Alzheimer disease-like neuropathologic changes in a geriatric baboon (Papio hamadryas).

IMPORTANCE: Alzheimer's disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, including the various genetic, environmental, and metabolic contributing factors. In an effort to better understand this complex disease, researchers have employed nonhuman primates as translational models. CASE PRESENTATION: This report aims to describe the AD-like neuropathology in the brain of a 37-year-old female baboon (Papio hamadryas), which at the time of her death made her the oldest hamadryas baboon at any member institution of the Association of Zoos and Aquariums. A diagnostic necropsy was performed, and the brain was evaluated for neurodegenerative disease. Frequent amyloid-ß deposits were identified, consistent with what has been described in other geriatric nonhuman primates. Phospho-tau pathology, including neurofibrillary tangles, a feature not well-described in other primate models, was also abundant. CONCLUSIONS AND RELEVANCE: Our results suggest that more detailed, prospective, longitudinal studies are warranted utilizing this particular species to see if they represent a viable model for human brain aging.

Sequential Nucleophilic Aromatic Substitution Reactions of Activated Halogens.

Building blocks have been identified that can be functionalised by sequential nucleophilic aromatic substitution. Some examples are reported that involve the formation of cyclic benzodioxin and phenoxathiine derivatives from 4,5-difluoro-1,2-dinitrobenzene, racemic quinoxaline thioethers, and sulfones from 2,3-dichloroquinoxaline and (2-aminophenylethane)-2,5-dithiophenyl-4-nitrobenzene from 1-(2-aminophenylethane)-2-fluoro-4,5-dinitrobenzene. Four X-ray single-crystal structure determinations are reported, two of which show short intermolecular N-O…N "π hole" contacts.

Provision of oral medicine in Scottish oral and maxillofacial surgery units: where are we and where are we going?

Introduction Oral medicine (OM) care occupies a significant quantity of oral and maxillofacial surgery (OMFS) outpatient clinical time. This survey aims to examine the current provision of OM care in OMFS units and explore opinions on how to improve the delivery of OM services across Scotland.Method An anonymous online questionnaire was distributed to all (33) OMFS consultants in Scotland. A range of questions were asked, covering place of work, formal OM training, proportion of time spent delivering OM clinical care, referral practices and support for a managed clinical network (MCN) in Scotland.Results A total of 18 (55%) OMFS consultants completed the survey. The majority of respondents (72%) worked in a university teaching hospital (UTH) setting. While none of the respondents were on the OM specialist register, most (72%) had received formal training in OM during their OMFS specialty training. Time dedicated to OM in outpatient clinics varied between less than 20% and 20-40% of clinical time. The majority of respondents (50%) referred 1-2 patients per month to OM. Most OMFS consultants (72%) felt that local OM services should be expanded and 78% would support the inclusion of OM specialists as part of the OMFS outpatient clinic team.Conclusion This study highlights the significant contribution to OM care within OMFS units in Scotland and emphasises the need for close collaboration between specialties. There is support for OM specialists to form part of the OMFS clinical team in UTHs or district general hospitals. Additionally, there is widespread support for the development of a MCN model of OM care in Scotland.

Epidemiology and Management of Pediatric Fractures in Malawi.

BACKGROUND: Pediatric fractures are common in Malawi, and surgical care, when needed, remains inaccessible to many. Understanding which children in Malawi receive surgery or nonsurgical treatment would help set priorities for trauma system development. METHODS: We used multivariate logistic regression to evaluate associations between surgical treatment and age, sex, school enrollment, injury mechanism, fracture type, open fracture, referral status, hospital of presentation, delayed presentation (≥2 days), healthcare provider, and inpatient vs outpatient treatment. RESULTS: From 2016 to 2020, 10,400 pediatric fractures were recorded in the Malawi Fracture Registry. Fractures were most commonly of the wrist (26%), forearm (17%), and elbow (14%). Surgical fixation was performed on 4.0% of patients, and 24 (13.0%) open fractures were treated nonsurgically, without débridement or fixation. Fractures of the proximal and diaphyseal humerus (odds ratio [OR], 3.72; 95% confidence interval [CI], 2.36 to 5.87), knee (OR, 3.16; 95% CI, 1.68 to 5.95), and ankle (OR, 2.63; 95% CI, 1.49 to 4.63) had highest odds of surgery. Odds of surgical treatment were lower for children referred from another facility (OR, 0.62; 95% CI, 0.49 to 0.77). CONCLUSIONS: Most Malawian children with fractures are treated nonsurgically, including many who may benefit from surgery. There is a need to increase surgical capacity, optimize referral patterns, and standardize fracture management in Malawi.

A computational account of transsaccadic attentional allocation based on visual gain fields.

Coordination of goal-directed behavior depends on the brain's ability to recover the locations of relevant objects in the world. In humans, the visual system encodes the spatial organization of sensory inputs, but neurons in early visual areas map objects according to their retinal positions, rather than where they are in the world. How the brain computes world-referenced spatial information across eye movements has been widely researched and debated. Here, we tested whether shifts of covert attention are sufficiently precise in space and time to track an object's real-world location across eye movements. We found that observers' attentional selectivity is remarkably precise and is barely perturbed by the execution of saccades. Inspired by recent neurophysiological discoveries, we developed an observer model that rapidly estimates the real-world locations of objects and allocates attention within this reference frame. The model recapitulates the human data and provides a parsimonious explanation for previously reported phenomena in which observers allocate attention to task-irrelevant locations across eye movements. Our findings reveal that visual attention operates in real-world coordinates, which can be computed rapidly at the earliest stages of cortical processing.

Poly[3-methyl-pyridinium [(µ2-di-hydrogen phosphito)bis(µ3-hydrogen phosphito)dizinc]].

In the title compound, {(C6H8N)[Zn2(HPO3)2(H2PO3)]}n, the constituent ZnO4, HPO3 and H2PO3 polyhedra of the inorganic component are linked into (010) sheets by Zn-O-P bonds (mean angle = 134.4°) and the layers are reinforced by O-H⋯O hydrogen bonds. The protonated templates are anchored to the inorganic sheets via bifurcated N-H⋯(O,O) hydrogen bonds.

Effects of neural oscillation power and phase on discrimination performance in a visual tilt illusion.

Neural oscillations reflect fluctuations in the relative excitation/inhibition of neural systems1,2,3,4,5 and are theorized to play a critical role in canonical neural computations6,7,8,9 and cognitive processes.10,11,12,13,14 These theories have been supported by findings that detection of visual stimuli fluctuates with the phase of oscillations prior to stimulus onset.15,16,17,18,19,20,21,22,23 However, null results have emerged in studies seeking to demonstrate these effects in visual discrimination tasks,24,25,26,27 raising questions about the generalizability of these phenomena to wider neural processes. Recently, we suggested that methodological limitations may mask effects of phase in higher-level sensory processing.28 To test the generality of phasic influences on perception requires a task that involves stimulus discrimination while also depending on early sensory processing. Here, we examined the influence of oscillation phase on the visual tilt illusion, in which a center grating has its perceived orientation biased away from the orientation of a surround grating29 due to lateral inhibitory interactions in early visual processing.30,31,32 We presented center gratings at participants' subjective vertical angle and had participants report whether the grating appeared tilted clockwise or counterclockwise from vertical on each trial while measuring their brain activity with electroencephalography (EEG). In addition to effects of alpha power and aperiodic slope, we observed robust associations between orientation perception and alpha and theta phase, consistent with fluctuating illusion magnitude across the oscillatory cycle. These results confirm that oscillation phase affects the complex processing involved in stimulus discrimination, consistent with its purported role in canonical computations that underpin cognition.

Chiral Thianthrenes.

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different Rf values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate.

Improving the management of open tibia fractures, Malawi.

Objective: To assess the impact of an open fracture intervention bundle on clinical management and patient outcomes of adults in Malawi with open tibia fractures. Methods: We conducted a before-and-after implementation study in Malawi in 2021 and 2022 to assess the impact of an open fracture intervention bundle, including a national education course for clinical officers and management guidelines for open fractures. We recruited 287 patients with open tibia fractures. The primary outcome was a before-and-after comparison of the self-reported short musculoskeletal function assessment score, a measure of patient function. Secondary outcomes included clinical management; and clinician knowledge and implementation evaluation outcomes of 57 health-care providers attending the course. We also constructed multilevel regression models to investigate associations between clinical knowledge, patient function, and implementation evaluation before and after the intervention. Findings: The median patient function score at 1 year was 6.8 (interquartile range, IQR: 1.5 to 14.5) before intervention and 8.4 (IQR: 3.8 to 23.2) after intervention. Compared with baseline scores, we found clinicians' open fracture knowledge scores improved 1 year after the intervention was implemented (mean posterior difference: 1.6, 95% highest density interval: 0.9 to 2.4). However, we found no difference in most aspects of clinicians' open fracture management practice. Conclusion: Despite possible improvement in clinician knowledge and positive evaluation of the intervention implementation, our study showed that there was no overall improvement in clinical management, and weak evidence of worsening patient function 1 year after injury, after implementation of the open fracture intervention bundle.

UrethroNAV: the aetiology and extent of idiopathic urethral stricture in an Australian population.

Background: Lichen sclerosus (LS) is considered a causative factor in 10% of cases of idiopathic urethral stricture disease (IUSD), which is important for determining management strategies due to the underlying pathophysiology. Traditional excision urethroplasty may not be effective as inflammation often extends beyond the macroscopic stricture. This pilot study aims to answer two research questions: is LS an underlying cause of some idiopathic cause of strictures, and, if there is histological evidence suggesting predisposition of the surrounding tissue to strictures. Methods: Biopsies were taken from the stricture site as well as 1 and 2 cm proximal and distal in patients with IUSD. Histological features, including macroscopic and microscopic findings, were reported, including the presence of LS, hyperkeratosis, epidermal changes, lichenoid infiltrates, ulceration, scarring, and inflammation. Methylene blue was used to aid in locating damaged urothelium. Patients were prospectively followed up after urethroplasty. Results: From 109 urethroplasties performed between 2019 to 2022, 15 male patients were enrolled after meeting specific inclusion criteria. These criteria included a diagnosis of IUSD and the absence of any evidence of trauma, macroscopic inflammatory disease, or previous endoscopic instrumentation of the urethra. Patients had to be at least 16 years old and medically suitable for undergoing urethroplasty. The study was approved by the hospitals ethics committees. None had macroscopic evidence of LS. One patient had microscopic evidence of LS at the 2 cm proximal biopsy only. A total of 93% of patients had scarring proximal and distal to the stricture, while 20-40% had inflammatory change. The patient with microscopic LS and two inflammatory change patients had stricture recurrence after urethroplasty. Additionally, one patient with inflammatory changes was diagnosed with penile intraepithelial neoplasia (PeIN) and underwent partial penectomy. Conclusions: Findings suggest that an underlying cause of IUSD could be LS. Additionally, the pathophysiology may involve scarring and inflammation beyond the limits of the stricture with extension distal from the stricture site. Careful evaluation for concomitant urethral pathology should be considered in cases of inflammatory changes. These findings should be considered in the surgical management of IUSD and warrant further research into the role of routine biopsy and drug targets in USD.

Epidemiology and Treatment of Distal Radius Fractures at Four Public Hospitals in Malawi.

BACKGROUND: Little is known about the burden or management of distal radius fractures (DRFs) in low- and middle-income countries. The purpose of this study was to describe the care of DRFs in Malawi. METHODS: We retrospectively reviewed a registry of all patients with fractures who presented to the orthopaedic departments at four public hospitals in Malawi. RESULTS: Totally, 1,440 patients (14.5%) were with a DRF. Average age was 40, and 888 (62.0%) were male. Surgery was done for 122 patients (9.5%). Patients presenting to Queen Elizabeth Hospital, patients presenting after a fall, and patients initially evaluated by an orthopaedic registrar or orthopaedic clinical officer had lower odds of receiving surgical treatment. Meanwhile, open injuries had the greatest odds of receiving surgery. CONCLUSION: The most common musculoskeletal injury among patients in the Malawi Fracture Registry was fractures of the distal radius. These most affected young adult male patients may benefit from surgery; however, the majority were managed nonsurgically. Lack of access to surgical fixation and conservative follow-up may have long-term functional consequences in a predominantly agrarian society. Outcomes-based research is needed to help guide management decisions and standardize patient care and referral protocols.

Fracture related infection in open tibial fractures.

Open tibia fractures frequently occur following high-energy trauma. Contamination of the fracture site combined with limited soft tissue coverage and blood supply means that these open fractures are associated with a high rate of complications, including fracture related infection (FRI). FRI is associated with lowered patient outcomes and requires early recognition and appropriate surgical and medical management. The current evidence on FRI after open tibial fractures largely is limited to case series, small retrospective cohort studies and expert opinion. Recent expert consensus has produced guidelines with the aim of standardising care for these patients. This review summarises the current management strategies employed in treating FRI following open tibial fractures and where possible the evidence behind them.

Robotic surgery education in Australia and New Zealand: primetime for a curriculum.

BACKGROUND: Globally, robotic surgery (RS) has witnessed remarkable growth, yet Australia and New Zealand (ANZ) lack dedicated RS training programs, creating a workforce gap. This narrative review synthesises international research to explore trends and challenges in robotic education. METHODS: We conducted a comprehensive literature review, searching PubMed, Google Scholar, and MEDLINE using keywords like 'robotic surgery', 'surgical education', 'robotic surgery training', and 'robotic surgery curriculum'. We selected studies contributing to understanding current curricula, training tools, and issues in robotic education, utilising the international experience and how it might apply to the ANZ context. RESULTS: RS in ANZ has grown significantly over two decades, but formal curricula for trainees are absent. North America and Europe employ diverse training tools and curricula. Barriers include cost, access, time constraints, equipment complexity, changing training environments, and competition from emerging robotic surgical systems. Balancing the curriculum's demands with trainees' existing requirements is essential. CONCLUSION: Developing a tailored RS curriculum within ANZ's surgical training is crucial for RS to become the primary surgical approach in the future. By working towards a national curriculum we can prepare skilled trainees in robotics to meet the rising demand. The most significant barrier is the lack of robotics in public hospital where trainees are based. This curriculum should encompass online teaching modules, bedside assistance, surgical simulation, dual console mentoring, and primary operator experience.

The influence of natural image statistics on upright orientation judgements.

Humans have well-documented priors for many features present in nature that guide visual perception. Despite being putatively grounded in the statistical regularities of the environment, scene priors are frequently violated due to the inherent variability of visual features from one scene to the next. However, these repeated violations do not appreciably challenge visuo-cognitive function, necessitating the broad use of priors in conjunction with context-specific information. We investigated the trade-off between participants' internal expectations formed from both longer-term priors and those formed from immediate contextual information using a perceptual inference task and naturalistic stimuli. Notably, our task required participants to make perceptual inferences about naturalistic images using their own internal criteria, rather than making comparative judgements. Nonetheless, we show that observers' performance is well approximated by a model that makes inferences using a prior for low-level image statistics, aggregated over many images. We further show that the dependence on this prior is rapidly re-weighted against contextual information, even when misleading. Our results therefore provide insight into how apparent high-level interpretations of scene appearances follow from the most basic of perceptual processes, which are grounded in the statistics of natural images.

A transparent synthetic peptide hydrogel as a haemostatic agent in athermal nerve sparing robot-assisted radical prostatectomy: an observational study.

Background: PuraStat® is a new synthetic haemostatic agent constituting peptides that self-assemble into sheets when exposed to ionic charges. The objective of this submission is to assess the perioperative, functional and user-reported outcomes of PuraStat® as an athermal topical haemostatic agent for use on the neurovascular bundle (NVB) in robot-assisted radical prostatectomy (RARP), and to inform further research into this developing field. Methods: Demographic and disease data for 29 consecutive patients undergoing RARP were recorded. PuraStat® was used as the primary haemostatic agent to the NVB, without thermal or suture haemostasis, unless necessary. Preoperative, 1-h postoperative and 24-h postoperative haemoglobin (Hb) were measured. Operative data including postoperative complications up to 30 days were noted. Urinary function, continence and erectile function (EF) were measured pre- and postoperatively with the International Prostate Symptom Score (IPSS), patient reporting of pad usage, and International Index of Erectile Function (IIEF)-5 respectively. A qualitative assessment of PuraStat® was made intraoperatively by the surgical assistant in the following categories: transparency, haemostatic efficacy, ready-to-use, handling, and overall satisfaction. Results: Twenty-nine males aged between 49 and 75 years underwent a nerve-sparing RARP under a single surgeon for clinically significant prostate cancer with PuraStat® used as the primary haemostatic agent at the NVB. One patient required an additional haemostatic suture. The median prostate volume was 36 mL. Mean blood loss was 363 mL. The mean Hb at 1 and 24 h postoperative was 135.2 and 125.1 mg/dL. Median Hb change from 1-24 h postoperative was 11 mg/dL. No transfusions were required, and there were no postoperative complications. Urinary function and continence were preserved. EF in our series was lower than published data. Conclusions: Our observational study suggests that PuraStat® is a safe haemostatic agent in RARP with similar perioperative bleeding outcomes, comparable long-term urinary outcomes and a high level of intraoperative user satisfaction. The effects on EF requires further investigation. PuraStat® appears to be a useful therapeutic tool for the urologist performing RARPs.

Association of Periprosthetic Fibula Fracture With Knotless Suture Button (TightRope) Fixation for Ankle Syndesmosis in Elite Athletes.

Background: Suture button fixation is frequently used to stabilize the distal tibiofibular syndesmosis in athletes sustaining an isolated ligamentous syndesmosis injury. Purpose: To report on a series of periprosthetic fibula fractures adjacent to the lateral suture button after a subsequent unrelated ankle injury or progressive stress injury after initial ankle syndesmosis stabilization using the knotless TightRope (Arthrex). Study Design: Case series; Level of evidence, 4. Methods: Eight elite athletes with periprosthetic fibula fractures and stress injuries around the lateral suture buttons were evaluated. In all athletes, the knotless TightRope had been used to stabilize an isolated ligamentous ankle syndesmotic injury, after which all patients recovered and returned to professional sports at their preinjury level. The athletes subsequently developed an acute fibula fracture or a fibula stress fracture related to the 3.7-mm drill hole in the fibula adjacent to the lateral suture buttons after a mean of 14.1 months (range, 5-29 months). The management of these complications was analyzed. Results: Five athletes sustained a periprosthetic fibula fracture in the form of undisplaced spiral Weber B injuries after a subsequent, unrelated injury. Poor healing response was noted with initial nonoperative treatment for the first 2 athletes, and surgical intervention was performed with successful union of the fracture and return to sports. The subsequent 3 athletes had early surgery with uneventful recovery. Another 3 athletes developed stress injuries adjacent to the fibula suture button without a history of acute trauma. In 2 of the 3 athletes, the position of lateral suture buttons was in the anterior third of the fibula. Initial nonoperative management yielded poor healing response, and subsequent surgical intervention was required to enable healing and return to sports. Conclusion: Nonoperative management of fractures adjacent to the fibula suture button of a knotless TightRope may lead to a delay in union. Therefore, early surgical intervention should be considered in elite athletes, whose return-to-sports time is critical. Care is needed to ensure that the fibula hole for the suture button is centrally located because the eccentric placement of the fibula hole in the anterior third of the fibula may contribute to the development of a stress reaction or stress fracture. Surgical intervention for a periprosthetic fibula stress fracture leads to satisfactory resolution of symptoms.

New Functionalized Phenoxazines and Phenothiazines.

The reaction of either 2-aminophenol or 2-(N-methylamino)phenol with 1,2-difluoro-4,5-dinitrobenzene and sodium carbonate in EtOH gives 2,3-dinitrophenoxazines. One nitro group, conjugated to the aryl ether, was displaced from 2,3-dinitro-10-methylphenoxazine with different nucleophiles: BuNH2, KOEt, and KOH. The reaction of 2-aminothiophenol with 1,2-difluoro-4,5-dinitrobenzene under the same conditions gives 2,3-dinitrophenothiazine. This reacted with BuNH2 forming 2-butylamino-3-nitrophenothiazine. The dihedral angles of the different compounds are compared.