Three-Dimensional Evaluation of the Accuracy of Zygomatic Implant Placement Through an In-House Fully Guided Approach.

Purpose: To validate guided surgery for zygomatic implants (ZIs) by analyzing the final position of the implants relative to the preoperatively planned position. Material and Methods: Five patients with fully edentulous atrophic maxillae treated with four ZIs through a fully guided implant surgical approach were evaluated. The preoperative phase included digital planning, through which the surgical guide was designed and created. Analysis of the guided surgery accuracy was carried out by superimposing the digital planning over the final position of the implants using preoperative and postoperative CBCT. The radiologic evaluation included implant angular deviation, entrance deviation, exit deviation, platform deviation, and apex apicocoronal and mesiodistal deviation. Results: All five patients (two men and three women; mean age: 61.8 ± 3 years) were each treated with four ZIs using a fully guided approach with an extrasinusal path, obtaining ideal emergence of the implants. Superimposition comparison found a mean axial angular implant deviation of 0.79 ± 0.41 degrees and a mean implant entrance deviation of 0.95 ± 0.26 degrees. The platform deviation was 0.62 ± 0.19 mm buccopalatally and 0.76 ± 0.14 mm mesiodistally, while the apical deviation was 0.42 ± 0.13 mm buccopalatally and 1.06 ± 0.37 mm mesiodistally. Conclusions: Guided surgery in zygomatic implants appears to be sufficiently accurate to make it a safe and predictable technique.

Pulse oximetry training landscape for healthcare workers in low- and middle-income countries: A scoping review.

Background: Pulse oximetry has been used in medical care for decades. Its use quickly became standard of care in high resource settings, with delayed widespread availability and use in lower resource settings. Pulse oximetry training initiatives have been ongoing for years, but a map of the literature describing such initiatives among health care workers in low- and middle-income countries (LMICs) has not previously been conducted. Additionally, the coronavirus disease 2019 (COVID-19) pandemic further highlighted the inequitable distribution of pulse oximetry use and training. We aimed to characterise the landscape of pulse oximetry training for health care workers in LMICs prior to the COVID-19 pandemic as described in the literature. Methods: We systematically searched six databases to identify studies reporting pulse oximetry training among health care workers, broadly defined, in LMICs prior to the COVID-19 pandemic. Two reviewers independently assessed titles and abstracts and relevant full texts for eligibility. Data were charted by one author and reviewed for accuracy by a second. We synthesised the results using a narrative synthesis. Results: A total of 7423 studies were identified and 182 screened in full. A total of 55 training initiatives in 42 countries met inclusion criteria, as described in 66 studies since some included studies reported on different aspects of the same training initiative. Five overarching reasons for conducting pulse oximetry training were identified: 1) anaesthesia and perioperative care, 2) respiratory support programme expansion, 3) perinatal assessment and monitoring, 4) assessment and monitoring of children and 5) assessment and monitoring of adults. Educational programmes varied in their purpose with respect to the types of patients being targeted, the health care workers being instructed, and the depth of pulse oximetry specific training. Conclusions: Pulse oximetry training initiatives have been ongoing for decades for a variety of purposes, utilising a multitude of approaches to equip health care workers with tools to improve patient care. It is important that these initiatives continue as pulse oximetry availability and knowledge gaps remain. Neither pulse oximetry provision nor training alone is enough to bolster patient care, but sustainable solutions for both must be considered to meet the needs of both health care workers and patients.

Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis.

The 26S proteasome is the largest and most complicated protease known, and changes to proteasome assembly or function contribute to numerous human diseases. Assembly of the 26S proteasome from its ~66 individual polypeptide subunits is a highly orchestrated process requiring the concerted actions of both intrinsic elements of proteasome subunits, as well as assistance by extrinsic, dedicated proteasome assembly chaperones. With the advent of near-atomic resolution cryo-electron microscopy, it has become evident that the proteasome is a highly dynamic machine, undergoing numerous conformational changes in response to ligand binding and during the proteolytic cycle. In contrast, an appreciation of the role of conformational dynamics during the biogenesis of the proteasome has only recently begun to emerge. Herein, we review our current knowledge of proteasome assembly, with a particular focus on how conformational dynamics guide particular proteasome biogenesis events. Furthermore, we highlight key emerging questions in this rapidly expanding area.

The Road Not Taken: Disconnection of a Human-Unique Cortical Pathway Underlying Naturalistic Social Perception in Schizophrenia.

Background: Efficient processing of complex and dynamic social scenes relies on intact connectivity of many underlying cortical areas and networks, but how connectivity anomalies affect the neural substrates of social perception remains unknown. Here we measured these relationships using functionally based localization of social perception areas, resting-state functional connectivity, and movie-watching data. Methods: In 42 participants with schizophrenia (SzPs) and 41 healthy control subjects, we measured the functional connectivity of areas localized by face-emotion processing, theory-of-mind (ToM), and attention tasks. We quantified the weighted shortest path length between visual and medial prefrontal ToM areas in both populations to assess the impact of these changes in functional connectivity on network structure. We then correlated connectivity along the shortest path in each group with movie-evoked activity in a key node of the ToM network (posterior temporoparietal junction [TPJp]). Results: SzPs had pronounced decreases in connectivity in TPJ/posterior superior temporal sulcus (TPJ-pSTS) areas involved in face-emotion processing (t81 = 4.4, p = .00002). In healthy control subjects, the shortest path connecting visual and medial prefrontal ToM areas passed through TPJ-pSTS, whereas in SzPs, the shortest path passed through the prefrontal cortex. While movie-evoked TPJp activity correlated with connectivity along the TPJ-pSTS pathway in both groups (r = 0.43, p = .002), it additionally correlated with connectivity along the prefrontal cortex pathway only in SzPs (rSzP = 0.56, p = .003). Conclusions: These results suggest that connectivity along the human-unique TPJ-pSTS pathway affects both the network architecture and functioning of areas involved in processing complex dynamic social scenes. These results demonstrate how focal connectivity anomalies can have widespread impacts across the cortex.

Anatomical predictors of need for decompressive craniectomy after stroke using voxel-based lesion symptom mapping.

BACKGROUND AND PURPOSE: Malignant cerebral edema (MCE) secondary to ischemic stroke is a highly morbid condition. Decompressive craniectomy (DC) is the only treatment for MCE that has been shown to reduce mortality. We examined whether early infarction and/or hypoperfusion in specific topographic regions was predictive of the need for later DC. METHODS: A retrospective database of patients evaluated for large vessel occlusion (LVO) stroke at Stanford between 2010 and 2019 was used. Thirty patients with LVO and baseline perfusion MRI who underwent DC were evaluated. Propensity matching based on age, lesion size, and recanalization status was performed on the remaining cohort. Baseline masks of apparent diffusion coefficient (ADC) + Tmax  >6 seconds lesions were generated using automated perfusion software. Voxel-based lesion symptom maping was used to perform logistic regression at each voxel to generate statistical maps of lesion location associated with DC. Hemispheres were combined to increase statistical power. RESULTS: Sixty patients were analyzed. After adjusting for age, lesion size, and recanalization status as covariates, scattered cortical regions, predominately within the temporal and frontal lobe, were mildly to moderately predictive of the need for DC (z-scores: 2.4-6.74, p < .01). CONCLUSIONS: Scattered temporal and frontal lobe regions on baseline diffusion and perfusion MRI were found to be mildly to moderately predictive of the need for subsequent DC in patients with LVO stroke.

TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ-IL-21-TNF-α+ CD4+ T cells the predominant population detected at later time points. Greater percentages of IFNγ-IL-21-TNF-α+ CD4+ T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

Accuracy of static fully guided implant placement in the posterior area of partially edentulous jaws: a cohort prospective study.

OBJECTIVE: A cohort prospective study was conducted to assess the three-dimensional positioning accuracy of the implant between pre-surgical and the final implant position using a static fully guided approach in the posterior area of the jaws. MATERIALS AND METHODS: A total of 60 implants (30 patients) were digitally analyzed after superimposing the Digital Imaging and Communications in Medicine (DICOM) files obtained from the Cone Beam Computed Tomography (CBCT) pre- and post-implant placement. The software calculations included deviations at the implant shoulder and at the implant apex, global deviation (3D offset), and angle deviation. Statistical analysis was performed with α = 0.05. RESULTS: Considering the total number of implants, mesiodistal, buccolingual, and apicocoronal mean deviations at the shoulder and implant apex were equal or below 0.21 ± 0.69 mm, and only the buccolingual mean deviation at the apex reached up to 0.67 ± 1.06 mm. The mesiodistal and apicocoronal deviations were not statistically significant at both the shoulder and apex levels of the implant. The mean total angular deviation was 5.62° ± 4.09. The main limitation of this surgical approach was the requirement for a wide mouth opening. CONCLUSIONS: Static fully guided surgery for dental implant placement exhibits minimum deviations respect to presurgical planning. The main limitation in the posterior areas is the requirement for a wide mouth opening. CLINICAL RELEVANCE: Even with minimum deviations clinically acceptable, precautions and safety margins must be respected when using static full-guided surgery to place dental implants.

Failure to engage the temporoparietal junction/posterior superior temporal sulcus predicts impaired naturalistic social cognition in schizophrenia.

Schizophrenia is associated with marked impairments in social cognition. However, the neural correlates of these deficits remain unclear. Here we use naturalistic stimuli to examine the role of the right temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS)-an integrative hub for the cortical networks pertinent to the understanding complex social situations-in social inference, a key component of social cognition, in schizophrenia. Twenty-seven schizophrenia participants and 21 healthy control subjects watched a clip of the film The Good, the Bad and the Ugly while high resolution multiband functional MRI images were collected. We used inter-subject correlation to measure the evoked activity, which we then compared to social cognition as measured by The Awareness of Social Inference Test (TASIT). We also compared between groups the TPJ-pSTS blood oxygen level-dependent activity (i) relationship with the motion content in the film; (ii) synchronization with other cortical areas involved in the viewing of the movie; and (iii) relationship with the frequency of saccades made during the movie. Activation deficits were greatest in middle TPJ (TPJm) and correlated significantly with impaired TASIT performance across groups. Follow-up analyses of the TPJ-pSTS revealed decreased synchronization with other cortical areas, decreased correlation with the motion content of the movie, and decreased correlation with the saccades made during the movie. The functional impairment of the TPJm, a hub area in the middle of the TPJ-pSTS, predicts deficits in social inference in schizophrenia participants by disrupting the integration of visual motion processing into the TPJ. This disrupted integration then affects the use of the TPJ to guide saccades during the visual scanning of the movie clip. These findings suggest that the TPJ may be a treatment target for improving deficits in a key component of social cognition in schizophrenia participants.

What you see is what you get: visual scanning failures of naturalistic social scenes in schizophrenia.

BACKGROUND: Impairments in social cognition contribute significantly to disability in schizophrenia patients (SzP). Perception of facial expressions is critical for social cognition. Intact perception requires an individual to visually scan a complex dynamic social scene for transiently moving facial expressions that may be relevant for understanding the scene. The relationship of visual scanning for these facial expressions and social cognition remains unknown. METHODS: In 39 SzP and 27 healthy controls (HC), we used eye-tracking to examine the relationship between performance on The Awareness of Social Inference Test (TASIT), which tests social cognition using naturalistic video clips of social situations, and visual scanning, measuring each individual's relative to the mean of HC. We then examined the relationship of visual scanning to the specific visual features (motion, contrast, luminance, faces) within the video clips. RESULTS: TASIT performance was significantly impaired in SzP for trials involving sarcasm (p < 10-5). Visual scanning was significantly more variable in SzP than HC (p < 10-6), and predicted TASIT performance in HC (p = 0.02) but not SzP (p = 0.91), differing significantly between groups (p = 0.04). During the visual scanning, SzP were less likely to be viewing faces (p = 0.0001) and less likely to saccade to facial motion in peripheral vision (p = 0.008). CONCLUSIONS: SzP show highly significant deficits in the use of visual scanning of naturalistic social scenes to inform social cognition. Alterations in visual scanning patterns may originate from impaired processing of facial motion within peripheral vision. Overall, these results highlight the utility of naturalistic stimuli in the study of social cognition deficits in schizophrenia.

Deficits and compensation: Attentional control cortical networks in schizophrenia.

Visual processing and attention deficits are responsible for a substantial portion of the disability caused by schizophrenia, but the source of these deficits remains unclear. In 35 schizophrenia patients (SzP) and 34 healthy controls (HC), we used a rapid serial visual presentation (RSVP) visual search task designed to activate/deactivate the cortical components of the attentional control system (i.e. the dorsal and ventral attention networks, lateral prefrontal regions in the frontoparietal network, and cingulo-opercular/salience networks), along with resting state functional connectivity, to examine the integrity of these components. While we find that behavioral performance and activation/deactivation of the RSVP task are largely similar between groups, SzP exhibited decreased functional connectivity within late visual components and between prefrontal and other components. We also find that performance correlates with the deactivation of the ventral attention network in SzP only. This relationship is mediated by the functional connectivity of critical components of the attentional control system. In summary, our results suggest that the attentional control system is potentially used to compensate for visual cortex deficits. Furthermore, prefrontal deficits in SzP may interfere with this compensatory use of the attentional control system. In addition to highlighting focal deficits and potential compensatory mechanisms in visual processing and attention, our findings point to the attentional control system as a potential target for rehabilitation and neuromodulation-based treatments for visual processing deficits in SzP.

Altered gene expression in busulfan-resistant human myeloid leukemia.

Busulfan (Bu) resistance is a major obstacle to hematopoietic stem cell transplantation (HSCT) of patients with chronic or acute myelogenous leukemia (CML or AML). We used gene expression analysis to identify cellular factors underlying Bu resistance. Two Bu-resistant leukemia cell lines were established, characterized and analyzed for differentially expressed genes. The CML B5/Bu250(6) cells are 4.5-fold more resistant to Bu than their parental B5 cells. The AML KBM3/Bu250(6) cells are 4.0-fold more Bu-resistant than KBM3 parental cells. Both resistant sublines evade Bu-mediated G2-arrest and apoptosis with altered regulations of CHK2 and CDC2 proteins, constitutively up-regulated anti-apoptotic genes (BCL-X(L), BCL2, BCL2L10, BAG3 and IAP2/BIRC3) and down-regulated pro-apoptotic genes (BIK, BNIP3, and LTBR). Bu-induced apoptosis is partly mediated by activation of caspases; use of the inhibitor Z-VAD-FMK completely abrogated PARP1 cleavage and reduced apoptosis by approximately 50%. Furthermore, Bu resistance in these cells may be attributed in part to up-regulation of HSP90 protein and activation of STAT3. The inhibition of HSP90 with geldanamycin attenuated phosphorylated STAT3 and made B5/Bu250(6) and KBM3/Bu250(6) more Bu-sensitive. The analysis of cells derived from patients classified as either clinically resistant or sensitive to high-dose Bu-based chemotherapy indicated alterations in gene expression that were analogous to those observed in the in vitro model cell lines, confirming the potential clinical relevance of this model for Bu resistance.