Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine.

VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.

Click detection rate variability of central North Pacific sperm whales from passive acoustic towed arrays.

Passive acoustic monitoring (PAM) is an optimal method for detecting and monitoring cetaceans as they frequently produce sound while underwater. Cue counting, counting acoustic cues of deep-diving cetaceans instead of animals, is an alternative method for density estimation, but requires an average cue production rate to convert cue density to animal density. Limited information about click rates exists for sperm whales in the central North Pacific Ocean. In the absence of acoustic tag data, we used towed hydrophone array data to calculate the first sperm whale click rates from this region and examined their variability based on click type, location, distance of whales from the array, and group size estimated by visual observers. Our findings show click type to be the most important variable, with groups that include codas yielding the highest click rates. We also found a positive relationship between group size and click detection rates that may be useful for acoustic predictions of group size in future studies. Echolocation clicks detected using PAM methods are often the only indicator of deep-diving cetacean presence. Understanding the factors affecting their click rates provides important information for acoustic density estimation.

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [18F]BCPP-EF PET study.

BACKGROUND: Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [18F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain. RESULTS: Analyses were performed in a voxel-wise manner and identified significant associations between [18F]BCPP-EF DVRCS-1 in the precentral gyrus and parietal lobes and WAIS-IV predicted IQ, WAIS-IV arithmetic and WAIS-IV symbol-digit substitution scores (voxel-wise Pearson's correlation coefficients transformed to Z-scores, thresholded at Z = 2.3 family-wise cluster correction at p < 0.05, n = 16). Arithmetic scores were associated with middle frontal and post-central gyri tracer uptake, symbol-digit substitution scores were associated with precentral gyrus tracer uptake. RAVLT recognition scores were associated with [18F]BCPP-EF DVRCS-1 in the middle frontal gyrus, post-central gyrus, occipital and parietal regions (n = 20). CONCLUSIONS: Taken together, our findings support the theory that mitochondrial function may contribute to general intelligence and indicate that interindividual differences in MC-I should be a key consideration for research into mitochondrial dysfunction in conditions with cognitive impairment.

Analyzing Linear and Angular Deviations After Guided Surgery for Dental Implant Placement: A Preliminary Study.

PURPOSE: This study aimed to assess the accuracy and precision of prosthetically-driven implant placement achieved through static computer-aided implant surgery. The primary objective was to analyze the linear and angular deviations of dental implants in patients treated at a university dental clinic. Various types of surgical techniques and templates were utilized to optimize implant positioning. MATERIALS AND METHODS: A total of fiftythree dental implants were included in this study. The implants were positioned using either tooth-supported templates or tooth-tissue-supported templates with fixation pins. Two distinct guided surgery approaches were used, these being pilot drill guided and fully guided. Three-dimensional (3D) data from the implant planning phase was superimposed with the 3D data from the final implant positions using the 'Treatment Evaluation' tool within CoDiagnostix. implant planning software (Straumann AG). This enabled the automatic calculation of deviations in implant placement accuracy. RESULTS: Average angular deviation observed was 3.90 degrees. For linear deviations, the mean 3D deviation at the most coronal point of the implants was 1.04 mm, while at the implant apex it was 1.56 mm. CONCLUSION: This research demonstrates the feasibility of a digital workflow for guided implant surgery, offering a promising treatment option. Nonetheless, it is important to note that deviations do occur, with the apical region of the implant being the most affected area. Care should be taken, particularly in cases of limited bone availability.

Narwhal (Monodon monoceros) echolocation click rates to support cue counting passive acoustic density estimation.

Estimating animal abundance is fundamental for effective management and conservation. It is increasingly done by combining passive acoustics with knowledge about rates at which animals produce cues (cue rates). Narwhals (Monodon monoceros) are elusive marine mammals for which passive acoustic density estimation might be plausible, but for which cue rates are lacking. Clicking rates in narwhals were investigated using a dataset from sound and movement tag records collected in August 2013-2016 and 2019 in East Greenland. Clicking rates were quantified for ∼1200 one-second-long systematic random samples from 8 different whales. Generalized additive models were used to model (1) the probability of being in a clicking state versus depth and (2) the clicking rate while in a clicking state, versus time and depth. The probability of being in a clicking state increased with depth, reaching ∼1.0 at ∼500 m, while the number of clicks per second (while in a clicking state) increased with depth. The mean cue production rate, weighted by tag duration, was 1.28 clicks per second (se = 0.13, CV = 0.10). This first cue rate for narwhals may be used for cue counting density estimation, but care should be taken if applying it to other geographical areas or seasons, given sample size, geographical, and temporal limitations.

Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium.

Background: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. Methods: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. Results: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. Conclusions: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Fin whale song evolution in the North Atlantic.

Animal songs can change within and between populations as the result of different evolutionary processes. When these processes include cultural transmission, the social learning of information or behaviours from conspecifics, songs can undergo rapid evolutions because cultural novelties can emerge more frequently than genetic mutations. Understanding these song variations over large temporal and spatial scales can provide insights into the patterns, drivers and limits of song evolution that can ultimately inform on the species' capacity to adapt to rapidly changing acoustic environments. Here, we analysed changes in fin whale (Balaenoptera physalus) songs recorded over two decades across the central and eastern North Atlantic Ocean. We document a rapid replacement of song INIs (inter-note intervals) over just four singing seasons, that co-occurred with hybrid songs (with both INIs), and a clear geographic gradient in the occurrence of different song INIs during the transition period. We also found gradual changes in INIs and note frequencies over more than a decade with fin whales adopting song changes. These results provide evidence of vocal learning in fin whales and reveal patterns of song evolution that raise questions on the limits of song variation in this species.

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35-45 Hz) power (n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power (t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

Synaptic Terminal Density Early in the Course of Schizophrenia: An In Vivo UCB-J Positron Emission Tomographic Imaging Study of SV2A.

BACKGROUND: The synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [11C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers. METHODS: Forty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio in the anterior cingulate, frontal, and dorsolateral prefrontal cortices; the temporal, parietal and occipital lobes; and the hippocampus, thalamus, and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale. RESULTS: We found no significant effects of group on [11C]UCB-J VT or distribution volume ratio in most regions of interest (effect sizes from d = 0.0-0.7, p > .05), with two exceptions: we found lower distribution volume ratio in the temporal lobe (d = 0.7, uncorrected p < .05) and lower VT/fp in the anterior cingulate cortex in patients (d = 0.7, uncorrected p < .05). The Positive and Negative Syndrome Scale total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r = -0.48, p = .03). CONCLUSIONS: These findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects. When taken together with previous evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of SCZ.

The 'social' in psychiatry and mental health: quantification, mental illness and society in international scientific networks (1920s-1950s).

The post-World War II international mental health movement placed significant emphasis on the concept of the 'social environment', a true paradigm shift in thinking about the causes of mental illness. Rather than focusing on individual risk factors, experts and policy-makers began to consider the interplay between social context and mental health and illness. Also, during this period, quantification gained prominence within the expanding field of Western psychiatry. Eventually, the concept of the 'social' became fragmented into quantifiable social determinants that could be correlated with mental illness and subjected to systematic neutralization. This trajectory paved the way for the prevailing biomedical psychiatric epidemiology. This broader inquiry challenges us to redefine our understanding of the 'social' in the context of mental health research and practice.

Mixed-Thickness Tunnel Access (MiTT) through a Linear Vertical Mucosal Incision for a Minimally Invasive Approach for Root Coverage Procedures in Anterior and Posterior Sites: Technical Description and Case Series with 1-Year Follow-Up.

PURPOSE: The goal of this article was to introduce a new root coverage (RC) technique, the mixed-thickness tunnel access (MiTT) technique, which approaches a full-split design and intends to augment soft tissues coronal to the gingival margin. It was shown step-by-step, and the results were presented in a case series. METHODS: Healthy individuals (non-diabetics) and non-smokers with gingival recession (GR) type 1 or 2 (RT1 or RT2) were included. After evaluation, prophylaxis was performed 14 days before the surgical procedure. During the surgical appointment, one or two vertical incision(s) on the mucosa (around 1-2 mm apical to the MGJ), lateral to the papilla base, was/were performed after anesthesia. Initially, there was a partial incision to detach the mucosa of the muscles (split design). It was permitted (but not mandatory) to perform intrasulcular incisions. Through the vertical incision, internally, subperiosteal access from the MGJ toward the gingival margin (coronally) was performed to create a full-thickness tunnel. Then, communication from the vertical incision with the gingival sulcus and the papilla base occurred, keeping the papilla tip intact. A connective tissue graft was harvested and inserted through the linear incision or intrasulcularly. There were interrupted sutures. An adjunctive material may be applied (e.g., Endogain). The root coverage was measured using a periodontal probe and considered fully covered when the gingival margin was 1 mm coronal to the cementum-enamel junction (CEJ). RESULTS: Nine healthy individuals (seven females and two males) aged 19 and 43 were enrolled. They were treated following the MiTT steps. Four cases had a single GR; two patients had two teeth involved; and three others had three or four GR. There were seven cases of RT1 and two RT2. All RT1 cases achieved 100% RC, while the mean RC obtained for RT2 was around 80%. CONCLUSION: The MiTT technique can be considered a more straightforward approach for minimally invasive surgical techniques, which is a feasible option to treat RC with a high success rate, predictability, and esthetic preservation. Therefore, there is a technical sensitivity to performing the full-split design procedure.

Implications of porpoise echolocation and dive behaviour on passive acoustic monitoring.

Harbour porpoises are visually inconspicuous but highly soniferous echolocating marine predators that are regularly studied using passive acoustic monitoring (PAM). PAM can provide quality data on animal abundance, human impact, habitat use, and behaviour. The probability of detecting porpoise clicks within a given area (P̂) is a key metric when interpreting PAM data. Estimates of P̂ can be used to determine the number of clicks per porpoise encounter that may have been missed on a PAM device, which, in turn, allows for the calculation of abundance and ideally non-biased comparison of acoustic data between habitats and time periods. However, P̂ is influenced by several factors, including the behaviour of the vocalising animal. Here, the common implicit assumption that changes in animal behaviour have a negligible effect on P̂ between different monitoring stations or across time is tested. Using a simulation-based approach informed by acoustic biologging data from 22 tagged harbour porpoises, it is demonstrated that porpoise behavioural states can have significant (up to 3× difference) effects on P̂. Consequently, the behavioural state of the animals must be considered in analysis of animal abundance to avoid substantial over- or underestimation of the true abundance, habitat use, or effects of human disturbance.

A sperm whale cautionary tale about estimating acoustic cue rates for deep divers.

Passive acoustic density estimation has been gaining traction in recent years. Cue counting uses detected acoustic cues to estimate animal abundance. A cue rate, the number of acoustic cues produced per animal per unit time, is required to convert cue density into animal density. Cue rate information can be obtained from animal borne acoustic tags. For deep divers, like beaked whales, data have been analyzed considering deep dive cycles as a natural sampling unit, based on either weighted averages or generalized estimating equations. Using a sperm whale DTAG (sound-and-orientation recording tag) example we compare different approaches of estimating cue rate from acoustic tags illustrating that both approaches used before might introduce biases and suggest that the natural unit of analysis should be the whole duration of the tag itself.

Influence of Implant Scanbody Material and Intraoral Scanner on the Accuracy of Complete-Arch Digital Implant Impressions.

PURPOSE: To evaluate the accuracy of complete-arch digital implant impressions using different intraoral scan body (ISB) materials and intraoral scanners (IOSs). MATERIALS AND METHODS: The mandibular dental cast of an edentulous patient with six tissue-level dental implants was used as master cast. Two types of ISBs, polyether-ether-ketone (PEEK) and plasma-coated medical titanium, were used with five IOSs: TRIOS 4 (T4), Virtuo Vivo (VV), Medit i700 (Mi700), iTero5D (i5D), and Primescan (PS). To assess accuracy, digital impressions (n=10) with each IOS and ISB were compared to two reference models obtained by digitizing the master cast with each ISB type using a desktop scanner (IScan4D LS3i) and importing the scan data into metrology software (Geomagic Control X). Root-mean-square (RMS) error was employed to evaluate overall deviation values (trueness), while precision was determined using the standard deviation (SD) of RMS values. Statistical significance was set at P < 0.05. The Kruskal-Wallis test was used, followed by the pairwise comparison method with Bonferroni correction (α=.05). RESULTS: An interaction between ISB material and IOS was found (P=0.001). Plasma-coated medical titanium ISBs demonstrated significantly higher trueness and precision compared to PEEK ISBs with T4 (P=0.001), Mi700 (P=0.001; P=0.004), and i5D (P=0.001). Conversely, VV exhibited higher trueness and precision values with PEEK ISBs (P=0.005; P=0.003). PS provided the highest trueness and precision regardless of the ISB material (P=0.912). T4 showed the lowest accuracy for PEEK ISBs, and VV for plasma-coated medical titanium ISBs. CONCLUSION: Except for PS, all IOSs showed significant differences between ISB materials. PS demonstrated the highest accuracy with both ISB materials, whereas T4 had the lowest accuracy for PEEK ISBs, and VV showed the lowest accuracy for plasma-coated medical titanium ISBs.

Effect of splinting scan bodies on the trueness of complete-arch digital implant scans with 5 different intraoral scanners.

STATEMENT OF PROBLEM: The absence of fixed reference points can affect the trueness of complete-arch intraoral digital implant scans. The effect of splinting intraoral scan bodies (ISBs) or the inclusion of artificial landmarks (AL) on the trueness of complete-arch digital implant scans is still unclear. PURPOSE: The purpose of this study was to analyze the effect of splinting ISBs or the inclusion of AL on the trueness of complete-arch digital implant scans with 5 intraoral scanners (IOSs). MATERIAL AND METHODS: Six tissue-level dental implants (Straumann Tissue Level) were placed in an edentulous patient, and the correspondent definitive cast was digitized with a desktop scanner (IScan4D LS3i) to obtain the reference digital cast. Digital scans (n=10) were performed with 5 IOSs: TRIOS 4, Virtuo Vivo, Medit i700, iTero Element 5D, and Cerec Primescan. Three different scanning techniques were evaluated: conventional (cIOSs), splinted (sIOSs), and AL (AL-IOSs). The scan data obtained were imported into a metrology software program and superimposed to the reference digital cast by using a best-fit algorithm. The overall deviations of the positions of the ISBs were evaluated by using the root-mean-square (RMS) error (α=.05). RESULTS: The mean ±standard deviation trueness values for the cIOSs, sIOSs, and AL-IOSs groups were 48 ±8 µm, 53 ±7 µm, and 49 ±11 µm, respectively, with no statistically significant differences (P=.06). Significant differences were found for the IOSs used with each technique (P<.001). Primescan (27 ±4 µm cIOSs; 28 ±3 µm sIOSs; 31 ±3 µm AL-IOSs) showed significantly higher trueness than iTero 5D (47 ±5 µm cIOSs; 47 ±4 µm sIOSs; 50 ±6 µm AL-IOSs) (P=.002) and TRIOS 4 (93 ±18 µm cIOSs; 76 ±18 µm sIOSs; 107 ±13 µm AL-IOSs) (P=.001) for all techniques. In addition, no significant differences were found between the techniques by using iTero 5D or Primescan (P=.348 and P=.059, respectively). CONCLUSIONS: The cIOSs, sIOSs, and AL-IOSs techniques showed similar trueness. The IOS used influenced the trueness of complete-arch digital implant scans.

Augmented Reality in Breast Surgery Education.

Introduction: Augmented reality (AR) has demonstrated a potentially wide range of benefits and educational applications in the virtual health ecosystem. The concept of real-time data acquisition, machine learning-aided processing, and visualization is a foreseen ambition to leverage AR applications in the healthcare sector. This breakthrough with immersive technologies like AR, mixed reality, virtual reality, or extended reality will hopefully initiate a new surgical era: that of the use of the so-called surgical metaverse. Methods: This paper focuses on the future use of AR in breast surgery education describing two potential applications (surgical remote telementoring and impalpable breast cancer localization using AR), along with the technical needs to make it possible. Conclusion: Surgical telementoring and impalpable tumors noninvasive localization are two examples that can have success in the future provided the improvements in both data transformation and infrastructures are capable to overcome the current challenges and limitations.

Reward processing in schizophrenia and its relation to Mu opioid receptor availability and negative symptoms: A [11C]-carfentanil PET and fMRI study.

BACKGROUND: Reward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. Here, we examined the association between MOR availability and the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging. METHOD: 37 subjects (18 with Schizophrenia with moderate severity negative symptoms and 19 age and sex-matched healthy controls) underwent a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. Participants also had a [11C]-carfentanil PET scan to measure MOR availability. RESULTS: Reward anticipation was associated with increased neural activation in a widespread network of brain regions including the striatum. Patients with schizophrenia had both significantly lower MOR availability in the striatum as well as striatal hypoactivation during reward anticipation. However, there was no association between MOR availability and striatal neural activity during reward anticipation in either patient or controls (Pearson's Correlation, controls df = 17, r = 0.321, p = 0.18, patients df = 16, r = 0.295, p = 0.24). There was no association between anticipation-related neural activation and negative symptoms (r = -0.120, p = 0.14) or anhedonia severity (social r = -0.365, p = 0.14 physical r = -0.120, p = 0.63). CONCLUSIONS: Our data suggest reduced MOR availability in schizophrenia might not underlie striatal hypoactivation during reward anticipation in patients with established illness. Therefore, other mechanisms, such as dopamine dysfunction, warrant further investigation as treatment targets for this aspect of the disorder.