Mineralized Peyronie's plaque has a phenotypic resemblance to bone.

Mineralized Peyronie's plaque (MPP) impairs penile function. The association, colocalization, and dynamic interplay between organic and inorganic constituents can provide insights into biomineralization of Peyronie's plaque. Human MPPs (n = 11) were surgically excised, and the organic and inorganic constituents were spatially mapped using multiple high-resolution imaging techniques. Multiscale image analyses resulted in spatial colocalization of elements within a highly porous material with heterogenous composition, lamellae, and osteocytic lacuna-like features with a morphological resemblance to bone. The lower (520 ±â€¯179 mg/cc) and higher (1024 ±â€¯155 mg/cc) mineral density regions were associated with higher (11%) and lower (7%) porosities in MPP. Energy dispersive X-ray and micro-X-ray fluorescent spectroscopic maps in the higher mineral density regions of MPP revealed higher counts of calcium (Ca) and phosphorus (P), and a Ca/P ratio of 1.48 ±â€¯0.06 similar to bone. More importantly, higher counts of zinc (Zn) were localized at the interface between softer (more organic to inorganic ratio) and harder (less organic to inorganic ratio) tissue regions of MPP and adjacent softer matrix, indicating the involvement of Zn-related proteins and/or pathways in the formation of MPP. In particular, dentin matrix protein-1 (DMP-1) was colocalized in a matrix rich in proteoglycans and collagen that contained osteocytic lacuna-like features. This combined materials science and biochemical with correlative microspectroscopic approach provided insights into the plausible cellular and biochemical pathways that incite mineralization of an existing fibrous Peyronie's plaque. STATEMENT OF SIGNIFICANCE: Aberrant human penile mineralization is known as mineralized Peyronie's plaque (MPP) and often results in a loss of form and function. This study focuses on investigating the spatial association of matrix proteins and elemental composition of MPP by colocalizing calcium, phosphorus, and trace metal zinc with dentin matrix protein 1 (DMP-1), acidic proteoglycans, and fibrillar collagen along with the cellular components using high resolution correlative microspectroscopy techniques. Spatial maps provided insights into cellular and biochemical pathways that incite mineralization of fibrous Peyronie's plaque in humans.

Upper Extremity Rehabilitation Using Fully Immersive Virtual Reality Games With a Head Mount Display: A Feasibility Study.

BACKGROUND: Rehabilitation therapy using a virtual reality (VR) system for stroke patients has gained attention. However, few studies have investigated fully immersive VR using a head-mount display (HMD) for upper extremity rehabilitation in stroke patients. OBJECTIVE: To investigate the feasibility, preliminary efficacy, and usability of a fully immersive VR rehabilitation program using a commercially available HMD for upper-limb rehabilitation in stroke patients. DESIGN: A feasibility study. SETTING: Two rehabilitation centers. PARTICIPANTS: Twelve stroke patients with upper extremity weakness. INTERVENTIONS: Five upper extremity rehabilitation tasks were implemented in a virtual environment, and the participants wore an HMD (HTC Vive) and trained with appropriate tasks. Participants received a total of 10 sessions two to three times a week, consisting of 30 minutes per session. MAIN OUTCOME MEASURES: Both patient participation and adverse effects of VR training were monitored. Primary efficacy was assessed using functional outcomes (Action Research Arm Test, Box and Block Test, and modified Barthel Index), before and after the intervention. Usability was assessed using a self-reported questionnaire. RESULTS: Three patients discontinued VR training, and nine patients completed the entire training sessions and there were no adverse effects due to motion sickness. The patients who received all sessions showed significant functional improvement in all outcome measures after training (P < .05 for all measures). The overall satisfaction was 6.3 ± 0.8 on a 7-point Likert scale in all participants. CONCLUSIONS: A fully immersive VR rehabilitation program using an HMD for rehabilitation of the upper extremities following stroke is feasible and, in this small study, no serious adverse effects were identified. LEVEL OF EVIDENCE: IV.

Controlled multiple neutral planes by low elastic modulus adhesive for flexible organic photovoltaics.

To protect brittle layers in organic photovoltaic devices, the mechanical neutral plane strategy can be adopted through placing the brittle functional materials close to the neutral plane where stress and strain are zero during bending. However, previous research has been significantly limited in the location and number of materials to protect through using a single neutral plane. In this study, multiple neutral planes are generated using low elastic modulus adhesives and are controlled through quantitative analyses in order to protect the multiple brittle materials at various locations. Moreover, the protection of multiple brittle layers at various locations under both concave and convex bending directions is demonstrated. Multilayer structures that have soft adhesives are further analyzed using the finite element method analysis in order to propose guidelines for structural design when employing multiple neutral planes.

Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice.

Molecular and cellular mechanisms for memory consolidation in the cortex are poorly known. To study the relationships between synaptic structure and function in the cortex and consolidation of long-term memory, we have generated transgenic mice in which catalytic activity of PAK, a critical regulator of actin remodeling, is inhibited in the postnatal forebrain. Cortical neurons in these mice displayed fewer dendritic spines and an increased proportion of larger synapses compared to wild-type controls. These alterations in basal synaptic morphology correlated with enhanced mean synaptic strength and impaired bidirectional synaptic modifiability (enhanced LTP and reduced LTD) in the cortex. By contrast, spine morphology and synaptic plasticity were normal in the hippocampus of these mice. Importantly, these mice exhibited specific deficits in the consolidation phase of hippocampus-dependent memory. Thus, our results provide evidence for critical relationships between synaptic morphology and bidirectional modifiability of synaptic strength in the cortex and consolidation of long-term memory.

Translational control by MAPK signaling in long-term synaptic plasticity and memory.

Enduring forms of synaptic plasticity and memory require new protein synthesis, but little is known about the underlying regulatory mechanisms. Here, we investigate the role of MAPK signaling in these processes. Conditional expression of a dominant-negative form of MEK1 in the postnatal murine forebrain inhibited ERK activation and caused selective deficits in hippocampal memory retention and the translation-dependent, transcription-independent phase of hippocampal L-LTP. In hippocampal neurons, ERK inhibition blocked neuronal activity-induced translation as well as phosphorylation of the translation factors eIF4E, 4EBP1, and ribosomal protein S6. Correspondingly, protein synthesis and translation factor phosphorylation induced in control hippocampal slices by L-LTP-generating tetanization were significantly reduced in mutant slices. Translation factor phosphorylation induced in the control hippocampus by memory formation was similarly diminished in the mutant hippocampus. These results suggest a crucial role for translational control by MAPK signaling in long-lasting forms of synaptic plasticity and memory.