Head‐locking durability of fixed and variable angle locking screws under repetitive loading

Polyaxial locking screws are increasingly applied in fracture fixation. To investigate the durability of the head‐locking mechanism, the removal torque of variable angle (VA) and fixed angle (FA) stainless steel and titanium locking screws was investigated without and after a cyclic loading test. Stainless steel (St) and titanium (Ti) 2.4 mm orthogonally inserted FA screws and 2.4 mm VA screws inserted in different inclinations (0°–15°) (n = 6 per group) were locked at 0.8 Nm. Removal torque was determined without (W) and after (A) cyclic loading (sinusoidal load, 5 Hz, constant amplitude of 25 N, up to 10′000 cycles, or failure). Significant differences in‐between the groups were detected by Student's t‐test (p < 0.05). Except VA Ti in 0deg and FA, all groups exhibited a drop in removal torque below the insertion torque without and after cyclic testing. The removal torque was (St: FA W:0.81 Nm ± 0.04 A:0.72Nm ± 0.04; VA0deg W:0.73 Nm ± 0.04 A:0.65 Nm ± 0.05; VA15deg W:0.51 Nm ± 0.05 A:0.50 Nm ± 0.08; Ti: FA W:0.82 Nm ± 0.03 A:0.70 Nm ± 0.04; VA0deg W:0.80 Nm ± 0.02 A:0.72 Nm ± 0.05; VA15deg W:0.55 Nm ± 0.03 A:0.54 Nm ± 0.06). In all groups, the removal torque after cyclic testing did not drop below 16% of the removal torque without cyclic testing. No head loosening was observed after cyclic testing. Stainless steel and titanium 2.4 mm fixed and variable angle locking screws provide a stable and lasting head‐locking mechanism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:949–952, 2016.     

Predictors and outcomes of unplanned early rehospitalization in the first year following lung transplantation

Unplanned early rehospitalization (UER), defined as an unscheduled admission within 30 days of a hospital discharge, is associated with graft loss and recipient mortality in some solid organ transplants but has not been investigated in lung transplant. In this retrospective study, we collected socio‐demographic and clinical factors to determine predictors and outcomes of UER in the first year following lung transplantation. There were 193 patients who underwent lung transplantation and survived to discharge during the 7.9‐year study period. There were 116 (60.1%) patients with at least one UER. Infections (32.8%) and post‐surgical complications (11.8%) were the most common reasons for UER. On multivariate analysis, the strongest predictor of having an UER was discharge to a long‐term acute care facility (odds ratio: 3.01, 95% confidence interval [CI] 1.46–6.20; P=.003). Patients with any UER in the first year following transplantation had worse adjusted survival (hazard ratio: 1.89, 95% CI 1.02–3.50; P=.04). It is unclear, however, to what extent UERs reflect preventable outcomes. Further large‐scale, prospective research is needed to identify the extent to which certain types of UER are modifiable and to define patients at high‐risk for preventable UER.     

Photodynamic inactivation of pathogenic species <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> and <Emphasis Type="Italic">Candida albicans</Emphasis> with lutetium (III) acetate phthalocyanines and specific light irradiation

Photodynamic inactivation (PDI) is a light-associated therapeutic approach suitable for treatment of local acute infections. The method is based on specific light-activated compound which by specific irradiation and in the presence of molecular oxygen produced molecular singlet oxygen and other reactive oxygen species, all toxic for pathogenic microbial cells. The study presents photodynamic impact of two recently synthesized water-soluble cationic lutetium (III) acetate phthalocyanines (LuPc-5 and LuPc-6) towards two pathogenic strains, namely, the Gram-negative bacterium Pseudomonas aeruginosa and a fungus Candida albicans. The photodynamic effect was evaluated for the cells in suspensions and organized in 48-h developed biofilms. The relatively high levels of uptakes of LuPc-5 and LuPc-6 were determined for fungal cells compared to bacterial cells. The penetration depths and distribution of both LuPcs into microbial biofilms were investigated by means of confocal fluorescence microscopy. The photoinactivation efficiency was studied for a wide concentration range (0.85–30 μM) of LuPc-5 and LuPc-6 at a light dose of 50 J cm^?2 from red light-emitting diode (LED; 665 nm). The PDI study on microbial biofilms showed incomplete photoinactivation (<3 logs) for the used gentle drug-light protocol.     

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.     

Possibilities and limitations of fibrin glue usage in nephron-sparing surgery: experimental study

INTRODUCTION: The possibilities and limitations of fibrin glue (FG) usage in nephron-sparing surgery were studied. MATERIALS AND METHODS: A prospective experimental study was carried out in 50 pigs: 30 with polar resection, and 20 with mediorenal wedge resection of the kidney. Hemostatic sutures, FG, and FG with a muscle 'cup' in animals with polar resection of the kidney were compared. FG and sutures in animals with the wedge resection of the kidney were studied as well. Bleeding, hot ischemia time, complication rate, and additional scarring were also analyzed. RESULTS: Suture hemostasis is safe but with significant adverse effects in both polar and wedge resection of kidney. FG was not efficient as a sole hemostatic agent for polar resection. It was as efficient as hemostatic suture for wedge resection of the kidney. FG with a muscle 'cup' on a pole of the kidney achieved good results in animals with polar resection of the kidney. Histological analysis confirmed better results with FG because of both the less intense and smaller area of additional scarring. CONCLUSION: FG is a reliable and efficient hemostatic agent for nephron-sparing surgery whenever both sided gluing is possible.     

Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis in the world, is characterized by IgA immune complex-mediated mesangial cell proliferation. The transferrin receptor (TfR) was identified previously as an IgA1 receptor, and it was found that, in biopsies of patients with IgAN, TfR is overexpressed and co-localizes with IgA1 mesangial deposits. Here, it is shown that purified polymeric IgA1 (pIgA1) is a major inducer of TfR expression (three- to four-fold increase) in quiescent human mesangial cells (HMC). IgA-induced but not cytokine-induced HMC proliferation is dependent on TfR engagement as it is inhibited by both TfR1 and TfR2 ectodomains as well as by the anti-TfR mAb A24. It is dependent on the continued presence of IgA1 rather than on soluble factors released during IgA1-mediated activation. In addition, pIgA1-induced IL-6 and TGF-beta production from HMC was specifically inhibited by mAb A24, confirming that pIgA1 triggers a TfR-dependent HMC activation. Finally, upregulation of TfR expression induced by sera from patients with IgAN but not from healthy individuals was dependent on IgA. It is proposed that deposited pIgA1 or IgA1 immune complexes could initiate a process of auto-amplification involving hyperexpression of TfR, allowing increased IgA1 mesangial deposition. Altogether, these data unveil a functional cooperation between pIgA1 and TfR for IgA1 deposition and HMC proliferation and activation, features that are commonly implicated in the chronicity of mesangial injuries observed in IgAN and that could explain the recurrence of IgA1 deposits in the mesangium after renal transplantation.     

Impact of obesity on dialysis and transplant and its management

Obesity is increasing to unprecedented levels, including in the end-stage kidney disease population, where upwards of 60% of kidney transplant patients are overweight or obese. Obesity poses additional challenges to the care of the dialysis patient, including difficulties in creating vascular access and inserting Tenckhoff catheters, higher rates of catheter malfunction and peritonitis, the need for longer and/or more frequent dialysis (or peritoneal dialysis [PD] exchanges) to achieve adequate clearance, increased metabolic complications particularly with PD, and obesity is a barrier to kidney transplantation. In this article, we review special considerations in performing PD, hemodialysis and transplant in the obese patient, as well as the evidence behind medical and surgical management of obesity in dialysis patients.     

Developing High-specificity Anti-hypertensive Alerts by Therapeutic State Analysis of Electronic Prescribing Records

Objective

This paper presents a model for analysis of chronic disease prescribing action over time in terms of transitions in status of therapy as indicated in electronic prescribing records. The quality of alerts derived from these therapeutic state transitions is assessed in the context of antihypertensive prescribing.

Design

A set of alert criteria is developed based on analysis of state-transition in past antihypertensive prescribing of a rural Australian General Practice. Thirty active patients coded as hypertensive with alerts on six months of previously un-reviewed prescribing, and 30 hypertensive patients without alerts, are randomly sampled and independently reviewed by the practice’s two main general practice physicians (GPs), each GP reviewing 20 alert and 20 non-alert cases (providing 10 alert and 10 non-alert cases for agreement assessment).

Measurements

GPs provide blind assessment of quality of hypertension management and retrospective assessment of alert relevance.

Results

Alerts were found on 66 of 611 cases with coded hypertension with 37 alerts on the 30 sampled alert cases. GPs assessed alerting sensitivity as 74% (CI 52% - 89%) and specificity as 61% (CI 45% - 74%) for the sample, which is estimated as 26% sensitivity and 93% specificity for the antihypertensive population. Agreement between the GPs on assessment of alert relevance was fair (kappa = 0.37).

Conclusions

Data-driven development of alerts from electronic prescribing records using analysis of therapeutic state transition shows promise for derivation of high-specificity alerts to improve the quality of chronic disease management activities.     

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen

By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite 1 lacking structural and binding similarity to known FTase inhibitors. Although multiple lines of evidence established the binding interaction, these ligands exhibited minimal inhibitory activity in a cell-free biochemical FTase inhibition assay. Subsequent modification of the biochemical assay by increasing anion concentration demonstrated FTase inhibitory activity in this novel class. We propose 1 binds together with the anion in the active site to inhibit farnesyl transferase. Implications for phenotypic screening deconvolution and HIV reactivation are discussed.     

Collar spine models in the genus <Emphasis Type="Italic">Echinostoma</Emphasis> (Trematoda: Echinostomatidae)

This paper discusses collar spine arrangements in the genus Echinostoma. All arrangements are of uneven numbers of collar spines on the oral collar. The total number of collar spines in these arrangements ranges from a low 31 to a high 51. There are 11 models of collar spine arrangements in the Echinostoma consisting of spine numbers 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, and 51. Representative species with these collar spine arrangements are given in the article. The number of collar spines in a species is identical in both the larval and adult forms. Reports of even numbered spine counts in the genus Echinostoma are erroneous and probably reflect counts on worms with lost, retracted, or supernumerary spines.