Visual cortex activation in kinesthetic guidance of reaching

The purpose of this research was to determine the cortical circuit involved in encoding and controlling kinesthetically guided reaching movements. We used ¹⁵O-butanol positron emission tomography in ten blindfolded able-bodied volunteers in a factorial experiment in which arm (left/right) used to encode target location and to reach back to the remembered location and hemispace of target location (left/right side of midsagittal plane) varied systematically. During encoding of a target the experimenter guided the hand to touch the index fingertip to an external target and then returned the hand to the start location. After a short delay the subject voluntarily moved the same hand back to the remembered target location. SPM99 analysis of the PET data contrasting left versus right hand reaching showed increased (P < 0.05, corrected) neural activity in the sensorimotor cortex, premotor cortex and posterior parietal lobule (PPL) contralateral to the moving hand. Additional neural activation was observed in prefrontal cortex and visual association areas of occipital and parietal lobes contralateral and ipsilateral to the reaching hand. There was no statistically significant effect of target location in left versus right hemispace nor was there an interaction of hand and hemispace effects. Structural equation modeling showed that parietal lobe visual association areas contributed to kinesthetic processing by both hands but occipital lobe visual areas contributed only during dominant hand kinesthetic processing. This visual processing may also involve visualization of kinesthetically guided target location and use of the same network employed to guide reaches to visual targets when reaching to kinesthetic targets. The present work clearly demonstrates a network for kinesthetic processing that includes higher visual processing areas in the PPL for both upper limbs and processing in occipital lobe visual areas for the dominant limb.     

Measurement of reaching kinematics and prehensile dexterity in nonhuman primates

A modified "Klüver" or dexterity board was developed to assess fine control of hand and digit movements by nonhuman primates during the acquisition of small food pellets from wells of different diameter. The primary advantages of the new device over those used previously include standardized positioning of target food pellets and controlled testing of each hand without the need for restraints, thereby allowing the monkey to move freely about the cage. Three-dimensional video analysis of hand motion was used to provide measures of reaching accuracy and grip aperture, as well as temporal measures of reach duration and food-pellet manipulation. We also present a validated performance score based on these measures, which serves as an indicator of successful food-pellet retrieval. Tests in three monkeys show that the performance score is an effective measure with which to study fine motor control associated with learning and handedness. We also show that the device and performance scores are effective for differentiating the effects of localized injury to motor areas of the cerebral cortex.     

Maternal Depressive Symptoms Mediate the Association between Socio-economic Status and Adolescent Weight Outcomes: A Longitudinal Analysis

Introduction The prevalence of pediatric obesity is an issue in the United States, in which approximately one-third of children and adolescents are overweight or obese. Youth living in low socioeconomic (SES) households are at an increased risk for developing obesity; yet, research is needed to understand the mechanisms that might better explain the relationship between SES and obesity risk. Maternal depression presents a potential mechanism by which SES might predict a later risk for obesity in pediatric populations. Methods The present study used a national dataset from the National Institute of Child Health and Human Development—Study of Early Child Care and Youth Development (NICHD-SECCYD) to examine whether maternal depressive symptoms (at an age of 9 years) mediated the association between early SES (the income-to-needs ratio measured at an age of 1 month) and adolescent weight outcomes [Body Mass Index z-scores (zBMI) for age and sex, at an age of 15 years]. Results The results suggested that greater maternal depressive symptoms helped to explain a significant amount of the variance of lower SES predicting poorer weight outcomes in adolescents. Discussion These findings illustrate the role of maternal depressive symptoms in explaining how SES predicts adolescent weight outcomes. Implications are discussed, and future research is needed to identify women from lower SES households who are experiencing depressive symptoms to provide support and initiate points of early intervention to address relevant health outcomes in youths.     

Cortical Bone Porosity in Rabbit Models of Osteoporosis

Cortical bone porosity is intimately linked with remodeling, is of growing clinical interest, and is increasingly accessible by imaging. Thus, the potential of animal models of osteoporosis (OP) to provide a platform for studying how porosity develops and responds to interventions is tremendous. To date, rabbit models of OP have largely focused on trabecular microarchitecture or bone density; some such as ovariectomy (OVX) have uncertain efficacy and cortical porosity has not been extensively reported. Our primary objective was to characterize tibial cortical porosity in rabbit-based models of OP, including OVX, glucocorticoids (GC), and OVX + GC relative to controls (SHAM). We sought to: (i) test the hypothesis that intracortical remodeling is elevated in these models; (ii) contrast cortical remodeling and porosity in these models with that induced by parathyroid hormone (1–34; PTH); and (iii) contrast trabecular morphology in the proximal tibia across all groups. Evidence that an increase in cortical porosity occurred in all groups was observed, although this was the least robust for GC. Histomorphometric measures supported the hypothesis that remodeling rate was elevated in all groups and also revealed evidence of uncoupling of bone resorption and formation in the GC and OVX + GC groups. For trabecular bone, a pattern of loss was observed for OVX, GC, and OVX + GC groups, whereas the opposite was observed for PTH. Change in trabecular number best explained these patterns. Taken together, the findings indicated rabbit models provide a viable and varied platform for the study of OP and associated changes in cortical remodeling and porosity. Intriguingly, the evidence revealed differing effects on the cortical and trabecular envelopes for the PTH model. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.