Minimizing delays to hemodialysis access maturation: A quality improvement analysis.

INTRODUCTION: Pre-operative process optimization can expedite time-to-intervention and reduce overall health care costs. We hypothesized that the longest delay to hemodialysis (HD) access creation would be from pre-operative vessel mapping (mandatory in our practice), and that this would be correlated with increased catheter days. METHODS: One hundred thirty patients (24 inpatients, 106 outpatients) who received initial hemodialysis (HD) access from 01/01/2017 to 12/31/2021, at the Veterans Affairs Puget Sound, Seattle, Washington, were identified. Median time differences between pre-operative events were compared between inpatients and outpatients using the Mann-Whitney U test. Outpatients were then stratified by time of catheter-based HD initiation (no catheter, pre-referral catheter, post-referral catheter) and compared. The impacts of mapping-related delays on catheter use were evaluated using regression. RESULTS: Inpatients had shorter referral to access maturation times (125 days inpatient vs 146 days outpatient; p = 0.03). This was driven by shorter referral to mapping (2 days inpatient vs 27 days outpatient; p < 0.01) and mapping to pre-surgical evaluation (1-day inpatient vs 6 days outpatients; p < 0.01) times. Pre-surgical evaluation to OR times represented the longest pre-operative delay in both groups (51 days inpatient vs 29 days outpatient; p = 0.59). Among outpatients, tunneled catheter placement post-referral resulted in longer maturation times (74 days no catheter vs 67 days pre-referral vs 149 days post-referral; p < 0.01) but not additional pre-operative delays. No trend existed between increased mapping times and catheter-based dialysis duration (R2 = 0.08). CONCLUSION: Preoperative vein mapping contributed up to 21% of referral to maturation times but was not associated with increased tunneled catheter duration. While tunneled catheter placement impacted access maturation it did not cause additional pre-operative delays. Earlier referrals for access creation and reduction of outpatient wait-time from referral to OR and increased AV graft placement may minimize catheter days in our system thereby mitigating the added delays caused by pre-operative vein mapping.

Using Multidisciplinary Teams to Improve Outcomes for Treating Chronic-Limb Threatening Ischemia.

Multidisciplinary teams are necessary to treat complex patients with chronic limb-threatening ischemia (CLTI). The need for adequate wound care and control of comorbid conditions cannot be accomplished by the vascular specialist alone. Numerous specialties have a role in this group to include surgical podiatrists, orthopedic surgery, plastic and reconstructive surgery endocrinology, and wound care. However, the vascular specialist must drive this team as the patients are usually referred to them and numerous studies have shown a direct correlation between major amputations and the lack of vascular involvement. Creating these teams is unique in each community and must consider practice patterns that are relevant in the local region. CLTI is a challenging disease to manage, and multidisciplinary teams have demonstrated an ability to improve outcomes and deliver superior care to this patient population.

Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat.

Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.

A shift of paradigm: From avoiding nanoparticular complement activation in the field of nanomedicines to its exploitation in the context of vaccine development.

The complement system plays a central role in our innate immunity to fight pathogenic microorganisms, foreign and altered cells, or any modified molecule. Consequences of complement activation include cell lysis, release of histamines, and opsonization of foreign structures in preparation for phagocytosis. Because nanoparticles interact with the immune system in various ways and can massively activate the complement system due to their virus-mimetic size and foreign texture, detrimental side effects have been described after administration like pro-inflammatory responses, inflammation, mild to severe anaphylactic crisis and potentially complement activated-related pseudoallergy (CARPA). Therefore, application of nanotherapeutics has sometimes been observed with restraint, and avoiding or even suppressing complement activation has been of utmost priority. In contrast, in the field of vaccine development, particularly protein-based immunogens that are attached to the surface of nanoparticles, may profit from complement activation regarding breadth and potency of immune response. Improved transport to the regional lymph nodes, enhanced antigen uptake and presentation, as well as beneficial effects on immune cells like B-, T- and follicular dendritic cells may be exploited by strategic nanoparticle design aimed to activate the complement system. However, a shift of paradigm regarding complement activation by nanoparticular vaccines can only be achieved if these beneficial effects are accurately elicited and overshooting effects avoided.

NMOSD IgG Impact Retinal Cells in Murine Retinal Explants.

Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells. In this exploratory study, we analysed the response of mouse retinal explants to NMOSD immunoglobulins (IgG). Mouse retinal explants were treated with purified IgG from patient or control sera for one and three days. We characterized tissue response patterns through morphological changes, chemokine secretion, and complement expression. Mouse retinal explants exhibited a basic proinflammatory response ex vivo, modified by IgG addition. NMOSD IgG, unlike control IgG, increased gliosis and decreased chemokine release (CCL2, CCL3, CCL4, and CXCL-10). Complement component expression by retinal cells remained unaltered by either IgG fraction. We conclude that human NMOSD IgG can possibly bind in the mouse retina, altering the local cellular environment. This intraretinal stress may contribute to retinal degeneration independent of relapse activity in NMOSD, suggesting a primary retinopathy.

Association of Pre and Perioperative Vein Mapping with Hemodialysis Access Characteristics and Outcomes.

BACKGROUND: We investigated the utility of both pre and perioperative vein mapping for evaluating vessel suitability for both arteriovenous fistula (AVF) and arteriovenous graft (AVG) creation. In our practice, we used both mapping methods to detect arterial issues and to maximize AVF creation. We hypothesized that the patients whose operative plan changed based on their perioperative mapping would ultimately benefit from more optimal access placement with maintained rates of maturation and functional patency. METHODS: We performed a retrospective chart review evaluating patients who received initial hemodialysis (HD) access from January 1, 2017, to December 31, 2021, at the Veterans Affairs (VA) Puget Sound in Seattle, Washington. Patients were separated by whether their final procedure was congruent with the best access predicted from the preoperative vein mapping or noncongruent. The primary outcome was fistula maturation. Secondary outcomes were functional patency and number of procedures required to achieve maturation or to maintain functional patency. Results were analyzed using Pearson's chi-squared, Moods median, Student's t-tests, and Kaplan-Meier curves. RESULTS: Preoperative vein mapping uncovered arterial issues in 42% of the patient population. Initial HD access was created in 130 patients (n = 69 congruent, n = 61 noncongruent). Perioperative ultrasound led to a change in the created access in 47% of patients. Within the noncongruent group, 74% received access creation at a more anatomically favorable site compared to their predicted access, 47% were changed to forearm fistula, 20% to brachiocephalic (BC) from previously planned brachiobasilic (BB) or graft, and 7% to BB from previously planned graft. Maturation rates were similar in both groups (congruent 86% and noncongruent 82%), and there were no significant differences in the duration of functional patency or the number of procedures needed to achieve maturation or maintain functional patency. CONCLUSIONS: Utilization of pre and perioperative ultrasound for all patients resulted in higher rates of native AVF, forearm placement, and one-stage operations, with maintained maturation rates and functional patency in patients who were otherwise unsuitable candidates based on preoperative vein mapping alone.

Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates.

To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze.SIGNIFICANCE STATEMENT Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions.

Oxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats.

In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialysis approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), is required for aggression in female rats. Accordingly, increased activity of putative OXT receptor-positive neurons in the vLS, and decreased activity of putative AVP receptor-positive neurons in the dLS, are likely to underly aggression in female rats. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data suggest a model showing that septal release of OXT and AVP differentially affects aggression in females by modulating the inhibitory tone within LS sub-networks.

Respiratory depression in a neonate born to mother on maximum dose sertraline: a case report.

BACKGROUND: Mood and anxiety disorders are common in women of childbearing age, especially during the peripartum period. As more women seek medical management for these conditions, there is an increasing need for studies to better examine the effects of exposure to selective serotonin reuptake inhibitors (SSRIs), and other antidepressants, on newborns at the time of delivery. CASE PRESENTATION: We report the case of a term Caucasian infant born to a 17-year-old white female taking 100 mg of sertraline daily for depression and anxiety who exhibited respiratory depression and hypoxia after an uncomplicated vaginal delivery. The neonate was treated with the use of continuous positive airway pressure (CPAP) and supplemental oxygen and subsequently the symptoms resolved without complication. CONCLUSIONS: We present this case with the suspicion of poor neonatal adjustment syndrome as the possible cause of the respiratory depression and hypoxia in this newborn.

Two port laparoscopic trachelectomy without the use of ureteral stents

Trachelectomy is a notoriously difficult laparoscopic procedure, often because of remaining scar tissue from a prior supracervical hysterectomy, as well as the necessity to clear vital organs, including the bladder and the rectum, out of the plane of dissection in order to remove the cervix. Many authors have suggested techniques involving ureteral stents to minimize the chance of ureteral injury. Our institute presents this two-port laparoscopic technique without the use of stents, which we believe safely accomplishes the trachelectomy through very minimally invasive means.

LESS hysterectomy through a bluntly created 11 mm incision

In the field of minimally invasive surgery, there is a constant drive to devise and execute the most minimally invasive surgeries possible. By the very nature of laparoscopy and robotic surgery, what one can accomplish with several ports of a given size will invariably be studied and attempted with fewer ports and with ports of smaller sizes. After researching the literature, we were not able to find any single port hysterectomies performed through a port size of smaller than 15 mm. We were able to perform, described here, a technique for performing laparoscopic hysterectomy through a single port of only 11 mm in diameter. We illustrate the technique in the accompanying video and believe the technique to be safe and reproducible.

Minimally invasive search for a missing vibrator.

OBJECTIVE: To report a unique surgical procedure that was utilized to locate a missing vibrator in the pelvis of a patient. Emergency room admissions and surgery secondary to the malfunctioning of devices intended for sexual stimulation are extremely common. Emergency room staff of hospitals in the United States usually are skilled in the detection and removal of these devices. Occasionally, surgical intervention is warranted if the device enters a cavity that cannot safely be explored in the emergency room setting. We report a case of a vibrator that was lost during sexual activity. A flat plate X-ray showed it to be in the abdominal cavity. Careful questioning of the patient revealed that the device had an unusually small diameter. Surgical intervention showed that the device ultimately ended up in the bladder without causing traumatic injury. METHODS: We created a narrated video to demonstrate the surgical procedure (Canadian Task Force Classification III). RESULTS: Laparoscopy and cystoscopy were used to visualize and successfully remove the device. The patient recovered uneventfully. CONCLUSION: Following laparoscopic confirmation of the location of the device, it was removed via cystoscopy. This case demonstrates how background information, such as the size of the missing device in this case, can be critical to providing high quality patient care.

Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells.

The retinal pigment epithelium (RPE) maintains visual function and preserves structural integrity of the retina. Chronic dysfunction of the RPE is associated with retinal degeneration, including age-related macular degeneration (AMD). The AMD pathogenesis includes both increased oxidative stress and complement dysregulation. Physiological sources of oxidative stress in the retina are well known, while complement sources and regulation are still under debate. Using human primary RPE (hpRPE) cells, we have established a model to investigate complement component expression on transcript and protein level in AMD-risk and non-risk hpRPE cells. We evaluated the effect of properdin, a complement stabilizer, on the hpRPE cell-dependent complement profile exposed to oxidative stress. hpRPE cells expressed complement components, receptors and regulators. Complement proteins were also stored and secreted by hpRPE cells. We associated AMD-risk single nucleotide polymorphisms with an increased secretion of complement factors D (CFD) and I (CFI). Furthermore, we detected hpRPE cell-associated complement activation products (C3a, C5a) independent of any extracellularly added complement system. Exogenous properdin increased the mRNA expression of CFI and CFD, but decreased levels of complement components (C1Q, C3), receptors (C3AR, C5AR1, CD11B) and inflammation-associated transcripts (NLRP3, IL1B) in hpRPE cells exposed to oxidative stress. This properdin effect was time-dependently counter regulated. In conclusion, our data unveiled a local, genotype-associated complement component production in hpRPE cells, regulated by exogenous properdin. The local complement production and activation via blood-independent mechanisms can be a new therapeutic target for AMD.

Single Port 11 mm Laparoscopic Hysterectomy Performed on a 32-Year-Old Female with Adhesive Disease.

In the field of minimally invasive surgery, there is constant drive to devise and execute the most minimally invasive surgeries possible. By the very nature of laparoscopy and robotic surgery, what one can accomplish with several ports of a given size will invariably be studied and attempted with fewer ports and with ports of smaller sizes. Although more complex pathology may require a more invasive approach, surgical cases without serious complicating factors may be amenable to extremely minimally invasive procedures. We report one such case where a 32-year-old female suffering from adenomyosis and endometriosis was able to receive a laparoscopic single-port hysterectomy and bilateral salpingo-oophorectomy through a single 11 mm port created with a blunt trochar.

Combinatorial Oxytocin Neuropharmacology in Social Cognition.

The efficacy and reliability of using intranasal oxytocin (OT) to clinically enhance social functions remains undependable. We discuss the potential benefit of concurrent administration of OT and naloxone (NAL) to robustly modulate social behavior. We further suggest that combinatorial neuropharmacology approaches should exploit the interactions between OT and serotonin to regulate social functions.

Framing the discussion of microorganisms as a facet of social equity in human health.

What do "microbes" have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the "health" of the environments we build. The loss, gain, and retention of microorganisms-their flow between humans and the environment-can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure.

Differences in how macaques monitor others: Does serotonin play a central role?

Primates must balance the need to monitor other conspecifics to gain social information while not losing other resource opportunities. We consolidate evidence across the fields of primatology, psychology, and neuroscience to examine individual, population, and species differences in how primates, particularly macaques, monitor conspecifics. We particularly consider the role of serotonin in mediating social competency via social attention, aggression, and dominance behaviors. Finally, we consider how the evolution of variation in social tolerance, aggression, and social monitoring might be explained by differences in serotonergic function in macaques. This article is categorized under: Economics > Interactive Decision-Making Psychology > Comparative Psychology Neuroscience > Behavior Cognitive Biology > Evolutionary Roots of Cognition.

Violent aggression predicted by multiple pre-adult environmental hits.

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

The effects of 5-hydroxytryptophan on attention and central serotonin neurochemistry in the rhesus macaque.

Psychiatric disorders, particularly depression and anxiety, are often associated with impaired serotonergic function. However, serotonergic interventions yield inconsistent effects on behavioral impairments. To better understand serotonin's role in these pathologies, we investigated the role of serotonin in a behavior frequently impaired in depression and anxiety, attention. In this study, we used a quantitative, repeated, within-subject, design to test how L-5-hydroxytryptophan (5-HTP), the immediate serotonin precursor, modulates central serotoninergic function and attention in macaques. We observed that intramuscular 5-HTP administration increased cisternal cerebrospinal fluid (CSF) 5-HTP and serotonin. In addition, individuals' baseline looking duration, during saline sessions, predicted the direction and magnitude in which 5-HTP modulated attention. We found that 5-HTP decreased looking duration in animals with high baseline attention, but increased looking duration in low baseline attention animals. Furthermore, individual differences in 5-HTP's effects were also reflected in how engaged individuals were in the task and how they allocated attention to salient facial features-the eyes and mouth-of stimulus animals. However, 5-HTP constricted pupil size in all animals, suggesting that the bi-directional effects of 5-HTP cannot be explained by serotonin-mediated changes in autonomic arousal. Critically, high and low baseline attention animals exhibited different baseline CSF concentrations of 5-HTP and serotonin, an index of extracellular functionally active serotonin. Thus, our results suggest that baseline central serotonergic functioning may underlie and predict variation in serotonin's effects on cognitive operation. Our findings may help inform serotonin's role in psychopathology and help clinicians predict how serotonergic interventions will influence pathologies.

The age of Homo naledi and associated sediments in the Rising Star Cave, South Africa.

New ages for flowstone, sediments and fossil bones from the Dinaledi Chamber are presented. We combined optically stimulated luminescence dating of sediments with U-Th and palaeomagnetic analyses of flowstones to establish that all sediments containing Homo naledi fossils can be allocated to a single stratigraphic entity (sub-unit 3b), interpreted to be deposited between 236 ka and 414 ka. This result has been confirmed independently by dating three H. naledi teeth with combined U-series and electron spin resonance (US-ESR) dating. Two dating scenarios for the fossils were tested by varying the assumed levels of 222Rn loss in the encasing sediments: a maximum age scenario provides an average age for the two least altered fossil teeth of 253 +82/-70 ka, whilst a minimum age scenario yields an average age of 200 +70/-61 ka. We consider the maximum age scenario to more closely reflect conditions in the cave, and therefore, the true age of the fossils. By combining the US-ESR maximum age estimate obtained from the teeth, with the U-Th age for the oldest flowstone overlying Homo naledi fossils, we have constrained the depositional age of Homo naledi to a period between 236 ka and 335 ka. These age results demonstrate that a morphologically primitive hominin, Homo naledi, survived into the later parts of the Pleistocene in Africa, and indicate a much younger age for the Homo naledi fossils than have previously been hypothesized based on their morphology.