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Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self-administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and KO (-/-) rats showed increased cue-induced reinstatement compared with wild-type (WT) rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 -/- rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 -/- and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ -/- mice, there was a significant increase in CPP to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.

Abstract Background Recently, the high-mobility group A1 gene (HMGA1) variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American populations. We sought to investigate the HMGA1-diabetes association and to characterize IVS5-13insC allele frequencies and linkage disequilibrium (LD) in 3,070 Caucasian, Hispanic, and African American patients from the INternational VErapamil SR-Trandolapril STudy (INVEST). Methods INVEST was a randomized, multicenter trial comparing two antihypertensive treatment strategies in an ethnically diverse cohort of hypertensive, coronary artery disease patients. Controls, who were diabetes-free throughout the study, and type 2 diabetes cases, either prevalent or incident, were genotyped for IVS5-13insC using Taqman®, confirmed with Pyrosequencing and Sanger sequencing. For LD analysis, genotyping for eight additional HMGA1 single nucleotide polymorphisms (SNPs) was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the HMGA1 IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry. Results We observed IVS5-13insC minor allele frequencies consistent with previous literature in Caucasians and African Americans (0.03 in cases and 0.04 in controls for both race/ethnic groups), and higher frequencies in Hispanics (0.07 in cases and 0.07 in controls). The IVS5-13insC was not associated with type 2 diabetes overall (odds ratio 0.98 [0.76-1.26], p=0.88) or in any race/ethnic group. Pairwise LD (r2) of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r2=0.47 in Caucasians, r2=0.25 in Hispanics, and r2=0.06 in African Americans). Furthermore, in silico analysis suggested a lack of functional consequences for the IVS5-13insC variant. Conclusions Our results suggest that IVS5-13insC is not a functional variant and not associated with type 2 diabetes in an ethnically diverse, hypertensive, coronary artery disease population. Larger, more adequately powered studies need to be performed to confirm our findings. Trial registration clinicaltrials.gov (NCT00133692)

NMDARs are ionotropic glutamate receptors widely expressed in the CNS, where they mediate phenomena as diverse as neurotransmission, information processing, synaptogenesis, and cellular toxicity. They function as glutamate-gated Ca 2+ -permeable channels, which require glycine as coagonist, and can be modulated by many diffusible ligands and cellular cues, including mechanical stimuli. Previously, we found that, in cultured astrocytes, shear stress initiates NMDAR-mediated Ca 2+ entry in the absence of added agonists, suggesting that more than being mechanosensitive, NMDARs may be mechanically activated. Here, we used controlled expression of rat recombinant receptors and noninvasive on-cell single-channel current recordings to show that mild membrane stretch can substitute for the neurotransmitter glutamate in gating NMDAR currents. Notably, stretch-activated currents maintained the hallmark features of the glutamate-gated currents, including glycine-requirement, large unitary conductance, high Ca 2+ permeability, and voltage-dependent Mg 2+ blockade. Further, we found that the stretch-gated current required the receptor's intracellular domain. Our results are consistent with the hypothesis that mechanical forces can gate endogenous NMDAR currents even in the absence of synaptic glutamate release, which has important implications for understanding mechanotransduction and the physiological and pathologic effects of mechanical forces on cells of the CNS. SIGNIFICANCE STATEMENT We show that, in addition to enhancing currents elicited with low agonist concentrations, membrane stretch can gate NMDARs in the absence of the neurotransmitter glutamate. Stretch-gated currents have the principal hallmarks of the glutamate-gated currents, including requirement for glycine, large Na + conductance, high Ca 2+ permeability, and voltage-dependent Mg 2+ block. Therefore, results suggest that mechanical forces can initiate cellular processes presently attributed to glutamatergic neurotransmission, such as synaptic plasticity and cytotoxicity. Given the ubiquitous presence of mechanical forces in the CNS, this discovery identifies NMDARs as possibly important mechanotransducers during development and across the lifespan, and during pathologic processes, such as those associated with traumatic brain injuries, shaken infant syndrome, and chronic traumatic encephalopathy., (Copyright © 2022 the authors.)

Aims: The goal was to explore the signaling pathways of PGE 2 to investigate therapeutic effects against secondary injuries following TBI., Methods: Young (4.9 ± 1.0 months) and aged (20.4 ± 1.4 months) male wild type (WT) C57BL/6 and PGE 2 EP1, 2, and 3 receptor knockout mice were selected to either receive sham or repetitive concussive head injury. Immunohistochemistry protocols with Iba1 and GFAP were performed to evaluate microgliosis and astrogliosis in the hippocampus, two critical components of neuroinflammation. Passive avoidance test measured memory function associated with the hippocampus., Results: No differences in hippocampal microgliosis were found when aged EP2 -/- and EP3 -/- mice were compared with aged WT mice. However, the aged EP1 -/- mice had 69.2 ± 7.5% less hippocampal microgliosis in the contralateral hemisphere compared with WT aged mice. Compared with aged EP2 -/- and EP3 -/- , EP1 -/- aged mice had 78.9 ± 5.1% and 74.7 ± 6.2% less hippocampal microgliosis in the contralateral hemisphere. Within the EP1 -/- mice, aged mice had 90.7 ± 2.7% and 81.1 ± 5.6% less hippocampal microgliosis compared with EP1 -/- young mice in the contralateral and ipsilateral hemispheres, respectively. No differences were noted in all groups for astrogliosis. There was a significant difference in latency time within EP1 -/- , EP2 -/- , and EP3 -/- on day 1 and day 2 in aged and young mice., Conclusion: These findings demonstrate that the PGE 2 EP receptors may be potential therapeutic targets to treat repetitive concussions and other acute brain injuries., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Parenteral nutrition (PN) is a life-sustaining therapy providing nutrients to individuals with impaired intestinal tract function and enteral access challenges. It is one of the most complex prescriptions written routinely in the hospital and home care settings. This article is to aid the nutrition support clinician in the safe provision of PN, including selecting appropriate patients for PN, vascular access, development of a PN admixture, appropriate therapy monitoring, recognition of preparation options, and awareness of preparation and stability concerns., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Background: Comprehensive neck ultrasound (US) examination has become an essential component of preoperative workup for patients with thyroid cancer. Regional cervical lymph nodes may be involved in cases of Hashimoto's thyroiditis (HT). This study seeks to examine the sonographic pattern of lymph nodes in patients with HT., Methods: This is a retrospective study looking at patients with confirmed diagnoses of HT on final surgical pathology who underwent preoperative comprehensive neck US. We compared preoperative ultrasound for patients with HT to euthyroid patients with goiter. Data collected included number, size and ultrasonographic features of cervical lymph nodes., Results: We included a total of 417 patients: 202 patients with HT in the study group, and 215 patients with goiter and euthyroid status in the control group. Patients with HT had a higher number of total cervical lymph nodes than the control group (2.00±2.35 vs. 0.76±1.36 mm; P<0.0001), most notably in cervical levels III and IV (P<0.05 for both)., Conclusions: HT seems to be associated with an ultrasonographic pattern of increased number of enlarged cervical lymph nodes, particularly in levels III, and IV.

Study Objective: To identify variables associated with weaning outcome in long-term ventilator-dependent patients. Using those variables, to construct models to predict weaning success and to test the accuracy of those models., Design: Retrospective medical record review., Setting: Regional weaning center (RWC)., Patients: An initial group of 421 and a subsequent group of 170 consecutive patients referred for attempted weaning after 6 weeks of mechanical ventilation., Measurements and Results: Data obtained on admission to our facility were analyzed for correlation with weaning outcome. In the initial patient group, selected variables which correlated with weaning success were alveolar-arterial oxygen pressure difference (P[A-a]O2), BUN, BUN/creatinine ratio (each with p < or = 0.001), and female gender (p = 0.04). We used these variables in logistic regression models to predict weaning success in this population. We then tested the models in the 170-patient validation group using both standard and receiver operating characteristic (ROC) curve analysis. The ROC analysis indicated 59% accuracy using P(A-a)O2 alone and 68% accuracy using all previously mentioned variables. We used data from all 565 patients with known outcome and omitted BUN/creatinine ratio to fashion a simple scoring system to predict weaning success with 70% accuracy using P(A-a)O2, BUN, and Gender--the A+B+G score., Conclusion: In patients suffering prolonged mechanical ventilation, models incorporating simple measurements allowed construction of a score to predict weaning success at our RWC.

Study Objective: The aim of this study was to describe the facility, patient population, outcome of treatment, and survival of patients transferred to a regional weaning center (RWC) after prolonged mechanical ventilation in the ICU setting., Design: Retrospective record review., Setting: Regional weaning center., Patients: Four hundred twenty-one consecutive ventilator dependent patients were transferred from ICU care for attempted weaning over a 36-month period., Measurement and Results: Acute catastrophic surgical, traumatic, or septic illness resulted in ventilator dependency with much greater frequency than decompensated COPD. Of the 421 patients, 116 died and 287 survived with outcome known at discharge. Of the 287 who survived, 212 were freed from ventilator support. Patients who weaned were ventilator-dependent for 46.9 +/- 2.9 days before transfer to the RWC. Almost half of those weaned were discharged to their homes. Survival at 6 months and 1 year after discharge was 44 percent and 28 percent respectively, and it was greater for those at home than for those discharged to an extended care facility (ECF). The RWC care was approximately $1,500 per patient day less costly than ICU care, and $208 per patient day less costly than noninvasive respiratory care unit care., Conclusions: Selected patients who become ventilator dependent for prolonged periods in the ICU may be transferred to an RWC with the expectation of successful weaning in a majority of cases.

Between 1978 and 1988, 215 patients with an average age of 67 years, underwent 246 carotid endarterectomies. Two hundred ten (85.4%) patients were symptomatic, and 36 (14.6%) were asymptomatic. Six patients (2.4%) had a postoperative stroke, and all had immediate reoperation. One of these patients died (30 day mortality rate, 0.4% for the series), and two (0.8%) recovered completely, whereas three (1.2%) had a mild permanent neurologic deficit. Two patients (0.8%) had nonfatal myocardial infarction. Mean follow-up of 42.2 months (range, 1 to 126 months) was achieved. At 5 and 8 years actuarial survival rates of 82% and 66% and stroke-free survival rates of 67% and 37% were observed. Actuarial stroke free rates of 90% at 5 and 8 years were noted. By introducing and observing guidelines that required preoperative study of most clearly defined classes of patients before admission for surgical treatment, the average length of stay for carotid endarterectomy was lowered from 9.5 days in the first 5 years of the study to 5.8 days in the second 5 years (p = 0.001). Average hospital charges, expressed in constant dollars, decreased from $3113 in the first 5 years to $2620 in the second 5 years (p = 0.02) despite an 88% inflationary increase in medical consumer price index. This experience shows that the length of hospitalization of patients with carotid endarterectomy can be reduced and the cost of admission lowered without untoward effect on perioperative morbidity and mortality rates.

Children from nursery school, kindergarten, and first grade were asked to select pictures which correctly represented the propositional content of six grammatical structures-active, passive, cleft-agent, cleft-patient, prepositional beneficiary, indirect object-presented under three context conditions-appropriate, inappropriate, isolation. In the appropriate-context condition the relationship between the target structure and its prior context sentence followed known discourse regularities about the allocation of given and new information, while in the inappropriate-context condition the relationship between the target structure and prior context violated these discourse regularities. Comprehension of two of the grammatical structures tested--the passive and the cleft-patient--was better under the appropriate-context treatment than under the inappropriate-context treatment, indicating that young children are in fact sensitive to discourse regularities about the allocation of given and new information.