Pain Hypervigilance is Associated with Greater Clinical Pain Severity and Enhanced Experimental Pain Sensitivity Among Adults with Symptomatic Knee Osteoarthritis

Background

Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA).

Purpose

The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA.

Methods

We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization.

Results

Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain.

Conclusions

Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA.     

Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men : A Population-Based Prospective Cohort Study

Background

Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI).

Objectives

The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men.

Methods

The population-based, prospective cohort of Swedish men comprised 45- to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling ≥40 min/day and exercising ≥1 h/week), and having no abdominal adiposity (waist circumference <95 cm).

Results

During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population.

Conclusions

Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior.     

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

The goal of this work was to develop an in silico model that allows predicting segmental-dependent permeability throughout the small intestine (SI). In vivo permeability of 11 model drugs in 3 SI segments (jejunum, mid-SI, ileum) was studied in rats, creating a data set that reflects the conditions throughout the SI. Then, a predictive model was developed, combining physicochemical drug properties influencing the underlying mechanism of passive permeability: Log p, polar surface area, M_W, H-bond count, and Log f_u, with microenvironmental SI conditions. Excellent correlation was evident between the predicted and experimental data (R² = 0.914), with similar predictability in each SI segment. Log p and Log f_u were identified as the major determinants of permeability, with similar contribution. Total H-bond count was also a significant determinant, followed by polar surface area and M_W. Leaving out any of the model parameters decreased its predictability. The model was validated against 5 external drugs, with excellent predictability. Notably, the model was able to predict the segmental-dependent permeability of all drugs showing this trend experimentally. Model predictability was better in the high-permeability versus low-permeability range. Overall, our approach of constructing a straightforward in silico model allowed reliable predictions of segmental-dependent intestinal permeability, providing new insights into relative effects of drug-related factors and gastrointestinal environment on permeability.     

The Microbe Farms: Microbial Biorepositories in Clinical Microbiology

Biorepositories aim to acquire, authenticate, preserve, develop, and distribute biological specimens, along with information, technology, intellectual property, and standards for the advancement and application of scientific knowledge. Biorepositories are critical components of modern healthcare, as they provide resources to advance translational biomedical research, navigation through the FDA process for in vitro devices, verification and validation of diagnostic methods, and personalized medicine. In order to fully realize the opportunities that biorepositories offer to medicine, laboratories must be able to guarantee high-quality biospecimens, associated information, and a system able to respond to the needs of method verification, quality control, or the requests of scientific colleagues. A biorepository requires funding resources and space, which are often difficult to find within existing health care resources, yet health care may benefit most from the resources biorepositories provide. It is crucial that institutions be able to recognize these issues and start preparing and releasing adequate resources to support the development of biorepositories with a common goal to improve health care by increasing the quality of biomedical research and diagnostic test development. The future of biorepositories depends on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need.     

Synthesis and characterization of osteoinductive visible light‐activated adhesive composites with antimicrobial properties

Orthopedic surgical procedures based on the use of conventional biological graft tissues are often associated with serious post‐operative complications such as immune rejection, bacterial infection, and poor osseointegration. Bioresorbable bone graft substitutes have emerged as attractive alternatives to conventional strategies because they can mimic the composition and mechanical properties of the native bone. Among these, bioactive glasses (BGs) hold great potential to be used as biomaterials for bone tissue engineering owing to their biomimetic composition and high biocompatibility and osteoinductivity. Here, we report the development of a novel composite biomaterial for bone tissue engineering based on the incorporation of a modified strontium‐ and lithium‐doped 58S BG (i.e., BG‐5/5) into gelatin methacryloyl (GelMA) hydrogels. We characterized the physicochemical properties of the BG formulation via different analytical techniques. Composite hydrogels were then prepared by directly adding BG‐5/5 to the GelMA hydrogel precursor, followed by photocrosslinking of the polymeric network via visible light. We characterized the physical, mechanical, and adhesive properties of GelMA/BG‐5/5 composites, as well as their in vitro cytocompatibility and osteoinductivity. In addition, we evaluated the antimicrobial properties of these composites in vitro, using a strain of methicillin‐resistant Staphylococcus Aureus. GelMA/BG‐5/5 composites combined the functional characteristics of the inorganic BG component, with the biocompatibility, biodegradability, and biomimetic composition of the hydrogel network. This novel biomaterial could be used for developing osteoinductive scaffolds or implant surface coatings with intrinsic antimicrobial properties and higher therapeutic efficacy.     

Aetiology and pathogenesis of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell-damage-associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin-1β and tumour necrosis factor-α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin-17 and interferon-γ), and effector mechanisms of neutrophilic granulocytes, macrophages and plasma cells are involved. Simultaneously, skin lesions contain anti-inflammatory mediators (e.g. interleukin-10) and show limited activity of Th22 and regulatory T cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction and scarring. Chronic inflammation in patients with HS is also frequently detected in organs other than the skin, as indicated by their comorbidities. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. This scholarly review focuses on the causes and pathogenetic mechanisms of HS and the potential therapeutic value of this knowledge.     

Myocardial mechanics and energetics in experimental iron-deficiency anemia.

The effect of iron-deficiency anemia on myocardial mechanics and energetics was studied in 10 anesthetized bealge puppies. Nine littermates served as controls. Left ventricular/body weight ratio was increased 14.2% (P less than 0.05) and cardiac index 36.5% (P less than 0.02) in the anemic puppies. Heart rate, mean systolic pressure, myocardial lactate extraction coefficient, and lactic dehydrogenase isozymes were similar in both groups. Contractile state measured in vivo (pressure-velocity curves) and in isolated muscles (isotonic force-velocity curves) was virtually identical in the littermate groups. Despite markedly increased coronary blood flow in the anemia animals, oxygen consumption per unit weight of myocardium was the same in both groups. Contractile element efficiency averaged 18.3% in 10 adult mongrel dogs studied in a similar fashion and was 27.1% and 39.8% in the normal puppies and anemic puppies, respectively. The oxygen cost of internal or force-generating work was similar among the three groups of dogs. It is concluded that the volume load produced by iron-deficiency anemia was associated with a normal contractile state, normal unit myocardial oxygen consumption, no evidence of chronic anaerobiosis, and a high contractile element efficiency, perhaps as a consequence of increased diastolic fiber stretch.     

Community attitudes toward childhood suicide and attempted suicide

To assess whether people's reactions to family members of child suicide attemptors were similar to reactions to family members of (a) actual suicides and (b) actual suicides that were preceded by a failed suicide attempt, 120 shoppers (60 men and 60 women) read and responded to one of five short newspaper articles about an incident of a 10-year-old child who either (a) attempted suicide, (b) committed suicide, (c) committed suicide after a previous suicide attempt, (d) died accidentally, or (e) died of a viral illness. Opinions about the psychological health of the victim and reactions to the surviving family varied depending on the nature of the incident. However, in many instances reactions to families of suicide attemptors could not be differentiated from reactions to families of actual suicides. Therefore, it is likely that the number of people affected by negative community reactions to suicidal behavior has been previously underestimated.     

Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo

Study Objective: To evaluate the efficacy of cisatracurium, rocuronium, and d-tubocurarine in preventing succinylcholine-induced fasciculations and postoperative myalgia in patients undergoing ambulatory surgery.

Design: Randomized, prospective, placebo-controlled trial

Setting: Teaching hospital.

Subjects: 80 ASA physical status I and II patients scheduled for elective ambulatory surgery with general anesthesia.

Intervention: A standardized balanced anesthetic technique was used for all patients.

Measurements and Main Results: Patients were randomized to receive cisatracurium 0.01 mg/kg, rocuronium 0.06 mg/kg, d-tubocurarine 0.05 mg/kg, or saline, 3 minutes prior to intravenous (IV) succinylcholine 1.5 mg/kg. The intensity of fasciculations and intubating conditions were assessed using a four-point rating scale. In addition, the severity of myalgia was assessed using a four-point rating scale in the postanesthesia care unit and at 24 hours postoperatively. No patient complained of any side effects after the administration of the study drug. Fasciculations were observed less frequently (p < 0.05) in the d-tubocurarine and rocuronium groups compared with the placebo and cisatracurium groups. However, there was no difference between the d-tubocurarine group and the rocuronium group (21% vs. 10%, respectively). Although fasciculations occurred less frequently in the cisatracurium group than in the placebo group (59% vs. 85%, respectively), this difference did not reach statistical significance. There was no difference among the four groups in the intubating conditions or the incidence of postoperative myalgia.

Conclusion: Pretreatment with rocuronium and d-tubocurarine was superior to cisatracurium in preventing succinylcholine-induced fasciculations. However, pretreatment did not have any effect on the incidence of myalgia after ambulatory surgery.