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Background: Psychological safety is a team-based phenomenon whereby group members are empowered to ask questions, take appropriate risks, admit mistakes, propose novel ideas, and candidly voice concerns. Growing research supports the benefits of psychological safety in healthcare and education for patient safety, learning, and innovation. However, there is a paucity of research on how to create psychological safety, especially within academic medicine. To meet this need, the present study describes and evaluates a multi-year, medical school-wide psychological safety initiative., Methods: We created, implemented, and assessed a multi-pronged psychological safety initiative including educational training sessions, departmental champions, videos, infographics, and targeted training for medical school leaders. Employees' perceptions of psychological safety at both the departmental and institutional levels were assessed annually. The impact of educational training sessions was quantified by post-session surveys., Results: Deidentified employee surveys revealed a statistically significant increase in departmental psychological safety between the first and second annual surveys. Perceived psychological safety remained lower at the institution-wide level than at the departmental level. No significant differences in psychological safety were observed based on gender, position, or employment length. Post-educational training session surveys showed that the sessions significantly increased knowledge of the topic as well as motivation to create a culture of psychological safety within the medical school., Conclusions: This study establishes an evidence-based method for increasing psychological safety within medical school departments and serves as a template for other health professions schools seeking to promote psychological safety. Training leadership, faculty, and staff is an important first step towards creating a culture of psychological safety for everyone, including trainees., (© 2024. The Author(s).)

Introduction: Historically, the requirement to produce scholarship for advancement has challenged health professions educators heavily engaged in teaching. As biomedical scientists or healthcare practitioners, few are trained in educational scholarship, and related faculty development varies in scope and quality across institutions. Currently, there is a need for faculty development and mentoring programs to support the development of these skills., Methods: The International Association of Medical Science Educators (IAMSE) established the Medical Educator Fellowship (MEF) Program to foster health professions educational scholarship. MEF addresses the following: curriculum design, teaching methods and strategies, assessment, educational scholarship, and leadership. Participants receive mentorship and faculty development, and complete an educational scholarship project. Using a logic model, we conducted a retrospective program evaluation with data from Program records, database searches, graduate surveys, and focus groups., Results: Over 14 years, MEF graduated 61 participants with diverse terminal degrees from five continents and six academic program areas. Graduate survey responses indicated enhanced post-Program skills in all focus areas, that the majority would recommend MEF to a colleague, and that mentorship, networking, and professional development were strengths. Focus group outcomes indicated professional growth, increased confidence, and increased sense of community., Conclusion: MEF addresses health professions educators' need for faculty development and mentorship in educational scholarship. Evaluation outcomes suggest that MEF effectively enhanced perceived skills across focus areas. Similar programs are essential to support faculty who dedicate significant time to teaching. Organizations like IAMSE can demonstrate the value of educational scholarship and positively impact health professions educator careers by supporting such programs., Competing Interests: Competing InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Mitochondria are critical cellular organelles that perform a wide variety of functions, including energy production and immune regulation. To perform these functions, mitochondria contain approximately 1,500 proteins, the majority of which are encoded in the nuclear genome, translated in the cytoplasm, and translocated to the mitochondria using distinct mitochondrial targeting sequences (MTS). Bacterial proteins can also contain MTS and localize to the mitochondria. For the obligate intracellular human pathogen Chlamydia trachomatis, interaction with various host cell organelles promotes intracellular replication. However, the extent and mechanisms through which Chlamydia cells interact directly with mitochondria remain unclear. We investigated the presence of MTS in the C. trachomatis genome and discovered 30 genes encoding proteins with around 70% or greater probability of mitochondrial localization. Five are translocated to the mitochondria upon ectopic expression in HeLa cells. Mass spectrometry of isolated mitochondria from infected cells revealed that two of these proteins localize to the mitochondria during infection. Comparison of mitochondria from infected and uninfected cells suggests that chlamydial infection affects the mitochondrial protein composition. Around 125 host proteins were significantly decreased or absent in mitochondria from infected cells. Among these were proapoptotic factors and those related to mitochondrial fission/fusion dynamics. Conversely, 82 host proteins were increased in or specific to mitochondria of infected cells, many of which act as antiapoptotic factors and upregulators of cellular metabolism. These data support the notion that C. trachomatis specifically targets host mitochondria to manipulate cell fate decisions and metabolic function to support pathogen survival and replication. IMPORTANCE Obligate intracellular bacteria have evolved multiple means to promote their intracellular survival and replication within the otherwise harsh environment of the eukaryotic cell. Nutrient acquisition and avoidance of cellular defense mechanisms are critical to an intracellular lifestyle. Mitochondria are critical organelles that produce energy in the form of ATP and regulate programmed cell death responses to invasive pathogenic microbes. Cell death prior to completion of replication would be detrimental to the pathogen. C. trachomatis produces at least two and possibly more proteins that target the mitochondria. Collectively, C. trachomatis infection modulates the mitochondrial protein composition, favoring a profile suggestive of downregulation of apoptosis.

Due to the Covid-19 pandemic, many academic institutions had to rapidly transition education to a remote online environment. While a hurdle for most educators, this transition posed an even greater challenge for anatomy educators, many of whom were forced to depart from the traditional cadaver-based laboratory to a virtual format. Recent publications have discussed the rapid transition to online formats necessitated by Covid-19 and the accompanying difficulties, but none have identified specific factors that influenced the difficulty of this transition. Anatomy educators were surveyed to examine how this transition was accomplished and perceived. Of the 165 educators who responded, the majority utilized cadaver-based laboratory instruction. Educators felt that transitioning the laboratory portion of their courses was significantly more difficult and required more time than converting lecture materials. Factors that impacted the difficulty of the transition included a number of pedagogical aspects of the pre-Covid-19 curricula, including the delivery format of prior content, availability of pre-existing electronic materials, and the laboratory technique previously used. Additionally, the length of time an educator had been teaching prior to Covid-19 impacted their perception of difficulty, with newer and more senior educators finding this much more challenging than mid-tenure educators. Ease of transition may be related to previous exposure to curricular reform, experience with multiple anatomy pedagogies, and educator adaptability. While not surprising that converting a cadaver-based laboratory to an online format was challenging, knowledge of the alignment of this difficulty with prior educator pedagogy can help guide future innovations to anatomy education., (© 2022 American Association for Anatomy.)

Cancer is not infrequently detected in the Emergency Department (ED) and is sometimes even an incidental finding on imaging. Since the ED is designed to identify and treat acutely ill patients, the time providers can spend with patients and the depth of investigation into patient conditions is limited. However, Emergency Medicine physicians must ensure the appropriate follow-up for patients with presumptive diagnosis of cancer to ensure timely confirmatory testing, prompt treatment, and accurate prognosis. A 26-year-old woman presented to the ED for evaluation of abdominal pain and urinary complaints and was ultimately found to have a 36cm ovarian mass that was suspicious for neoplasm. The mass caused obstruction of urinary outflow leading the patient to develop a urinary tract infection. Emergency Medicine physicians are faced with the challenge of having limited time and short-lived doctor-patient relationships. In cases of suspicious findings, balancing the urgency of follow-up without causing undue harm from heightened anxiety for patients is essential. It is important to discuss findings that may be concerning for cancer with both clear verbal and written communication. Employ strategies such as direct communication with primary care physicians and outpatient specialists via phone consultation and electronic medical record messaging, as well as providing clear discharge instructions in-person and in-writing to the patient including whom to call and the time frame for follow-up., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ekpo et al.)

INTRODUCTION In 2013, the United States Preventive Services Task Force recommended annual low-dose computed tomography (CT) screening for lung cancer in high-risk adults with a significant smoking history. These screenings result in large numbers of incidental findings, and although most of these do not warrant further investigation, there have been reported cases of incidental findings identified on CT screening that led to successful treatment of a previously undiagnosed comorbidity. CASE HISTORY Here, we report a case of papillary renal cell carcinoma that was detected incidentally on low-dose CT in an asymptomatic individual, a rare diagnosis considering that renal neoplasms account for <1% of incidental findings on these screenings. CONCLUSION This case highlights the value of investigating these incidental findings, with the goal of detecting underlying disease in some cases before it would have presented symptomatically.

Objectives: Opioid overdoses have become a significant problem across the United States resulting in respiratory depression and risk of death. Basic Life Support (BLS) first responders have had the option to treat respiratory depression using a bag-valve-mask device, however naloxone, an opioid antagonist, has been shown to quickly restore normal respiration. Since the introduction of naloxone and recent mandates across many states for BLS personnel to carry and administer naloxone, investigation into the adherence of naloxone use standing protocols is warranted., Methods: This preliminary study examined 100 initial cases of BLS first responder administration of naloxone for appropriate indications and protocol adherence., Results: This study found that n=22/100 naloxone administrations were inappropriate, often given to patients who were not suffering from respiratory depression (n=11/22). Positive pressure ventilation (PPV) was not administered prior to naloxone in n=56/100 cases, of which n=42/100 had an inadequate respiratory effort documented. For patients with a known history of substance use disorder, there was a significant increase in administration of naloxone prior to PPV (60%; n=33/55) compared to patients without a known history (30%; n=9/30)., Conclusion: Overall these preliminary data suggest that during BLS naloxone administration, the majority of cases did not follow at least one component of the standard protocol for patients with respiratory depression. This study suggests that further education and more research are needed to better understand the decision-making processes of prehospital providers to ensure adherence to standard protocols., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Mastenbrook et al.)

This study identified charcoal-based dentifrices and abrasive powders sold in Brazil and analyzed their label information. The products were searched in four online shopping platforms. The same products were searched on Instagram and their engagement metrics were investigated. Furthermore, a literature review of international publications assessing charcoal dentifrices and powders was conducted, and altmetrics were collected (Altmetric and PlumX). Thirty-six products were found with prices between $0.4-22 USD. Most frequent words in product description were sodium, stain, whitening, oil, xylitol, and coconut. Only 3 products contained fluoride. Bactericidal, antiviral, antifungal, and anti-inflammatory activities were indicated, in addition to non-scientific claims such as calming teeth or increasing oral immunity. In total, 72% of products had Instagram profiles, which generally showed low engagement rates (81%) and medium audience quality scores (65%). Twenty-two articles were found in the literature, from which 21 were in vitro studies. The single clinical study was sponsored by a charcoal product and had no control group. In total, 23% of studies showed positive results and 55% reported negative results for the charcoal products, which included no whitening ability, increased roughness, surface alterations, and lower demineralization prevention ability. Altmetric scores for the included articles varied from 0 to 55, with 40.9% of studies mentioned online. In conclusion, charcoal-based products are using marketing strategies on Instagram but their current engagement with the public is not high. Consumers are being exposed to charcoal products whose potential risks to health are still unknown.

Vertebral osteomyelitis is an infection of the vertebrae that can lead to spinal degeneration, most commonly caused by Staphylococcus aureus Here, we report an unusual case of pyogenic osteomyelitis caused by Gardnerella vaginalis and Streptococcus parasanguinis in a 61-year-old postmenopausal woman. The patient presented with a 2-week history of worsening lower back pain and fever and a recent episode of cystitis following re-engagement of sexual activity. Imaging revealed a deterioration of vertebrae discs and spinal canal stenosis at the L3-L4 levels with a formation of abscess in the right psoas muscle. Needle aspiration of the abscess identified G. vaginalis and S. parasanguinis and the patient was successfully treated with a 6-week course of ceftriaxone and metronidazole. This case describes an unusual coinfection of two pathogens that normally reside in the urogenital tract and oral cavity, respectively, and highlights the risk posed when these organisms breach the body's normal barriers., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Crossbow fatalities are a rare occurrence, but crossbow use is on the rise. The manner of death in crossbow fatalities is overwhelmingly opined accident or suicide, not homicide. Despite their increasing use and reports of at least 14 crossbow-related homicides in the media for the last 5 years, crossbow homicides are rarely reported in the medical literature; only 10 articles that discussed 20 crossbow homicides were identified in the PubMed database. Here, we describe a case of a 20-year-old man who was found dead in his driveway after being shot in the abdomen with a crossbow by another person. The crossbow bolt had a mechanical 2-blade broadhead that transected the descending aorta and lodged in his vertebra. When completing a medicolegal death investigation and postmortem examination on suspected crossbow-related deaths, knowledge of crossbow components, its utility as a weapon, wound patterns, and how it can cause death are important. This case serves to build on the limited medical literature of crossbow homicides, educate forensic pathologists about the features of crossbow deaths, and highlight manner of death considerations.

Brainstem infarction typically presents with vague symptoms, including headache, nausea, vomiting, and vertigo. Rarely do patients present with complete unilateral facial paralysis, mimicking Bell's palsy. Here we report the case of a 40-year-old woman who presented to the emergency department with intractable nausea, vomiting, and vertigo upon waking along with left-sided upper and lower extremity numbness and right-sided facial paralysis. Her atypical presentation of unilateral facial nerve paralysis in the context of nausea, vomiting, and vertigo prompted neurological studies, which were significant for a small punctate infarct in the pons involving the right facial colliculus. ​History, physical examination, and clinical suspicion are important to prevent anchoring bias. Physicians rely on history and physical examination to help distinguish true Bell's palsy from other causes of facial nerve paralysis. Stroke and other clinically emergent etiologies should be considered high on the differential diagnosis when patients have neurological signs and symptoms in addition to facial nerve palsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Burson et al.)

The majority of hanging deaths are relatively straightforward when opining the manner of death, typically determined to be suicide. However, there are rare hanging deaths that require the forensic pathologist to seek additional information. Forensic pathologists commonly consider an accidental manner of death when the hanging death scene includes evidence of solitary sexual activity consistent with autoerotic asphyxia. Here, the authors present a case of an initially apparent suicidal hanging where important death scene details photographed by the medical examiner investigator and history provided by family members during subsequent conversations ultimately helped the forensic pathologist conclude an opinion that the hanging was accidental, likely due to autoerotic activity. The decedent, who hanged himself in the closet of his bedroom, was wearing shorts that were initially believed to be inadvertently torn; however, further investigation revealed his shorts were intentionally modified to expose his genitalia. Additional evidence documented from the death scene photographs and conversations with his mother revealed items and activities consistent with autoerotic behavior. Before opining a manner of death in hanging deaths, forensic pathologists are encouraged to consider details beyond that obtained from the initial death scene investigation and postmortem examination. A thorough medicolegal death investigation should not be viewed as introducing cognitive bias, but rather as necessary information needed to determine the most accurate cause and manner of death.

Acute changes in electrolyte levels can result in severe physiologic complications. Rapid treatment of abnormally elevated potassium levels is essential due to the increased risk of potentially fatal cardiac arrhythmias. However, there are a number of circumstances that can lead to falsely elevated serum potassium levels, including fist clenching during phlebotomy and hemolysis of hematocytes during laboratory processing. Here we present a case of an elderly woman with chronic lymphocytic leukemia who presented with lower left quadrant pain and hematochezia. Laboratory tests revealed an elevated serum potassium level (7.5 mmol/L) on initial testing, in the absence of hyperkalemia symptoms, EKG changes, and hemolysis of the blood specimen. Abdominal CT revealed inflammatory changes consistent with diverticulitis. She was treated with intravenous calcium, insulin, glucose, and bicarbonate for her hyperkalemia and admitted for treatment for diverticulitis. A subsequent serum potassium level (3.9 mmol/L) and discussion with the hospitalist suggested a diagnosis of leukolysis-induced pseudohyperkalemia, and further treatment of hyperkalemia was halted. This case serves to remind current and future physicians about the importance of maintaining clinical suspicion and clarifying unexpected laboratory readings when the clinical picture and results do not completely align., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Dewey et al.)

Case: Infantile Blount disease results from deceleration of growth by the proximal posteromedial tibial physis causing tibia vara. In advanced disease stages, surgical treatment is indicated. Owing to the young age and advanced Langenskiöld stage in this patient, a novel technique was performed combining lateral proximal physeal tethering with medial hemiplateau elevation osteotomy to correct the articular surface and unload the medial proximal tibial physis., Conclusion: Together, these procedures allow for correction of alignment while preserving growth potential. This technique was successful in correcting tibia vara due to infantile Blount disease while allowing continued growth in a 5-year-old patient.

Few discussions regarding instructional methods incite as much passion as the debate over dissection versus prosection. Despite numerous analyses, few studies have isolated the impact of dissection versus prosection from the numerous variables that are involved in anatomy education. This study used a retrospective design to assess the effect of peer teaching with dissection or prosection on anatomical knowledge retention of the peer teachers. Exam scores were analyzed from three cohorts of students ( N = 184) who were enrolled in a Musculoskeletal System course in an allopathic medical school between academic years 2014-2017. Students in the first 2 yr learned anatomy of an assigned region through traditional dissection, whereas students in the third year learned anatomy of the same regions on prosected specimens. The effect of these instructional methods on anatomical knowledge retention was measured by student performance on a teaching-readiness quiz, written exam, and practical examination. One advantage of this study is the stability of variables between cohorts. Student groups peer taught the same objectives; course sequencing and content remained consistent between years; students spent the same amount of time learning their material, regardless of learning modality (dissection or prosection); and students were tested in the same manner. Comparisons of student performance data suggest that anatomy knowledge was equivalent, regardless of the instructional method (dissection or prosected cadavers) but is strongly associated with prior anatomy experience. Findings from this study support previous studies that conclude that there are no disparities in the effectiveness of learning anatomy via dissection or prosection.

The majority of opioid-related deaths are accidental. However, the number of opioid-related suicidal deaths is likely under recognized. Presented here is a case of suicide by heroin overdose. The manner of death would have likely been deemed accidental if not for critical information shared by the decedent's family during follow-up telephone interviews between the forensic pathologist and the decedent's family, which included text messages that were sent by the decedent just before his death that were not known at the time of the initial medicolegal death scene investigation. This case highlights that when a forensic pathologist establishes an engaged relationship with the decedent's family, the information elucidated can prove to be invaluable in reaching an informed opinion about the manner of death. For overdose cases, identifying an accurate manner of death allows the design of public health efforts that adequately address the health risks in the community. For aid in the determination of the manner of death for overdose cases, we propose a five-step checklist that may assist forensic pathologists and medicolegal death investigators when approaching similar cases., (© 2020 American Academy of Forensic Sciences.)

Objective: To evaluate the safety and effectiveness of infrainguinal artery revascularization via atherectomy supplemented with other endovascular techniques in an office endovascular center (OEC) setting., Methods: A retrospective study was conducted examining 352 lower extremity atherectomy revascularization procedures between 2011 and 2016 at an OEC by five board-certified vascular surgeons. Patients received laser atherectomy or orbital atherectomy followed by angioplasty or angioplasty and stent placement as needed. Reintervention was indicated based on evidence of clinical symptoms and imaging studies. Demographics, vessel-specific data, treatment information, and outcome of procedures were recorded. Data analysis was carried out using Kaplan-Meier survival curves., Results: Lower extremity atherectomy was carried out in 282 patients in 352 limbs with average age of 69 ± 11 years. Technical success of <30% residual stenosis by angiogram was achieved in 571/594 vessels treated. Within 30 days of procedure, 23/352 limbs required major amputation resulting from pre-existing disease, ranging from 3 Rutherford class 4, 17 Rutherford class 5, to 3 Rutherford class 6 limbs. No 30-day mortality was noted. The primary patency of the 571 treated vessels at 12 months was 90%, and 84% at 29 months. The patency of treated vessels that reached >50% stenosis on follow-up and required reintervention (51/571 vessels) or did not require reintervention (79/571) was 72% and 87% at 23 months' follow-up, respectively, with no difference in risk of occlusion identified (P = .181). There was a significantly increased risk of occlusion for vessels treated with laser atherectomy as compared with orbital atherectomy (odds ratio, 2.552; 95% confidence interval, 1.375-4.735; P = .003). No significant difference in risk of occlusion was found between treatment with atherectomy and angioplasty (466/571 vessels) compared with atherectomy, angioplasty, and stenting (102/571) with secondary patency of 90% and 85% at 6 months' follow-up, respectively. There was no difference in patency between claudicants and patients with critical limb ischemia., Conclusions: Atherectomy in conjunction with angioplasty and/or stenting has satisfactory patency with minimal complications when the procedure is carried out in an OEC. Asymptomatic >50% restenosis of treated vessels does not warrant reintervention unless the patient presents with clinical symptoms. Various atherectomy devices may result in different outcomes., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A Morel-Lavallée lesion (MLL) is a rare injury caused by blunt force trauma causing separation of subcutaneous tissue from the deep fascia. It is frequently seen in orthopaedic cases involving fractures of the hip or pelvis but is rare in the lower leg. The rarity of this condition often leads to misdiagnosis. A 66-year-old man presented to the emergency department after a 300-pound safe sheered across his left anterolateral leg causing skin avulsion, tenderness, swelling, ecchymosis, and erythema. The patient was treated for suspected cellulitis with oral antibiotics, but the lesion evolved into a necrotic eschar necessitating surgical intervention. In hindsight, MLL is a more appropriate diagnosis based on injury mechanism, disease progression and intraoperative findings. A history of shearing trauma with diffuse ecchymosis and erythema should prompt consideration of MLL. Due to rampant misdiagnosis, this case aims to increase awareness, as early diagnosis of MLL will improve patient outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Medical laboratory tests are becoming more reliable with increased specificity and sensitivity, leading to their use as definitive diagnostic tests for many medical conditions. Enzyme-linked immunosorbent assay (ELISA) tests are convenient, sensitive, and standardly used for rapid detection and quantification of antigens or patient antibodies against specific antigens. However, based upon the specificity and sensitivity of an ELISA test, the results may not be definitive for a specific disease but merely suggestive, due to potential cross-reactivity of antigens and antibodies. Here, we present a case of a 15-year-old male who presented with fever, nausea, and right upper quadrant pain. Computed tomography scan showed an 18-cm liver mass with cystic features. Biopsy results confirmed a diagnosis of undifferentiated embryonal sarcoma of the liver; however, the clinical picture was complicated by positive ELISA results for Echinococcus, Entamoeba histolytica, and histoplasmosis. Due to the absence of travel and positive ELISA result for three different infectious agents, we hypothesize that tumor molecular mimicry might have led to false-positive ELISA results in the absence of infection in this case, demonstrating a limitation of ELISA serology. Critical appraisal of all possible evidence to ensure alignment when assigning the final diagnosis is essential for optimal patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Letherer et al.)

Development of professional behaviors, including communication and interprofessional collaboration, is an important competency during medical school that is difficult to teach in the classroom. We developed an approach to peer evaluation for use in Team-Based Learning that has two novel components: inclusion of a non-numeric sliding scale ranging from "apprentice" to "expert" to assess professional development on a continuum, and incorporation of a structured face-to-face feedback session. Students liked the format of the face-to-face feedback session, felt it gave them an opportunity to better understand their peers' comments, and thought it was more effective than the anonymous written evaluation tool., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2019.)

Polydactyly of the foot occurs in 1.7 cases per 1000 live births, comprising 45% of congenital abnormalities of the foot. Most reported cases of polydactyly of the foot are postaxial, and 15% are preaxial; of those, tarsal type preaxial polydactyly (a true prehallux) occurs in only 3% of cases. Because of this rarity, there is minimal literature available to guide management or surgical reconstruction. Two newborns presented with similar tarsal type preaxial polydactylies in the context of multiple congenital anomalies at a single institution. Patient 1 presented at birth with an accessory digit arising medially from the right foot at the medial malleolus. Two weeks later, genetically unrelated, patient 2 presented at birth with an accessory digit arising medially from the right foot at the talus. Both patients underwent resection of the extra digit and reconstruction including transfer of the accessory anterior tibial tendon arising from the preaxial extra digit to the remaining first ray. Two years after surgery, both patients are walking well with preserved dorsiflexion strength. Given the rarity of true prehallux cases, reported surgical treatment and outcomes are lacking. This case demonstrates the management of 2 patients to better guide future patient care. Although nonsurgical treatment with shoewear modification is an option, surgical reconstruction facilitated wearing typical shoes while preserving ambulatory ability. Both patients in this series had an accessory anterior tibial tendon. Surgical transfer of the tendon prevented loss of dorsiflexion strength and foot drop postoperatively., (Copyright © 2018 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

A 21-year-old young man with no history of diabetes or thyroid disease presented to the emergency department with simultaneous thyroid storm and diabetic ketoacidosis. Notable findings on admission were a ventricular rate of 235 beats/min, tachypnoea, tremors, polydipsia and a lack of fever. Due to the unusual constellation of symptoms, diagnosis was only possible after initial laboratory results came back. While the lack of fever is unusual in thyroid storm, diabetic ketoacidosis has previously been reported to suppress fever, and this case supports the occurrence of this phenomenon. This case was highly unusual because the patient had not previously been diagnosed with either type 1 diabetes or Graves' disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Liver transplantation is the second most common transplant procedure in the United States. A leading cause of post-transplantation organ dysfunction is I/R injury. During I/R injury, the serine/threonine kinase Akt is activated, stimulating downstream mediators to promote cellular survival. Due to the cellular effects of Akt, therapeutic manipulation of the Akt pathway can help reduce cellular damage during hepatic I/R that occurs during liver transplantation., Objective: A full description of therapeutic options available that target Akt to reduce hepatic I/R injury has not been addressed within the literature. The purpose of this review is to illuminate advances in the manipulation of Akt that can be used to therapeutically target I/R injury in the liver., Methods: An in depth literature review was performed using the Scopus and PubMed databases. A total of 75 published articles were utilized for this manuscript. Terminology searched includes a combination of "hepatic ischemia/reperfusion injury", "Akt/PKB", "preconditioning" and "postconditioning.", Results: Four principal methods that reduce I/R injury include hepatic pre- and postconditioning, pharmacological intervention and future miRNA/gene therapy. Discussed therapies used serum alanine aminotransferase levels, liver histology and phosphorylation of downstream mediators to confirm the Akt protective effect., Conclusion: The activation of Akt from the reviewed therapies has resulted in predictable reduction in hepatocyte damage using the previously mentioned measurements. In a clinical setting, these therapies could potentially be used in combination to achieve better outcomes in hepatic transplant patients. Evidence supporting reduced I/R injury through Akt activation warrants further studies in human clinical trials.

Unlabelled: Chlamydia trachomatis is an obligate intracellular pathogen that is the etiological agent of a variety of human diseases, including blinding trachoma and sexually transmitted infections. Chlamydiae replicate within a membrane-bound compartment, termed an inclusion, which they extensively modify by the insertion of type III secreted proteins called Inc proteins. IncA is an inclusion membrane protein that encodes two coiled-coil domains that are homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) motifs. Recent biochemical evidence suggests that a functional core, composed of SNARE-like domain 1 (SLD-1) and part of SNARE-like domain 2 (SLD-2), is required for the characteristic homotypic fusion of C. trachomatis inclusions in multiply infected cells. To verify the importance of IncA in homotypic fusion in Chlamydia, we generated an incA::bla mutant. Insertional inactivation of incA resulted in the formation of nonfusogenic inclusions, a phenotype that was completely rescued by complementation with full-length IncA. Rescue of homotypic inclusion fusion was dependent on the presence of the functional core consisting of SLD-1 and part of SLD-2. Collectively, these results confirm in vitro membrane fusion assays identifying functional domains of IncA and expand the genetic tools available for identification of chlamydia with a method for complementation of site-specific mutants., Importance: Chlamydia trachomatis replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusions are nonfusogenic with vesicles in the endocytic pathway but, in multiply infected cells, fuse with each other to form a single large inclusion. This homotypic fusion is dependent upon the presence of a chlamydial inclusion membrane-localized protein, IncA. Specificity of membrane fusion in eukaryotic cells is regulated by SNARE (soluble N-ethylmaleimide sensitive factor attachment receptor) proteins on the cytosolic face of vesicles and target membranes. IncA contains two SNARE-like domains. Newly developed genetic tools for the complementation of targeted mutants in C. trachomatis are used to confirm the minimal requirement of SNARE-like motifs necessary to promote the homotypic fusion of inclusions., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a membrane-bound vacuole termed the inclusion. Early in the infection cycle, the pathogen extensively modifies the inclusion membrane through incorporation of numerous type III secreted effector proteins, called inclusion membrane proteins (Incs). These proteins are characterized by a bilobed hydrophobic domain of 40 amino acids. The presence of this domain has been used to predict up to 59 putative Incs for C. trachomatis; however, localization to the inclusion membrane with specific antibodies has been demonstrated for only about half of them. Here, we employed recently developed genetic tools to verify the localization of predicted Incs that had not been previously localized to the inclusion membrane. Expression of epitope-tagged putative Incs identified 10 that were previously unverified as inclusion membrane localized and thus authentic Incs. One novel Inc and 3 previously described Incs were localized to inclusion membrane microdomains, as evidenced by colocalization with phosphorylated Src (p-Src). Several predicted Incs did not localize to the inclusion membrane but instead remained associated with the bacteria. Using Yersinia as a surrogate host, we demonstrated that many of these are not secreted via type III secretion, further suggesting they may not be true Incs. Collectively, our results highlight the utility of genetic tools for demonstrating secretion from chlamydia. Further mechanistic studies aimed at elucidating effector function will advance our understanding of how the pathogen maintains its unique intracellular niche and mediates interactions with the host., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a vacuole termed the inclusion. Many of the interactions of chlamydiae with the host cell are dependent upon bacterial protein synthesis and presumably exposure of these proteins to the cytosol. Because of the dearth of genetic tools for chlamydiae, previous studies examining secreted proteins required the use of heterologous bacterial systems. Recent advances in genetic manipulation of chlamydia now allow for transformation of the bacteria with plasmids. We describe here a shuttle vector system, pBOMB4, that permits expression of recombinant proteins under constitutive or conditional promoter control. We show that the inclusion membrane protein IncD is secreted in a type III-dependent manner from Yersinia pseudotuberculosis and also secreted from C. trachomatis in infected cells where it localizes appropriately to the inclusion membrane. IncD truncated of the first 30 amino acids containing the secretion signal is no longer secreted and is retained by the bacteria. Cytosolic exposure of secreted proteins can be confirmed by using CyaA, GSK, or microinjection assays. A protein predicted to be retained within the bacteria, NrdB is indeed localized to the chlamydia. In addition, we have shown that the chlamydial effector protein, CPAF, which is secreted into the host cell cytosol by a Sec-dependent pathway, also accesses the cytosol when expressed from this system. These assays should prove useful to assess the secretion of other chlamydial proteins that are potentially exposed to the cytosol of the host cell.

We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in suppressing anti-bacterial immunity.

The past decade and a half has witnessed the discovery of a large, evolutionarily conserved family of cellular genes bearing homology to the prototype baculovirus Inhibitor of Apoptosis (IAP). The logical decision in the field to also refer to these cellular proteins as IAPs fails to do justice to this versatile group of factors that play a wide range of roles in eukaryotic development and homeostasis which include, but are not limited to, the regulation of programmed cell death. Here we describe the shared functional characteristics of several well-characterized IAPs whose defining motifs place them more in the category of multifunctional modular protein interaction domains.

The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice deficient in XIAP had a higher bacterial burden 48 h after infection than wild-type littermates, and exhibited substantially decreased survival. XIAP enhanced NF-kappaB activation upon L. monocytogenes infection of activated macrophages, and prolonged phosphorylation of Jun N-terminal kinase (JNK) specifically in response to cytosolic bacteria. Additionally, XIAP promoted maximal production of pro-inflammatory cytokines upon bacterial infection in vitro or in vivo, or in response to combined treatment with NOD2 and TLR2 ligands. Together, our data suggest that XIAP regulates innate immune responses to L. monocytogenes infection by potentiating synergy between Toll-like receptors (TLRs) and Nod-like receptors (NLRs) through activation of JNK- and NF-kappaB-dependent signaling.