase, Epub, and Scopus was conducted from inception to October 28, 2021. Eligible studies reported patients older than 18 years with a diagnosis of rotator cuff disease. This review was registered in PROSPERO (ID: CRD42021278740). Twelve studies met eligibility criteria (n = 639) of patients receiving either PRP or CS. At short-term follow-up, a difference favored CS compared to PRP in baseline change for disability of arm, shoulder, and hand (DASH) score (MD = −5.08, 95% CI: −8.00, −2.15; p = 0.0007; I² = 0%) and simple shoulder test (SST) (MD = 1.25, 95% CI: 0.33, 2.18; p = 0.008; I² = 0%). At intermediate follow-up, a difference favored PRP to CS baseline change of the DASH score (MD = 3.41, 95% CI: 0.67, 6.15; p = 0.01; I² = 0%). At medium-term, a difference favored PRP to CS baseline change of the American Shoulder and Elbow Surgeons Shoulder (ASES) score (MD = −4.42, 95% CI: −8.16, −0.67; p = 0.02; I² = 0%). Both treatments achieved individual MCID for each score. Despite favoring CS at short-term follow-up and PRP at intermediate- and medium-term follow-up, functional and pain scores did not demonstrate any clinical difference between the two treatment modalities in management of rotator cuff disease at all follow-up periods.     

Antiplatelet Therapy is Associated with Stent Patency After Iliocaval Venous Stenting

CardioVascular and Interventional Radiology - To examine the effectiveness of antithrombotic medications to prevent venous stent malfunction for iliocaval occlusive disease. A retrospective...     

Applications of engineered exosomes in drugging noncoding RNAs for cancer therapy

Noncoding RNAs (ncRNAs) are engaged in key cell biological and pathological events, and their expression alteration is connected to cancer progression both directly and indirectly. A huge number of studies have mentioned the significant role of ncRNAs in cancer prevention and therapy that make them an interesting subject for cancer therapy. However, there are several limitations, including delivery, uptake, and short half-life, in the application of ncRNAs in cancer treatment. Exosomes are introduced as promising options for the delivery of ncRNAs to the target cells. In this review, we will briefly discuss the application and barriers of ncRNAs. After that we will focus on exosome-based ncRNAs delivery and their advantages as well as the latest achievements in drugging ncRNAs with exosomes.     

Uptake and release of [(3)H]GABA in human dental pulp

The purpose of this study was to determine whether (a) an uptake system for gamma-aminobutyric acid (GABA) exists in human dental pulp, (b) GABA can be released from nerves in this tissue, and (c) GABA(B) autoreceptors modulate release of this transmitter. Segments of vital pulp were incubated in [(3)H]GABA (0.1-10 microM) for up to 120 min, washed, and the retained [(3)H] extracted and assayed. Some tissues were treated with GABA uptake inhibitors (nipecotic acid or NO-711) prior to incubation. At concentrations of 0.1 and 1.0 microM the uptake of [(3)H]GABA was saturated after 90 min of incubation. At 10 microM, at least two uptake compartments were apparent, and the amount of [(3)H]GABA retained was five-fold greater than 0.1 microM. The uptake inhibitors reduced [(3)H]GABA accumulation by more than 80%. In the release study, pulp was incubated in [(3)H]GABA (0.5 microM) for 90 min, and superfused with Krebs solution containing NO-711 (5 microM). Electrical stimulation increased the overflow of [(3)H]; a GABA(B) autoreceptor agonist (baclofen) inhibited, whilst an antagonist, Sch 50911, enhanced this release. The effects of baclofen were reversed by Sch 50911. These results imply that GABA can be taken up and bound firmly in compartments within human dental pulp, GABA can be released from isolated pulp segments by electrical stimulation, and this release is modulated by GABA(B) autoreceptors.     

Endovenous laser ablation of the great saphenous vein versus high ligation: long-term results

Endovenous laser therapy (EVLT) for greater saphenous vein (GSV) insufficiency is a relatively new method of treatment only recently made available in Iran. This is the first long-term randomized trial comparing EVLT with high ligation of saphenous vein (HLS) in the Iranian population. Sixty-five patients met the inclusion criteria and were divided into homogenous treatment groups of EVLT (n?=?30) or HLS (n?=?35). Clinical severity, etiology, anatomy, pathophysiology (CEAP) classification and Aberdeen Varicose Vein Symptom Severity Scores (AVSS) were used to determine disease severity and symptoms before and after the procedure in both groups. Outcome was measured by the rate of recurrence as shown in Doppler ultrasonography evaluation. Follow-up was conducted 1 week and 3, 6, 12, and 18 months after the intervention. The occlusion rate of GSV was similar in both groups (93.6 % for EVLT, 88.3 for HLS) at 18 months of follow-up. The median CEAP score showed a dramatic decrease in both groups after 1 week which was sustained for the rest of the study. The Aberdeen Varicose Vein Symptom Severity score was significantly lower in the EVLT group at 12 and 18 months of follow-up. There was no significant difference in patient satisfaction in both groups. Our findings show that EVLT may offer a better long-term relief of symptoms. This, alongside its better cosmetic outcome, and less invasive anesthesia requirements may make it the favorable choice for treatment of GSV insufficiency.     

Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma.

BACKGROUND: Although the role of eosinophils in airway inflammation in chronic asthma has been extensively studied, a role for neutrophils has not been well characterized. Furthermore, prior studies have not systematically sought or controlled for factors that might confound the relationship between cellular markers of inflammation and physiologic measures of airway function. OBJECTIVE: The purpose of this study was to determine whether eosinophilic and neutrophilic inflammation independently contribute to abnormalities of airway function in asthma. METHODS: Multivariate analysis of data collected during screening and enrollment of 205 asthmatic adults for clinical trials was conducted to examine the relationships between cellular inflammation in induced sputum and FEV(1) and methacholine responsiveness (PC(20)) while confounding factors were controlled for. RESULTS: We found that age, sex, ethnicity, and use of inhaled corticosteroids were important confounding factors of the relationship between cellular inflammation and airway function. When these factors were controlled for, multivariate analysis showed that eosinophil percentage in induced sputum is independently associated with lower FEV(1) and lower PC(20) (P = .005 and P = .005, respectively). In the same models, increased sputum neutrophil percentage is independently associated with lower FEV(1) (P = .038) but not with PC(20) (P = .49). CONCLUSIONS: These results suggest that both eosinophilic inflammation and neutrophilic inflammation independently contribute to abnormalities of FEV(1) in asthma. Therapies directed specifically at control of neutrophilic inflammation might be useful in improving airway caliber in patients with chronic asthma.