Insulin resistance and the endothelium

There is increasing evidence of a parallel progression between insulin resistance and endothelial dysfunction, suggesting a close association between insulin action and the endothelium. Numerous studies have demonstrated that endothelial dysfunction occurs early in the insulin-resistant state and is predictive of future cardiovascular events. Similarly, insulin resistance has been associated with the metabolic syndrome, which also increases the risk of adverse cardiovascular outcomes. Approaches that improve endothelial dysfunction, such as treatment with statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or peroxisome proliferator-activated receptor gamma ligands, have been shown to prevent both diabetes and cardiovascular disease. This article reviews the relation between endothelial dysfunction and cardiovascular disease, assesses the endothelium in the spectrum of insulin resistance, and examines the effect of the thiazolidinediones on endothelial function.     

Evaluation of Hybridization Capture Versus Amplicon‐Based Methods for Whole‐Exome Sequencing

Next‐generation sequencing has aided characterization of genomic variation. While whole‐genome sequencing may capture all possible mutations, whole‐exome sequencing remains cost‐effective and captures most phenotype‐altering mutations. Initial strategies for exome enrichment utilized a hybridization‐based capture approach. Recently, amplicon‐based methods were designed to simplify preparation and utilize smaller DNA inputs. We evaluated two hybridization capture‐based and two amplicon‐based whole‐exome sequencing approaches, utilizing both Illumina and Ion Torrent sequencers, comparing on‐target alignment, uniformity, and variant calling. While the amplicon methods had higher on‐target rates, the hybridization capture‐based approaches demonstrated better uniformity. All methods identified many of the same single‐nucleotide variants, but each amplicon‐based method missed variants detected by the other three methods and reported additional variants discordant with all three other technologies. Many of these potential false positives or negatives appear to result from limited coverage, low variant frequency, vicinity to read starts/ends, or the need for platform‐specific variant calling algorithms. All methods demonstrated effective copy‐number variant calling when evaluated against a single‐nucleotide polymorphism array. This study illustrates some differences between whole‐exome sequencing approaches, highlights the need for selecting appropriate variant calling based on capture method, and will aid laboratories in selecting their preferred approach.     

Kinesio Tape and Shoulder-Joint Position Sense

Context

Joint position sense (JPS) is a key neuromuscular factor for developing and maintaining control of muscles around a joint. It is important when performing specialized tasks, especially at the shoulder. No researchers have studied how Kinesio Tape (KT) application affects JPS.

Objective

To investigate the effects of KT application and no tape on shoulder JPS at increasing shoulder elevations in athletes.

Design

Cross-sectional study.

Setting

University laboratory.

Patients or Other Participants

A total of 27 healthy athletes who did not participate in overhead sports (age = 20.44 ± 1.05 years, height = 175.02 ± 11.67 cm, mass = 70.74 ± 9.65 kg) with no previous pathologic shoulder conditions volunteered for the study. All participants were from 1 university.

Intervention(s)

Shoulder JPS was assessed at increasing elevations with and without KT application. Participants attempted to actively replicate 3 target positions with and without the KT and without visual guidance.

Main Outcome Measure(s)

We examined absolute and variable repositioning errors at increasing shoulder-elevation levels with and without KT application.

Results

Data revealed an interaction between tape and position for absolute error (F_2,52 = 4.07, P = .02); simple effects revealed an increase in error, with KT demonstrating a 2.65° increase in error at 90° of elevation compared with no tape (t₂₆ = 2.65, P = .01). The effect size was medium (ω² = .135). Variable error showed no interaction of tape and position (F_2,52 = .709, P = .50). Further analysis of simple effects was not needed. However, we still calculated the effect size and observed small effect sizes for tape (ω² = .002), position (ω² = .072), and tape by position (ω² = .027).

Conclusions

At 90° of elevation, shoulder JPS was impaired by the application of KT.Key Words: proprioception, taping, shoulder, neuromuscular, rehabilitation

Key Points

• Short-term Kinesio-Tape application to the shoulder reduced joint position sense acuity at 90° of elevation but did not affect JPS at 50° or 110°.
• Kinesio Tape may negatively affect shoulder joint position sense, especially as the shoulder position approaches 90° of elevation.

Athletes, especially those who participate in overhead activities, place much stress on their shoulder joints during activity, so they are at increased risk for developing shoulder injuries. Given that the shoulder allows for much mobility, stability is sacrificed; therefore, the shoulder is considered one of the most vulnerable joints in the body.¹ Numerous factors within the shoulder complex contribute to this lack of stability, including limited glenohumeral bony congruity, limited ligamentous support, and joint capsular laxity. However, stability is still needed to perform precise tasks for activities of daily living or sporting events.² Factors that provide stability to the joint include support of surrounding muscles, the intra-articular pressure of the joint, and the integration of the central nervous system with peripheral mechanoreceptors, a sensory system termed proprioception.³Proprioception is a specialized sensory capability that includes a person''s sense of movement, joint position, and tension.⁴ Joint position sense (JPS) consists of both static and dynamic abilities to detect the position of the joint in space.⁵ Researchers⁶ have suggested that increased muscle activation leads to increased afferent feedback from muscle spindles, resulting in enhanced JPS. The JPS is enabled via sensory feedback from peripheral receptors in sites such as skin, muscles, ligaments, and tendons that the central nervous system processes, and JPS is a key factor for controlling joint movement.⁴Investigators⁷ have observed that shoulder JPS improves as the shoulder-elevation angle approaches 90°. These results may indicate that as the elevation angle increases, the amount of gravitational torque increases, which increases muscle activation. Suprak et al⁷ hypothesized that this increase in muscle activation and the increase in activity from the musculotendinous mechanoreceptors contributed to improved JPS. Suprak et al⁸ supported these results, demonstrating that as resistance increased (via wrist weights) at a given shoulder position, shoulder repositioning error decreased. However, other authors⁵ have suggested that this effect of elevation on shoulder JPS may also be related to intrinsic factors of joint position, such as muscle-spindle and cutaneous-receptor activation.Researchers⁹ believe the application of tape may improve proprioceptive abilities by increasing stimulation of cutaneous mechanoreceptors within the skin, which increases pressure on underlying muscles and, therefore, affects the joint''s proprioception. Robbins et al¹⁰ reported that the application of ankle tape enhanced JPS when a person was on a surface with a slope greater than 10°. Traditional athletic tape can constrict joint range of motion (ROM) but can be a beneficial preventive measure; however, the integrity of the tape is not maintained for extended periods because of such extraneous factors as sweat, lotion, dirt, and hair. Therefore, the development of more specialized tapes that have longer-lasting effects and limit impairments has advanced in recent years. Effective tape application can last up to 1 to 2 days, and some of these specialty tapes can resist extraneous factors.Kinesio Tape (KT; Kinesio Precut, Albuquerque, NM) is a specialized elastic tape that mimics the elasticity of skeletal muscle as it stretches up to 140% of its original length, allowing for no ROM restrictions.^2,11 According to KT creator Kenzo Kase, it can strengthen an already weakened muscle by correcting the muscle''s function, improving circulation of blood and lymph, decreasing pain, repositioning subluxed joints, and improving joint position and kinesthetic awareness.¹² These effects allow the fascia and muscle to return to normal function by relieving the buildup of abnormal muscle tension and can improve joint function by increasing sensory mechanisms.^11,13The constant shear force produced by KT application against the skin leads to increased stimulation of the cutaneous mechanoreceptors.¹⁴ Murray¹⁴ observed an increase in electromyographic measurements after the application of KT to the thigh. He hypothesized that this increased mechanoreceptor activity would result in increased JPS acuity. His research also supported the claim that KT application to the thigh can improve active ROM of a joint compared with no tape.¹⁴ Murray¹⁴ asserted that KT can positively affect proprioception. However, other investigators¹¹ have demonstrated no effect of KT application on the ability to actively replicate a passive ankle position. This discrepancy in observations warrants further investigation given the popularity of KT use in athletics and rehabilitation. No one has examined how KT affects shoulder JPS. Therefore, the purpose of our study was to assess the effects of KT application on shoulder JPS at increasing shoulder elevations in athletes. We hypothesized that the application of KT (1) would result in enhanced shoulder JPS at all elevation angles tested and (2) would not alter the effect of increased JPS acuity with elevation.     

The McConnell Sign is Seen in Patients With Acute Chest Syndrome

Bedside ultrasound is often used as a part of the evaluation of patients who are critically ill. The McConnell sign is an important echocardiographic finding in some critically ill patients with pulmonary embolism and an acute right ventricular infarct. We present 3 critically ill patients with confirmed acute chest syndrome who showed the McConnell sign on echocardiography. In patients with sickle cell disease presenting with chest pain and shortness of breath, the presence of the McConnell sign does not narrow the differential diagnosis between pulmonary embolism, an acute right ventricular infarct, and acute chest syndrome.     

Epitope map and processing scheme for the 195,000-dalton surface glycoprotein of Plasmodium falciparum merozoites deduced from cloned overlapping segments of the gene.

DNA fragments from human malaria parasites were cloned into lambda gt11 to produce a genomic DNA expression library. A pool of monoclonal antibodies (mAbs) recognizing three domains of the 195-kDa major merozoite surface glycoprotein (gp195) reacted with seven clones expressing malaria antigens. mAbs recognizing the 83-kDa product of gp195 reacted with the clones, but mAbs recognizing a glycosylated 45-kDa and a nonglycosylated 45-kDa domain did not. Restriction enzyme mapping revealed that the clones contained overlapping segments encoding about 70% of the gene beginning at the 5' end and ending at an EcoRI restriction enzyme site 3.3 kilobase pairs downstream. The mAbs recognizing the 83-kDa domain reacted differently with the clones, allowing the mapping of three epitopes, one of which was repetitive. Affinity-purified antibodies were selected from immune monkey serum with recombinant expression proteins adsorbed to nitrocellulose filters. When used to probe electrophoretic immunoblots of parasite extracts, these antigen-selected antibodies reacted with specific sets of processed products of gp195, including those associated with the 83- and the nonglycosylated 45-kDa domains. This information, combined with the mAb epitope map, allowed a tentative scheme for processing gp195 from the Camp strain to be proposed.     

Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults

PURPOSE: This study reports the prevalence, incidence, and regression of thyroid abnormalities in a population observed from adolescence to adulthood. PATIENTS AND METHODS: Examinations for thyroid abnormalities were performed in 4,819 school-age children, ages 11 to 18, in 1965 to 1968; two thirds of this original cohort (3,121) were re-examined 20 years later (1985 to 1986). Each subject with a thyroid abnormality detected by physical examination was studied by means of a series of re-examinations, and tests of thyroid function, imaging, and biopsy to determine the exact nature of the thyroid abnormality. RESULTS: In the initial examinations (1965 to 1968), 185 thyroid abnormalities were found (3.7%). Diffuse hypertrophy with normal function (adolescent goiter) was the most common abnormality (19.3/1,000); 12.7/1,000 had chronic lymphocytic thyroiditis, and 4.6/1,000 had thyroid nodules, including two papillary carcinomas. Hyperthyroidism or hypothyroidism was found in 1.9/1,000. In the follow-up examinations in 1985 to 1986, 298 subjects had thyroid abnormalities (10.5%), of whom 81 (28.7/1,000) had simple goiters, 145 (51.3/1,000) had chronic thyroiditis, 45 (15.9/1,000) had hypothyroidism, 11 (3.9/1,000) had hyperthyroidism, and 66 (23.2/1,000) had nodules, which included 10 carcinomas. Of the 92 subjects with simple or adolescent goiter in 1965 to 1968, 60% were normal by 1985 to 1986, 20% were unchanged, and a few had developed thyroiditis (10%) or colloid goiters (3.0%). Of 61 subjects with thyroiditis, 27% had become normal, 33% remained unchanged, and 33% had become hypothyroid. Of the 22 subjects with thyroid nodules, two had complete disappearance of the nodules, and three had nodules considered to be variants of normal. The others exhibited a variety of nodular pathologic conditions. CONCLUSIONS: The natural history of thyroid disorders, including simple goiter, chronic thyroiditis, hyperthyroidism, hypothyroidism, and nodular diseases of the thyroid, indicates they are dynamic and changeable in form, function, appearance, and disappearance.     

The gene triplet Rw W Ph controls murine haematopoiesis

Having shown a haematopoietic role for Patch (Ph), especially when doubly heterozygous with the mutant Wct (Loutit & Cattanach, 1983) we have similarly examined the Rw locus, the third member of the triplet. Mature Rw/+mice have a just detectable macrocytic anaemia. When doubly heterozygous with Wct and Wv the mild anaemia of these W mutants is exaggerated but with W19H (not anaemic as single heterozygote) red cell factors are as for Rw/+. Rw/+mice are strikingly more sensitive to the lethal effects of X-irradiation (MLD 6.66 +/- 0.10 Gy) on haematopoiesis than comparable +/+ mice (MLD 8 Gy). Those mice that do recover after X-irradiation do not exhibit the delay in recovery of erythropoiesis that is evident with characteristic W mutants in both single and double dose. Furthermore the double heterozygote Wct+/+Rw has a significantly lower MLD (5.19 +/- 0.17 Gy) for X-radiation than Wct/+ (MLD 6.48 +/- 0.24 Gy). We argue that all three loci W, Ph and Rw, influence haematopoietic stem cells, leading to increased radiosensitivity when deletions or mutant genes are present.     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.