Coronal and Sagittal Component Position in Contemporary Total Knee Arthroplasty: Targeting Native Alignment Optimizes Clinical Outcomes.

BACKGROUND: Advanced technologies, like robotics, provide enhanced precision for implanting total knee arthroplasty components; however, optimal component position and limb alignment remain unknown. This study sought to identify sagittal and coronal alignment targets that correlate with minimal clinically important differences (MCIDs) in patient-reported outcome measures (PROMs). METHODS: A total of 1,311 consecutive total knee arthroplasties were retrospectively reviewed. Posterior tibial slope (PTS), femoral flexion (FF), and tibio-femoral alignment (TFA) were measured radiographically. Patients were grouped based on whether they achieved multiple MCIDs for PROM scores. Classification and regression tree machine learning models were utilized to identify optimal alignment zones. The mean follow-up was 2.4 years (range, 1 to 11). RESULTS: The change in PTS and postoperative TFA were most predictive for achieving MCIDs in 90% of the models. Approximating native PTS within 4° correlated with MCID achievement and superior PROMs. Preoperative varus and neutral aligned knees were more likely to meet MCIDs and superior PROM scores when not overcorrected into valgus postoperatively (≥7°). Preoperative valgus-aligned knees correlated with MCID achievement when postoperative TFA was not overcorrected into substantial varus (<0°). Albeit less impactful, FF ≤ 7° correlated with MCID achievement and superior PROMs regardless of preoperative alignment. Sagittal and coronal alignment measurements had moderate to strong interactions in 13 of 20 models. CONCLUSION: Optimized PROM MCIDs correlated with approximating native PTS while maintaining similar preoperative TFA and incorporating moderate FF. Study findings demonstrate interactions between sagittal and coronal alignment which may optimize PROMs, highlighting the importance of three-dimensional implant alignment targets. LEVEL OF EVIDENCE: III.

In vitro analysis of partially hydrolyzed guar gum fermentation on identified gut microbiota.

BACKGROUND: Prebiotic dietary fibers resist digestion in the upper gastrointestinal tract and allow for stimulation of bacteria in the distal intestine and colon. Stimulation of bacteria among different individuals varies greatly, depending on a wide range of variables. OBJECTIVE: To determine the range of differences in response between individuals, a preclinical in vitro fermentation was conducted with six fecal donors. The primary objective was to compare the fecal microbiota of six individuals at baseline, 12 h and 24 h post-exposure to partially hydrolyzed guar gum (PHGG). METHOD: Fecal donations were collected from six healthy individuals consuming a non-specific Western diet, free of antibiotic treatments in the past year, not affected by any GI diseases and not consuming any probiotic or prebiotic supplements. Fecal samples were exposed to 0.5 g of PHGG and measured for bacterial changes at 0, 12 and 24 h based on 16S rRNA sequencing. RESULTS: Parabacteroides increased from 3.48% of sequence reads to 10.62% of sequence reads after 24 h (p = 0.0181) and Bacteroidetes increased from 45.89% of sequence reads to 50.29% of sequence reads (p = 0.0008). CONCLUSIONS: PHGG stimulates growth of Parabacteroides, a genus of bacteria that have been inversely associated with IBS and ulcerative colitis. PHGG provides stimulation of beneficial Bacteroidetes (Bacteroides and Parabacteroides), which may be correlated with many positive health markers and outcomes. PHGG is a prebiotic dietary fiber that is readily fermentable.

Health Effects and Sources of Prebiotic Dietary Fiber.

Prebiotic dietary fibers act as carbon sources for primary and secondary fermentation pathways in the colon, and support digestive health in many ways. Fructooligosaccharides, inulin, and galactooligosaccharides are universally agreed-upon prebiotics. The objective of this paper is to summarize the 8 most prominent health benefits of prebiotic dietary fibers that are due to their fermentability by colonic microbiota, as well as summarize the 8 categories of prebiotic dietary fibers that support these health benefits. Although not all categories exhibit similar effects in human studies, all of these categories promote digestive health due to their fermentability. Scientific and regulatory definitions of prebiotics differ greatly, although health benefits of these compounds are uniformly agreed upon to be due to their fermentability by gut microbiota. Scientific evidence suggests that 8 categories of compounds all exhibit health benefits related to their metabolism by colonic taxa.

Fermentability of Novel Type-4 Resistant Starches in In Vitro System.

Resistant starches are non-digestible starches that are fermented in the colon by microbiota. These carbohydrates are prebiotic and can be beneficial to consumer health. Many types of resistant starch exist with varying physical properties that may result in differences in fermentability. The objective of this research project was to compare potential prebiotic effects and fermentability of four novel resistant starches using an in vitro fermentation system and measuring changes in total gas production, pH, and formation of SCFAs (short chain fatty acids). Fecal donations were collected from seven healthy volunteers. Four novel resistant starches, modified potato starch (MPS), modified tapioca starch (MTS), and modified maize starches (MMS-1 and MMS-2), were analyzed and compared to polydextrose and short chain fructooligosaccharides (FOS) as controls. After twenty-four hours of fermentation, MPS and MTS responded similarly in gas production (74 mL; 70.6 mL respectively), pH (5.93; 5.93 respectively), and SCFA production (Acetate: 115; 124, Propionate: 21; 26, Butyrate: 29; 31 µmol/mL respectively). While MMS-1 had similar gas production and individual SCFA production, the pH was significantly higher (6.06). The fermentation of MMS-2 produced the least amount of gas (22 mL), with a higher pH (6.34), and lower acetate production (78.4 µmol/mL). All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Prebiotic Dietary Fiber and Gut Health: Comparing the in Vitro Fermentations of Beta-Glucan, Inulin and Xylooligosaccharide.

Prebiotic dietary fiber supplements are commonly consumed to help meet fiber recommendations and improve gastrointestinal health by stimulating beneficial bacteria and the production of short-chain fatty acids (SCFAs), molecules beneficial to host health. The objective of this research project was to compare potential prebiotic effects and fermentability of five commonly consumed fibers using an in vitro fermentation system measuring changes in fecal microbiota, total gas production and formation of common SCFAs. Fecal donations were collected from three healthy volunteers. Materials analyzed included: pure beta-glucan, Oatwell (commercially available oat-bran containing 22% oat ß-glucan), xylooligosaccharides (XOS), WholeFiber (dried chicory root containing inulin, pectin, and hemi/celluloses), and pure inulin. Oatwell had the highest production of propionate at 12 h (4.76 µmol/mL) compared to inulin, WholeFiber and XOS samples (p < 0.03). Oatwell's effect was similar to those of the pure beta-glucan samples, both samples promoted the highest mean propionate production at 24 h. XOS resulted in a significant increase in the genus Bifidobacterium after 24 h of fermentation (0 h:0.67 OTUs (operational taxonomic unit); 24 h:5.22 OTUs; p = 0.038). Inulin and WholeFiber increased the beneficial genus Collinsella, consistent with findings in clinical studies. All analyzed compounds were fermentable and promoted the formation of beneficial SCFAs.

Correction: In vitro analysis of partially hydrolyzed guar gum fermentation differences between six individuals.

Correction for 'In vitro analysis of partially hydrolyzed guar gum fermentation differences between six individuals' by Justin Carlson, et al., Food Funct., 2016, DOI: 10.1039/c5fo01232e.

In vitro analysis of partially hydrolyzed guar gum fermentation differences between six individuals.

Partially hydrolyzed guar gum (PHGG) is a fermentable, soluble, non-gelling fiber consumed as both a supplement and ingredient. PHGG supports bifidogenic and lactogenic growth, and increases the concentration of short chain fatty acids (SCFAs) in the distal intestine due to its fermentability. Changes in SCFA development due to the fermentation of dietary fibers in the colon have been widely studied, but there are limited studies analyzing the differences in SCFA development across multiple individuals (ages 23-68) exposed to the same dietary fiber (PHGG). With the six donors analyzed in this study, gas production varied from 59-80 mL/0.5 g fiber at 12 h and 85-93 mL/0.5 g fiber at 24 h between the six donors. At 12 h butyrate concentrations varied from 6.99 µmol mL(-1) to 23.84 µmol mL(-1) and from 8.78 µmol mL(-1) to 22.84 µmol mL(-1) at 24 h. Total SCFA concentration at 24 h ranged from 42.85 µmol mL(-1) to 91.17 µmol mL(-1). The overall average SCFA ratio for the six fecal donors was 30 : 45 : 25 (acetate : propionate : butyrate), which is similar to other fermentable fibers analyzed using in vitro systems. SCFA development in the distal intestine increases the amount of metabolizable energy from the diet, but varies greatly among people based primarily on the composition and changes of their gut microflora. With over a 2-fold difference in SCFA production, significant differences were found among healthy individuals fecal microflora when exposed to PHGG. Donor 6 SCFA concentrations decreased at 24 h, indicating a quicker fermentation process than the other five donors. All SCFAs measured fluctuated greatly among the six individuals within 24 h of analysis. Results of in vitro fermentation analyses are limited by the wide variation found with fecal donor.

Prebiotic Effects and Fermentation Kinetics of Wheat Dextrin and Partially Hydrolyzed Guar Gum in an In Vitro Batch Fermentation System.

Scientific research demonstrates that two indigenous gut bacteria, Lactobacillus and Bifidobacterium can contribute to human health. Although these bacteria can be consumed as probiotics, they can also be produced in the gut by bacteria, and are then called prebiotics. The primary objective of this in vitro study was to quantitatively analyze at the genus level how two dietary fibers, wheat dextrin (WD) and partially hydrolyzed guar gum (PHGG) changed the levels of these two gut bacteria at 12 and 24 h, via real time qualitative polymerase chain reaction (qPCR). Secondary objectives were changes in fecal pH, short chain fatty acids (SCFAs) and total gas volume produced. At 12 h WD was more bifidogenic (9.50 CFU log10/mL) than PHGG (9.30 CFU log10/mL) (p = 0.052), and also at 24 h WD (9.41 CFU log10/mL) compared with PHGG (9.27 CFU log10/mL) (p = 0.043). WD produced less total SCFAs at both 12 and 24 h than PHGG, and produced significantly lower amounts of gas at 12 and 24 h (p < 0.001). Both PHGG and WD also promoted growth of Lactobacilli when measured at 12 and 24 h compared with the 0 h analysis, indicating that both fibers are lactogenic. These results demonstrate the prebiotic effect of WD and PHGG. Based on fermentation kinetics, PHGG is more rapidly fermented than WD, and both fibers show prebiotic effects as early as 12 h.

Delayed embolization of an Amplatz(®) canine duct occluder in a dog.

A 5-year old, 5.8 kg, castrated male Pomeranian was diagnosed with a type IIa patent ductus arteriosus (PDA) with a minimal ductal diameter of 3.5 mm and ampulla width of 7.1 mm based on angiographic assessment. A 6 mm Amplatz(®) Canine Duct Occluder (ACDO) was deployed within the PDA. Once deployed, the device assumed it's native shape and back-and-forth maneuvering was performed with the delivery cable to assess device stability. Device position and complete occlusion were confirmed with both angiography and transesophageal echocardiography prior to and after release of the device. The device location was confirmed within the ductus arteriosus by echocardiography prior to discharge. The dog was discharged with instructions for strict activity restriction. Two days after discharge, the dog was left unsupervised in the backyard and shortly afterwards was found coughing with severe respiratory distress. The dog was evaluated at an emergency hospital and thoracic radiographs documented embolization of the ACDO to the main pulmonary artery along with a severe alveolar pattern throughout the right lung fields. Shortly after obtaining thoracic radiographs, the dog experienced cardiopulmonary arrest with unsuccessful resuscitation. This case describes a possible complication of transcatheter PDA occlusion with an ACDO, which has not been previously reported. An incident report, or catalog of adverse events with these devices, may prove useful in identifying additional fatal complications that others may have encountered, but are not reported in the literature. The report of this complication emphasizes the importance of strict activity restriction after device placement in dogs.

Hybrid technique for ventricular septal defect closure in a dog using an Amplatzer® Duct Occluder II.

A left-to-right shunting muscular ventricular septal defect (VSD) was diagnosed in a 4-month-old, female, 1.8 kg Bichon Frise - poodle mix dog. Echocardiographic evidence of cardiac remodeling, calculated pulmonary blood flow (Qp) to systemic blood flow (Qs) ratio of 2.8, and radiographic evidence of pulmonary edema supported the diagnosis of a hemodynamically important VSD. Using a combination of surgery and interventional catheter-based techniques to approach the VSD through the right ventricle, the VSD was occluded with an Amplatzer(®) Duct Occluder (ADO) II device. The ADO II is a low profile, flexible device originally developed for patent ductus arteriosus closure in humans that has been used to close muscular and perimembranous VSD in children. This report describes the hybrid procedure and imaging that was essential for successful occlusion of the VSD in this dog.

Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails.

Human brahma-related gene 1 (Brg1) is a core protein in human SWI/SNF chromatin-remodeling complex which regulates gene expression. Brg1 contains a bromodomain that has been shown to anchor the entire complex to promoter nucleosomes by interacting with histones that are acetylated at specific lysine residues. The Brg1 bromodomain belongs to an important subclass of the bromodomain family for which no structural information is known. Here we report the solution structure of the Brg1 bromodomain determined by NMR. The Brg1 bromodomain conserves the left-handed, four-helix bundle topology found in other bromodomain structures. However, the alphaZ helix of Brg1 bromodomain is about 4 residues shorter relative to previously published bromodomain structures. Using NMR perturbation studies, we demonstrate the Brg1 bromodomain binds acetyllysine in the context of histone tails, with no comparable affinity for unacetylated peptides. The estimated dissociation constants (KD) for acetylated histone peptides H4-AcK8 and H4-AcK12 are 4.0 and 3.6 mM, respectively. In this study the dominant substrate was H3-AcK14 (KD approximately 1.2 mM). Mutagenesis analysis reveals several residues important for the binding specificity. Using molecular dynamics simulations, we present a model of the Brg1 bromodomain in complex with H3-AcK14 and discuss the potential interactions which provide the selectivity of the Brg1 bromodomain for histone H3-AcK14.

Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.

The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat stimulates transcription of the integrated HIV-1 genome and promotes viral replication in infected cells. Tat transactivation activity is dependent on lysine acetylation and its association with nuclear histone acetyltransferases p300/CBP (CREB binding protein) and p300/CBP-associated factor (PCAF). Here, we show that the bromodomain of PCAF binds specifically to HIV-1 Tat acetylated at lysine 50 and that this interaction competes effectively against HIV-1 TAR RNA binding to the lysine-acetylated Tat. The three-dimensional solution structure of the PCAF bromodomain in complex with a lysine 50-acetylated Tat peptide together with biochemical analyses provides the structural basis for the specificity of this molecular recognition and reveals insights into the differences in ligand selectivity of bromodomains.

Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase.

Transcriptional repression is based on the selective actions of recruited corepressor complexes, including those with enzymatic activities. One well-characterized developmentally important corepressor is the C-terminal binding protein (CtBP). Although intriguingly related in sequence to D2 hydroxyacid dehydrogenases, the mechanism by which CtBP functions remains unclear. We report here biochemical and crystallographic studies which reveal that CtBP is a functional dehydrogenase. In addition, both a cofactor-dependent conformational change, with NAD(+) and NADH being equivalently effective, and the active site residues are linked to the binding of the PXDLS consensus recognition motif on repressors, such as E1A and RIP140. Together, our data suggest that CtBP is an NAD(+)-regulated component of critical complexes for specific repression events in cells.