Concomitant Achalasia and Barrett's Esophagus: A Rare Coincidence.

The pathophysiologies of achalasia and gastroesophageal reflux disease with Barrett's esophagus are highly distinct, though the clinical signs and symptoms of both are highly overlapped. The concomitant development of both achalasia and Barrett's esophagus is rare. We describe a case of a patient with a concomitant diagnosis of both pathologies and further explain the epidemiology of carrying both diseases simultaneously.

Augmented Stress Weight-bearing CT for Evaluation of Subtle Lisfranc Injuries in the Elite Athlete.

BACKGROUND: Lisfranc injuries refer to a disruption or displacement of the tarsometatarsal joint of the foot. Subtle Lisfranc injuries can go undiagnosed on conventional imaging leading to devastating consequences and poor functional outcomes for elite athletes. Objective. The objective of this case study is to present a novel imaging technique using weight-bearing computed tomography (CT) with enhanced stress to identify subtle, dynamically unstable Lisfranc injuries. We illustrate this with a case presentation of an elite athlete who ultimately required surgical fixation for a subtle Lisfranc injury. MATERIALS AND METHODS: To perform an augmented stress weight-bearing CT, the patient was positioned standing, with their feet facing forward, and weight equally distributed. The patient was then coached to symmetrically raise both heels from the scanner platform. This plantarflexion provided augmented stress on the midfoot, allowing for more sensitive imaging of the Lisfranc injury. The weight-bearing CT and augmented stress images undergo 3D reconstruction and postprocessing to render coronal and sagittal images, allowing for comparison of the standard weight-bearing and augmented stress images. RESULTS: We present the case of a 22-year-old collegiate football lineman sustaining a Lisfranc injury. The injury diagnosis was made by magnetic resonance imaging (MRI) and clinical examination, without evidence of injury on weight-bearing XR or standard weight-bearing CT. With augmented stress CT imaging, the Lisfranc instability was noted, leading to surgical fixation, and return to sport the next season. CONCLUSION: We propose this technique for diagnosing subtle, unstable Lisfranc injuries where clinical suspicion persists despite inconclusive imaging, particularly in elite athletes. Further research is needed with larger sample sizes to investigate the sensitivity of this novel imaging technique for the detection of Lisfranc injury. LEVELS OF EVIDENCE: Level 4: Case Report.

Augmented stress weightbearing CT for evaluation of subtle tibiofibular syndesmotic injuries in the elite athlete.

OBJECTIVE: We aim to present a novel imaging technique utilizing weight-bearing CT with syndesmotic stress to identify subtle, unstable syndesmotic injuries. We illustrate this with a case presentation of such an injury in an elite athlete that ultimately required operative fixation. MATERIALS AND METHODS: In order to perform an augmented stress weightbearing CT, the patient is in the standing position, feet facing forward, and with weight distributed equally. The patient is then coached to internally rotate the shin and knee. This places an external rotational moment on the TFS due to the planted foot and ankle. The augmented stress images undergo 3D reconstruction and post-processing to render coronal and sagittal images. These are subsequently compared to standard, conventional weightbearing CT images performed without the external rotation stress. RESULTS: We illustrate this technique by presenting a case in which a 21-year-old collegiate athlete sustained a Grade II syndesmotic injury, diagnosed by MRI and clinical exam without evidence of instability by standard weightbearing CT or weightbearing radiographs. After undergoing the augmented stress weightbearing CT, the instability was noted. This prompted subsequent operative fixation and ultimately return to sport. CONCLUSION: We propose this technique for diagnosing unrecognized, subtle dynamically unstable syndesmosis injuries where clinical suspicion persists despite negative imaging, particularly in the elite athlete.

S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive.

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.

Comparing Sex-Specific Outcomes After Rotator Cuff Repair: A Meta-analysis.

Background: Rotator cuff repair (RCR) is a well-studied procedure. However, the impact of patient sex on outcomes after RCR has not been well studied. Purpose: To conduct a systematic review and meta-analysis of sex-based differences in outcomes after RCR and to record what proportion of studies examined this as a primary or secondary purpose. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using multiple databases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were included if they were written in English, performed on humans, consisted of patients who underwent RCR, evaluated at least 1 of the selected outcomes based on patient sex, and had statistical analysis available for their sex-based claim. Excluded were case reports, review studies, systematic reviews, cadaveric studies, and studies that did not report at least 1 sex-specific outcome or included certain other injuries associated with a rotator cuff injury. Results: Of 9998 studies screened and 1283 full-text studies reviewed, 11 (0.11%) studies with 2860 patients (1549 male and 1329 female) were included for quantitative analysis. None of these 11 studies examined the impact of patient sex on outcomes after RCR as a primary outcome. Postoperative Constant-Murley scores were analyzed for 7 studies. Male patients had a postoperative Constant-Murley score of 76.77 ± 15.94, while female patients had a postoperative Constant-Murley score of 69.88 ± 17.02. The random-effects model showed that male patients had significantly higher scores than female patients, with a mean difference of 7.33 (95% CI, 5.21-9.46; P < .0001). Analysis of retear rates in 5 studies indicated that there was no difference in the retear rate between sexes (odds ratio, 0.91 [95% CI, 0.49-1.67]). Conclusion: Female patients had lower postoperative Constant-Murley scores compared with male patients, but there was no difference in the retear rate. However, these results were based on an analysis of only 11 studies. The paucity of studies examining the impact of sex suggests that more research is needed on the impact of patient sex on outcomes after RCR.

Primary Repair, Reconstruction, and Suture Tape Augmentation All Provide Excellent Outcomes for Lateral Ligament Instability: A Systematic Review.

Purpose: To analyze the literature to compare outcomes and complications following primary lateral ankle ligament repair compared with lateral ankle ligament reconstruction and the suture tape augmentation in patients with lateral ankle instability. Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, a systematic literature review using the PubMed/Ovid Medline database was performed (October 11, 1947, to October 1, 2019). Clinical trials that included all the following criteria were considered eligible; published in the English language; patients undergoing primary lateral ankle repair or reconstruction with/without autograft or allograft (anterior talofibular ligament, anterior talofibular ligament + calcaneofibular ligament) or suture tape augmentation; a follow-up at least 1 year; reported least 1 of the measured outcomes (The American Orthopaedic Foot Ankle Score, Karlsson Score, return to sport [RTS], complications, skin wound complications, reoperation). Surgical techniques were evaluated, and studies were subdivided by the following categories: primary repair (PR), reconstruction with graft (GR), and suture tape augmentation (STA). Complications, radiographic outcomes, functional outcome scores, and RTS were analyzed. Results: A total of 41 of 1,991 studies met the criteria for final analysis. This included 1,920 patients who underwent surgical intervention for chronic lateral instability with at least a 1-year follow-up. There were 350 patients who had GR, 1,486 who underwent the PR, and 84 who had STA. GR group appeared to have the lowest rate of complications: GR 3.1% (11 of 350), PR 4.2% (63 of 1486), and STA 10.7% (9 of 84). Postoperative American Orthopaedic Foot Ankle Score ranged from 89.0 to 95.1 for GR and 90.0 to 98.8 for PR. Postoperative Karlsson scores ranged from 80.9 to 94.4 for GR and from 89.2 to 94.1 for PR. Anterior drawer postoperative scores ranged from 1.4 to 30.3 mm for GR, 2.7 to 8.6 mm for PR, and 4.1 to 4.2 mm for STA. Postoperative talar tilt ranged from 2.4 to 7.3° for GR, 1.9 to 6.0° for PR, and 3.6 to 4.5° for STA. RTS ranged from 9.5 to 20.4 weeks for the PR group; one study reported a RTS of 10.6 weeks for STA. Conclusions: Excellent outcomes were noted across all intervention groups. Current literature may suggest there is no difference in functional outcomes between patients treated with PR versus GR. However, there may be a potential improvement in functional outcomes with PR versus STA. Level of Evidence: Level IV, systematic review of Level I to Level IV studies.

Sex-Specific Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: Despite the significant difference between men and women in incidence of anterior cruciate ligament (ACL) injuries, there is a paucity of consistent information on the influence of patient sex on outcomes after ACL reconstruction. A previous meta-analysis has demonstrated that female patients have worse outcomes with regard to laxity, revision rate, Lysholm score, and Tegner activity score and are less likely to return to sports (RTS). PURPOSE: To conduct a systematic review and meta-analysis to evaluate and compare sex-specific outcomes after ACL reconstruction. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed using PubMed, PubMed Central, Embase, OVID, and Cochrane databases per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following search terms were used: "anterior cruciate ligament reconstruction" OR "ACL reconstruction" OR "anterior cruciate ligament" OR "ACL" AND "gender" OR "sex" OR "male" OR "female" AND "outcome" AND "2015-Present" to gather all relevant articles between 2015 and 2020. A risk-of-bias assessment and quality assessment was conducted on included studies. RESULTS: Of 9594 studies initially identified, 20 studies with 35,935 male and 21,455 female patients were included for analysis. The 7 studies reporting International Knee Documentation Committee (IKDC) scores showed that male patients had statistically significantly higher postoperative scores (mean difference, 3.02 [95% CI, 1.19-4.84]; P< .01; I 2 = 66%), and 7 studies that reported the rate of ACL revision showed there was no significant difference between male and female patients (odds ratio, 0.85 [95% CI, 0.45-1.60]; P = .61; I 2 = 94%). The 7 studies that reported rates of rerupture showed that males were significantly more likely than females to have a graft rerupture (odds ratio, 1.35 [95% CI, 1.22-1.50]; P < .01; I 2 = 0%). Male patients reported a higher RTS rate than did their female counterparts (59.82% compared with 42.89%); however, no formal statistical analysis could be done because of the variability in reporting techniques. CONCLUSION: Male and female patients with ACL injuries demonstrated similar outcomes regarding their rates of revision; however, male patients were found to have statistically significantly higher postoperative IKDC scores but at the same time higher rerupture rates. Our findings suggest that sex-based differences in outcomes after ACL reconstruction vary based on which metric is used. These results must be considered when counseling patients with ACL injuries.

Sex-specific differences in outcomes after anterior shoulder surgical stabilization: a meta-analysis and systematic review of literature.

BACKGROUND: Anterior shoulder instability frequently occurs in young, physically active individuals and may be treated with surgical stabilization. Previous studies have shown that males more often require surgical management for anterior shoulder instability and may have a higher frequency of recurrent instability episodes after surgical management, but females have been found to have increased incidence of apprehension after surgical stabilization. The purpose of this study is to review the literature and assess anterior shoulder surgical stabilization postoperative outcomes between males and females to identify and describe sex-based differences. METHODS: A systematic search of electronic databases was conducted to identify level I-IV clinical studies on anterior shoulder instability published between 1960 and August 2020. We included studies that evaluated sex-specific outcomes in patients who underwent anterior shoulder instability procedures. A meta-analysis of the data was performed to analyze sex-specific outcomes. RESULTS: Thirty studies (2.1%) met inclusion criteria, representing 9829 patients. Of the studies that reported the number of male and female patients, 74% were male and 26% were female. Twenty-six studies used Bankart repair alone, two used open Latarjet procedure alone, and two had a Bankart repair group and Latarjet procedure group. Instability recurrence, return to sport, and apprehension were included in the meta-analysis. Our meta-analysis demonstrated a significantly higher rate of instability recurrence for males than for females who underwent arthroscopic Bankart repair (risk ratio [RR] = 1.25; 95% confidence interval [CI] = 1.03, 1.52; P = .0239). We did not identify a significant difference between males and females in rates of apprehension (RR = 0.68; 95% CI = 0.37, 1.27; P = .2300) or return to sport (RR = 0.98; 95% CI = 0.81, 1.18; I2 = 0%; P = .8110) for arthroscopic Bankart repair or open Latarjet procedure. CONCLUSION: For patients who underwent arthroscopic Bankart repair for anterior shoulder stabilization, recurrent rates of instability were significantly higher for males than for females. When open Bankart and Latarjet procedures were included, there was no difference. No difference was seen between males and females after arthroscopic Bankart repair or open Latarjet procedures with regard to return to sport or apprehension.

The wtf4 meiotic driver utilizes controlled protein aggregation to generate selective cell death.

Meiotic drivers are parasitic loci that force their own transmission into greater than half of the offspring of a heterozygote. Many drivers have been identified, but their molecular mechanisms are largely unknown. The wtf4 gene is a meiotic driver in Schizosaccharomyces pombe that uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inherit wtf4. Here, we show that the Wtf4 proteins can function outside of gametogenesis and in a distantly related species, Saccharomyces cerevisiae. The Wtf4poison protein forms dispersed, toxic aggregates. The Wtf4antidote can co-assemble with the Wtf4poison and promote its trafficking to vacuoles. We show that neutralization of the Wtf4poison requires both co-assembly with the Wtf4antidote and aggregate trafficking, as mutations that disrupt either of these processes result in cell death in the presence of the Wtf4 proteins. This work reveals that wtf parasites can exploit protein aggregate management pathways to selectively destroy spores.

Meiotic drivers are genes that break the normal rules of inheritance. Usually, a gene has a 50% chance of passing on to the next generation. Meiotic drivers force their way into the next generation by poisoning the gametes (the sex cells that combine to form a zygote) that do not carry them. Harnessing the power of genetic drivers could allow scientists to spread beneficial genes across populations. One group of meiotic drivers found in fission yeast is called the 'with transposon fission yeast', or 'wtf' gene family. The wtf drivers act during the production of spores, which are the fission yeast equivalent of sperm, and they encode both a poison that can destroy the spores and its antidote. The poison spreads through the sac holding the spores, and can affect all of them, while the antidote only protects the spores that make it. This means that the spores carrying the wtf genes survive, while the rest of the spores are killed. To understand whether it is possible to use the wtf meiotic drivers to spread other genes, perhaps outside of fission yeast, scientists must first establish exactly how the proteins coded for by genes behave. To do this, Nuckolls et al. examined a member of the wtf family called wtf4. Attaching a fluorescent label to the poison and antidote proteins produced by wtf4 made it possible to see what they do. This revealed that the poison clumps, forming toxic aggregates that damage yeast spores. The antidote works by mopping up these aggregates and moving them to the cell's main storage compartment, called the vacuole. Mutations that disrupted the ability of the antidote to interact with the poison or its ability to move the poison into storage stopped the antidote from working. Nuckolls et al. also showed that if genetic engineering was used to introduce wtf4 into a distantly related species of budding yeast the effects of this meiotic driver were the same. This suggests that the wtf genes may be good candidates for future genetic engineering experiments. Engineered systems known as 'gene drives' could spread beneficial genetic traits through populations. This could include disease-resistance genes in crops, or disease-preventing genes in mosquitoes. The wtf genes are small and work independently of other genes, making them promising candidates for this type of system. These experiments also suggest that the wtf genes could be useful for understanding why clumps of proteins are toxic to cells. Future work could explore why clumps of wtf poison kill spores, while clumps of poison plus antidote do not. This could aid research into human ailments caused by protein clumps, such as Huntington's or Alzheimer's disease.

Biasing visual selection: functional neuroimaging of the interplay between spatial cueing and feature memory guidance.

The authors investigate the interplay between spatial attention and memory-based feature guidance of visual selection. Three types of guidance were tested: working memory, spatial cueing and passive memory. In all cases the memory-cue was not relevant to a subsequent search task, whilst the spatial cue always provided valid information. Behaviourally, search performance was influenced by spatial cueing and by feature-based cueing from the contents of working memory; both forms of guidance interacted, with feature guidance being more effective when the target's location was not pre-cued. Spatial cueing recruited the dorsal fronto-parietal network which was silent during the WM-only condition. Memory guidance of selection was reflected in activity in a frontal-temporal-occipital network. Interestingly, when spatial and memory guidance were pitted against each other, neural activity in this latter network was greatly attenuated. Connectivity analysis showed that the posterior parietal cortices inhibit the responses of occipital and temporal regions to the onset of memory-items in the search display. In the presence of a reliable spatial cue the posterior parietal cortex resumes control of attentional deployment. These results illustrate how different forms of attention guidance interact to optimise visual selection.

Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis.

Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G(1) phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound.