A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception.

The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus (LHPBN) are nociceptive yet distinct from danger-encoding central amygdala-projecting (CeAPBN) neurons. Activation of LHPBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of LHPBN, but not CeAPBN, sustained motivation to obtain food. The effect of LHPBN neurons on feeding was reversed by suppressing downstream LHVGluT2 neurons. Thus, distinct from a circuit for fear and escape responses, LHPBN neurons channel nociceptive signals to LHVGluT2 neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli.

Regulation of feeding by somatostatin neurons in the tuberal nucleus.

The tuberal nucleus (TN) is a surprisingly understudied brain region. We found that somatostatin (SST) neurons in the TN, which is known to exhibit pathological or cytological changes in human neurodegenerative diseases, play a crucial role in regulating feeding in mice. GABAergic tuberal SST (TNSST) neurons were activated by hunger and by the hunger hormone, ghrelin. Activation of TNSST neurons promoted feeding, whereas inhibition reduced it via projections to the paraventricular nucleus and bed nucleus of the stria terminalis. Ablation of TNSST neurons reduced body weight gain and food intake. These findings reveal a previously unknown mechanism of feeding regulation that operates through orexigenic TNSST neurons, providing a new perspective for understanding appetite changes.

Long-term survival of high tibial osteotomy for medial compartment osteoarthritis of the knee.

BACKGROUND: The management of degenerative arthritis of the knee in the younger, active patient presents a challenge to the orthopaedic surgeon. Surgical treatment options include high tibial osteotomy (HTO), unicompartmental knee arthroplasty, and total knee arthroplasty. PURPOSE: To examine the long-term survival of closing wedge HTO in a large series of patients up to 19 years after surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Four hundred fifty-five consecutive patients underwent lateral closing wedge HTO for medial compartment osteoarthritis between 1990 and 2001. Between 2008 and 2009, patients were contacted via telephone, and assessment included incidence of further surgery, current body mass index (BMI), Oxford Knee Score, and British Orthopaedic Association Patient Satisfaction Scale. Failure was defined as the need for revision HTO or conversion to unicompartmental knee arthroplasty or total knee arthroplasty. Survival analysis was completed using the Kaplan-Meier method. RESULTS: High tibial osteotomy survival was determined in 413 patients (91%). Of the 397 remaining living patients at the time of final review, 394 (99%) were contacted for follow-up via telephone interview. The probability of survival for HTO at 5, 10, and 15 years was 95%, 79%, and 56%, respectively. Multivariate regression analysis showed that age under 50 years (P = .001), BMI less than 25 (P = .006), and ACL deficiency (P = .03) were associated with better odds of survival. Mean Oxford Knee Score was 40 of 48 (range, 17-48). Overall, 85% of patients were enthusiastic or satisfied, and 84% would undergo HTO again at a mean 12 years of follow-up. CONCLUSION: High tibial osteotomy can be effective for periods longer than 15 years; however, results do deteriorate over time. Age less than 50 years, normal BMI, and ACL deficiency were independent factors associated with improved long-term survival of HTO.

Fifteen-year outcome of endoscopic anterior cruciate ligament reconstruction with patellar tendon autograft for "isolated" anterior cruciate ligament tear.

BACKGROUND: Few studies report the long-term results of anterior cruciate ligament rupture and single-incision endoscopic reconstructive surgery. Outcomes are often clouded by concomitant meniscal, chondral, or ligament injuries. PURPOSE: To determine the 15-year outcomes of anterior cruciate ligament ruptures treated with endoscopic anterior cruciate ligament reconstruction using middle-third patellar tendon autograft. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between January 1993 and April 1994, 333 consecutive patients underwent anterior cruciate ligament reconstruction. Patients with associated ligamentous injury requiring surgery, previous meniscectomy, or meniscal injury requiring more than one-third meniscectomy; chondral injury diagnosed at arthroscopy; and an abnormal contralateral knee were excluded. Ninety patients met the inclusion criteria. Outcomes included range of motion, Lachman and pivot-shift tests, instrumented ligament testing, single-legged hop test, Lysholm Knee Score, the International Knee Documentation Committee evaluation, and radiographic assessment. RESULTS: Thirty percent of patients had further anterior cruciate ligament injury. Twenty-four percent of patients (n = 22) sustained contralateral anterior cruciate ligament ruptures, and 8% (n = 7) ruptured the graft (P = .009). Graft rupture was associated with a graft inclination angle <17° (P = .02). Contralateral anterior cruciate ligament rupture was associated with age <18 years at time of primary injury (P = .001). All patients had normal or nearly normal (International Knee Documentation Committee evaluation) Lachman and instrumented testing, and 91% had a negative pivot-shift result. Seventy percent of patients had kneeling pain. Median subjective International Knee Documentation Committee evaluation was 91 of 100. Fifty-one percent of patients had radiographic evidence of osteoarthritis (41% grade B; 10% grade C). CONCLUSION: Good results are maintained at 15 years after surgery with respect to ligamentous stability, subjective outcomes, and range of motion. Kneeling pain remains a significant problem. Concern remains regarding the incidence of further anterior cruciate ligament injury and the increasing number of patients with radiographic and clinical signs of osteoarthritis despite surgical stabilization.

Influence of platelet-derived growth factor on lens epithelial cell proliferation and differentiation.

The expression pattern of platelet-derived growth factor (PDGF) and its receptor suggest a role in lens cell proliferation. PDGF is strongly expressed in the iris and ciliary body, situated opposite the proliferative cells of the lens epithelium which express the PDGF-alpha receptor. In this study, using lens epithelial explant cultures, we report that PDGF can induce a dose and time dependent increase in lens cell DNA synthesis. Culturing lens explants with both PDGF and FGF (a mitogen and differentiation factor for lens cells) resulted in responses greater than those induced by either growth factor alone. PDGF did not induce any changes typical of fibre differentiation; however, in combination with FGF it potentiated the fibre differentiating activity of FGF. Results obtained in this study support previous indications that PDGF has an important role in regulating lens cell proliferation. In addition, PDGF may have a role in potentiating FGF-induced lens fibre differentiation in vivo.