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Kent H. Redford contends that the illusion of an 'ecologically noble savage' can be dangerous in the formulation of environmental policies. Although he stresses the importance of the study and preservation of indigenous cultures, he resists the idea of the implementation of development plans in accordance with cultural values. He strongly criticizes the idealized notion regarding the inherent superiority of the indigenous way of life.

Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c+/−(Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death. Accordingly, Mef2c-het mice exhibit decreased neurogenesis, enhanced neuronal apoptosis, and an increased ratio of excitatory to inhibitory (E/I) neurotransmission. Importantly, neurobehavioral deficits, E/I imbalance, and histological damage are all ameliorated by treatment with NitroSynapsin, a new dual-action compound related to the FDAapproved drug memantine, representing an uncompetitive/fast off-rate antagonist of NMDAtype glutamate receptors. These results suggest that MEF2C haploinsufficiency leads to abnormal brain development, E/I imbalance, and neurobehavioral dysfunction, which may be mitigated by pharmacological intervention. [ABSTRACT FROM AUTHOR]

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats' choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The Hippo pathway plays a central role in tissue development and homeostasis. However, the function of Hippo in pancreatic endocrine development remains obscure. Here, we generated novel conditional genetically engineered mouse models to examine the roles of Hippo pathway-mediated YAP1/TAZ inhibition in the development stages of endocrine specification and differentiation. While YAP1 protein was localized to the nuclei in bipotent progenitor cells, Neurogenin 3 expressing endocrine progenitors completely lost YAP1 expression. Using genetically engineered mouse models, we found that inactivation of YAP1 requires both an intact Hippo pathway and Neurogenin 3 protein. Gene deletion of Lats1 and 2 kinases ( Lats1&2 ) in endocrine progenitor cells of developing mouse pancreas using Neurog3 Cre blocked endocrine progenitor cell differentiation and specification, resulting in reduced islets size and a disorganized pancreas at birth. Loss of Lats1&2 in Neurogenin 3 expressing cells activated YAP1/TAZ transcriptional activity and recruited macrophages to the developing pancreas. These defects were rescued by deletion of Yap1/Wwtr1 genes, suggesting that tight regulation of YAP1/TAZ by Hippo signaling is crucial for pancreatic endocrine specification. In contrast, deletion of Lats1&2 using β-cell-specific Ins1 CreER resulted in a phenotypically normal pancreas, indicating that Lats1&2 are indispensable for differentiation of endocrine progenitors but not for that of β-cells. Our results demonstrate that loss of YAP1/TAZ expression in the pancreatic endocrine compartment is not a passive consequence of endocrine specification. Rather, Hippo pathway-mediated inhibition of YAP1/TAZ in endocrine progenitors is a prerequisite for endocrine specification and differentiation., Competing Interests: YW, KQ, YX, SR, TV, KL, JL, MN, JD, XY, LR, ZY, YL, HA, PW No competing interests declared

Introduction: Nerve conduction study (NCS) and electromyography (EMG) are electrodiagnostic studies that are highly tolerated by patients despite their nature of causing pain and discomfort. However, few studies have focused on the true tolerability of these procedures in patients. This study aimed to determine the true tolerance rate of NCS and EMG in patient populations and the factors that might be associated with them., Methods: Participants scheduled for electrodiagnostic studies were prospectively recruited between March 2023 and September 2023. After completion of the study, the physicians completed a questionnaire on each patient's tolerance of the studies., Results: Of the 103 patients enrolled in the study, 98 were able to tolerate both tests, and 5 patients were intolerant to 1 or both tests. The overall tolerance rate of NCS and EMG was 95.1% (0.951, 95% CI 0.897 to 0.981). Age, sex, ethnicity, the type of NCS performed and the type of EMG performed were not associated with NCS or EMG intolerance., Conclusion: Most patients tolerated the NCS and EMG; however, a small percentage of patients were intolerant. Clinicians should recognise the intolerance of certain patients when introducing and performing electrodiagnostic tests., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Amputation is a major condition that requires inpatient rehabilitation. Some research has been conducted to explore the risk factors for readmission of patients from inpatient rehabilitation facilities to acute care hospitals. However, few studies have included patients with amputation in the study population., Objective: To identify the risk factors for readmission of patients with amputation to acute care hospitals from an inpatient rehabilitation facility., Design: Retrospective cohort study., Setting: An acute rehabilitation hospital associated with a community-based tertiary medical center., Patients: A retrospective review of 156 independent admissions of 145 patients from June 2019 to July 2022., Main Outcome Measure: The study outcome measure was readmission to acute care from an acute rehabilitation unit., Results: Of the 156 independent admissions, the readmission rate was 19% (29/156). The most common cause of transfer was incision-site complications (9/29, 31%), including wound infection and wound dehiscence. Patients with amputation readmitted to acute care are more likely to be receiving dialysis (p < .001), have a longer length of stay in acute care before admission to the rehabilitation facility (p = .039), and have a lower Section GG score on admission (p < .001). Age, sex, ethnicity, amputation level, and history of diabetes mellitus were not associated with acute care hospital readmission. The logistic regression model revealed that patients being on dialysis was the only significant risk factor predictive of readmission to acute care (odds ratio [OR] 4.82, p = .006)., Conclusions: This study showed that incision-site complications were the most common cause of disruption in inpatient rehabilitation via acute hospital readmission in patients with amputation. Being on dialysis was associated with a higher risk of readmission to acute care hospitals. Based on the results of this study, specific rehabilitation plans might be required for patients with amputation who carry certain risk factors to reduce rehospitalization to the acute care unit., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Mucinous cystic neoplasms (MCNs) are rare tumors of the liver, occasionally seen in the biliary tree. Epidemiologic data are limited by their indolence and recent changes to diagnostic criteria. They are considered premalignant lesions capable of invasive behavior. While their etiology remains unknown, their female predominance, age of onset, and hormonally responsive ovarian-type stroma suggest ectopic organogenesis during embryologic development. MCNs can typically be recognized on imaging; yet, invasiveness is often indeterminate, and percutaneous tissue biopsy has shown limited value. Therefore, complete excision is recommended for all lesions as focal malignant transformation and metastatic disease has been reported., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Hutchens et al.)

Context: Current information-rich electronic health record (EHR) interfaces require large, high-resolution screens running on desktop computers. This interface compromises the provider's already limited time at the bedside by physically separating the patient from the doctor. The case study presented here describes a patient-centered clinical decision support (CDS) design process that aims to bring the physician back to the bedside by integrating a patient decision aid with CDS for shared use by the patient and provider on a touchscreen tablet computer for deciding whether or not to obtain a CT scan for minor head injury in the emergency department, a clinical scenario that could benefit from CDS but has failed previous implementation attempts., Case Description: This case study follows the user-centered design (UCD) approach to build a bedside aid that is useful and usable, and that promotes shared decision-making between patients and their providers using a tablet computer at the bedside. The patient-centered decision support design process focuses on the prototype build using agile software development, but also describes the following: (1) the requirement gathering phase including triangulated qualitative research (focus groups and cognitive task analysis) to understand current challenges, (2) features for patient education, the physician, and shared decision-making, (3) system architecture and technical requirements, and (4) future plans for formative usability testing and field testing., Lessons Learned: We share specific lessons learned and general recommendations from critical insights gained in the patient-centered decision support design process about early stakeholder engagement, EHR integration, external expert feedback, challenges to two users on a single device, project management, and accessibility., Conclusions: Successful implementation of this tool will require seamless integration into the provider's workflow. This protocol can create an effective interface for shared decision-making and safe resource reduction at the bedside in the austere and dynamic clinical environment of the ED and is generalizable for these purposes in other clinical environments as well.

Objective: Teleretinal screening with nonmydriatic cameras has been presented as a means of increasing the number of patients assessed for diabetic retinopathy in urban safety net clinics. It has been hypothesized that automated nonmydriatic cameras may improve screening rates by reducing the learning curve for camera use. In this article, we examine the impact of introducing automated nonmydriatic cameras to urban safety net clinics whose photographers had previously used manual cameras., Materials and Methods: We evaluated the impact of manual and automated digital nonmydriatic cameras on teleretinal screening using a quantitative analysis of readers' image quality ratings as well as a qualitative analysis, through in-depth interviews, of photographers' experiences., Results: With the manual camera, 68% of images were rated "adequate" or better, including 24% rated "good" and 20% rated "excellent." With the automated camera, 61% were rated "adequate" or better, including 9% rated "good" and 0% rated "excellent." Photographers expressed frustration with their inability to control image-taking settings with the automated camera, which led to unexpected delays., Conclusions: For safety net clinics in which medical assistants are already trained to take photographs for diabetic retinopathy screening with a manual camera, the introduction of automated cameras may lead to frustration and paradoxically contribute to increased patient wait times. When photographers have achieved a high degree of aptitude with manual cameras and value the control they have over camera features, the introduction of automated cameras should be approached with caution and may require extensive training to increase user acceptability.