Long-Term Outcomes in Anterior Cruciate Ligament Reconstruction: A Systematic Review of Patellar Tendon Versus Hamstring Autografts.

BACKGROUND: Much controversy still exists surrounding graft choice in anterior cruciate ligament (ACL) reconstruction. Over the past decade, an increase in comparative studies with longer follow-up has enhanced our understanding of current graft options and outcomes. PURPOSE: To describe the long-term comparative outcomes of ACL reconstruction with autograft bone-patellar tendon-bone (BPTB) versus autograft hamstring (HS) ACL reconstruction with regard to clinical and radiographic outcomes. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A search of the PubMed, MEDLINE, Cochrane, and Scopus databases was performed to identify studies in the English language with outcome data comparing ACL reconstruction utilizing autograft BPTB and autograft HS; only studies with a minimum 5-year follow-up were included. Outcome data included failure and complications, manual and instrumented laxity, patient-reported outcomes, and radiographic risk of osteoarthritis. RESULTS: Twelve studies with a total of 953 patients met the inclusion criteria. Of these studies, 8 were level 1 evidence and 2 were level 2. Mean follow-up was 8.96 years (range, 5-15.3 years). No differences in graft failure or manual or instrumented laxity were seen in any studies. Lower clinical outcomes scores and greater motion loss were seen in BPTB patients in 1 and 2 studies, respectively. Two of 4 studies reporting on anterior knee pain, and 3 of 7 that recorded kneeling pain found it more frequently among BPTB patients. One study found significantly increased reoperation rates in HS patients, while another found a similar result in BPTB, and 1 study reported a significant increase in contralateral ACL tears in BPTB patients. Three of 5 studies reporting on radiographic evidence of osteoarthritis noted significantly increased rates in BPTB patients. CONCLUSION: This systematic review comparing long-term outcomes after ACL reconstruction with either autograft BPTB or autograft HS suggests no significant differences in manual/instrumented laxity and graft failures between graft types. An increase in long-term anterior knee pain, kneeling pain, and higher rates of osteoarthritis were noted with BPTB graft use

Cardiomyocyte generation from somatic sources — current status and future directions

Transdifferentiation of one cell type to another has garnered significant research efforts in recent years. As cardiomyocyte loss following myocardial infarction becomes debilitating for cardiac patients, the option of an autologous source of cardiomyocytes not derived from multi/pluripotent stem cell sources is an attractive option. Such direct programming has been clearly realized with the use of transcription factors, microRNAs and more recently small molecule delivery to enhance epigenetic modifications, all albeit with low efficiencies in vitro. In this review, we aim to present a brief overview of the current in vitro and in vivo transdifferentiation strategies in the generation of cardiomyocytes from somatic sources. The interdisciplinary fields of tissue, cell, material and regenerative engineering offer many opportunities to synergistically achieve directly programmed cardiac tissue in vitro and enhance transdifferentiation in vivo. This review aims to present a concise outlook on this topic with these fields in mind

Composition Mixing during Blue Straggler Formation and Evolution

We use smoothed-particle hydrodynamics to examine differences between direct collisions of single stars and binary star mergers in their roles as possible blue straggler star formation mechanisms. We find in all cases that core helium in the progenitor stars is largely retained in the core of the remnant, almost independent of the type of interaction or the central concentration of the progenitor stars. We have also modelled the subsequent evolution of the hydrostatic remnants, including mass loss and energy input from the hydrodynamical interaction. The combination of the hydrodynamical and hydrostatic models enables us to predict that little mixing will occur during the merger of two globular cluster stars of equal mass. In contrast to the results of Proctor Sills, Bailyn, & Demarque (1995), we find that neither completely mixed nor unmixed models can match the absolute colors of observed blue stragglers in NGC 6397 at all luminosity levels. We also find that the color distribution is probably the crucial test for explanations of BSS formation - if stellar collisions or mergers are the correct mechanisms, a large fraction of the lifetime of the straggler must be spent away from the main sequence. This constraint appears to rule out the possibility of completely mixed models. For NGC 6397, unmixed models predict blue straggler lifetimes ranging from about 0.1 to 4 Gyr, while completely mixed models predict a range from about 0.6 to 4 Gyr.Comment: AASTeX, 28 pg., accepted for ApJ, also available at http://ucowww.ucsc.edu/~erics/bspaper.htm

A deeper understanding of intestinal organoid metabolism revealed by combining fluorescence lifetime imaging microscopy (FLIM) and extracellular flux analyses

Stem cells and the niche in which they reside feature a complex microenvironment with tightly regulated homeostasis, cell-cell interactions and dynamic regulation of metabolism. A significant number of organoid models has been described over the last decade, yet few methodologies can enable single cell level resolution analysis of the stem cell niche metabolic demands, in real-time and without perturbing integrity. Here, we studied the redox metabolism of Lgr5-GFP intestinal organoids by two emerging microscopy approaches based on luminescence lifetime measurement - fluorescence-based FLIM for NAD(P)H, and phosphorescence-based PLIM for real-time oxygenation. We found that exposure of stem (Lgr5-GFP) and differentiated (no GFP) cells to high and low glucose concentrations resulted in measurable shifts in oxygenation and redox status. NAD(P)H-FLIM and O-2-PLIM both indicated that at high 'basal' glucose conditions, Lgr5-GFP cells had lower activity of oxidative phosphorylation when compared with cells lacking Lgr5. However, when exposed to low (0.5 mM) glucose, stem cells utilized oxidative metabolism more dynamically than non-stem cells. The high heterogeneity of complex 3D architecture and energy production pathways of Lgr5-GFP organoids were also confirmed by the extracellular flux (XF) analysis. Our data reveals that combined analysis of NAD(P)H-FLIM and organoid oxygenation by PLIM represents promising approach for studying stem cell niche metabolism in a live readout

Kinetic Energy Decay Rates of Supersonic and Super-Alfvenic Turbulence in Star-Forming Clouds

We present numerical studies of compressible, decaying turbulence, with and without magnetic fields, with initial rms Alfven and Mach numbers ranging up to five, and apply the results to the question of the support of star-forming interstellar clouds of molecular gas. We find that, in 1D, magnetized turbulence actually decays faster than unmagnetized turbulence. In all the regimes that we have studied 3D turbulence-super-Alfvenic, supersonic, sub-Alfvenic, and subsonic-the kinetic energy decays as (t-t0)^(-x), with 0.85 < x < 1.2. We compared results from two entirely different algorithms in the unmagnetized case, and have performed extensive resolution studies in all cases, reaching resolutions of 256^3 zones or 350,000 particles. We conclude that the observed long lifetimes and supersonic motions in molecular clouds must be due to external driving, as undriven turbulence decays far too fast to explain the observations.Comment: Submitted to Phys. Rev. Letters, 29 Nov. 1997. 10 pages, 2 figures, also available from http://www.mpia-hd.mpg.de/theory/preprints.html#maclo

Longitudinal telomere dynamics within natural lifespans of a wild bird

Telomeres, the nucleotide sequences that protect the ends of eukaryotic chromosomes, shorten with each cell division and telomere loss may be influenced by environmental factors. Telomere length (TL) decreases with age in several species, but little is known about the sources of genetic and environmental variation in the change in TL (∆TL) in wild animals. In this study, we tracked changes in TL throughout the natural lifespan (from a few months to almost 9 years) of free-living house sparrows (Passer domesticus) in two different island populations. TL was measured in nestlings and subsequently up to four times during their lifetime. TL generally decreased with age (senescence), but we also observed instances of telomere lengthening within individuals. We found some evidence for selective disappearance of individuals with shorter telomeres through life. Early-life TL positively predicted later-life TL, but the within-individual repeatability in TL was low (9.2%). Using genetic pedigrees, we found a moderate heritability of ∆TL (h2 = 0.21), which was higher than the heritabilities of early-life TL (h2 = 0.14) and later-life TL measurements (h2 = 0.15). Cohort effects explained considerable proportions of variation in early-life TL (60%), later-life TL (53%), and ∆TL (37%), which suggests persistent impacts of the early-life environment on lifelong telomere dynamics. Individual changes in TL were independent of early-life TL. Finally, there was weak evidence for population differences in ∆TL that may be linked to ecological differences in habitat types. Combined, our results show that individual telomere biology is highly dynamic and influenced by both genetic and environmental variation in natural conditions

Compensatory Growth Impairs Adult Cognitive Performance

Several studies have demonstrated that poor early nutrition, followed by growth compensation, can have negative consequences later in life. However, it remains unclear whether this is attributable to the nutritional deficit itself or a cost of compensatory growth. This distinction is important to our understanding both of the proximate and ultimate factors that shape growth trajectories and of how best to manage growth in our own and other species following low birth weight. We reared sibling pairs of zebra finches on different quality nutrition for the first 20 d of life only and examined their learning performance in adulthood. Final body size was not affected. However, the speed of learning a simple task in adulthood, which involved associating a screen colour with the presence of a food reward, was negatively related to the amount of growth compensation that had occurred. Learning speed was not related to the early diet itself or the amount of early growth depression. These results show that the level of compensatory growth that occurs following a period of poor nutrition is associated with long-term negative consequences for cognitive function and suggest that a growth-performance trade-off may determine optimal growth trajectories

Characteristics and Impact of Drug Detailing for Gabapentin

BACKGROUND: Sales visits by pharmaceutical representatives (“drug detailing”) are common, but little is known about the content of these visits or about the impact of visit characteristics on prescribing behavior. In this study, we evaluated the content and impact of detail visits for gabapentin by analyzing market research forms completed by physicians after receiving a detail visit for this drug. METHODS AND FINDINGS: Market research forms that describe detail visits for gabapentin became available through litigation that alleged that gabapentin was promoted for “off-label” uses. Forms were available for 97 physicians reporting on 116 detail visits between 1995 and 1999. Three-quarters of recorded visits (91/116) occurred in 1996. Two-thirds of visits (72/107) were 5 minutes or less in duration, 65% (73/113) were rated of high informational value, and 39% (42/107) were accompanied by the delivery or promise of samples. During the period of this study, gabapentin was approved by the US Food and Drug Administration only for the adjunctive treatment of partial seizures, but in 38% of visits (44/115) the “main message” of the visit involved at least one off-label use. After receiving the detail visit, 46% (50/108) of physicians reported the intention to increase their prescribing or recommending of gabapentin in the future. In multivariable analysis, intent to increase future use or recommendation of gabapentin was associated with receiving the detail in a small group (versus one-on-one) setting and with low or absent baseline use of the drug, but not with other factors such as visit duration, discussion of “on-label” versus “off-label” content, and the perceived informational value of the presentation. CONCLUSIONS: Detail visits for gabapentin were of high perceived informational value and often involved messages about unapproved uses. Despite their short duration, detail visits were frequently followed by physician intentions to increase their future recommending or prescribing of the drug

Class A Orphans in GtoPdb v.2023.1

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [161], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [121]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3GPR4GPR6GPR12GPR15GPR17GPR20 GPR22GPR26GPR31GPR34GPR35GPR37GPR39 GPR50GPR63GPR65GPR68GPR75GPR84GPR87 GPR88GPR132GPR149GPR161GPR183LGR4LGR5 LGR6MAS1MRGPRDMRGPRX1MRGPRX2P2RY10TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119)