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Ribosomes are universal translators of the genetic code into protein and represent macromolecular structures that are asymmetric, often heterogeneous, and contain dynamic regions. These properties pose considerable challenges for modern-day structural biology. Despite these obstacles, high-resolution x-ray structures of the 30S and 50S subunits have revealed the RNA architecture and its interactions with proteins for ribosomes from Thermus thermophilus, Deinococcus radiodurans, and Haloarcula marismortui. Some regions, however, remain inaccessible to these high-resolution approaches because of their high conformational dynamics and potential heterogeneity, specifically the so-called L7/ L12 stalk complex. This region plays a vital role in protein synthesis by interacting with GTPase factors in translation. Here, we apply tandem MS, an approach widely applied to peptide sequencing for proteomic applications but not previously applied to MDa complexes. Isolation and activation of ions assigned to intact 30S and 50S subunits releases proteins S6 and L12, respectively. Importantly, this process reveals, exclusively while attached to ribosomes, a phosphorylation of L12, the protein located in multiple copies at the tip of the stalk complex. Moreover, through tandem MS we discovered a stoichiometry for the stalk protuberance on Thermus thermophilus and other thermophiles and contrast this assembly with the analogous one on ribosomes from mesophiles. Together with evidence for a potential interaction with the degradosome, these results show that important findings on ribosome structure, interactions, and modifications can be discovered by tandem MS, even on well studied ribosomes from Thermus thermophilus. bacterial ribosomes | LT/L12 stalk complex | mass spectrometry

Objectives: Post-traumatic amnesia (PTA) is a transient period of recovery following traumatic brain injury (TBI) characterised by disorientation, amnesia, and cognitive disturbance. Agitation is common during PTA and presents as a barrier to patient outcome. A relationship between cognitive impairment and agitation has been observed. This prospective study aimed to examine the different aspects of cognition associated with agitation. Methods: The sample comprised 82 participants (75.61% male) admitted to an inpatient rehabilitation hospital in PTA. All patients had sustained moderate to extremely severe brain injury as assessed using the Westmead Post-Traumatic Amnesia Scale (WPTAS) (mean duration = 42.30 days, SD = 35.10). Participants were assessed daily using the Agitated Behaviour Scale and WPTAS as part of routine clinical practice during PTA. The Confusion Assessment Protocol was administered two to three times per week until passed criterion was achieved (mean number assessments = 3.13, SD = 3.76). Multilevel mixed modelling was used to investigate the association between aspects of cognition and agitation using performance on items of mental control, orientation, memory free recall, memory recognition, vigilance, and auditory comprehension. Results: Findings showed that improvement in orientation was significantly associated with lower agitation levels. A nonsignificant trend was observed between improved recognition memory and lower agitation. Conclusions: Current findings suggest that the presence of disorientation in PTA may interfere with a patient's ability to understand and engage with the environment, which in turn results in agitated behaviours. Interventions aimed at maximizing orientation may serve to minimize agitation during PTA. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background and Purpose: Physical therapy is important in the management of traumatic brain injury (TBI) and associated multitrauma. Providing therapy during the posttraumatic amnesia (PTA) phase is challenging, given that hallmark features including confusion, amnesia, agitation, and fatigue may impede the person's ability to engage in and benefit from rehabilitation. To date, there is little empirical evidence to guide the provision of therapy during PTA. This observational study aimed to explore the frequency, duration, location, and engagement of physical therapy provision during PTA and the impact of cognition, agitation, and fatigue. Summary of Key Points: The majority of patients were found to meaningfully engage and participate in physical therapy for the majority of sessions. Only a small proportion were unable to participate in physical therapy. Patient refusal and fatigue were identified as the most prominent barriers to rehabilitation. Despite fatigue and agitation reaching clinical levels, therapy could still successfully proceed on most occasions. Recommendations for Clinical Practice: Physical therapy is feasible during the acute recovery stages after TBI. Current results support the notion that therapy should commence early to minimize secondary complications and promote the recovery of mobility. A patient-centered therapeutic model that tailors the therapeutic approach to meet the individual's current physical and fluctuating cognitive capabilities may be most suited for this population. Clinicians working with people after TBI need experience in understanding and managing the cognitive limitations and associated symptoms of PTA to optimize the provision of therapy. These findings could inform guidelines for the management of patients in PTA. Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A368). [ABSTRACT FROM AUTHOR]

Background: The duration of the acute period of recovery following traumatic brain injury (TBI) remains a widely used criterion for injury severity and clinical management. Consensus regarding its most appropriate definition and assessment method has yet to be established. Objective: The present study compared the trajectory of recovery using 3 measures: the Westmead Post-Traumatic Amnesia Scale (WPTAS), the Galveston Orientation and Amnesia Test (GOAT), and the Confusion Assessment Protocol (CAP). Patterns of symptom recovery using the CAP were explored. Participants: Eighty-two participants with moderate to severe TBI in posttraumatic amnesia (PTA) on admission to an inpatient rehabilitation hospital. Design: Prospective longitudinal study. Outcome Measures: Length of PTA (days), agreement between measures (%, x coefficient), and pattern of symptom recovery. Results: Participants emerged from PTA earliest on the CAP followed the GOAT, and last on the WPTAS. There was good agreement between the CAP and the GOAT as to PTA status, but both tests had poor agreement with the WPTAS. Of patients considered out of PTA on the CAP, the majority exhibited signs of amnesia on the WPTAS and onethird had clinical levels of agitation. Conclusion: The WPTAS identifies a later stage of PTA recovery that requires specialized management due to ongoing amnesia and agitation. The CAP and the GOAT are less sensitive to this extended period of PTA. [ABSTRACT FROM AUTHOR]

Objective: This study examined the use of antipsychotics for managing agitation during posttraumatic amnesia (PTA) after traumatic brain injury (TBI) and its relationship with agitated behavior. Design: Observational prospective study with correlational design. Setting: Inpatient rehabilitation hospital for TBI. Participants: A total of 125 consecutive admissions who were in PTA and had moderate-severe TBI. Measures: Antipsychotic use was compared with agitation levels as measured by the total scores on the Agitated Behavior Scale (ABS). Results: Atypical antipsychotics were used in one-third of participants to manage agitation. Antipsychotic use was more common in participants with high levels of global agitation; however, there were many on antipsychotics who had mild or even no agitation according to the ABS. Uncontrolled observational data found no reduction in agitation after antipsychotic commencement or dose increase. Conclusions: Antipsychotics are commonly used to manage agitation after TBI despite limited evidence of efficacy. Agitation should be formally monitored in PTA to ensure antipsychotics are used to manage more severe agitation and for evaluating treatment response. Research is needed to understand why prescribers are using antipsychotics when agitation is mild or below clinical thresholds. [ABSTRACT FROM AUTHOR]

Agitation is common during the post-traumatic amnesia (PTA) period after traumatic brain injury (TBI), although our knowledge of what causes or predicts agitation is limited. The current study aimed to examine the association of agitation in PTA with the concurrent impairments in orientation and memory while controlling for covariates of agitation. Participants were 125 patients in PTA following moderate to extremely severe TBI recruited from an inpatient brain injury rehabilitation service who were assessed throughout PTA on the Agitated Behavior Scale (ABS) and the Westmead PTA Scale (WPTAS). Agitation was observed in 42.4% of participants (ABS score > 21), with disinhibited behaviours (e.g., distractibility and impulsivity) most common. Multilevel modelling found daily ABS scores to be associated with daily scores on the WPTAS but in a non-linear pattern. Analysis of covariates found that shorter time post-admission, younger age, presence of infection and higher antipsychotic doses were associated with higher ABS scores. These results support a relationship between agitation and the concurrent cognitive impairment during PTA. While a causal link cannot yet be inferred, management strategies that can potentially interfere with cognition (e.g., sedating medications, environmental changes) should be used cautiously in case they exacerbate agitation. [ABSTRACT FROM AUTHOR]

It is uncertain whether therapy delivered during posttraumatic amnesia (PTA) following traumatic brain injury can be effective due to risk of agitation and poor learning capacity. This study used goal attainment scaling (GAS) to assess gains in activities of daily living (ADL) retraining during PTA. Occupational therapists' perspectives on goal setting and therapy delivery were also explored qualitatively. Forty-nine rehabilitation inpatients were provided with manualised ADL retraining following errorless and procedural learning principles during PTA. From 104 GAS goals, 90% were achieved at PTA emergence. GAS T-scores changed significantly (p < .001) from baseline (M = 26.94, SD = 4.90) to post-intervention (M = 61.44, SD = 11.45). Mean post-intervention T-scores correlated significantly (p < .001) with change in Functional Independence Measure scores. The four therapists reported that GAS was unfamiliar and time-consuming initially, although it aided goal-directed therapy and measurement of patient performance. Application of manualised skill retraining using errorless and procedural learning techniques was described as novel and challenging, but providing valuable structure. The intervention reportedly promoted therapeutic alliance, skill-building and meaningful time-use without elevating agitation, but fatigue impeded therapy. Overall, GAS captured positive individual change following ADL retraining during PTA and therapists indicated that the intervention and use of GAS was generally beneficial and feasible within clinical practice. [ABSTRACT FROM AUTHOR]

A systematic investigation of a series of noncovalent complexes representing a range of different sizes and architectures is conducted to investigate the origins of the broadening of peaks in mass spectral peaks and to develop the optimal method for analyzing mass spectra of large protein complexes. The results show that, rather than uniform particles, gas-phase ribosomes consist of a number of discrete populations.

The objective of this study was to evaluate the effectiveness of individual cognitive behavioural therapy (CBT) for post-stroke fatigue and sleep disturbance compared to treatment as usual (TAU). In a parallel two-group pilot randomised controlled trial of 15 participants, nine were allocated to eight weekly sessions of adapted CBT and six continued usual care rehabilitation. The primary outcome was the Fatigue Severity Scale (FSS-7) at two and four months from baseline. Secondary outcomes included measures of sleep, mood and quality of life. Outcomes were assessed by a rater who was blind to group membership. At the four-month endpoint, the CBT group demonstrated significantly reduced fatigue relative to TAU (FSS-7 mean difference: 1.92, 95% CI: 0.24 to 3.60). Significant group differences also emerged for sleep quality and depression, favouring the CBT group. Insomnia and physical quality of life improved immediately post-therapy but were no longer superior to TAU at follow-up. Overall, CBT is a promising treatment for improving post-stroke fatigue, sleep quality and depression. Gains were maintained for two months after therapy cessation and represented large treatment effects. These findings highlight the feasibility of the intervention and warrant extension to a phase III clinical trial. [ABSTRACT FROM AUTHOR]

Despite clinical guidelines recommending an interdisciplinary approach to persisting post-concussion symptom (PPCS) management, evaluations of interdisciplinary interventions remain scant. This pilot study aimed to explore the feasibility and preliminary efficacy of an interdisciplinary intervention for PPCSs. A single-case experimental design with randomisation to multiple baselines (2, 4, or 6 weeks) was repeated across 15 participants (53% female) with mild traumatic brain injury (mean age 38.3 years, SD 15.7). The 12-week treatment incorporated psychology, physiotherapy, and medical interventions. Feasibility outcomes included recruitment and retention rates, adverse events, treatment adherence and fidelity. Patient-centred secondary outcomes included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessed 3 times per week during the baseline and treatment phases, and at the 1- and 3-month follow-ups. Other secondary outcomes included measures of mood, sleep and fatigue, physical functioning, health-related quality of life, illness perceptions, and goal attainment. Changes in PPCSs were evaluated using systematic visual analysis and Tau- U. Clinically significant changes in secondary outcomes were explored descriptively. 16/26 individuals assessed for eligibility were enroled (61% recruitment rate); 15 completed the post-treatment follow-ups, and 13 completed the 1- and 3-month follow-up assessments (81% retention rate). High treatment adherence and competence in delivering treatments was observed. Moderate-large effect sizes for reducing PPCSs were observed in 12/15 cases, with 7/15 reaching statistical significance. Improvements were maintained at the 1- and 3-month follow-ups and were accompanied by reductions in fatigue, sleep difficulties, and mood symptoms, and changes in illness perceptions. All participants had clinically significant improvements in at least 1 outcome, with 81% of individual therapy goals achieved. This pilot study provided preliminary support for a subsequent randomised controlled trial (RCT), with satisfactory recruitment, retention, treatment compliance, and treatment fidelity. Improvement was evident on participant outcomes including symptom reduction and goal attainment, suggesting that progressing to a phase-II RCT is worthwhile. Findings highlight the potential benefit of individualized interdisciplinary treatments. [ABSTRACT FROM AUTHOR]

Purpose: To identify predictors of treatment response to cognitive behavior therapy (CBT) for sleep disturbance following acquired brain injury (ABI). Methods: Classification and regression tree (CART) analysis was conducted on individual patient data from two pilot randomized controlled trials (RCTs): one in traumatic brain injury (TBI), the other in stroke. The combined sample comprised 32 participants; 15 receiving CBT and 17 allocated to treatment as usual (TAU). The outcome was reliable improvement on the Pittsburgh Sleep Quality Index (PSQI). Results: Study group was a statistically significant predictor of outcome, with CBT participants more likely to achieve reliable improvements than TAU (OR = 4.88, p = 0.042). Study group (CBT vs. TAU) exhibited an area under the ROC curve (AUROC) of 69%. In separate CART analyzes, verbal memory (CVLT-II >45.5), age (<47.5) and baseline depression (HADS-D > 6) predicted positive outcomes in CBT recipients. Each of these variables added a small (∼5%) but not statistically significant amount to AUROC over study group. Conclusions: In this ABI sample, better memory, younger age, and higher baseline depression were associated with positive treatment response to CBT although individually these variables were not better than group alone in predicting outcomes. The present findings generate hypotheses for further investigation in future studies. Implications for rehabilitation: Cognitive behavior therapy improves sleep quality over treatment as usual in persons with acquired brain injury. Individuals who are younger in age with better memory and co-morbid symptoms of depression are more likely to respond to the treatment. These findings are based on a small sample and can be considered hypothesis generating for future clinical studies. [ABSTRACT FROM AUTHOR]

Primary objective:Increasing physical activity (PA) among people with severe traumatic brain injury (TBI) represents an important long-term rehabilitation goal. To design effective interventions to promote PA, the factors associated with PA engagement post-TBI need to be understood. Research design:A qualitative study design was employed to investigate the factors influencing PA engagement in people with severe TBI living in the community. Methods and Procedures:Face-to-face interviews were conducted with eight people with severe TBI three to five years post-injury. A constant comparative method of data collection and analysis was adopted. Main outcomes and results:Interviews were analysed using thematic analysis. Three themes were identified: continuance of self and PA (perception of self, stage of life, and PA normality), beliefs about PA (knowledge of PA and associated benefits), and purpose of PA engagement (reasons for being physically active). Lifelong PA habits and current life priorities impacted on PA engagement post-TBI and influenced whether TBI-associated impairments were considered as a barrier to PA. Conclusion:Among this group of people, PA engagement post-TBI was influenced by perceptions of lifelong PA habits and current life priorities. Interventions to increase PA need to address these perceptions and adapt PA to account for life priorities within the context of TBI-associated impairments. [ABSTRACT FROM AUTHOR]