Increased frequencies of the killer immunoglobulin-like receptor genes KIR2DL2 and KIR2DS2 are associated with neuroblastoma.

Neuroblastoma is the most common extra-cranial solid tumour in children. Natural killer (NK) cells are innate lymphocytes that are known to mediate the direct cytotoxicity of neuroblastoma tumour cells. Natural variation in the highly polymorphic killer immunoglobulin-like receptors (KIR) and their cognate human leukocyte antigen (HLA) class I ligands results in considerable diversity in NK cell function. As the early onset of neuroblastoma suggests the contribution of genetic factors, we investigated if individual KIR genes, combined KIR gene haplotypes or compound KIR-HLA ligand genotypes could influence susceptibility to neuroblastoma. Genotype analysis of the KIR genes as well as their three major HLA class I ligand groups, HLA-C1, HLA-C2 and HLA-Bw4, was carried out in a cohort of 201 neuroblastoma patients compared with 240 healthy control subjects using polymerase chain reaction with sequence-specific primers. We found a significant increase in the frequency of KIR2DL2 (P = 0.019) as well as KIR2DS2 (P = 0.008) in patients with neuroblastoma compared with the healthy control group. While the incidence of the least inhibitory compound KIR-HLA-C genotype, KIR2DL3 in the presence of HLA-C1 was slightly reduced in neuroblastoma patients, this did not reach statistical significance (P = 0.069). In summary, while KIR-HLA compound genotypes have previously been implicated in predicting treatment outcomes in neuroblastoma, here we show that the presence of the individual KIR genes, KIR2DL2 and KIR2DS2, irrespective of HLA-C genotype is associated with the onset of this embryonal malignancy.

Effects of exercise intensity on gut microbiome composition and function in people with type 2 diabetes.

Exercise is positively associated with higher microbial diversity, but there is limited information on exercise intensity's effect on gut microbiome composition and function in clinical populations. This study examines whether different intensities of exercise exert differential effects on gut microbiome composition and function in low active people with type 2 diabetes. This is a sub-study of the Exercise for Type 2 Diabetes Study, a single centre, prospective, randomised controlled trial. Participants (n = 12) completed 8-weeks of combined aerobic and resistance moderate intensity continuous training (C-MICT) or combined aerobic and resistance high-intensity interval training (C-HIIT). Faecal samples were collected before and after intervention to measure gut microbiome composition and metabolic pathways (metagenome shotgun sequencing) and short-chain fatty acids. Post-exercise α-diversity was different between groups as was the relative abundance of specific taxa was (p < .05). Post-exercise relative abundance of Bifidobacterium, A. municiphila, and butyrate-producers Lachnospira eligens, Enterococcus spp., and Clostridium Cluster IV were higher at lower exercise intensity. Other butyrate-producers (from Eryspelothrichales and Oscillospirales), and methane producer Methanobrevibacter smithii were higher at higher exercise intensity. Pyruvate metabolism (ko00620),COG "Cell wall membrane envelope biogenesis" and "Unknown function" pathways were significantly different between groups and higher in C-MICT post-exercise. Differential abundance analysis on KO showed higher expression of Two-component system in C-HIIT. Transcription factors and "unknown metabolism" related pathways decreased in both groups. There were no significant between group changes in faecal short chain fatty acids. Exercise intensity had a distinct effect on gut microbiome abundance and metabolic function, without impacting short-chain fatty acid output.HighlightsEvidence of exercise effect on gut microbiome outcomes is limited to healthy and athletic populationsIn low active people with type 2 diabetes, different exercise intensities increased specific health promoting and butyrate producers species, and showed differentially abundant gut microbiome metabolic pathways.Further investigation is warranted, and if this supports the present findings, then specific exercise intensities may be promoted to target specific species and optimise gut health.

A systematic review and meta-analysis of interval training versus moderate-intensity continuous training on body adiposity.

Interval training (including high-intensity interval training [HIIT] and sprint interval training [SIT]) is promoted in both scientific and lay media as being a superior and time-efficient method for fat loss compared with traditional moderate-intensity continuous training (MICT). We evaluated the efficacy of HIIT/SIT when directly compared with MICT for the modulation of body adiposity. Databases were searched to 31 August 2016 for studies with exercise training interventions with minimum 4-week duration. Meta-analyses were conducted for within-group and between-group comparisons for total body fat percentage (%) and fat mass (kg). To investigate heterogeneity, we conducted sensitivity and meta-regression analyses. Of the 6,074 studies netted, 31 were included. Within-group analyses demonstrated reductions in total body fat (%) (HIIT/SIT: -1.26 [95% CI: -1.80; -0.72] and MICT: -1.48 [95% CI: -1.89; -1.06]) and fat mass (kg) (HIIT/SIT: -1.38 [95% CI: -1.99; -0.77] and MICT: -0.91 [95% CI: -1.45; -0.37]). There were no differences between HIIT/SIT and MICT for any body fat outcome. Analyses comparing MICT with HIIT/SIT protocols of lower time commitment and/or energy expenditure tended to favour MICT for total body fat reduction (p = 0.09). HIIT/SIT appears to provide similar benefits to MICT for body fat reduction, although not necessarily in a more time-efficient manner. However, neither short-term HIIT/SIT nor MICT produced clinically meaningful reductions in body fat.

Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis.

Ectopic adipose tissue surrounding the intra-abdominal organs (visceral fat) and located in the liver, heart, pancreas and muscle, is linked to cardio-metabolic complications commonly experienced in type 2 diabetes. A systematic review and meta-analysis was performed to determine the effect of exercise on ectopic fat in adults with type 2 diabetes. Relevant databases were searched to February 2016. Included were randomised controlled studies, which implemented≥4 weeks of aerobic and/or resistance exercise and quantified ectopic fat via magnetic resonance imaging, computed tomography, proton magnetic resonance spectroscopy or muscle biopsy before and after intervention. Risk of bias and study quality was assessed using Egger's funnel plot test and modified Downs and Black checklist, respectively. Of the 10,750 studies retrieved, 24 were included involving 1383 participants. No studies were found assessing the interaction between exercise and cardiac or pancreas fat. One study assessed the effect of exercise on intramyocellular triglyceride concentration. There was a significant pooled effect size for the meta-analysis comparing exercise vs. control on visceral adiposity (ES=-0.21, 95% CI: -0.37 to -0.05; P=0.010) and a near-significant pooled effect size for liver steatosis reduction with exercise (ES=-0.28, 95% CI: -0.57 to 0.01; P=0.054). Aerobic exercise (ES=-0.23, 95% CI: -0.44 to -0.03; P=0.025) but not resistance training exercise (ES=-0.13, 95% CI: -0.37 to 0.12; P=0.307) was effective for reducing visceral fat in overweight/obese adults with type 2 diabetes. These data suggest that exercise effectively reduces visceral and perhaps liver adipose tissue and that aerobic exercise should be a key feature of exercise programs aimed at reducing visceral fat in obesity-related type 2 diabetes. Further studies are required to assess the relative efficacy of exercise modality on liver fat reduction and the effect of exercise on pancreas, heart, and intramyocellular fat in type 2 diabetes and to clarify the effect of exercise on ectopic fat independent of weight loss.

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing. AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease. METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope. RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use. CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

Predicting step time from step length and velocity.

This study was designed to investigate the relationship between step time and step length in a healthy population of young adults. The sample was composed of 10 females and 10 males with ages ranging from 19 to 25 years. The subjects walked along a resistive grid walkway at an audio-controlled cadence of 80 steps per minute. These trials consisted of two walks with asymmetrical step lengths (2/4 time), two walks with asymmetrical step times (3/4 time) and two in which the only constraint was the cadence. The results indicate that the values of average velocity and average step length can be used to calculate step time with reasonable accuracy in a symmetrical walking pattern, but not under conditions of induced step length or step time asymmetries. It is suggested that stride frequency rather than cadence be used, particularly when measurements are made from patients with asymmetrical walking patterns.

First metatarsophalangeal joint implant as a salvage procedure.

First metatarsophalangeal joint implants are used to correct deformity, to restore or improve motion, and to relieve pain. The authors report on a patient with pain in the first metatarsophalangeal joint that was not relieved by multiple first metatarsophalangeal joint surgical procedures. A two-component first metatarsophalangeal joint titanium implant was successfully used as a salvage procedure to relieve pain and restore foot function following a failed first metatarsophalangeal joint fusion.

An analysis of some variables influencing the effectiveness of reprimands.

Although several studies have shown that social reprimands can function as punishers, no study reported to data has isolated any of the factors influencing reprimand efficacy. Three experiments were conducted to investigate several factors. Experiment 1 used an alternating treatments design and was conducted on two elementary school boys, one of whom was in a special education class. Results showed that verbal reprimands delivered with eye contact and firm grasp of the student's shoulders reduced disruptive behavior to a greater extent than did verbal reprimands delivered without eye contact and grasp. Both types of reprimand were more effective than a baseline condition during which disruptive behavior was ignored. Experiment 2 also used an alternating treatments design and was conducted on one elementary school boy. Results demonstrated that reprimands delivered from one meter away were considerably more effective than reprimands delivered from seven meters away. Experiment 3 used a reversal design and was conducted on two pairs of elementary school children, one a pair of boys and the other a pair of girls. Results demonstrated that reprimands delivered to just one member of the pair reduced the disruptive behavior of both members of the pair. Thus, the effects of reprimands "spilled" over to nonreprimanded students.

Overcorrection: Reviewed, revisited and revised.

Overcorrection is a widely used behavior management procedure, the success of which has been well documented. However, overcorrection is not a simple, single procedure. Rather, it is a complex combination of procedures that often make it a complicated strategy to understand conceptually and to implement correctly. The complex nature of overcorrection combined with the use of multiple labels has created much confusion and debate among both researchers and practitioners. A number of issues relating to overcorrection are examined and evaluated. A proposal is made for revising the present overcorrection terminology. Finally, directions for future research are suggested.

A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat.

It is increasingly recognized that the location of excess adiposity, particularly increased deposition of visceral adipose tissue (VAT), is important when determining the adverse health effects of overweight and obesity. Exercise therapy is an integral component of obesity management, but the most potent exercise prescription for VAT benefit is unclear. We aimed to evaluate the independent and synergistic effects of aerobic exercise (AEx) and progressive resistance training (PRT) and to directly compare the efficacy of AEx and PRT for beneficial VAT modulation. A systematic review and meta-analysis was performed to assess the efficacy of exercise interventions on VAT content/volume in overweight and obese adults. Relevant databases were searched to November 2010. Included studies were randomized controlled designs in which AEx or PRT in isolation or combination were employed for 4 weeks or more in adult humans, where computed tomography (CT) or magnetic resonance imaging (MRI) was used for quantification of VAT pre- and post-intervention. Of the 12196 studies from the initial search, 35 were included. After removal of outliers, there was a significant pooled effect size (ES) for the comparison between AEx therapy and control (-0.33, 95% CI: -0.52 to -0.14; P < 0.01) but not for the comparison between PRT therapy and control (0.09, 95% CI: -0.17 to -0.36; P = 0.49). Of the available nine studies which directly compared AEx with PRT, the pooled ES did not reach statistical significance (ES = 0.23, 95% CI: -0.02 to 0.50; P = 0.07 favouring AEx). The pooled ES did not reach statistical significance for interventions that combined AEx and PRT therapy vs. control (-0.28, 95% CI: -0.69 to 0.14; P = 0.19), for which only seven studies were available. These data suggest that aerobic exercise is central for exercise programmes aimed at reducing VAT, and that aerobic exercise below current recommendations for overweight/obesity management may be sufficient for beneficial VAT modification. Further investigation is needed regarding the efficacy and feasibility of multi-modal training as a means of reducing VAT.

A new instrumentation for heel spur resection.

Numerous procedures are available for resecting an inferior calcaneal exostosis (heel spur) when conservative management of the condition fails. A study was conducted with Sheridan Park Hospital patients by using the Kazanjian nasal forceps for spur removal. This procedure minimizes soft tissue destruction, bone pain, and iatrogenic calcaneal fractures.

Angioleiomyoma.

Angioleiomyoma is a benign tumor that occurs rarely, but it must be considered in the differential diagnosis in patients who have a painful subcutaneous nodule on the lower extremity. The treatment of choice in all cases is surgical excision.

Osteomyelitis of the foot in diabetic patients: evaluation with magnetic resonance imaging.

Magnetic resonance (MR) imaging examination was performed with a 1.5-Tesla superconducting magnet on a diabetic patient's right foot that had extensive deformities due to previous surgery, infection, and neuropathy. The purpose of the examination was to help identify areas of active infection in preparation for surgical debridement. This manuscript reviews current concepts on the use of radionucleotide scanning and computed tomography (CT) as compared to MR imaging when used to assist in the diagnosis of osteomyelitis in the diabetic foot. MR imaging was found to be useful in identifying areas of active bone infection in the presence of underlying osseous pathology when radiographic images and radionucleotide scans were unreliable.

Control of postoperative pain in foot surgery using a combination of anesthetic and steroid for local infiltration.

The authors examine a technique that is performed for control of postoperative pain. Sixty-eight patients were evaluated who had received a combination of Marcaine with no epinephrine, plus Hexadrol, at the surgical site immediately postoperatively. It was found that 65% did not require any form of analgesia within the first 4 hours postsurgically; 44% the first 8 hours, and 28% the first 12 hours. Sixteen percent of the patients required no form of analgesia during their entire hospital stay.

Prophylactic antibiotic usage in podiatric implant surgery of the first metatarsophalangeal joint.

All first metatarsophalangeal joint implants used at Sheridan Park Hospital from 1979 through 1984 were evaluated for postoperative infection and subsequent implant removal. Thirteen (1.3%) of 929 implants used were removed due to infection. Antibiotic prophylaxis was not determined to be necessary to avoid this complication. However, in all cases in which prophylaxis was used, no infection occurred.

The use of naproxen in controlling postoperative pain in podiatric surgery.

The study was conducted with 110 patients admitted to Sheridan Park Hospital to determine the efficacy of the nonsteroidal anti-inflammatory drug, naproxen, in relieving postoperative pain. Aspirin, as well as compounds classified as nonsteroidal, anti-inflammatory drugs (NSAID), such as naproxen, are known to inhibit synthesis of certain prostaglandins that are involved in the inflammation process. This is the cause of a significant percentage of postoperative pain.

Reverse Austin osteotomy for correction of acquired static hallux adductus.

Hallux adductus, a horizontal plane deformity, often has an iatrogenic etiology especially as a complication of hallux abducto valgus surgery. A case at Sheridan Park Hospital is described in which the patient developed a steadily worsening static hallux adductus following foot surgery. She underwent further corrective procedures for the hallux adductus 11/2 years later. The authors conclude that if a mild static hallux adductus is observed in conjunction with bunionectomy or other surgery, it should be corrected at that time rather than some years later.

Topical hemostatic agents to reduce bleeding from cancellous bone surfaces: a comparison of Gelfoam paste and bone wax.

This article reviews the history of topical bone hemostatic agents, listing advantages and disadvantages of the more commonly used agents. Gelfoam paste and bone wax were chosen to study the effects that bone hemostatic agents have on the occurrence and severity of postoperative edema and pain. The authors discovered 80% of the patients utilizing bone wax, and 91% of the patients receiving Gelfoam paste, had markedly decreased amounts of immediate postoperative edema. Furthermore, 90% of the patients treated with bone wax, and 75% of the patients treated with Gelfoam paste, reported less postoperative pain than anticipated with the surgical procedure performed.

Tibial sesamoid planing procedure: an appraisal of 26 feet.

The authors present their findings upon evaluation of 26 feet that had undergone a tibial sesamoid planing procedure. A preoperative method of radiographic evaluation is also presented. The subjective success rate was determined to be 88.8%, whereas the objective success rate was 76.9%, and a successful procedure was performed on feet with a first metatarsal declination angle not exceeding 8 degrees. It was also determined that the apparent postoperative changes in the hallux abductus and intermetatarsal angles were 0.73 degrees and 0.6 degrees, respectively. The authors believe this procedure does not significantly alter the biomechanics of the first metatarsophalangeal joint postoperatively.

Bacteriology of diabetic foot ulcers.

Diabetic foot ulcerations exhibit a wide range of the bacterial spectrum. A long-standing question is whether any particular bacterium or class of bacteria is responsible for the more involved ulcers. A review of such cases at Sheridan Park Hospital reveals that there may be factors other than bacterial type that may account for the virulence of diabetic ulcers. Multifactorial causes host a vital role in this common, but potentially serious, podiatric problem.