Purpose Compare side-to-side differences for knee kinematics between anatomic single-bundle (SB) and anatomic double-bundle (DB) ACLR during downhill running at 6 and 24 months post ACLR using high-accuracy dynamic stereo X-ray imaging. It was hypothesized that anatomic DB ACLR would better restore tibio-femoral kinematics compared to SB ACLR, based on comparison to the contralateral, uninjured knee. Methods Active individuals between 14 and 50 years of age that presented within 12 months of injury were eligible to participate. Individuals with prior injury or surgery of either knee, greater than a grade 1 concomitant knee ligament injury, or ACL insertion sites less than 14 mm or greater than 18 mm were excluded. Subjects were randomized to undergo SB or DB ACLR with a 10 mm-wide quadriceps tendon autograft harvested with a patellar bone block and were followed for 24 months. Dynamic knee function was assessed during treadmill downhill running using a dynamic stereo X-ray tracking system at 6 and 24 months after surgery. Three-dimensional tibio-femoral kinematics were calculated and compared between limbs (ACLR and uninjured contralateral) at each time point. Results Fifty-seven subjects were randomized (29 DB) and 2-year follow-up was attained from 51 (89.5%). No significant differences were found between SB and DB anatomic ACLR for any of the primary kinematic variables. Conclusions Contrary to the study hypothesis, double-bundle reconstruction did not show superior kinematic outcomes compared to the single-bundle ACLR. While neither procedure fully restored normal knee kinematics, both anatomic reconstructions were similarly effective for restoring near-normal dynamic knee function. The findings of this study indicate both SB and DB techniques can be used for patients with average size ACL insertion sites. Level of evidence Level I

Substance use disorder (SUD) is associated with disruptions in circadian rhythms. The circadian transcription factor neuronal PAS domain protein 2 (NPAS2) is enriched in reward-related brain regions and regulates reward, but its role in SU is unclear. To examine the role of NPAS2 in drug taking, we measured intravenous cocaine self-administration (acquisition, dose-response, progressive ratio, extinction, cue-induced reinstatement) in wild-type (WT) and Npas2 mutant mice at different times of day. In the light (inactive) phase, cocaine self-administration, reinforcement, motivation and extinction responding were increased in all Npas2 mutants. Sex differences emerged during the dark (active) phase with Npas2 mutation increasing self-administration, extinction responding, and reinstatement only in females as well as reinforcement and motivation in males and females. To determine whether circulating hormones are driving these sex differences, we ovariectomized WT and Npas2 mutant females and confirmed that unlike sham controls, ovariectomized mutant mice showed no increase in self-administration. To identify whether striatal brain regions are activated in Npas2 mutant females, we measured cocaine-induced DFosB expression. Relative to WT, DFosB expression was increased in D11 neurons in the nucleus accumbens (NAc) core and dorsolateral (DLS) striatum in Npas2 mutant females after dark phase self-administration. We also identified potential target genes that may underlie the behavioral responses to cocaine in Npas2 mutant females. These results suggest NPAS2 regulates reward and activity in specific striatal regions in a sex and time of day (TOD)-specific manner. Striatal activation could be augmented by circulating sex hormones, leading to an increased effect of Npas2 mutation in females.

The menisci represent indispensable intraarticular components of a well-functioning knee joint. Sports activities, traumatic incidents, or simply degenerative conditions can cause meniscal injuries, which often require surgical intervention. Efforts in biomechanical and clinical research have led to the recommendation of a meniscus-preserving rather than a meniscusresecting treatment approach. Nevertheless, partial or even total meniscal resection is sometimes inevitable. In such circumstances, techniques of meniscal substitution are required. Autologous, allogenic, and artificial meniscal substitutes are available which have evolved in recent years. Basic anatomical and biomechanical knowledge, clinical application, radiological and clinical outcomes as well as future perspectives of meniscal substitutes are presented in this article. A comprehensive knowledge of the different approaches to meniscal substitution is required in order to integrate these evolving techniques in daily clinical practice to prevent the devastating effects of lost meniscal tissue.

The present study was undertaken to prepare proliposomes of Cyclosporine A (CsA) to increase its oral bioavailability. The proliposomes were prepared by spraying a solution of CsA, egg lecithin and cremophor EL in methanol-chloroform mixture onto directly compressible lactose (carrier) in a rotary evaporator. A dry free flowing powder of proliposomes was obtained. The dry proliposomal powder was characterized for surface morphology by scanning electron microscopy (SEM). Then the proliposomes were hydrated with distilled water to produce liposomes, which were characterized for particle size distribution, % drug entrapment, and morphological characteristics by transmission electron microscopy (TEM). The liposomes exhibited good entrapment of about 99%. The entrapment of CsA in liposomes was found to be dependent mainly on the drug:lipid ratio. Bioavailability studies were carried out for three different formulations of CsA i.e., free drug suspension; proliposomes derived liposomes and marketed formulation (Pannimun Bioral, Microemulsion) on male SD rats. The results of bioavailability studies indicated that the difference in the mean drug concentration of the free drug and the liposomes was found to be statistically significant (p < 0.05, p value is 0.032). The absorption constant for liposomal product was much greater (10.26 h(-1)) than for free drug solution (1.2 h(-1)) or the marketed sample of microemulsion (2.51 h(-1)) and the volume of distribution was found to be less for liposomes (7629.88 ml/kg) than that of the free drug solution (10971.92 ml/kg) and marketed microemulsion (9012.07 ml/kg). The results of these studies have shown that a stable proliposomal formulation of CsA for oral administration can be prepared which can be easily hydrated into liposomes from which CsA can exert its clinical effects with a better oral bioavailability.