Prevalence of thiamine deficiency in anorexia nervosa: a systematic review and narrative synthesis.

Thiamine is an essential vitamin that plays a crucial role in many biochemical processes in the body. Anorexia nervosa (AN) is one potential cause of a state of deficiency which can result in grave medical sequelae. There is limited available evidence of the prevalence of thiamine deficiency in patients who suffer from AN. The current study aimed to systematically review all available evidence on the prevalence of thiamine deficiency in cohorts with AN. Studies were included where thiamine status in a group of participants with AN was measured, either through self-reporting or objective measurement. Eight databases (Scopus, CINAHL complete, Medline complete, EMBASE, WEB OF SCIENCE, PROSPERO, COCHRANE DATABASE OF SYSTEMATIC REVIEWS and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. PRISMA guidelines were followed. The study was registered on PROSPERO. A minimum of two researchers conducted each part of the review. The search identified 42 articles whose full texts were screened for eligibility, with 17 retained for qualitative synthesis. The prevalence rates of thiamine deficiency in AN varied from 5.9% to 100% when based on self-report dietary intake. When objective measurements were taken, rates ranged from 0% to 56.7%. The review suggested that age, body mass index (BMI), duration of illness and subtype of AN were not associated with thiamine status. The limited available evidence suggested that the use of supplements, prior treatment and higher energy intakes were associated with a reduced risk of developing a thiamine deficiency among individuals with AN. Poor study methodology including small sample size, inconsistent deficiency definition and study heterogeneity limits the conclusions that can be drawn. Ultimately, there is insufficient strength of evidence to draw definitive clinical recommendations. This review highlights the need for further studies with more robust methodology to help further inform clinical practice.

Biologics in rotator cuff repair.

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Partial-Thickness Rotator Cuff Tears: Current Concepts.

¼ Partial-thickness rotator cuff tears (PTRCTs) are a common pathology with a likely high asymptomatic incidence rate, particularly in the overhead athlete.¼ The anatomy, 5-layer histology, and relationship to Ellman's classification of PTRCTs have been well studied, with recent interest in radiographic predictors such as the critical shoulder angle and acromial index.¼ Depending on the definition of tear progression, rates of PTRCT progression range from 4% to 44% and appear related to symptomatology and work/activity level.¼ Nearly all PTRCTs should be managed conservatively initially, particularly in overhead athletes, with those that fail nonoperative management undergoing arthroscopic debridement ± acromioplasty if <50% thickness or arthroscopic conversion repair or in situ repair if >50% thickness.¼ Augmentation of PTRCTs is promising, with leukocyte-poor platelet-rich plasma having the most robust body of supportive data. Mesenchymal signaling cell biologics and the variety of scaffold onlay augments require more rigorous studies before regular usage.

TFIIB-Termination Factor Interaction Affects Termination of Transcription on Genome-Wide Scale.

Apart from its well-established role in the initiation of transcription, the general transcription factor TFIIB has been implicated in the termination step as well. The ubiquity of TFIIB involvement in termination as well as mechanistic details of its termination function, however, remain largely unexplored. Using GRO-seq analyses, we compared the terminator readthrough phenotype in the sua7-1 mutant (TFIIBsua7-1) and the isogenic wild type (TFIIBWT) strains. Approximately 74% of genes analyzed exhibited a 2-3-fold increase in readthrough of the poly(A)-termination signal in the TFIIBsua7-1 mutant compared to TFIIBWT cells. To understand the mechanistic basis of TFIIB's role in termination, we performed the mass spectrometry of TFIIB-affinity purified from chromatin and soluble cellular fractions-from TFIIBsua7-1 and TFIIBWT cells. TFIIB purified from the chromatin fraction of TFIIBWT cells exhibited significant enrichment of CF1A and Rat1 termination complexes. There was, however, a drastic decrease in TFIIB interaction with CF1A and Rat1 complexes in the TFIIBsua7-1 mutant. ChIP assays revealed about a 90% decline in the recruitment of termination factors in the TFIIBsua7-1 mutant compared to wild type cells. The overall conclusion of these results is that TFIIB affects the termination of transcription on a genome-wide scale, and the TFIIB-termination factor interaction plays a crucial role in the process.

Genome-wide analysis of TFIIB's role in termination of transcription.

This study provides evidence that the role of TFIIB extends beyond initiation to include the termination step of transcription. Using GRO-seq analyses, we compared terminator readthrough phenotype in sua7-1 mutant (TFIIB sua7-1 ) and the isogenic wild type (TFIIB WT ) strains. Approximately 74% of genes analyzed exhibited a 2-3-fold increase in readthrough of the poly(A)-termination signal in the TFIIB sua7-1 mutant compared to TFIIB WT cells. Mass spectrometry of affinity purified TFIIB from chromatin fraction found TFIIB exhibiting interaction with CF1A and Rat1 termination complexes in TFIIB WT cells. There was, however, a drastic decrease in TFIIB interaction with CF1A and Rat1 termination complexes in the TFIIB sua7-1 mutant. ChIP assays revealed about 90% decline in recruitment of termination factors in TFIIB sua7-1 mutant compared to wild type cells. The overall conclusion of these results is that TFIIB affects termination of transcription on a genome-wide scale, and TFIIB-termination factor interaction may play a crucial role in the process.

Vergence and accommodation deficits in paediatric and adolescent patients during sub-acute and chronic phases of concussion recovery.

INTRODUCTION: Visual function deficits have been reported in adolescents following concussion. We compared vergence and accommodation deficits in paediatric and adolescent patients at a tertiary medical centre in the sub-acute (15 days to 12 weeks) and chronic (12 weeks to 1 year) phases of concussion recovery. METHODS: The study included patients aged 7 to <18 years seen between 2014 and 2021, who had a binocular vision (BV) examination conducted within 15 days and 1 year of their concussion injury. Included patients had to have 0.10 logMAR monocular best-corrected vision or better in both eyes and be wearing a habitual refractive correction. BV examinations at near included measurements of near point of convergence, convergence and divergence amplitudes, vergence facility, monocular accommodative amplitude and monocular accommodative facility. Vergence and accommodation deficits were diagnosed using established clinical criteria. Group differences were assessed using nonparametric statistics and ANCOVA modelling. RESULTS: A total of 259 patients were included with 111 in the sub-acute phase and 148 in the chronic phase of concussion recovery. There was no significant difference in the rates of vergence deficits between the two phases of concussion recovery (sub-acute = 48.6%; chronic = 49.3%). There was also no significant difference in the rates of accommodation deficits between the two phases of concussion recovery (sub-acute = 82.0%; chronic = 77.0%). CONCLUSION: Patients in both the sub-acute and chronic phases of concussion recovery exhibited a high frequency of vergence and accommodation deficits, with no significant differences between groups. Results indicate that patients exhibiting vision deficits in the sub-acute phase may not resolve without intervention, though a prospective, longitudinal study is required to test the hypothesis.

Rehabilitation following periacetabular osteotomy for acetabular dysplasia: A qualitative interview study exploring challenges, hopes and expectations among patients in Denmark and Australia.

INTRODUCTION: Guidelines have been proposed for post-operative rehabilitation following periacetabular osteotomy (PAO). However, the perspectives of individuals undergoing PAO have not been considered. AIM: The present study aimed to explore the perceived challenges of everyday life and hopes for and expectations of post-PAO rehabilitation from the perspective of individuals with acetabular dysplasia living in Denmark and Australia. METHODS: In this qualitative study, we used a hermeneutic phenomenological approach with semi-structured interviews to explore the perspectives of 25 participants (four males), aged 16-43 years, who underwent a PAO. Purposeful sampling was used to provide variations in age and sex. Inclusion criteria were age above 15 years, radiographic evidence of acetabular dysplasia, PAO within the last seven weeks and undergoing post-operative rehabilitation. Inductive content analysis was adopted to code and analyse interviews. RESULTS: The analysis of the interview transcripts revealed four major themes: different expectations, self-confidence, tailored rehabilitation and aligning expectations. Several subthemes emerged within each theme, and similar patterns with minor variations were identified across countries. However, the financial burden of self-funded surgery and rehabilitation challenged some Australian participants, whereas none of the Danish participants mentioned this challenge. CONCLUSION: Our findings elucidate the diverse range of hopes and expectations in individuals undergoing PAO, and how these relate to their perceived challenges. In particular, the findings highlight the importance of aligning expectations between individuals and clinicians when designing the rehabilitation.

"I could not find the strength to resist the pressure of the medical staff, to refuse to give commercial milk formula": a qualitative study on effects of the war on Ukrainian women's infant feeding.

Introduction: During emergencies, breastfeeding protects infants by providing essential nutrients, food security, comfort, and protection and is a priority lifesaving intervention. On February 24, 2022, the war in Ukraine escalated, creating a humanitarian catastrophe. The war has resulted in death, injuries, and mass internal displacement of over 5 million people. A further 8.2 million people have taken refuge in neighboring countries, including Poland. Among those impacted are infants and young children and their mothers. We conducted a study to explore the infant feeding challenges and needs of Ukrainian women affected by the war. Methods: We conducted a qualitative descriptive study involving in-depth interviews (IDIs) with 75 war-affected Ukrainian mothers who had at least one infant aged less than 12 months at the time of the interview. Eligible mothers were either (1) living as Ukrainian refugees in Poland, having crossed the border from Ukraine on or after February 24, 2022, when the war started (n = 30) or (2) living in Ukraine as internally displaced persons or as residents in the community (n = 45). All interviews were audio-recorded (either transcribed or had responses summarized as expanded notes) and analyzed using qualitative thematic analysis using a two-step rapid analysis process. Results: Participants in Ukraine who wanted to initiate breastfeeding right after birth faced opposition from healthcare workers at maternity hospitals. Ukrainian refugees who gave birth in Poland faced language barriers when seeking breastfeeding support. Half of the participants in Ukraine received commercial milk formula (CMF) donations even if they said they did not need them. Most respondents stated that breastfeeding information and support were urgently needed. Conclusion: Our data suggests that healthcare workers in Ukrainian maternity hospitals require additional training and motivation on delivering breastfeeding support. In addition, lactation consultants in maternity ward are needed in Ukraine, and interpretation support is needed for refugees to overcome language barriers. There is a need to control the indiscriminate donations of commercial milk formula and to ensure that complementary foods and commercial milk formula are available to those that need it. This study confirms the need for actions to ensure infant and young child feeding (IYCF) support is provided during emergencies.

Genome-wide analysis of TFIIB's role in termination of transcription.

Apart from its well-established role in initiation of transcription, the general transcription factor TFIIB has been implicated in the termination step as well. The ubiquity of TFIIB involvement in termination as well as mechanistic details of its termination function, however, remains largely unexplored. To determine the prevalence of TFIIB's role in termination, we performed GRO-seq analyses in sua7-1 mutant (TFIIB sua7-1 ) and the isogenic wild type (TFIIB WT ) strains of yeast. Almost a three-fold increase in readthrough of the poly(A)-termination signal was observed in TFIIB sua7-1 mutant compared to the TFIIB WT cells. Of all genes analyzed in this study, nearly 74% genes exhibited a statistically significant increase in terminator readthrough in the mutant. To gain an understanding of the mechanistic basis of TFIIB involvement in termination, we performed mass spectrometry of TFIIB, affinity purified from chromatin and soluble cellular fractions, from TFIIB sua7-1 and TFIIB WT cells. TFIIB purified from the chromatin fraction of TFIIB WT cells exhibited significant enrichment of CF1A and Rat1 termination complexes. There was, however, a drastic decrease in TFIIB interaction with both CF1A and Rat1 termination complexes in TFIIB sua7-1 mutant. ChIP assay revealed that the recruitment of Pta1 subunit of CPF complex, Rna15 subunit of CF1 complex and Rat1 subunit of Rat1 complex registered nearly 90% decline in the mutant over wild type cells. The overall conclusion of these results is that TFIIB affects termination of transcription on a genome-wide scale, and TFIIB-termination factor interaction may play a crucial role in the process.

On the multiscale dynamics of punctuated evolution.

For five decades, paleontologists, paleobiologists, and ecologists have investigated patterns of punctuated equilibria in biology. Here, we step outside those fields and summarize recent advances in the theory of and evidence for punctuated equilibria, gathered from contemporary observations in geology, molecular biology, genetics, anthropology, and sociotechnology. Taken in the aggregate, these observations lead to a more general theory that we refer to as punctuated evolution. The quality of recent datasets is beginning to illustrate the mechanics of punctuated evolution in a way that can be modeled across a vast range of phenomena, from mass extinctions hundreds of millions of years ago to the possible future ahead in the Anthropocene. We expect the study of punctuated evolution to be applicable beyond biological scenarios.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

Medial Ulnar Collateral Ligament Reconstruction With Allograft Provides Excellent Clinical Outcomes, High Rates of Return to Play, and a Low Incidence of Postoperative Complications: A Systematic Review.

PURPOSE: To perform a systematic review evaluating clinical outcomes in patients undergoing medial ulnar collateral ligament reconstruction (MUCLR) with soft-tissue allograft. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes evaluated were patient-reported outcome scores, return to play (RTP) rates, incidence of postoperative complications, and rates of graft rupture or mechanical failure. RESULTS: The literature search identified 395 articles, and 5 studies met final inclusion criteria after full-text review. A total of 274 patients were analyzed in the included studies and follow-up ranged from 3.0 to 7.6 years. Two studies (number of patients = 141) reported outcomes exclusively of MUCLR with allograft, whereas 3 studies (number of patients = 133) reported outcomes in patients undergoing MUCLR with either allograft or autograft. Allograft sources included gracilis, semitendinosus, plantaris, peroneus longus, and palmaris longus. Level of patient athletic competition ranged from recreational athletes to the professional level; however, nonathletes in the setting of trauma were also included. The RTP rate after MUCLR with soft-tissue allograft was 95.3%, and 89.3% of patients returned to a similar or greater level of play postoperatively. The Timmerman-Andrews score was reported in 2 studies, and the means postoperatively ranged from 94.55 to 97. Postoperative complication rates were low (range, 0% to 20%), and there were no reported incidences of allograft rupture or mechanical failure. CONCLUSIONS: Based on the available data, soft-tissue allograft for MUCLR in athletic patient populations provides excellent clinical outcomes, high rates of RTP, and low rates of postoperative complications and graft failure at short-term follow-up. There remains a lack of high-quality evidence directly comparing autograft versus allograft outcomes in elite overhead-throwing athletes to support allograft as an acceptable alternative for MUCLR in this patient population. LEVEL OF EVIDENCE: Level IV, systematic review of Level III-IV studies.

Operative Treatment of Ulnar Collateral Ligament Injury in Female Athletes.

Background: Ulnar collateral ligament (UCL) reconstruction has been the standard surgical intervention for elite male athletes with UCL insufficiency. Recently, UCL repair and augmentation with an internal brace has been increasingly performed. Purpose: To evaluate the clinical and functional outcomes as well as return-to-sport rate after UCL repair in female athletes. Study Design: Case series; Level of evidence, 4. Methods: Included were 15 female athletes (mean age, 16.5 ± 3.5 years) who underwent UCL repair between 2011 and 2021 at a single institution. Data collected included age, sport played, competition level, symptom onset, previous surgeries, mechanism of injury, surgical intervention, and return to sport. Patients were contacted via phone at minimum 24-month follow-up, and postoperative outcomes were evaluated using the Mayo Elbow Performance Score (MEPS) and the Single Assessment Numeric Evaluation (SANE). Results: Of the 15 female athletes, there were 4 cheerleaders, 3 softball players, 2 volleyball players, 2 soccer players, 1 gymnast, 1 tennis player, 1 dancer, and 1 javelin thrower. Ten of the 15 athletes (67%) competed at the high school level, 4 (26%) at the collegiate level, and 1 patient (7%) was a recreational volleyball player. In all patients, there was an acute onset of symptoms after injury. Ten patients underwent UCL repair with an internal brace (67% of athletes), while 5 underwent standard UCL repair. The median MEPS for athletes with and without an internal brace was 100 (range, 80-100). There was no significant difference of MEPS (P = .826) or SANE scores (P = .189) between the patients who received an internal brace and those who did not. Thirteen of the 15 athletes (86.7%) returned to sport. Conclusion: The UCL injuries in the female athletes in this study were the result of acute trauma. Primary UCL repair, both with and without internal bracing, was an effective surgical treatment for returning these athletes to sport.

Cardiometabolic Improvements After Metabolic Surgery and Related Presurgery Factors.

Context: Metabolic surgery remains the most effective and durable treatment for severe obesity and related metabolic diseases. Objective: We examined cardiometabolic improvements after metabolic surgery and associated presurgery demographic and clinical factors in a large multiracial cohort. Methods: Included were 7804 patients (20-79 years) undergoing first-time metabolic surgery at Vanderbilt University Medical Center from 1999 to 2022. Pre- and 1-year postsurgery cardiometabolic profiles were extracted from medical records, including body mass index (BMI), blood pressure, blood lipids, glucose, and hemoglobin A1c. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated per American College of Cardiology/American Heart Association equations. Pre- to postsurgery cardiometabolic profiles were compared by paired t-test, and associated factors were identified by multivariable linear and logistic regression. Results: Among 7804 patients, most were women and White, while 1618 were men and 1271 were Black; median age and BMI were 45 years [interquartile range (IQR): 37-53] and 46.4 kg/m2 (IQR: 42.1-52.4). At 1-year postsurgery, patients showed significant decreases in systolic blood pressure (10.5 [95% confidence interval: 10.1, 10.9] mmHg), total cholesterol (13.5 [10.3, 16.7] mg/dL), glucose (13.6 [12.9, 14.4] mg/dL), hemoglobin A1c (1.13% [1.06, 1.20]), and 10-year ASCVD risk (absolute reduction: 1.58% [1.22, 1.94]; relative reduction: 34.4% [29.4, 39.3]); all P < .0001. Older, male, or Black patients showed less reduction in 10-year ASCVD risk and lower odds of diabetes/hypertension/dyslipidemia remission than younger, female, or White patients. Patients with a history of diabetes, hypertension, dyslipidemia, or cardiovascular disease showed less cardiometabolic improvements than those without. Results were similar with or without further adjusting for weight loss and largely sustained at 2-year postsurgery. Conclusion: Metabolic surgery results in significant cardiometabolic improvements, particularly among younger, female, or White patients and those without comorbidities.

Bornean tropical forests recovering from logging at risk of regeneration failure.

Active restoration through silvicultural treatments (enrichment planting, cutting climbers and liberation thinning) is considered an important intervention in logged forests. However, its ability to enhance regeneration is key for long-term recovery of logged forests, which remains poorly understood, particularly for the production and survival of seedlings in subsequent generations. To understand the long-term impacts of logging and restoration we tracked the diversity, survival and traits of seedlings that germinated immediately after a mast fruiting in North Borneo in unlogged and logged forests 30-35 years after logging. We monitored 5119 seedlings from germination for ~1.5 years across a mixed landscape of unlogged forests (ULs), naturally regenerating logged forests (NR) and actively restored logged forests via rehabilitative silvicultural treatments (AR), 15-27 years after restoration. We measured 14 leaf, root and biomass allocation traits on 399 seedlings from 15 species. Soon after fruiting, UL and AR forests had higher seedling densities than NR forest, but survival was the lowest in AR forests in the first 6 months. Community composition differed among forest types; AR and NR forests had lower species richness and lower evenness than UL forests by 5-6 months post-mast but did not differ between them. Differences in community composition altered community-weighted mean trait values across forest types, with higher root biomass allocation in NR relative to UL forest. Traits influenced mortality ~3 months post-mast, with more acquisitive traits and relative aboveground investment favoured in AR forests relative to UL forests. Our findings of reduced seedling survival and diversity suggest long time lags in post-logging recruitment, particularly for some taxa. Active restoration of logged forests recovers initial seedling production, but elevated mortality in AR forests lowers the efficacy of active restoration to enhance recruitment or diversity of seedling communities. This suggests current active restoration practices may fail to overcome barriers to regeneration in logged forests, which may drive long-term changes in future forest plant communities.

A restauração ativa por meio de tratamentos silviculturais (plantio de enriquecimento, corte de trepadeiras e desbaste) é considerada uma intervenção importante em florestas com exploração de madeira. No entanto, sua capacidade de melhorar a regeneração, essencial para a recuperação de longo prazo das florestas exploradas, permanece pouco compreendida, especialmente no que diz respeito à produção e sobrevivência de mudas em gerações subsequentes. Para compreender os impactos de longo prazo da exploração madeireira e da restauração, acompanhamos a diversidade, sobrevivência e características de plântulas que germinaram imediatamente após uma frutificação em massa no norte de Bornéu, em florestas com e sem exploração de madeira, 30-35 anos após o fim da extração. Monitoramos 5119 mudas desde a germinação por aproximadamente 1,5 anos em uma paisagem mista de florestas não exploradas (UL), florestas exploradas em regeneração natural (NR) e florestas exploradas restauradas ativamente por meio de tratamentos silviculturais de reabilitação (AR), 15-27 anos após a restauração. Medimos 14 traços funcionais de folhas, raízes e alocação de biomassa em 399 mudas de 15 espécies. Logo após a frutificação, as florestas UL e AR apresentaram densidades de mudas mais altas do que as florestas NR, mas a sobrevivência foi mais baixa nas florestas AR nos primeiros seis meses. A composição da comunidade diferiu entre os tipos de floresta; as florestas AR e NR teviram menor riqueza de espécies e menor equidade do que as florestas UL 5-6 meses após a frutificação, mas não diferiram entre si. As diferenças na composição da comunidade alteraram os valores de média ponderada pela comunidade das características entre os tipos de floresta com maior alocação de biomassa radicular nas florestas NR em relação às florestas UL. As características influenciaram a mortalidade aproximadamente 3 meses após a frutificação, com traços mais aquisitivos maior investimento em biomassa relativa acima do solo nas florestas AR em relação às florestas UL. Nossas descobertas de redução na sobrevivência e diversidade de plântulas sugerem que há longos retardos no recrutamento após o fim da exploração de madeira, particularmente para alguns táxons. A restauração ativa de florestas exploradas recupera a produção inicial de plântulas, mas a mortalidade elevada nas florestas AR diminui a eficácia da restauração ativa no melhorio do recrutamento e da diversidade das comunidades de mudas. Isso sugere que as práticas atuais de restauração ativa podem não superar as barreiras à regeneração em florestas exploradas, o que pode levar a mudanças de longo prazo nas comunidades florestais no futuro.

Projected Colorectal Cancer Incidence and Mortality Based on Observed Adherence to Colonoscopy and Sequential Stool-Based Screening.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (single-screening colonoscopy vs ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable-as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations.

Monocyte NLRP3 inflammasome and interleukin-1ß activation modulated by alpha-1 antitrypsin therapy in deficient individuals.

INTRODUCTION: Altered complement component 3 (C3) activation in patients with alpha-1 antitrypsin (AAT) deficiency (AATD) has been reported. To understand the potential impact on course of inflammation, the aim of this study was to investigate whether C3d, a cleavage-product of C3, triggers interleukin (IL)-1ß secretion via activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. The objective was to explore the effect of AAT augmentation therapy in patients with AATD on the C3d/complement receptor 3 (CR3) signalling axis of monocytes and on circulating pro-inflammatory markers. METHODS: Inflammatory mediators were detected in blood from patients with AATD (n=28) and patients with AATD receiving augmentation therapy (n=19). Inflammasome activation and IL-1ß secretion were measured in monocytes of patients with AATD, and following C3d stimulation in the presence or absence of CR3 or NLRP3 inhibitors. RESULTS: C3d acting via CR3 induces NLRP3 and pro-IL-1ß production, and through induction of endoplasmic reticulum (ER) stress and calcium flux, triggers caspase-1 activation and IL-1ß secretion. Treatment of individuals with AATD with AAT therapy results in decreased plasma levels of C3d (3.0±1.2 µg/mL vs 1.3±0.5 µg/mL respectively, p<0.0001) and IL-1ß (115.4±30 pg/mL vs 73.3±20 pg/mL, respectively, p<0.0001), with a 2.0-fold decrease in monocyte NLRP3 protein expression (p=0.0303), despite continued ER stress activation. DISCUSSION: These results provide strong insight into the mechanism of complement-driven inflammation associated with AATD. Although the described variance in C3d and NLRP3 activation decreased post AAT augmentation therapy, results demonstrate persistent C3d and monocyte ER stress, with implications for new therapeutics and clinical practice.

Current use of simulation for EPA assessment in emergency medicine.

OBJECTIVE: Approximately five years ago, the Royal College emergency medicine programs in Canada implemented a competency-based paradigm and introduced the use of Entrustable Professional Activities (EPAs) for assessment of units of professional activity to assess trainees. Many competency-based medical education (CBME) based curricula, involve assessing for entrustment through observations of EPAs. While EPAs are frequently assessed in clinical settings, simulation is also used. This study aimed to characterize the use of simulation for EPA assessment. METHODS: A study interview guide was jointly developed by all study authors and followed best practices for survey development. A national interview was conducted with program directors or assistant program directors across all the Royal College emergency medicine programs across Canada. Interviews were conducted over Microsoft Teams, interviews were recorded and transcribed, using Microsoft Teams transcribing service. Sample transcripts were analyzed for theme development. Themes were then reviewed by co-authors to ensure they were representative of the participants' views. RESULTS: A 64.7% response rate was achieved. Simulation has been widely adopted by EM training programs. All interviewees demonstrated support for the use of simulation for EPA assessment for many reasons, however, PDs acknowledged limitations and thematic analysis revealed certain themes and tensions for using simulation for EPA assessment. Thematic analysis revealed six major themes: widespread support for the use of simulation for EPA assessment, concerns regarding the potential for EPA assessment to become a "tick- box" exercise, logistical barriers limiting the use of simulation for EPA assessment, varied perceptions about the authenticity of using simulation for EPA assessment, the potential for simulation for EPA assessment to compromise learner psychological safety, and suggestions for the optimization of use of simulation for EPA assessment. CONCLUSIONS: Our findings offer insight for other programs and specialties on how simulation for EPA assessment can best be utilized. Programs should use these findings when considering using simulation for EPA assessment.

RéSUMé: OBJECTIF: Il y a environ cinq ans, les programmes de médecine d'urgence du Collège royal au Canada ont mis en place un paradigme basé sur les compétences et ont introduit l'utilisation d'activités professionnelles confiables (APC) pour l'évaluation des unités d'activité professionnelle afin d'évaluer les stagiaires. De nombreux programmes d'enseignement médical basés sur les compétences (CBME) prévoient l'évaluation des compétences par l'observation des APC. Bien que les APC soient fréquemment évaluées en milieu clinique, la simulation est également utilisée. Cette étude visait à caractériser l'utilisation de la simulation pour l'évaluation de l'APC. MéTHODES: Un guide d'entretien d'étude a été élaboré conjointement par tous les auteurs de l'étude et a suivi les meilleures pratiques en matière d'élaboration d'enquêtes. Un entretien national a été réalisé avec les directeurs de programmes ou les directeurs adjoints de tous les programmes de médecine d'urgence du Collège royal au Canada. Les entretiens ont été menés sur Microsoft Teams, enregistrés et transcrits à l'aide du service de transcription de Microsoft Teams. Les transcriptions des échantillons ont été analysées pour développer des thèmes. Les thèmes ont ensuite été revus par les co-auteurs pour s'assurer qu'ils étaient représentatifs des points de vue des participants. RéSULTATS: Un taux de réponse de 64,7 % a été obtenu. La simulation a été largement adoptée par les programmes de formation en médecine d'urgence. Toutes les personnes interrogées se sont montrées favorables à l'utilisation de la simulation pour l'évaluation de l'APE pour de nombreuses raisons. Cependant, les DP ont reconnu des limites et l'analyse thématique a révélé certains thèmes et tensions liés à l'utilisation de la simulation pour l'évaluation de l'APC. L'analyse thématique a révélé six thèmes majeurs : un appui généralisé à l'utilisation de la simulation pour l'évaluation de l'APC, inquiétudes concernant la possibilité que l'évaluation de l'APC devienne un exercice de type « case à cocher ¼, des obstacles logistiques limitant l'utilisation de la simulation pour l'évaluation de l'APC, les perceptions variées quant à l'authenticité de l'utilisation de la simulation pour l'évaluation de l'APC, le potentiel de la simulation pour l'évaluation de l'APC de compromettre la sécurité psychologique des apprenants, et des suggestions pour l'optimisation de l'utilisation de la simulation pour l'évaluation de l'APC. CONCLUSIONS: Nos résultats offrent un aperçu à d'autres programmes et spécialités sur la meilleure façon d'utiliser la simulation pour l'évaluation de l'APC. Les programmes devraient utiliser ces résultats lorsqu'ils envisagent d'utiliser la simulation pour l'évaluation de l'APC.