Obtaining well-diffracting crystals of macromolecules remains a significant barrier to structure determination. Here we propose and test a new approach to crystallization, in which the crystallization target is fused to a polymerizing protein module, so that polymer formation drives crystallization of the target. We test the approach using a polymerization module called 2TEL, which consists of two tandem sterile alpha motif (SAM) domains from the protein translocation Ets leukemia (TEL). The 2TEL module is engineered to polymerize as the pH is lowered, which allows the subtle modulation of polymerization needed for crystal formation. We show that the 2TEL module can drive the crystallization of 11 soluble proteins, including three that resisted prior crystallization attempts. In addition, the 2TEL module crystallizes in the presence of various detergents, suggesting that it might facilitate membrane protein crystallization. The crystal structures of two fusion proteins show that the TELSAM polymer is responsible for the majority of contacts in the crystal lattice. The results suggest that biological polymers could be designed as crystallization modules.

Central nervous system (CNS) histoplasmosis is rare and difficult to diagnose because it is often overlooked or mistaken for other pathologies due to its nonspecific symptoms. A 32-year-old Hispanic man with advanced acquired immunodeficiency virus presented with altered mental status and reported confusion for the past 3 months. He had a Glasgow Coma Scale of 12, repetitive nonfluent speech, and a disconjugate gaze with a right gaze preference. Lung computed tomography (CT) findings indicated a pulmonary histoplasmosis infection. Magnetic resonance imaging of the brain revealed a ring-enhancing lesion in the left caudate nucleus. A CT-guided left retroperitoneal node biopsy was performed and indicated a benign inflammatory process with organisms compatible with fungal yeast. Treatment with amphotericin B followed by itraconazole was initiated in spite of negative cerebrospinal fluid (CSF) cultures and proved effective in mitigating associated CNS lesions and resolving neurologic deficits. The patient was discharged 3 weeks later in stable condition. Six weeks later, his left basal ganglia mass decreased. Early recognition of symptoms and proper steps is key in improving outcomes of CNS histoplasmosis. Aggressive medical management is possible in the treatment of intracranial deep mass lesions, and disseminated histoplasmosis with CNS involvement can be appropriately diagnosed and treated, despite negative CSF and serology studies.

Background Traumatic brain injury (TBI) has a complex pathophysiology that has historically been poorly understood. New evidence on the pathophysiology, molecular biology, and diagnostic studies involved in TBI have shed new light on optimizing rehabilitation and recovery. The goal of this study was to assess the effect of osteopathic manipulative treatment (OMT) on peripheral and central glial lymphatics in patients with severe TBI, brain edema, and elevated intracranial pressure (ICP) by measuring changes in several parameters regularly used in management. Methodology This was a retrospective study at a level II trauma center that occurred in 2018. The study enrolled patients with TBI, increased ICP, or brain edema who had an external ventricular drain placed. Patients previously underwent a 51-minute treatment with OMT with an established protocol. Patients received 51 minutes of OMT to the head, neck, and peripheral lymphatics. The ICP, cerebrospinal fluid (CSF) drainage, optic nerve sheath diameter (ONSD) measured by ultrasonography, and Neurological Pupil Index (NPi) measured by pupillometer were recorded before, during, and after receiving OMT. Results A total of 11 patients were included in the study, and 21 points of data were collected from the patients meeting inclusion criteria who received OMT. There was a mean decrease in the ONSD of 0.62 mm from 6.24 mm to 5.62 mm (P = 0.0001). The mean increase in NPi was 0.18 (P = 0.01). The mean decrease in ICP was 3.33 mmHg (P = 0.0001). There was a significant decrease in CSF output after treatment (P = 0.0001). Each measurement of ICP, ONSD, and NPi demonstrated a decrease in overall CSF volume and pressure after OMT compared to CSF output and ICP prior to OMT. Conclusions This study demonstrates that OMT may help optimize glial lymphatic clearance of CSF and improve brain edema, interstitial waste product removal, NPi, ICP, CSF volume, and ONSD. A holistic approach including OMT may be considered to enhance management in TBI patients. As TBI is a spectrum of disease, utilizing similar techniques may be considered for all forms of TBI including concussions and other diseases with brain edema. The results of this study can better inform future trials to specifically study the effectiveness of OMT in post-concussive treatment and in those with mild-to-moderate TBI.

Purpose: The COVID-19 pandemic disrupted the professional, social, and spiritual activities of resident physicians around the world, impacting wellness and personal relationships. Moreover, social distancing caused significant limitations or shutdown of places of worship, including churches, synagogues, mosques, etc. Our goal was to survey resident physicians in primary care and surgical subspecialties in the United States (U.S.) and Canada and to examine the effect of the COVID-19 pandemic on their well-being. Methods: An international cross-sectional study was performed in November 2020, using an anonymous survey of programs in the U.S. and Canada, containing 20 questions to assess the impact of the pandemic on resident participation in social and spiritual activities and the effects on their wellness, and personal relationships. The emails with survey links attached were sent to individual program coordinators from accredited residency training programs in the United States and Canada. This consisted of programs accredited by the American Osteopathic Association (AOA), The Royal College of Physicians and Surgeons of Canada (RCPSC), and the Accreditation Council of Graduate Medical Education (ACGME). The survey was evenly divided among surgical programs (General Surgery, Neurological Surgery, Orthopedic Surgery, Urological Surgery, and Integrated Surgical Residency Programs such as Plastic Surgery, Cardiothoracic Surgery, Pediatric Surgery, and Vascular Surgery) as well as primary care programs (Internal Medicine and Family Medicine). Results: A total of 196 residents, 60 primary care residents, and 136 surgery residents participated in the study. Ninety-six participants (49%) were female, and 98 of the participants (50%) were male, with the remainder two residents identifying as “Other.” Of the primary care residents, the majority (39, 65%) were female. Conversely, the majority (77, 57%) of surgery residents were male. Conclusion: The COVID-19 pandemic has affected the social lives, relationships, and spiritual well-being of both surgical and primary care resident physicians. However, primary care residents reported significantly greater engagement in personal relationships and were more likely to express feelings of mental and physical exhaustion, prohibiting social attendance.

Background:Seizures account for significant morbidity and mortality early in the course of traumatic brain injury (TBI). Although there is sufficient literature suggesting short-term benefits of antiepileptic drugs (AEDs) in post-TBI patients, there has been no study to suggest a time frame for continuing AEDs in patients who have undergone a decompressive craniectomy for more severe TBI. We examined trends in a level-II trauma center in southern California that may provide guidelines for AED treatment in craniectomy patients.Methods:A retrospective analysis was performed evaluating patients who underwent decompressive craniectomy and those who underwent a standard craniotomy from 2008 to 2012.Results:Out of the 153 patients reviewed, 85 were included in the study with 52 (61%) craniotomy and 33 (39%) craniectomy patients. A total of 78.8% of the craniotomy group used phenytoin (Dilantin), 9.6% used levetiracetam (Keppra), 5.8% used a combination of both, and 3.8% used topiramate (Topamax). The craniectomy group used phenytoin 84.8% and levetiracetam 15.2% of the time without any significant difference between the procedural groups. Craniotomy patients had a 30-day seizure rate of 13.5% compared with 21.2% in craniectomy patients (P = 0.35). Seizure onset averaged on postoperative day 5.86 for the craniotomy group and 8.14 for the craniectomy group. There was no significant difference in the average day of seizure onset between the groups P = 0.642.Conclusion:Our study shows a trend toward increased seizure incidence in craniectomy group, which does not reach significance, but suggests they are at higher risk. Whether this higher risk translates into a benefit on being on AEDs for a longer duration than the current standard of 7 days cannot be concluded as there is no significant difference or trend on the onset date for seizures in either group. Moreover, a prospective study will be necessary to more profoundly evaluate the duration of AED prophylaxis for each one of the stated groups.