Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. Since the brain salience network is likely the common denominator for insomnia, neuropsychiatric and neurodegenerative disorders, here, we focus on the pathology of this neuronal assembly and its likely driver, the dysfunctional neuronal and mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to mitochondrial transplantation. The aims of this review are threefold: 1. Examining the causes of insomnia in forensic detainees with severe mental illness, as well as its role in predisposing them to neurodegenerative disorders. 2. Educating State hospital and prison clinicians on frontotemporal dementia behavioral variant, a condition increasingly diagnosed in older first offenders which is often missed due to the absence of memory impairment. 3. Introducing clinicians to natural compounds that are potentially beneficial for insomnia and severe mental illness.

Minimally invasive cytoreductive radical prostatectomy, exploring the safety and feasibility of a single-port or multi-port robotic platform.

BACKGROUND: Consolidative resection or cytoreductive radical prostatectomy (CRP) may benefit men with non-organ confined prostate cancer. We report the safety, feasibility, and outcomes of robot-assisted laparoscopic CRP using a single-port (SP) or multi-port (MP) platform. METHODS: We reviewed consecutive men with clinical node positive or metastatic castrate-sensitive prostate cancer who underwent IRB-approved CRP and extended pelvic lymph node dissection using the da Vinci SP or MP Surgical Systems (Intuitive Surgical, Sunnyvale, CA) from 2015-2022. Perioperative data and Clavien-Dindo 90-day complications were recorded. RESULTS: Twenty-four men with a median age of 61 (IQR 56-69) years and prostate-specific antigen of 32.1 (IQR 21.9-62.3) ng/mL were included. Clinical N1, M1, or N1 + M1 disease were detected in 8 (33%), 9 (38%), 7 (29%) patients, respectively. There was no difference in positive margins, 41% vs. 29% (P = 0.67), lymph node yield, 21 (IQR 14-28) vs. 20 (IQR 13.5-21) nodes (P = 0.31), or estimated blood loss, 150 mL (IQR 100-200) vs. 50 mL (IQR 50-125) (P = 0.06), between the MP and SP cohorts, respectively. Hospital length of stay was significantly shorter for the SP group, same-day discharge (IQR 0-0), compared to MP, 1-day (IQR 1-1), P < 0.001. One grade III bowel obstruction and lymphocele occurred in the MP cohort. No major complications occurred in the SP cohort. CONCLUSION: Robot-assisted laparoscopic CRP is safe and feasible for select men with advanced castrate-sensitive prostate cancer.

Long-term Outcomes and Patient Satisfaction Following Salvage Robot-assisted Radical Prostatectomy: A Modern Perspective.

Background and objective: Approximately two-thirds of men who undergo primary treatment for prostate cancer (PC) will experience biochemical recurrence (BCR). Salvage robot-assisted radical prostatectomy (sRARP) offers curative treatment in this disease setting and men who choose this option may avoid palliative androgen deprivation therapy (ADT). The purpose of this study was to describe long-term outcomes and patient feedback following sRARP. Methods: We reviewed data for consecutive men with biopsy-proven localized BCR who underwent sRARP and pelvic lymph node dissection at a single tertiary referral center between 2004 and 2021. Perioperative data, Clavien-Dindo complications, and functional outcomes were recorded. The Kaplan-Meier method was used to estimate prostate-specific antigen-free (≥0.2 ng/ml) survival (PSAFS) and metastasis-free survival (MFS). Three Likert-type items (score 1-5) from the validated Surgical Satisfaction Questionnaire-8 were distributed to patients postoperatively. Key findings and limitations: We included 78 men, of whom 72 (92%) had undergone primary radiotherapy and six (8%) had received primary prostate ablation. Median follow-up was 10.1 yr (interquartile range 5.8-12.4). Final pathology identified ≥pT3N0M0 in 35 patients (45%) and positive margins in 23 (29%). The overall complication rate was 50%. Of the 26 (33%) major (grade ≥III) complications, anastomotic stricture (32%) was most common. The estimated 3-, 5-, and 10-yr survival rates were 85.6% and 80.2%, 83.5% for PSAFS (n = 11), and 74.1%, 83.5%, and 70.5% for MFS (n = 23), respectively. At last follow-up, postoperative ADT had been administered to 17 patients (22%), and 39 men (50%) remained alive a decade after sRARP. Continence and potency were maintained in 33/62 (53%) and 1/16 (6%) patients, respectively. Thirty-five respondents (45%) reported median questionnaire scores (≥4) in favor of sRARP. Limitations include the small single-center series and a single query point for patient feedback. Conclusions and clinical implications: Long-term outcomes of sRARP suggest that the technical challenges and morbidity of the procedure are qualified by patient feedback and the opportunity to evade the morbidity and mortality of biochemically recurrent PC. Patient summary: We reviewed the cancer outcomes and side effects of robot-assisted surgical removal of the prostate after treatment failure with radiation or ablation for prostate cancer. We found that this type of treatment has substantial risks and long-term side effects, but the surgery provides an opportunity to cure prostate cancer and/or avoid the consequences of indefinite hormonal treatment. Overall, most men who underwent this surgery were not disappointed with their decision despite the higher risks and consequences.

Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ('Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a 'motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system.

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury.

BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.

Identifying the core genome of the nucleus-forming bacteriophage family and characterization of Erwinia phage RAY.

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were still to be determined. Here, we show that phages encoding the major phage nucleus protein chimallin share 72 conserved genes encoded within seven gene blocks. Of these, 21 core genes are unique to nucleus-forming phage, and all but one of these genes encode proteins of unknown function. We propose that these phages comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryoelectron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication are conserved among diverse chimalliviruses and reveal variations on this replication mechanism. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.

Identifying the core genome of the nucleus-forming bacteriophage family and characterization of Erwinia phage RAY.

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were unknown. By studying phages that encode the major phage nucleus protein chimallin, including previously sequenced yet uncharacterized phages, we discovered that chimallin-encoding phages share a set of 72 highly conserved genes encoded within seven distinct gene blocks. Of these, 21 core genes are unique to this group, and all but one of these unique genes encode proteins of unknown function. We propose that phages with this core genome comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryo-electron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication encoded in the core genome are conserved among diverse chimalliviruses, and reveal that non-core components can confer intriguing variations on this replication mechanism. For instance, unlike previously studied nucleus-forming phages, RAY doesn't degrade the host genome, and its PhuZ homolog appears to form a five-stranded filament with a lumen. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.

Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

A Case Study of the Impact of Language Concordance on Patient Care, Satisfaction, and Comfort with Sharing Sensitive Information During Medical Care.

Linguistic barriers continue to be a source of difficulty and inappropriate treatment in our healthcare system. Several studies have shown the importance of language concordance, which leads to increased trust and higher patient satisfaction. The aim of this is study is to determine patients' satisfaction and comfort levels with sharing sensitive information in Spanish with either the health care provider or an interpreter, respectively, and to compare the results to find out if there is an option that patients prefer. There were two different groups of participants in the study. The experimental group was directly seen by Spanish-speaking student doctors while the control group was seen by English-speaking student doctors that had the aid of an interpreter. Several questions were asked to participants via survey in order to measure their comfort levels during the encounter. The results of this study demonstrate that having Spanish-speaking healthcare providers providing health care to Hispanic patients can raise patients' comfort levels and satisfaction in contrast to having the aid of an interpreter. Providing second language training to student doctors can potentially improve patient care and reduce health inequities facing LEP patients. Given the small sample size of our study, future projects should expand the study to include more participants.

Reflected appraisals across multiple reference groups: Discrepancies in self and individual delinquency.

We explore the implications of multiple reference groups for symbolic interaction explanations of delinquency. Specifically, we test the idea that dissimilarity in reflected appraisals across reference groups weakens the effect of the appraisals of a single group on behavior. We also assess whether the relative influence of different reflected appraisals is moderated by differences in the amount of time spent in and attachment to the roles taken among specific reference groups. Using data from the National Youth Survey, our findings mostly support symbolic interactionist predictions: Dissimilarity in reference groups' reflected appraisals weakens the influence of a single group's appraisals on behavior. We also found some evidence that, relatively, the more time an individual spends and the more attached they are to a role in a particular reference group, the more strongly correlated the respective appraisals are with delinquent behavior. Contrary to our predictions, we found that relatively strong attachments to one's role with their parents weakens the influence of parental reflected appraisals as a rule violator.

Surgical management of advanced hidradenitis suppurativa via a one-stage procedure: A single-center experience.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating skin condition; in severe forms it requires excision and skin grafting for cure. This is commonly performed as a multi-stage procedure; we explored single-stage operation as a more efficient alternative. METHODS: Retrospective review 2007-2018 evaluating outcomes of patients undergoing single-stage surgery. RESULTS: 139 one-stage procedures were performed: 35 excision and primary closure, 104 split-thickness skin grafting (STSG). Success rate was higher for STSG at 75% versus 60% with primary closure. Of failed primary closures, 57% required revision by grafting due to recurrence. Axilla procedures were most successful at 91% compared to 70%, 54%, and 50% for inguinal, gluteal, and perineal areas, respectively. Infection was the most common complication (17%), with 38% requiring readmission. CONCLUSION: Compared to prior literature on multi-stage HS treatment, one-stage operations are a feasible, cost-effective alternative. STSG should remain the procedure of choice, even when primary closure appears feasible.

Exploring Teens as Robot Operators, Users and Witnesses in the Wild.

As social robots continue to show promise as assistive technologies, the exploration of appropriate and impactful robot behaviors is key to their eventual success. Teens are a unique population given their vulnerability to stress leading to both mental and physical illness. Much of teen stress stems from school, making the school environment an ideal location for a stress reducing technology. The goal of this mixed-methods study was to understand teens' operation of, and responsiveness to, a robot only capable of movement compared to a robot only capable of speech. Stemming from a human-centered approach, we introduce a Participatory Wizard of Oz (PWoz) interaction method that engaged teens as operators, users, and witnesses in a uniquely transparent interaction. In this paper, we illustrate the use of the PWoz interaction method as well as how it helps identify engaging robot interactions. Using this technique, we present results from a study with 62 teens that includes details of the complexity of teen stress and a significant reduction in negative attitudes toward robots after interactions. We analyzed the teens' interactions with both the verbal and non-verbal robots and identified strong themes of (1) authenticity, (2) empathy, (3) emotional engagement, and (4) imperfection creates connection. Finally, we reflect on the benefits and limitations of the PWoz method and our study to identify next steps toward the design and development of our social robot.

Modulation of Klotho expression in injured muscle perturbs Wnt signalling and influences the rate of muscle growth.

NEW FINDINGS: What is the central question of this study? Does modulating the expression of Klotho affect myogenesis following acute injury of healthy, non-senescent muscle? What is the main finding and its importance? Klotho can accelerate muscle growth following acute injury of healthy, adult mice, which supports the possibility that increased delivery of Klotho could have therapeutic value for improving repair of damaged muscle. ABSTRACT: Skeletal muscle injuries activate a complex programme of myogenesis that can restore normal muscle structure. We tested whether modulating the expression of klotho influenced the response of mouse muscles to acute injury. Our findings show that klotho expression in muscle declines at 3 days post-injury. That reduction in klotho expression coincided with elevated expression of targets of Wnt signalling (Ccnd1; Myc) and increased MyoD+ muscle cell numbers, reflecting the onset of myogenic cell differentiation. klotho expression subsequently increased at 7 days post-injury with elevated expression occurring primarily in inflammatory lesions, which was accompanied by reduced expression of Wnt target genes (Ccnd1: 91%; Myc: 96%). Introduction of a klotho transgene maintained high levels of klotho expression over the course of muscle repair and attenuated the increases in Ccnd1 and Myc expression that occurred at 3 days post-injury. Correspondingly, transgene expression reduced Wnt signalling in Pax7+ cells, reflected by reductions in Pax7+ cells expressing active ß-catenin, and reduced the numbers of MyoD+ cells at 3 days post-injury. At 21 days post-injury, muscles in klotho transgenic mice showed increased Pax7+ and decreased myogenin+ cell densities and large increases in myofibre size. Likewise, treating myogenic cells in vitro with Klotho reduced Myod expression but did not affect Pax7 expression. Muscle inflammation was only slightly modulated by increased klotho expression, initially reducing the expression of M2-biased macrophage markers Cd163 and Cd206 at 3 days post-injury and later increasing the expression of pan-macrophage marker F480 and Cd68 at 21 days post-injury. Collectively, our study shows that Klotho modulates myogenesis and that increased expression accelerates muscle growth after injury.

Common knowledge, coordination, and strategic mentalizing in human social life.

People often coordinate for mutual gain, such as keeping to opposite sides of a stairway, dubbing an object or place with a name, or assembling en masse to protest a regime. Because successful coordination requires complementary choices, these opportunities raise the puzzle of how people attain the common knowledge that facilitates coordination, in which a person knows X, knows that the other knows X, knows that the other knows that he knows, ad infinitum. We show that people are highly sensitive to the distinction between common knowledge and mere private or shared knowledge, and that they deploy this distinction strategically in diverse social situations that have the structure of coordination games, including market cooperation, innuendo, bystander intervention, attributions of charitability, self-conscious emotions, and moral condemnation.

How Does Cilium Length Affect Beating?

The effects of cilium length on the dynamics of cilia motion were investigated by high-speed video microscopy of uniciliated mutants of the swimming alga, Chlamydomonas reinhardtii. Cells with short cilia were obtained by deciliating cells via pH shock and allowing cilia to reassemble for limited times. The frequency of cilia beating was estimated from the motion of the cell body and of the cilium. Key features of the ciliary waveform were quantified from polynomial curves fitted to the cilium in each image frame. Most notably, periodic beating did not emerge until the cilium reached a critical length between 2 and 4 µm. Surprisingly, in cells that exhibited periodic beating, the frequency of beating was similar for all lengths with only a slight decrease in frequency as length increased from 4 µm to the normal length of 10-12 µm. The waveform average curvature (rad/µm) was also conserved as the cilium grew. The mechanical metrics of ciliary propulsion (force, torque, and power) all increased in proportion to length. The mechanical efficiency of beating appeared to be maximal at the normal wild-type length of 10-12 µm. These quantitative features of ciliary behavior illuminate the biophysics of cilia motion and, in future studies, may help distinguish competing hypotheses of the underlying mechanism of oscillation.

Battery-free, skin-interfaced microfluidic/electronic systems for simultaneous electrochemical, colorimetric, and volumetric analysis of sweat.

Wearable sweat sensors rely either on electronics for electrochemical detection or on colorimetry for visual readout. Non-ideal form factors represent disadvantages of the former, while semiquantitative operation and narrow scope of measurable biomarkers characterize the latter. Here, we introduce a battery-free, wireless electronic sensing platform inspired by biofuel cells that integrates chronometric microfluidic platforms with embedded colorimetric assays. The resulting sensors combine advantages of electronic and microfluidic functionality in a platform that is significantly lighter, cheaper, and smaller than alternatives. A demonstration device simultaneously monitors sweat rate/loss, pH, lactate, glucose, and chloride. Systematic studies of the electronics, microfluidics, and integration schemes establish the key design considerations and performance attributes. Two-day human trials that compare concentrations of glucose and lactate in sweat and blood suggest a potential basis for noninvasive, semi-quantitative tracking of physiological status.

Maimonides' ladder: States of mutual knowledge and the perception of charitability.

Why do people esteem anonymous charitable giving? We connect normative theories of charitability (captured in Maimonides' Ladder of Charity) with evolutionary theories of partner choice to test predictions on how attributions of charitability are affected by states of knowledge: whether the identity of the donor or of the beneficiary is revealed to the other. Consistent with the theories, in Experiments 1-2 participants judged a double-blind gift as more charitable than one to a revealed beneficiary, which in turn was judged as more charitable than one from a revealed donor. We also found one exception: Participants judged a donor who revealed only himself as slightly less, rather than more, charitable than one who revealed both identities. Experiment 3 explains the exception as a reaction to the donor's perceived sense of superiority and disinterest in a social relationship. Experiment 4 found that donors were judged as more charitable when the gift was shared knowledge (each aware of the other's identity, but unsure of the other's awareness) than when it was common knowledge (awareness of awareness). Experiment 5, which titrated anonymity against donation size, found that not even a hundredfold larger gift could compensate for the disapproval elicited by a donor revealing his identity. Experiment 6 showed that participants' judgments of charitability flip depending on whose perspective they take: Observers disapprove of donations that they would prefer as beneficiaries. Together, these experiments provide insight into why people care about how a donor gives, not just how much. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Perioperative Considerations for the Patient with Opioid Use Disorder on Buprenorphine, Methadone, or Naltrexone Maintenance Therapy.

As part of a national effort to combat the current US opioid epidemic, use of currently Food and Drug Administration-approved drugs for the treatment of opioid use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on the rise. To provide optimal pain control and minimize the risk of relapse and overdose, providers need to have an in-depth understanding of how to manage these medications in the perioperative setting. This article reviews key principles and discusses perioperative considerations for patients with opioid use disorder on buprenorphine, methadone, or naltrexone.