Neural correlates of disparity-defined shape discrimination in the human brain

Binocular disparity, the slight differences between the images registered by our two eyes, provides an important cue when estimating the three-dimensional (3D) structure of the complex environment we inhabit. Sensitivity to binocular disparity is evident at multiple levels of the visual hierarchy in the primate brain, from early visual cortex to parietal and temporal areas. However, the relationship between activity in these areas and key perceptual functions that exploit disparity information for 3D shape perception remains an important open question. Here we investigate the link between human cortical activity and the perception of disparity-defined shape, measuring fMRI responses concurrently with psychophysical shape judgments. We parametrically degraded the coherence of shapes by shuffling the spatial position of dots whose disparity defined the 3D structure and investigated the effect of this stimulus manipulation on both cortical activity and shape discrimination. We report significant relationships between shape coherence and fMRI response in both dorsal (V3, hMT+/V5) and ventral (LOC) visual areas that correspond to the observers' discrimination performance. In contrast to previous suggestions of a dichotomy of disparity-related processes in the ventral and dorsal streams, these findings are consistent with proposed interactions between these pathways that may mediate a continuum of processes important in perceiving 3D shape from coarse contour segmentation to fine curvature estimation.     

The risks of radiation therapy and lymphedema in shoulder surgery

BackgroundRadiation therapy has proven efficacy for cancer treatment but is not without short- and long-term side effects, including radiation-induced lymphedema. There has been limited evidence on the secondary effects of prior radiation therapy on shoulder surgery. The purpose of this study is to evaluate the short-term outcomes of shoulder arthroplasty and rotator cuff repair (RCR) in patients who have undergone ipsilateral radiation therapy and/or have preoperative upper extremity lymphedema.MethodsDuke Enterprise Data Unified Content Explorer was used to query for patients who underwent RCR at our institution. Patients with radiation therapy for breast or lung cancer prior to ipsilateral RCR or shoulder arthroplasty were included. Patients with less than 2 years of follow-up were excluded. Data variables included primary tumor type, dates of cancer diagnoses, radiation treatment, axillary lymph node dissection (aLND), presence of lymphedema, index shoulder operations, most recent follow-up, and surgical and medical complications within the 90-day postoperative period. Additional oncologic variables included total Gray (Gy) delivered.ResultsTwenty-one patients underwent radiation therapy and subsequent shoulder arthroplasty or RCR (13 RCR, 3 total shoulder arthroplasty, 5 reverse shoulder arthroplasty). There were 20 females and 1 male with an average age of 65.6 years (47-82) and average clinical follow-up of 4.4 years (2.0-7.4). Oncologic diagnoses included lung (4.8%) and breast (95.2%) cancer. Average radiation dose delivered was 53.3 Gy (38.5-64) in the cohort. The average time from last external beam radiation therapy to shoulder surgery was 4.3 years (0.3-18.0). One of 13 (7.7%) 90-day postoperative complications was reported in the RCR cohort: a superficial vein thrombosis. One of 8 (12.5%) 90-day complications was reported in the arthroplasty cohort: a clinically suspected but radiographically absent acromial stress fracture in a reverse shoulder arthroplasty that did not require operative intervention. Overall, there were no revisions, reoperations, or shoulder-related unplanned inpatient 90-day readmissions. Among 10 patients with prior aLND, 3 (30%) (2 RCR, 1 arthroplasty) experienced new or worsening upper extremity lymphedema within the immediate postoperative period.ConclusionA minority of patients having undergone prior radiation therapy and aLND who subsequently underwent ipsilateral shoulder surgery experienced worsening subjective upper extremity lymphedema. Although 10% of these radiation therapy patients experienced minor complications within 90 days of their shoulder surgery, none were severe enough to merit inpatient admission or revision surgery.     

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow‐up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs’ NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.     

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase

Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic-based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10-year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss-of-function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

The effects of a temporarily manipulated dental occlusion on the position of the spine: a comparison during standing and walking

Background context

The relationship between dental occlusion and body posture or even the spine position is often analyzed and confirmed. However, this relationship has not been systematically investigated for standing and walking.

Purpose

To examine whether a symmetric or asymmetric dental occlusion block, using 4 mm thick silicon panels, can significantly change the spine position (cervical, thoracic, or lumbar region) during standing and walking.

Study design

The following study is a cross-sectional study.

Patient sample

This study was carried out with 23 healthy subjects (18 women, 5 men) without discomfort in the temporomandibular system or body movement apparatus.

Outcome measures

Position changes (millimeter) of the spine (cervical, thoracic, lumbar) in frontal, sagittal, and transverse planes of motion.

Methods

The upper spine position was quantified with an ultrasonic distance measurement system (sonoSens Monitor). Every subject placed the 4 mm thick silicon panel systematically between the left/right premolars or the front teeth. Differences between the habitual and manipulated occlusion positions were determined by the Friedman test, followed by pairwise comparisons with applied Bonferroni-Holm correction.

Results

During standing and walking there were significant (p≤.05) differences between the occlusion block conditions and the habitual dental position in all body planes except in the right lumbar region during walking. In addition, differences within the manipulated occlusion position could be detected. Significant differences were also shown between the standing and walking trials in the frontal, sagittal, and transverse planes, particularly with respect to the lumbar region (p≤.001).

Conclusions

Symmetrical and asymmetrical occlusion blocks in the premolar region can be associated with changes in all three spine regions during standing and walking. The results showed highly similar reaction patterns in all spine positions, regardless of the location of the silicon panel. Between standing and walking, the main differences were in the lumbar spine. The results suggest a relationship between the chewing and the movement system. However, it must be stated that this study has no direct clinical impact. The study design cannot determine the causality of the observed associations; also the clinical significance of the small postural changes remains unknown.     

Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.

Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins.     

A Critical Role for Thioredoxin-Interacting Protein in Diabetes-Related Impairment of Angiogenesis

Impaired angiogenesis in ischemic tissue is a hallmark of diabetes. Thioredoxin-interacting protein (TXNIP) is an exquisitely glucose-sensitive gene that is overexpressed in diabetes. As TXNIP modulates the activity of the key angiogenic cytokine vascular endothelial growth factor (VEGF), we hypothesized that hyperglycemia-induced dysregulation of TXNIP may play a role in the pathogenesis of impaired angiogenesis in diabetes. In the current study, we report that high glucose–mediated overexpression of TXNIP induces a widespread impairment in endothelial cell (EC) function and survival by reducing VEGF production and sensitivity to VEGF action, findings that are rescued by silencing TXNIP with small interfering RNA. High glucose–induced EC dysfunction was recapitulated in normal glucose conditions by overexpressing either TXNIP or a TXNIP C247S mutant unable to bind thioredoxin, suggesting that TXNIP effects are largely independent of thioredoxin activity. In streptozotocin-induced diabetic mice, TXNIP knockdown to nondiabetic levels rescued diabetes-related impairment of angiogenesis, arteriogenesis, blood flow, and functional recovery in an ischemic hindlimb. These findings were associated with in vivo restoration of VEGF production to nondiabetic levels. These data implicate a critical role for TXNIP in diabetes-related impairment of ischemia-mediated angiogenesis and identify TXNIP as a potential therapeutic target for the vascular complications of diabetes.