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Koji J Duncan, Jaclyn N Chopp-Hurley, Monica R Maly School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada Purpose: Among a variety of conservative and surgical options to treat anterior cruciate ligament (ACL) injuries, we do not understand which options could potentially prevent knee osteoarthritis (OA). The aim of this systematic review was to examine the evidence pertaining to exercise treatment of ACL injuries in the context of knee OA. Methods: Medline, Embase, CINAHL, PubMed, and PEDro (Physiotherapy Evidence Database) databases were systematically searched using keywords encompassed within four primary key terms: knee, osteoarthritis, anterior cruciate ligament, and exercise. Clinical studies evaluating the effect of an exercise treatment for ACL injuries on the development of knee OA in adult humans were included. The PEDro scale was used to critically assess the studies included in the review. Results: Eighteen studies were included in this review, with a median PEDro score of 6/11 (range, 2/11–9/11). Three studies provided statistical evidence that exercise following ACL injury lowered the risk for knee OA development. Nine studies demonstrated no benefit of exercise in preventing knee OA incidence relative to either operative treatment or the contralateral, unaffected knee. However, exercise resulted in higher knee instability. Nonetheless, there were no significant differences in subjective or objective knee outcomes for early versus late ACL reconstruction. Limitations: This review was not registered through PROSPERO. Conclusion: The relationship between a rehabilitative exercise for ACL injuries and long-term knee OA prevalence is inconclusive. However, research suggests initial conservative treatment with optional late ACL reconstruction because this treatment strategy may reduce the risk of knee OA. More research, ideally randomized controlled trials or comparable designs, is required prior to establishing clinical guidelines for ACL injury management. Keywords: exercise therapy, knee, ligament, articular, osteoarthrosis, rehabilitation

The use of face masks has become ubiquitous. Although mask wearing is a convenient way to reduce the spread of disease, it is important to know how the mask affects our communication via facial expression. For example, when we are wearing the mask and meet a friend, are our facial expressions different compared to when we are not? We investigated the effect of face mask wearing on facial expression, including the area around the eyes. We measured surface electromyography from zygomaticus major, orbicularis oculi, and depressor anguli oris muscles, when people smiled and talked with or without a mask. Only the actions of the orbicularis oculi were facilitated by wearing the mask. We thus concluded that mask wearing may increase the recruitment of the eyes during smiling. In other words, we can express joy and happiness even when wearing a face mask., (© 2021. The Author(s).)

During word and object recognition, extensive activation has consistently been observed in the left ventral occipito-temporal cortex (vOT), focused around the occipito-temporal sulcus (OTs). Previous studies have shown that there is a hierarchy of responses from posterior to anterior vOT regions (along the y-axis) that corresponds with increasing levels of recognition - from perceptual to semantic processing, respectively. In contrast, the functional differences between superior and inferior vOT responses (i.e. along the z-axis) have not yet been elucidated. To investigate, we conducted an extensive review of the literature and found that peak activation for reading varies by more than 1 cm in the z-axis. In addition, we investigated functional differences between superior and inferior parts of left vOT by analysing functional MRI data from 58 neurologically normal skilled readers performing 8 different visual processing tasks. We found that group activation in superior vOT was significantly more sensitive than inferior vOT to the type of task, with more superior vOT activation when participants were matching visual stimuli for their semantic or perceptual content than producing speech to the same stimuli. This functional difference along the z-axis was compared to existing boundaries between cytoarchitectonic areas around the OTs. In addition, using dynamic causal modelling, we show that connectivity from superior vOT to anterior vOT increased with semantic content during matching tasks but not during speaking tasks whereas connectivity from inferior vOT to anterior vOT was sensitive to semantic content for matching and speaking tasks. The finding of a functional dissociation between superior and inferior parts of vOT has implications for predicting deficits and response to rehabilitation for patients with partial damage to vOT following stroke or neurosurgery., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Unlike most languages that are written using a single script, Japanese uses multiple scripts including morphographic Kanji and syllabographic Hiragana and Katakana. Here, we used functional magnetic resonance imaging with dynamic causal modeling to investigate competing theories regarding the neural processing of Kanji and Hiragana during a visual lexical decision task. First, a bilateral model investigated interhemispheric connectivity between ventral occipito-temporal (vOT) cortex and Broca's area ("pars opercularis"). We found that Kanji significantly increased the connection strength from right-to-left vOT. This is interpreted in terms of increased right vOT activity for visually complex Kanji being integrated into the left (i.e. language dominant) hemisphere. Secondly, we used a unilateral left hemisphere model to test whether Kanji and Hiragana rely preferentially on ventral and dorsal paths, respectively, that is, they have different intrahemispheric functional connectivity profiles. Consistent with this hypothesis, we found that Kanji increased connectivity within the ventral path (V1 ↔ vOT ↔ Broca's area), and that Hiragana increased connectivity within the dorsal path (V1 ↔ supramarginal gyrus ↔ Broca's area). Overall, the results illustrate how the differential processing demands of Kanji and Hiragana influence both inter- and intrahemispheric interactions.

In Japanese, the same word can be written in either morphographic Kanji or syllabographic Hiragana and this provides a unique opportunity to disentangle a word's lexical frequency from the frequency of its visual form - an important distinction for understanding the neural information processing in regions engaged by reading. Behaviorally, participants responded more quickly to high than low frequency words and to visually familiar relative to less familiar words, independent of script. Critically, the imaging results showed that visual familiarity, as opposed to lexical frequency, had a strong effect on activation in ventral occipito-temporal cortex. Activation here was also greater for Kanji than Hiragana words and this was not due to their inherent differences in visual complexity. These findings can be understood within a predictive coding framework in which vOT receives bottom-up information encoding complex visual forms and top-down predictions from regions encoding non-visual attributes of the stimulus., (Copyright © 2012 Elsevier Inc. All rights reserved.)

During speech production, auditory processing of self-generated speech is used to adjust subsequent articulations. The current study investigated how the proposed auditory-motor interactions are manifest at the neural level in native and non-native speakers of English who were overtly naming pictures of objects and reading their written names. Data were acquired with functional magnetic resonance imaging and analyzed with dynamic causal modeling. We found that (1) higher activity in articulatory regions caused activity in auditory regions to decrease (i.e., auditory suppression), and (2) higher activity in auditory regions caused activity in articulatory regions to increase (i.e., auditory feedback). In addition, we were able to demonstrate that (3) speaking in a non-native language involves more auditory feedback and less auditory suppression than speaking in a native language. The difference between native and non-native speakers was further supported by finding that, within non-native speakers, there was less auditory feedback for those with better verbal fluency. Consequently, the networks of more fluent non-native speakers looked more like those of native speakers. Together, these findings provide a foundation on which to explore auditory-motor interactions during speech production in other human populations, particularly those with speech difficulties.

A critical assumption underlying the practice of functional localization is that the voxels identified by functional localization are essentially the same as those activated in the main experiment for a particular anatomical area. Violations of this assumption bias the resulting analyses and can dramatically increase the likelihood of both Type I and Type II errors. Here we investigated how the amount of data affects the reliability of a set of common functionally-defined regions-of-interest (fROIs). Four participants were scanned ten times each to functionally localize extrastriate regions sensitive to visually presented words, objects and faces. A within-subject random-effects analysis was used as the "gold standard" for identifying the fROIs and the results were compared to within-subject, fixed-effect analyses typically used for functional localization. By varying the quantity of data included in the analyses, we empirically assessed the amount needed to ensure reliable identification of the fROIs. The results demonstrated that the most consistent fROIs were based on either stringent statistical thresholding (Z>5.0) of large quantities of data or on lenient thresholding (Z>2.3) of a modest amount of data, with both methods yielding 70-80% overlap between the functional localization results and the "gold standard." Stringent statistical thresholds on typical quantities of localizer data led to the poorest reliability (<20% overlap). These findings suggest that the most reliable and cost-efficient method for functional localization involves collecting a relatively small amount of data (~10 min) and using a lenient statistical threshold to identify all voxels in a given region that are sensitive to the process-of-interest., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although interactivity is considered a fundamental principle of cognitive (and computational) models of reading, it has received far less attention in neural models of reading that instead focus on serial stages of feed-forward processing from visual input to orthographic processing to accessing the corresponding phonological and semantic information. In particular, the left ventral occipito-temporal (vOT) cortex is proposed to be the first stage where visual word recognition occurs prior to accessing nonvisual information such as semantics and phonology. We used functional magnetic resonance imaging (fMRI) to investigate whether there is evidence that activation in vOT is influenced top-down by the interaction of visual and nonvisual properties of the stimuli during visual word recognition tasks. Participants performed two different types of lexical decision tasks that focused on either visual or nonvisual properties of the word or word-like stimuli. The design allowed us to investigate how vOT activation during visual word recognition was influenced by a task change to the same stimuli and by a stimulus change during the same task. We found both stimulus- and task-driven modulation of vOT activation that can only be explained by top-down processing of nonvisual aspects of the task and stimuli. Our results are consistent with the hypothesis that vOT acts as an interface linking visual form with nonvisual processing in both bottom up and top down directions. Such interactive processing at the neural level is in agreement with cognitive and computational models of reading but challenges some of the assumptions made by current neuro-anatomical models of reading., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Behavioral studies have demonstrated that learning to read and write affects the processing of spoken language. The present study investigates the neural mechanism underlying the emergence of such orthographic effects during speech processing. Transcranial magnetic stimulation (TMS) was used to tease apart two competing hypotheses that consider this orthographic influence to be either a consequence of a change in the nature of the phonological representations during literacy acquisition or a consequence of online coactivation of the orthographic and phonological representations during speech processing. Participants performed an auditory lexical decision task in which the orthographic consistency of spoken words was manipulated and repetitive TMS was used to interfere with either phonological or orthographic processing by stimulating left supramarginal gyrus (SMG) or left ventral occipitotemporal cortex (vOTC), respectively. The advantage for consistently spelled words was removed only when the stimulation was delivered to SMG and not to vOTC, providing strong evidence that this effect arises at a phonological, rather than an orthographic, level. We propose a possible mechanistic explanation for the role of SMG in phonological processing and how this is affected by learning to read.

The debate regarding the role of ventral occipito-temporal cortex (vOTC) in visual word recognition arises, in part, from difficulty delineating the functional contributions of vOTC as separate from other areas of the reading network. Here, we investigated the feasibility of using TMS to interfere with vOTC processing in order to explore its specific contributions to visual word recognition. Three visual lexical decision experiments were conducted using neuronavigated TMS. The first demonstrated that repetitive stimulation of vOTC successfully slowed word, but not nonword, responses. The second confirmed and extended these findings by demonstrating the effect was specific to vOTC and not present in the adjacent lateral occipital complex. The final experiment used paired-pulse TMS to investigate the time course of vOTC processing for words and revealed activation starting as early as 80-120 msec poststimulus onset-significantly earlier than that expected based on electrophysiological and magnetoencephalography studies. Taken together, these results clearly indicate that TMS can be successfully used to stimulate parts of vOTC previously believed to be inaccessible and provide a new tool for systematically investigating the information processing characteristics of vOTC. In addition, the findings provide strong evidence that lexical status and frequency significantly affect vOTC processing, findings difficult to reconcile with prelexical accounts of vOTC function.

A critical assumption underlying the use of functional localiser scans is that the voxels identified as the functional region-of-interest (fROI) are essentially the same as those activated by the main experimental manipulation. Intra-subject variability in the location of the fROI violates this assumption, reducing the sensitivity of the analysis and biasing the results. Here we investigated consistency and variability in fROIs in a set of 45 volunteers. They performed two functional localiser scans to identify word- and object-sensitive regions of ventral and lateral occipito-temporal cortex, respectively. In the main analyses, fROIs were defined as the category-selective voxels in each region and consistency was measured as the spatial overlap between scans. Consistency was greatest when minimally selective thresholds were used to define "active" voxels (p<0.05 uncorrected), revealing that approximately 65% of the voxels were commonly activated by both scans. In contrast, highly selective thresholds (p<10(-4) to 10(-6)) yielded the lowest consistency values with less than 25% overlap of the voxels active in both scans. In other words, intra-subject variability was surprisingly high, with between one third and three quarters of the voxels in a given fROI not corresponding to those activated in the main task. This level of variability stands in striking contrast to the consistency seen in retinotopically-defined areas and has important implications for designing robust but efficient functional localiser scans.

The chymotrypsin-like serine protease inhibitor, succinyl-alanine-alanine-proline-phenylalanine chloromethyl ketone (AAPF(CMK)), has been shown to have anticarcinogenic activity in a number of model systems and to be relatively selective for a nuclear protease. This inhibitor also has substantial effects on growth of tumorigenic human papillomavirus (HPV)-infected keratinocytes in organotypic raft cultures. Here, we examined the effects of AAPF(CMK) on cell growth, cell-cycle kinetics, apoptosis induction, and DNA synthesis in two human cervical carcinoma cell lines: SiHa cells, which have integrated high-risk HPV-16; and C33a cells, which do not contain HPV DNA. AAPF(CMK) inhibited growth of both cell lines in a time- and dose-dependent manner. Apoptosis studies showed no significant difference in drug-treated versus vehicle-treated cells in the C33a cell line. However, a significant dose-dependent increase in apoptosis occurred at a late time point in SiHa cells. Cell-cycle progression and DNA synthesis assays showed that the cellular mechanisms of growth inhibition by AAPF(CMK) differ between the HPV16-positive and HPV-negative tumorigenic cell lines. Drug-treated C33a cells showed a significant accumulation of cells in the G(2) phase of the cell cycle. In SiHa cells, growth inhibition produced by AAPF(CMK) seemed to result from a global arrest of the cell cycle. Although the molecular mechanisms involved in AAPF(CMK)-induced growth inhibition are distinct between the two tumorigenic cell lines, such differences may ultimately prove to have therapeutic utility. Novel therapies for treating established HPV infections are needed, because HPV is a causative agent in the development of multiple types of cancer.