Prelimbic cortex responds to male ultrasonic vocalizations in the presence of a male pheromone in female mice.

Sensory signals are critical to perform adaptive social behavior. During copulation, male mice emit ultrasonic vocalizations (USVs). Our previous studies have shown that female mice exhibit approach behavior toward sound sources of male USVs and that, after being exposed to a male pheromone, exocrine gland-secreting peptide 1 (ESP1), female mice exhibited a preference toward a particular type of male USVs. These findings suggest that male USVs modulate female courtship behavior. However, it remains unclear which brain regions and what cell types of neurons are involved in neuronal processing of male USVs. To clarify this issue, immediate early gene analysis, behavioral analysis, and neurochemical analysis were performed. The in situ hybridization analysis of c-fos mRNA in multiple brain regions showed that neurons in the prelimbic cortex were responsive to presentation of male USVs in the presence of ESP1. Furthermore, this study found that activity of prelimbic cortex was correlated with the duration of female exploration behavior toward a sound source of the USVs. Finally, by using double immunohistochemistry, the present study showed that the prelimbic neurons responding to the presentation of male USVs were presumably excitatory glutamatergic neurons. These results suggest that the prelimbic cortex may facilitate female courtship behavior in response to male USVs.

Tibiofemoral Relationship 3 Weeks After Anatomic Triple-Bundle Anterior Cruciate Ligament Reconstruction With 10 N of Initial Tension Is Closer to Normal Knee Versus That With 20 N of Initial Tension.

PURPOSE: This study aimed to clarify the effect of initial graft tension on the ensuing tibiofemoral relationship and on 2-year clinical outcomes after anatomic triple-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 31 patients with primary unilateral ACL rupture (mean age, 25.1 years) were enrolled. Anatomic triple-bundle ACL reconstruction was performed using semitendinosus tendon autografts, and patients were grouped according to the total initial tension at graft fixation: 20 N for 16 patients between January 2012 and December 2012 and 10 N for 15 patients between January 2013 and December 2013. Three-dimensional computed tomography scans were performed preoperatively and at 3 weeks and 6 months postoperatively. The side-to-side difference of the 3-dimensional tibial position relative to the femur was compared at each time point. The side-to-side difference in anterior laxity was sequentially compared preoperatively, immediately after surgery, and at 6 months and 2 years postoperatively. Clinical outcomes at 2 years were likewise compared. RESULTS: One patient in each group was excluded because of secondary ACL injury. At 3 weeks postoperatively, 2.5 ± 1.3 and 1.0 ± 1.3 mm of posterior tibial displacement and 3.8° ± 2.4° and 2.0° ± 1.7° of external rotation were observed in the 20- and 10-N initial tension groups, respectively, with significant differences (P = .006 and .033). At 6 months postoperatively, anterior displacement was 0.1/0.1 mm and external rotation was 0.8°/0.4° in both groups, without any significant differences. The 2-year clinical outcomes were satisfactory, including mean side-to-side difference in anterior knee laxity of 0.5 mm in both groups. CONCLUSION: The tibiofemoral relationship 3 weeks after anatomic triple-bundle ACL reconstruction with 10 N of initial tension is less constrained than that with 20 N. Six-month tibiofemoral relationship and 2-year clinical outcomes are satisfactory in both groups. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Anatomical rectangular tunnel anterior cruciate ligament reconstruction provides excellent clinical outcomes.

PURPOSE: The purpose of this study was to prospectively evaluate the clinical outcomes following anatomical rectangular tunnel anterior cruciate ligament (ACL) reconstruction with a bone-patellar tendon-bone (BTB) graft using an adjustable-length femoral cortical fixation device with enough patients and a high follow-up rate. METHODS: This study included 125 patients who underwent anatomical rectangular tunnel ACL reconstruction with a BTB graft. A BTB TightRope® was used for femoral graft fixation. Clinical evaluations were performed more than 2 years after surgery using the International Knee Documentation Committee (IKDC) Form. Patients interviewed by telephone were only subjectively evaluated. The side-to-side difference in anterior laxity at a manual maximum force was measured using the KT-2000 Arthrometer®. RESULTS: Among the 125 patients, 99 were ultimately included and 26 were lost to follow-up (follow-up rate: 79%). Eight patients had re-tear (re-tear rate: 8%) and six patients had ACL injuries to the contralateral knee. Three patients did not follow our rehabilitation programme. One patient suffered septic arthritis. These 18 patients were considered ineligible for clinical evaluations. Therefore, clinical evaluations were performed in 81 of the 99 patients (64 were available for direct follow-up and 17 were available for a telephone interview). The follow-up period was 30 ± 10 months (range 24-68 months). According to the IKDC subjective assessment, 48 (59%) and 33 (41%) knees were graded as normal and nearly normal, respectively. A loss of extension (3°-5°) was observed in five patients (8%), whereas one patient (2%) exhibited a loss of flexion (3°-5°). The Lachman test was negative in 63 patients (98%). The pivot shift test was negative in 59 patients (92%). The side-to-side difference in KT value was 0.4 ± 0.7 mm (range - 1-4 mm). CONCLUSION: Anatomical rectangular tunnel ACL reconstruction with a BTB graft using an adjustable-length femoral cortical fixation device provided excellent clinical outcomes both subjectively and objectively more than 2 years after surgery, whereas 8 of the 99 patients had re-tear of the graft. The adjustable-length femoral cortical fixation device could be safely used in anatomical rectangular tunnel ACL reconstruction with a BTB graft. LEVEL OF EVIDENCE: III.

The lateral meniscal extrusion after repair with concomitant anterior cruciate ligament reconstruction at a mean follow-up of 3.5 years.

BACKGROUND: A meniscal repair is often performed on radial/flap or longitudinal tears of the lateral meniscus (LM) combined with anterior cruciate ligament reconstruction (ACLR). However, it is unknown if meniscal extrusion changes over time after repair. This study evaluated whether meniscal extrusion of the LM is maintained after repair or progresses with time using magnetic resonance imaging (MRI). METHODS: Among 574 patients who underwent primary anatomic ACLR, 123 patients followed up for more than 2 years were retrospectively analyzed. Forty patients with concomitant radial/flap tears of the LM (group R), 43 with longitudinal LM tears (group L), and 40 with intact LM (group C, matched-control group) were included. Clinical findings (pain, range of motion, swelling, and anterior laxity), lateral joint space on radiograph, and meniscal extrusion on MRI were assessed. Lateral/posterior meniscal extrusions were examined preoperatively, within 3 weeks after surgery, and at the final follow-up, and the absolute values and relative values (the preoperative values as baseline) were assessed respectively. RESULTS: There were no significant differences in the clinical and roentgenographic findings among the groups. No difference was observed in the relative values within 3 weeks after surgery among three groups, although the absolute values were larger in the repaired groups than in group C. At the final follow-up, however, the lateral extrusion in group L had progressed significantly, compared with that in group C (P = 0.033), while no significant difference was detected in the lateral extrusion between groups R and C (P = 0.177). The posterior extrusion in groups R and L had progressed significantly compared with that in group C (P < 0.001). CONCLUSIONS: LM extrusion could not be improved even immediately after meniscal repair, and it progressed laterally and posteriorly for more than 2 years after surgery.

Energy-sparing by 2-methyl-2-thiazoline protects heart from ischaemia/reperfusion injury.

AIMS: Cardiac ischaemia/reperfusion (I/R) injury remains a critical issue in the therapeutic management of ischaemic heart failure. Although mild hypothermia has a protective effect on cardiac I/R injury, more rapid and safe methods that can obtain similar results to hypothermia therapy are required. 2-Methyl-2-thiazoline (2MT), an innate fear inducer, causes mild hypothermia resulting in resistance to critical hypoxia in cutaneous or cerebral I/R injury. The aim of this study is to demonstrate the protective effect of systemically administered 2MT on cardiac I/R injury and to elucidate the mechanism underlying this effect. METHODS AND RESULTS: A single subcutaneous injection of 2MT (50 mg/kg) was given prior to reperfusion of the I/R injured 10 week-old male mouse heart and its efficacy was evaluated 24 h after the ligation of the left anterior descending coronary artery. 2MT preserved left ventricular systolic function following I/R injury (ejection fraction, %: control 37.9 ± 6.7, 2MT 54.1 ± 6.4, P < 0.01). 2MT also decreased infarct size (infarct size/ischaemic area at risk, %: control 48.3 ± 12.1, 2MT 25.6 ± 4.2, P < 0.05) and serum cardiac troponin levels (ng/mL: control 8.9 ± 1.1, 2MT 1.9 ± 0.1, P < 0.01) after I/R. Moreover, 2MT reduced the oxidative stress-exposed area within the heart (%: control 25.3 ± 4.7, 2MT 10.8 ± 1.4, P < 0.01). These results were supported by microarray analysis of the mouse hearts. 2MT induced a transient, mild decrease in core body temperature (°C: -2.4 ± 1.4), which gradually recovered over several hours. Metabolome analysis of the mouse hearts suggested that 2MT minimized energy metabolism towards suppressing oxidative stress. Furthermore, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography imaging revealed that 2MT reduced the activity of brown adipose tissue (standardized uptake value: control 24.3 ± 6.4, 2MT 18.4 ± 5.8, P < 0.05). 2MT also inhibited mitochondrial respiration and glycolysis in rat cardiomyoblasts. CONCLUSIONS: We identified the cardioprotective effect of systemically administered 2MT on cardiac I/R injury by sparing energy metabolism with reversible hypothermia. Our results highlight the potential of drug-induced hypothermia therapy as an adjunct to coronary intervention in severe ischaemic heart disease.

Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation.

Thiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed in Trpa1 knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.

Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors.

Innate fear intimately connects to the life preservation in crises, although this relationships is not fully understood. Here, we report that presentation of a supernormal innate fear inducer 2-methyl-2-thiazoline (2MT), but not learned fear stimuli, induced robust systemic hypothermia/hypometabolism and suppressed aerobic metabolism via phosphorylation of pyruvate dehydrogenase, thereby enabling long-term survival in a lethal hypoxic environment. These responses exerted potent therapeutic effects in cutaneous and cerebral ischemia/reperfusion injury models. In contrast to hibernation, 2MT stimulation accelerated glucose uptake in the brain and suppressed oxygen saturation in the blood. Whole-brain mapping and chemogenetic activation revealed that the sensory representation of 2MT orchestrates physiological responses via brain stem Sp5/NST to midbrain PBN pathway. 2MT, as a supernormal stimulus of innate fear, induced exaggerated, latent life-protective effects in mice. If this system is preserved in humans, it may be utilized to give rise to a new field: "sensory medicine."

Outcomes More Than 2 Years After Meniscal Repair for Longitudinal Tears of the Lateral Meniscus Combined With Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Meniscal function after repair of longitudinal tears of the lateral meniscus (LM) with anterior cruciate ligament reconstruction (ACLR) has not been comprehensively investigated. PURPOSE: To evaluate not only the clinical outcomes and radiographic findings of patients who underwent repair of longitudinal tears of the LM combined with ACLR but also the healing status of the repaired meniscus and changes in chondral status with second-look arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Among 548 patients who underwent primary anatomic ACLR at our institution between 2010 and 2017, 39 who had concomitant longitudinal tears of the LM and underwent repair were studied. During follow-up for more than 2 years, all patients were evaluated clinically (pain, range of motion, swelling, and knee instability) and with imaging (plain radiograph and magnetic resonance imaging [MRI]), and compared with a matched control group (based on age, sex, body mass index, and follow-up period) without any concomitant injuries who underwent ACLR. Measurements on MRI were recorded preoperatively, immediately after surgery, and at final follow-up, and the change in the values over time was assessed. Of the 39 patients in each group, 24 were assessed by second-look arthroscopy with hardware removal 2 years postoperatively. RESULTS: The mean follow-up times of the study and control group were at a mean of 42.4 and 45.4 months, respectively. There were no significant differences in clinical findings, lateral joint space narrowing on radiographs, and chondral status at the lateral compartment between groups, whereas lateral and posterior meniscal extrusion on MRI progressed significantly in the study group (0.43 ± 1.0 mm vs -0.29 ± 1.1 mm, P = .003; 1.9 ± 1.9 mm vs 0.14 ± 1.1 mm, P < .0001, respectively). Second-look arthroscopy revealed complete healing in 12 patients (50%), partial healing in 9 (37.5%), and failure in 3 (12.5%) in the study group, and no new tear in the control group. CONCLUSION: The clinical and imaging outcomes after repair of longitudinal tears of the LM combined with anatomic ACLR were successful and comparable with those after isolated ACLR without any other injuries at 42 months postoperatively, although meniscal extrusion showed progression on coronal/sagittal MRI. Based on the MRI findings and the result that only half of patients achieved complete healing, meniscal function could not be fully restored even after repair. Although degenerative changes were not apparent, longer-term follow-up is needed.

Chronological changes in cross-sectional area of the bone-patellar tendon-bone autograft after anatomic rectangular tunnel ACL reconstruction.

PURPOSE: The purpose of this study was to evaluate the change in cross-sectional area (CSA) of bone-patellar tendon-bone (BTB) autografts up to 5 years after the anatomic rectangular tunnel (ART) anterior cruciate ligament reconstruction (ACLR). The changing pattern in CSA might be a potential indicator of the graft remodeling process. METHODS: Ninety-six (62 males, 34 females, mean age 27.0 years) patients were enrolled in this study with a total of 220 MRI scans after ART BTB ACLR to evaluate the CSA of the ACL autografts. The patients with first time unilateral ACLR that consented to undergo MRI evaluations at postoperative periods were included in this study. Intraoperatively, the CSA of the graft was measured directly using a custom-made area micrometer at the midpoint of the graft. Postoperatively, using an oblique axial slice MRI that was perpendicular to the long axis of the graft, the CSA of the graft was measured with digital radiology viewing program "SYNAPSE" at the midpoint of the graft. The postoperative MRI scans were classified into seven groups according to the period from ACLR to MRI evaluation: Group 0-2 months (m.), Group 3-6 m., Group 7-12 m., Group 1-2 years (y.), Group 2-3 y., Group 3-4 y., and Group 4 y.-. The percent increase of the CSA was calculated by dividing the postoperative CSA by the intraoperative CSA. RESULTS: The postoperative CSA was significantly larger than the intraoperative CSA in each group, with the exception of Group 0-2 m. The mean percent increase of the CSA in Group 0-2 m., 3-6 m., 7-12 m., 1-2 y., 2-3 y., 3-4 y., 4 y.- was 101.8 ± 18.2, 188.9 ± 27.4, 190.9 ± 43.7, 183.3 ± 28.9, 175.2 ± 27.9, 163.9 ± 19.8, 164.5 ± 25.4% respectively. The percent increase in Group 3-6 m., 7-12 m., 1-2 y., 2-3 y., 3-4 y., and 4 y.- was significantly greater than that in Group 0-2 m. CONCLUSIONS: The CSA of the BTB autografts after the ART BTB ACLR increases rapidly by 3-6 months after ACLR, reached a maximum value of 190% at around 1 year, decreases gradually after that, and reaches a plateau at around 3 years. The current study might help clinicians to estimate an individual BTB autograft's remodeling stages when considering returning patients to sports. LEVEL OF EVIDENCE: IV.

Sequential analysis of three-dimensional tibiofemoral relationship through anatomic anterior cruciate ligament reconstruction with gravity-assisted radiographic technique in prone position.

BACKGROUND/OBJECTIVES: It is important to restore the tibiofemoral relationship as well as the anterior knee laxity for more successful anterior cruciate ligament (ACL) reconstruction, since a residual abnormality in the tibiofemoral relationship would lead an abnormal stress on the articular cartilages/menisci and consequently increase the risk of osteoarthritis in the future. This study aimed to sequentially clarify the three-dimensional tibiofemoral relationship before and after anatomic anterior cruciate ligament (ACL) reconstruction under an anterior tibial load with a gravity-assisted radiographic technique in the prone position. METHODS: Fifteen patients with unilateral ACL injury participated in the study. Anatomic triple-bundle ACL reconstruction was performed using semitendinosus tendon autografts. During the computed tomography scans that were performed preoperatively, and those performed at 3 weeks and at 6 months postoperatively, the patients lay in the prone position with the knee flexed at 15°, wherein the calf weight could exert an anterior drawer force on the tibia due to gravity. Three-dimensional the tibial position relative to the femur were evaluated for each time point, followed by calculation of side-to-side differences in the parameters between the ACL-deficient/ACL-reconstructed knees and the contralateral intact knees. Seven healthy volunteers were enrolled in the control group and the side-to-side differences (right minus left) in these parameters were calculated. RESULTS: The tibia in the ACL-deficient knee was located anteriorly by 3.5 ±â€¯1.1 mm and rotated internally by 2.4° ± 2.3°; these values were significantly larger than the corresponding values of -0.2 ±â€¯1.5 mm and 0.1° ± 2.2° in the control group. However, at 3 weeks postoperatively, the tibia in the ACL-reconstructed knee was over-constrained as compared to that in the control group; it was located posteriorly by 2.5 ±â€¯1.4 mm and rotated externally by 3.4° ± 3.4°. At 6 months postoperatively, no significant difference was observed in the tibial displacements/rotations between the patient and control groups. The side-to-side difference in the anterior knee laxity at the manual maximum anterior load was 0.1 ±â€¯1.2 mm at 6 months postoperatively, with a significant improvement over the preoperative value of 7.4 ±â€¯2.5 mm. CONCLUSIONS: Anatomic ACL reconstruction could restore not only the normal anterior knee laxity, but also the normal tibiofemoral relationship even under an anterior tibial load.

Outcomes More Than 2 Years After Meniscal Repair for Radial/Flap Tears of the Posterior Lateral Meniscus Combined With Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Meniscal function after repair of radial/flap tears of the posterior horn of the lateral meniscus (LM) with anterior cruciate ligament reconstruction (ACLR) has not been comprehensively investigated. PURPOSE: To evaluate not only the clinical and radiographic outcomes of patients with repair of radial/flap tears of the posterior LM with ACLR but also the healing status of the repaired meniscus and changes of chondral status with second-look arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From January 2008 to April 2016, 41 patients of a consecutive series of 505 primary anatomic ACLR cases had a concomitant radial/flap tear of the posterior horn of the LM and underwent side-to-side repair with an inside-out or all-inside technique. All patients were followed for >2 years, evaluated clinically and radiologically (radiograph and magnetic resonance imaging [MRI]), and compared with a control group without any concomitant injuries that underwent ACLR. Of the 41 patients, 30 were assessed by second-look arthroscopy 2 years postoperatively. RESULTS: The mean follow-up times of the study and control groups were 3.4 and 3.9 years, respectively. The study group showed no significant differences in clinical findings, lateral joint space narrowing on radiograph, and coronal extrusion on MRI as compared with the control group, whereas sagittal extrusion on MRI progressed significantly in the study group (1.2 ± 1.5 mm vs 0.32 ± 1.0 mm, P < .001). Eighteen patients (60%) obtained complete healing; 9 (30%) showed partial healing; and 3 (10%) failed to heal on second-look arthroscopy. Changes of chondral status in the femoral condyle showed no significant difference between the groups (P = .29). However, chondral status of the lateral tibial plateau worsened significantly in the study group (P = .0011). CONCLUSION: The clinical and radiographic outcomes after repair of radial/flap tears of the posterior horn of the LM as combined with anatomic ACLR were successful and comparable with those after isolated ACLR without any other injuries at a mean postoperative follow-up of 3.4 years, except for sagittal extrusion on MRI. Chondral lesions of the lateral tibial plateau deteriorated regardless of meniscal healing at 2 years postoperatively. Surgeons should keep in mind that chondral injuries might progress over the midterm.

Discoid lateral meniscal repair without saucerization for adolescents with peripheral longitudinal tear.

Recently, successful clinical outcomes for symptomatic discoid lateral meniscus (DLM) have been reported following partial meniscectomy (saucerization) with repair. In contrast, some studies using radiography and magnetic resonance imaging (MRI) have suggested that function of load transmission might not be appropriately maintained after saucerization with repair. Therefore, in pursuit to uphold load transmission after surgery for DLM, this study tried to preserve the DLM shape to keep the original DLM function. Discoid lateral meniscus repair without saucerization was indicated, with strict criteria, for those who had a painful peripheral longitudinal tear with purely intact body caused after a single traumatic incidence. The repair was performed without saucerization for four adolescents (two males, two females; mean age 16.2 years; three complete types of DLM, and one incomplete type of DLM). Postoperatively, the following were evaluated with radiography and MRI at six, 12, and 24 months after surgery: clinical outcomes, degenerative changes, and morphology of repaired DLM. They all showed good clinical outcomes. Furthermore, no degeneration, deformation, nor extrusion was observed at the two-year follow-up after surgery. For limited cases of DLM, as mentioned above, DLM repair without saucerization can be one treatment option.

Arthroscopic minimum saucerization and inferior-leaf meniscectomy for a horizontal tear of a complete discoid lateral meniscus: Report of two cases.

INTRODUCTION: Treatment of a horizontal tear of a complete discoid lateral meniscus (DLM) is still controversial. Preserving peripheral rim as a normal shape of the meniscus with single-leaf resection is a conventional treatment, however meniscal function could not be fully restored. PRESENTATION OF CASE: A 28-year old woman and a 34-year old woman experienced knee pain and had restricted knee extension. MRI showed horizontal tears of complete DLM in both patients. Arthroscopic minimum saucerization preserving more than 10 mm peripheral rim and inferior-leaf meniscectomy was performed. Two years after the surgery, the patient had no pain and no restriction of ROM. MRI showed the remaining superior-leaf maintained about half its width and no progression of coronal/sagittal extrusion. DISCUSSION AND CONCLUSION: As resecting more meniscal tissue has been considered to be a cause of degeneration or extrusion of the meniscus, arthroscopic minimum saucerization, preserving more meniscal tissue than standard saucerization, and inferior-leaf meniscectomy can be an alternative treatment option of horizontal tears of complete DLM with satisfying clinical and radiological results.

Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors.

Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice. We find that loss of Trpa1, a pungency/irritancy receptor, diminishes TMT/2MT and snake skin-evoked innate fear/defensive responses. Accordingly, Trpa1 -/- mice fail to effectively activate known fear/stress brain centers upon 2MT exposure, despite their apparent ability to smell and learn to fear 2MT. Moreover, Trpa1 acts as a chemosensor for 2MT/TMT and Trpa1-expressing trigeminal ganglion neurons contribute critically to 2MT-evoked freezing. Our results indicate that Trpa1-mediated nociception plays a crucial role in predator odor-evoked innate fear/defensive behaviors. The work establishes the first forward genetics screen to uncover the molecular mechanism of innate fear, a basic emotion and evolutionarily conserved survival mechanism.

tRNA production links nutrient conditions to the onset of sexual differentiation through the TORC1 pathway.

Target of rapamycin (TOR) kinase controls cell growth and metabolism in response to nutrient availability. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1) promotes vegetative growth and inhibits sexual differentiation in the presence of ample nutrients. Here, we report the isolation and characterization of mutants with similar phenotypes as TORC1 mutants, in that they initiate sexual differentiation even in nutrient-rich conditions. In most mutants identified, TORC1 activity is downregulated and the mutated genes are involved in tRNA expression or modification. Expression of tRNA precursors decreases when cells undergo sexual differentiation. Furthermore, overexpression of tRNA precursors prevents TORC1 downregulation upon nitrogen starvation and represses the initiation of sexual differentiation. Based on these observations, we propose that tRNA precursors operate in the S. pombe TORC1 pathway to switch growth mode from vegetative to reproductive.

Vibration acceleration promotes bone formation in rodent models.

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

Biomechanical testing of transcapsular meniscal repair.

BACKGROUND: All of previous biomechanical studies on meniscal repair have examined the meniscus itself without synovial membrane and capsule, although in the clinical setting, the meniscal repair is generally performed including capsule. Therefore, biomechanical properties of transcapsular meniscal repair are unclear. Thus, this study aimed to clarify the biomechanical properties of transcapsular meniscal repair. METHODS: In 70 porcine femur-medial meniscus-tibia complexes with capsules, longitudinal meniscal tears were repaired using different suture techniques (inside-out or all-inside technique), suture methods (vertical or horizontal methods), and numbers of sutures (single or double). A cyclic loading test between 5 and 20 N for 300 cycles was performed followed by a load-to-failure test. RESULTS: Tears repaired by the all-inside technique presented significantly larger widening (0.88 ± 0.38 mm) than those by the inside-out technique (0.51 ± 0.39 mm) during the cyclic loading test (P = 0.035). The horizontal suture presented significantly lower ultimate failure load (62.5 ± 15.5 N) in the all-inside technique than in the vertical suture (79.7 ± 13.0 N; P = 0.018). The stacked suture had a significantly higher failure load (104.6 ± 12.5 N) than the parallel suture (83.3 ± 12.6 N; P = 0.001). Furthermore, the double suture presented significantly higher failure loads (83.3 ± 12.6 N and 104.6 ± 20.4 N) than the single suture with both inside-out (58.8 ± 8.3 N; P = 0.001) and all-inside (79.7 ± 13.0 N; P = 0.022) techniques. CONCLUSIONS: Upon comparison of the suture techniques, the inside-out technique provided a more stable fixation at the repair site than the all-inside technique during the cyclic test. Among the suture methods, the vertical suture had more desirable biomechanical properties than the horizontal suture as demonstrated by smaller widening during the cyclic test and the larger load to failure. The stacked suture created a stronger fixation than the parallel suture. In terms of the number of sutures, the double suture had superior biomechanical properties compared with the single suture.

Post-operative deformation and extrusion of the discoid lateral meniscus following a partial meniscectomy with repair.

PURPOSE: The purpose of this study was to investigate the morphology of the discoid lateral meniscus sequentially following a partial meniscectomy with repair using magnetic resonance imaging (MRI). METHODS: Nine patients with a symptomatic discoid lateral meniscus with a peripheral tear were enrolled in this study, and a partial meniscectomy with repair was performed arthroscopically. An MRI examination was performed 2 weeks after surgery (before weight bearing was permitted) and again 6 months after surgery (when sporting activities could resume). The width, height and distance of the discoid lateral meniscus were measured. The distance was defined as the distance between the edges of the discoid lateral meniscus and the tibia. RESULTS: The width of the anterior, middle and posterior segments significantly decreased from 2 weeks to 6 months after surgery. The height of the middle and posterior segments significantly increased from 2 weeks to 6 months after surgery, whereas the height of the anterior segment did not significantly change. The distance of the anterior, middle and posterior segments significantly decreased from 2 weeks to 6 months after surgery. CONCLUSION: The discoid lateral meniscus exhibited deformation and extrusion from 2 weeks to 6 months after a partial meniscectomy with repair. Therefore, the function of load transmission might not be maintained appropriately after surgery. LEVEL OF EVIDENCE: IV.

Cross-sectional area of hamstring tendon autograft after anatomic triple-bundle ACL reconstruction.

PURPOSE: The purpose was to evaluate the cross-sectional area changes in hamstring tendon autografts up to 5 years after the anatomic triple-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 178 MRI scans from 139 patients (35 males, 104 females, mean age 30.4 years) with the anatomic triple-bundle ACL reconstructions were obtained to evaluate the cross-sectional area of the ACL grafts. They were classified into seven groups according to the period from reconstruction to MRI evaluation: Group -2 months (m.), Group 3-6 m., Group 7-12 m, Group 1-2 years (y.), Group 2-3 y., Group 3-4 y., and Group 4 y.-. Intra-operatively, the cross-sectional area of the graft was measured directly using a custom-made area micrometre. Post-operatively, the cross-sectional area of the grafts' mid-substance was measured with oblique axial MRI slices perpendicular to the long axis of the grafts using a digital radiology viewing program. The percent increase in the cross-sectional area was calculated by dividing the post-operative cross-sectional area by the intra-operative cross-sectional area. RESULTS: The mean percent increase in the cross-sectional area in Groups -2 m., 3-6 m., 7-12 m., 1-2 y., 2-3 y., 3-4 y., and 4 y.- was 105.7 ± 14.0, 134.9 ± 20.0, 137.3 ± 27.8, 129.4 ± 22.2, 124.1 ± 20.4, 117.8 ± 16.9, and 117.1 ± 17.2 %, respectively. The percent increase in Groups 3-6 m., 7-12 m., and 1-2 y. was significantly greater than in Group -2 m., while that in Group 4 y.- was significantly less than in Group 7-12 m. CONCLUSIONS: The cross-sectional area of the hamstring tendon autografts after the anatomic triple-bundle ACL reconstruction increases over time up to 1 year post-operatively, decreases gradually thereafter, and reaches plateau at around 3 years. LEVEL OF EVIDENCE: Retrospective case series, Level IV.