Depression in neurodegenerative diseases: Common mechanisms and current treatment options.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a major cause of disability worldwide. This neurological condition is commonly associated with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), and has a significant impact on the increasing burden of these neuropathologies. Over the past decades, some of the pathophysiological and molecular mechanisms that contribute to these diseases have been elucidated and these findings indicate that, despite presenting distinct features, there are several similarities between the neurobiological alterations that lead to MDD and neurodegeneration in AD, PD, and HD. For instance, disturbances in monoaminergic transmission and the hypothalamic-pituitary-adrenal (HPA) axis, increased oxidative and neuroinflammatory events, and impaired trophic support are thought to contribute to neuronal atrophy and death in all these diseases. In addition, neuroimaging findings have helped elucidate the structural and functional changes implicated in the relationship between depression and neurodegeneration, thus establishing a neuroanatomical signature to explain, at least in part, the comorbidity between MDD and AD, PD, and HD. The present review summarizes these findings and the current evidence regarding the effectiveness of common antidepressant therapies for the treatment of MDD in patients with these neurodegenerative diseases. This population is particularly vulnerable to the drawdowns of conventional antidepressant therapy (namely inadequate response and high risk of side effects), and the development of emerging therapeutic approaches to treat MDD in patients with AD, PD, and HD is thus of paramount importance to improve the quality of life of these individuals.

Lateral retinacular release rates in mobile- versus fixed-bearing TKA.

UNLABELLED: Controversy exists as to whether bearing mobility facilitates centralization of the extensor mechanism after TKA. To assess the incidence of lateral retinacular release, we retrospectively reviewed 1318 consecutive primary TKAs (1032 patients) performed by one surgeon using either a rotating-platform bearing (940) or a fixed bearing (378) from the same implant system. The selection of a fixed- versus mobile-bearing TKA was primarily based on age with patients younger than 70 years receiving a mobile-bearing TKA. We performed a lateral release whenever continuous symmetric patellar facet contact with the trochlear groove from 0 degrees to 90 degrees of flexion was not obtained using the rule of no thumb after tourniquet release. One hundred four of 1318 knees (7.9%) had a lateral release. We performed more lateral releases in the fixed-bearing group (14.3% [54 of 378]) than in the mobile-bearing group (5.3% [50 of 940]). Patellar tilt occurred more often in the mobile-bearing group (10% [94 of 940]) than in the fixed-bearing group (6.9% [26 of 378]), although the magnitude of mean patellar tilt was small in both groups (mobile-bearing 3.0 degrees ; fixed bearing 2.55 degrees ). No patient had patellar subluxation greater than 5 mm. We suspect the fewer lateral releases in the mobile-bearing group is the result of better extensor mechanism centralization provided by bearing rotation. LEVEL OF EVIDENCE: Level III, prognostic study. See the Guidelines for a complete description of levels of evidence.

Use of a distraction plate for distal radial fractures with metaphyseal and diaphyseal comminution. Surgical technique.

BACKGROUND: Distal radial fractures with extensive comminution involving the metaphyseal-diaphyseal junction present a major treatment dilemma. Of particular difficulty are those fractures involving the articular surface. One approach is to apply a dorsal 3.5-mm plate extra-articularly from the radius to the third metacarpal, stabilizing the diaphysis and maintaining distraction across the radiocarpal joint. METHODS: Twenty-two patients treated with a distraction plate for a comminuted distal radial fracture were included in the study. With use of three limited incisions, a 3.5-mm ASIF plate was applied in distraction dorsally from the radial diaphysis, bypassing the comminuted segment, to the long-finger metacarpal, where it was fixed distally. The articular surface was anatomically reduced and was secured with Kirschner wires or screws. Eleven of the twenty-two fractures were treated with bone-grafting. The plate was removed after fracture consolidation (at an average of 124 days), and wrist motion was initiated. All patients were followed prospectively with use of radiographs, physical examination, and DASH (Disabilities of the Arm, Shoulder and Hand) scores. RESULTS: All fractures united by an average of 110 days. Radiographs showed an average palmar tilt of 4.6 degrees and an average ulnar variance of neutral (0 degrees), whereas loss of radial length averaged 2 mm. Flexion and extension averaged 57 degrees and 65 degrees, respectively, and pronation and supination averaged 77 degrees and 76 degrees, respectively. The average DASH scores were 34 points at six months, 15 points at one year, and 11.5 points at the time of final follow-up (at an average of 24.8 months). According to the Gartland-Werley rating system, fourteen patients had an excellent result, six had a good result, and two had a fair result. Grip strength and the range of motion of the wrist at one year correlated inversely with the proximal extent of fracture comminution into the diaphysis. The duration of plate immobilization did not correlate with the range of motion of the wrist or with the DASH score at one year. CONCLUSIONS: The use of a distraction plate combined with reduction of the articular surface and bone-grafting when needed can be an effective technique for treatment of fractures of the distal end of the radius with extensive metaphyseal and diaphyseal comminution. A functional range of motion with minimal disability can be achieved despite a prolonged period of fixation with a distraction plate across the wrist joint.

Use of a distraction plate for distal radial fractures with metaphyseal and diaphyseal comminution.

BACKGROUND: Distal radial fractures with extensive comminution involving the metaphyseal-diaphyseal junction present a major treatment dilemma. Of particular difficulty are those fractures involving the articular surface. One approach is to apply a dorsal 3.5-mm plate extra-articularly from the radius to the third metacarpal, stabilizing the diaphysis and maintaining distraction across the radiocarpal joint. METHODS: Twenty-two patients treated with a distraction plate for a comminuted distal radial fracture were included in the study. With use of three limited incisions, a 3.5-mm ASIF plate was applied in distraction dorsally from the radial diaphysis, bypassing the comminuted segment, to the long-finger metacarpal, where it was fixed distally. The articular surface was anatomically reduced and was secured with Kirschner wires or screws. Eleven of the twenty-two fractures were treated with bone-grafting. The plate was removed after fracture consolidation (at an average of 124 days), and wrist motion was initiated. All patients were followed prospectively with use of radiographs, physical examination, and DASH (Disabilities of the Arm, Shoulder and Hand) scores. RESULTS: All fractures united by an average of 110 days. Radiographs showed an average palmar tilt of 4.6 degrees and an average ulnar variance of neutral (0 degrees), whereas loss of radial length averaged 2 mm. Flexion and extension averaged 57 degrees and 65 degrees, respectively, and pronation and supination averaged 77 degrees and 76 degrees , respectively. The average DASH scores were 34 points at six months, 15 points at one year, and 11.5 points at the time of final follow-up (at an average of 24.8 months). According to the Gartland-Werley rating system, fourteen patients had an excellent result, six had a good result, and two had a fair result. Grip strength and the range of motion of the wrist at one year correlated inversely with the proximal extent of fracture comminution into the diaphysis. The duration of plate immobilization did not correlate with the range of motion of the wrist or with the DASH score at one year. CONCLUSIONS: The use of a distraction plate combined with reduction of the articular surface and bone-grafting when needed can be an effective technique for treatment of fractures of the distal end of the radius with extensive metaphyseal and diaphyseal comminution. A functional range of motion with minimal disability can be achieved despite a prolonged period of fixation with a distraction plate across the wrist joint.

Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP-stimulated ion transport in human intestinal epithelial cells.

Human colon epithelial cells express the G protein-coupled receptor CCR6, the sole receptor for the chemokine CCL20 (also termed MIP-3alpha). CCL20 produced by intestinal epithelial cells is upregulated in response to proinflammatory stimuli and microbial infection, and it chemoattracts leukocytes, including CCR6-expressing immature myeloid dendritic cells, into sites of inflammation. The aim of this study was to determine whether CCR6 expressed by intestinal epithelial cells acts as a functional receptor for CCL20 and whether stimulation with CCL20 alters intestinal epithelial cell functions. The human colon epithelial cell lines T84, Caco-2, HT-29, and HCA-7 were used to model colonic epithelium. Polarized intestinal epithelial cells constitutively expressed CCR6, predominantly on the apical side. Consistent with this, apical stimulation of polarized intestinal epithelial cells resulted in tyrosine phosphorylation of the p130 Crk-associated substrate (Cas), an adaptor/scaffolding protein that localizes in focal adhesions and has a role in regulating cytoskeletal elements important for cell attachment and migration. In addition, CCL20 stimulation inhibited agonist-stimulated production of the second messenger cAMP and cAMP-mediated chloride secretory responses by intestinal epithelial cells. Inhibition was abrogated by pertussis toxin, consistent with signaling through Galphai proteins that negatively regulate adenylyl cyclases and cAMP production. These data indicate that signaling events, occurring via the activation of the apically expressed chemokine receptor CCR6 on polarized intestinal epithelial cells, alter specialized intestinal epithelial cell functions, including electrogenic ion secretion and possibly epithelial cell adhesion and migration.