Alternative splicing generates a novel ferroportin isoform with a shorter C-terminal and an intact iron- and hepcidin-binding property.

Ferroportin (FPN) is a transmembrane protein and is the only known iron exporter that helps in maintaining iron homeostasis in vertebrates. To maintain stable iron equilibrium in the body, ferroportin works in conjunction with a peptide called hepcidin. In this study, we have identified an alternatively spliced novel isoform of the human SLC40A1 gene, which encodes for the FPN protein and is found to be expressed in different tissues. The novel transcript has an alternate last exon and encodes 31-amino acid long peptide sequence that replaces 104 amino acids at C-terminal in the novel transcript. Molecular modelling and molecular dynamics (MD) simulation studies revealed key structural features of the novel isoform (FPN-N). FPN-N was predicted to have 12 transmembrane domains similar to the reported isoform (FPN), despite being much smaller in size. FPN-N was found to interact with hepcidin, a key regulator of ferroportin activity. Also, the iron-binding sites were retained in the novel isoform as revealed by the MD simulation of FPN-N in bilipid membrane. The novel isoform identified in this study may play important role in iron homeostasis. However, further studies are required to characterize the FPN-N isoform and decipher its role inside the cell.

Management of status epilepticus in pregnancy: a clinician survey.

BACKGROUND: Status epilepticus in pregnancy (SEP) is rare and life-threatening for both mother and fetus. There are well-established guidelines for the management of women with epilepsy during pregnancy; however, there is little evidence guiding the management of SEP, leading to uncertainty among treating physicians. Therefore, this survey aims to investigate the real-world practices of physicians treating SEP to explore management approaches for improvements in care. METHODS: An anonymous, electronic survey was created and distributed to neurointensivists and neurologists between September and December 2021. RESULTS: One hundred physicians initiated the survey and 95 completed it in full: 87 (87%, 87/100) identified neurology as their primary specialty, 31 had subspecialty training in neurocritical care, and 48 had subspecialty training in epilepsy and/or clinical neurophysiology. Over half of the survey respondents (67%, 67/100) reported having participated in the management of SEP, with 48.9% (49/98) having done so in the past year. Most survey respondents (73%, 73/100) reported that their management approach to SEP is different than that of non-pregnant patients. Survey respondents were more likely to involve epilepsy consultants when treating SEP (58.5%, 58/99) and the vast majority involved Obstetrics/Maternal Fetal Medicine consultants (90.8%, 89/98). Survey respondents showed a clear preference for levetiracetam (89.7%, 87/97) in the treatment of benzodiazepine refractory status epilepticus followed by lacosamide (61%, 60/98) if an additional second line agent was needed. Valproate and phenobarbital were unlikely to be used. There was less agreement for the management of refractory and super-refractory SEP. CONCLUSIONS: Levetiracetam is the most frequently used anti-seizure medication (ASM) for benzodiazepine-refractory SEP. Survey participants tended to manage SEP differently than in non-pregnant patients including greater involvement of interdisciplinary teams as well as avoidance of ASMs associated with known teratogenicity.

A strip-based assay for detection of CrfA enzyme activity to differentiate Mycobacterium tuberculosis and non-tuberculous mycobacteria.

There is an unmet need for tools that permit diagnosis of Tuberculosis (TB) that are affordable, low-tech, and can differentiate Mycobacterium tuberculosis (M.tb) from non-tuberculous mycobacteria (NTM). In this study, we have developed a strip-based assay to detect the activity of a unique Carbapenem Resistance Factor A (CrfA) enzyme present only in M.tb. The strip comprises of PVDF (Polyvinylidene fluoride) membrane that has an immobilized anti-CrfA antibody to capture the CrfA enzyme from M.tb lysate. Lysate of mycobacteria is applied to the strip, washed, and incubated in the presence of chromogenic reporter dye which is a substrate for CrfA. A change in the color of the dye that is readily visible to the naked eye is the readout. We evaluated lysates from M.tb and various NTMs namely, M. abscessus, M. chelonae, M. avium, M. obuense, M. paraintracellulare, M. kansasi, including the patient-derived sputum samples. The strip assay selectively identified only those samples containing M.tb. Based on this evidence, this new assay enables the identification and differentiation of M.tb from NTMs in patient sputum samples. As this tool can be simple to use, therefore has the potential to serve the unmet need for diagnosis of TB and NTM infections in resource-limited settings.

A 25-Year-Old Patient With Chest Wall Erythema and Tenderness Who Was Ventilated Mechanically.

CASE PRESENTATION: A 25-year-old man with cerebral palsy, scoliosis, and ventilator dependence since SARS-CoV-2 infection 11 months earlier presented with a 2-week history of chest redness and swelling. The area of erythema and edema was located on the left side of the anterior chest and had grown to approximately 9 cm in diameter over the 2 weeks. It was tender to palpation. There was no history of trauma, injury, or bug bites at that site. He had not had a rash or similar lesions elsewhere on his body and had not taken any new medications. He did have increased, thick, yellow secretions from his tracheostomy, but no fevers. He was born in the Dominican Republic and moved to the United States as a child. He had not traveled anywhere outside the United States in more than a decade.

For Clinicians to Do Less, Organizations Must Do More.

Medicine is defined by doing; however, bias, error, and burnout are potential consequences of speed and constant activity. On an individual level, slowing down might reduce bias; resting might reduce error; mindfulness might reduce burnout. Despite its benefits, stillness can be an unattainable privilege for some due to systems of power, including gender, race, and capitalism. In response, institutions must confront these systems and support individual clinicians through radical acts of solidarity because, just as we have fought to make doing-speaking, learning, and working-equal opportunity, so must we ensure that "non-doing" belongs to everyone.

Twitter Journal Club Impact on Engagement Metrics of the Neurocritical Care Journal.

BACKGROUND: Twitter journal clubs are a modern way of highlighting articles published in a scientific journal. The Neurocritical Care journal (NCC) initiated a bimonthly, Twitter-based, online journal club in 2015 to increase the outreach of its published articles. We hypothesize that articles included in the Neurocritical Care Society Twitter Journal Club (NCSTJC) had greater engagement than other articles published during the same time period. We also investigated the relationship between number of citations and Altmetric score to assess whether the enhanced online activity resulted in higher citations. METHODS: We gathered data in August 2020 on engagement metrics (number of downloads, Altmetric score, relative citation ratio, and number of citations) of all articles published in NCC between 2015 and 2018. Articles were analyzed into two groups: one featured in NCSTJC and the rest that were not (non-NCSTJC1), and the other comprised those that were not in NCSTJC but published under a similar category of articles as NCSTJC (non-NCSTJC2). Results were analyzed using descriptive statistics, and summary measures were used to report the spread. The groups were compared by using the Wilcoxon rank sum test, given that the data were not normally distributed. Spearman's rank correlation was used to assess correlation between Altmetric score and citations for the articles in the NCSTJC and non-NCSTJC groups. For comparison, the top ten cited articles in NCC were analyzed for similar correlations. RESULTS: Between 2015 and 2018, NCC published 529 articles, 24 of which were included in the Twitter journal club. A total of 406 articles were published in the same category as the category of articles selected for NCSTJC. The articles discussed as a part of NCSTJC had a statistically significant trend toward a higher number of downloads, Altmetric score, relative citation ratio, and number of citations than rest of the articles published in the journal during the same time period and the rest of the articles published in same categories. Three NCSTJC articles were among the ten most-cited articles published by NCC between 2015 and 2018. We did not find a correlation between Altmetric scores and number of citations in the NCSTJC or non-NCSTJC1 or non-NCSTJC2 group, but there was a strong correlation between these two variables in high performing articles when the top ten cited articles were analyzed. CONCLUSIONS: Scientific journals are evolving their social media strategies in attempt to increase the outreach of their articles to the medical community. Platforms such as Twitter journal clubs can enhance such engagement. The long-term influence of such strategies on the impact factor of a medical journal and traditional engagement metrics, such as citations, calls for further research.

An Evidence-Based Approach to Diagnosis and Prognosis in a Young Woman with New-Onset Super-Refractory Status Epilepticus: A Case Report.

New-onset refractory status epilepticus (NORSE) is a rare clinical diagnosis. Autoimmune encephalitis and paraneoplastic encephalitis are the most common identifiable etiologies of NORSE; of the known autoimmune encephalitides, <200 cases of GAD65-related epilepsy have been reported in the literature. We describe a case of a 24-year-old female who presented with confusion and myoclonus. Electroencephalogram revealed NORSE that evolved into super-refractory status epilepticus. Her CSF showed a mild lymphocytic pleocytosis, and her MRI demonstrated changes in the bilateral temporal lobes. She was ultimately diagnosed with GAD65 autoimmune encephalitis and treated with immune-modulating therapy. This case highlights the complex diagnostic workup of patients with NORSE and the utility of validated prediction models for diagnosis and prognosis. While maintaining a broad differential, the patient's Antibody Prevalence in Epilepsy (APE) score was a helpful clinical tool to support the pursuit of an autoimmune etiology. We also underline the need to concomitantly treat patients quickly during diagnostic workup because earlier treatment increases the Response to Immunotherapy in Epilepsy (RITE) score, indicating a more favorable prognosis.

Review of Achilles Tendon Reattachment Using Double-Row Knotted and Knotless Techniques in the Management of Insertional Achilles Tendinopathy.

Insertional Achilles tendinopathy represents a chronic degenerative condition affecting the insertion of the Achilles. Surgery is indicated in recalcitrant cases and often involves extensive debridement followed by subsequent repair of the insertion. In the present study, we evaluate the results of knotted and knotless double-row suture systems for Achilles reattachment. Despite the popularity of double-row repairs, there is a relative paucity of clinic data regarding efficacy of the available implants. In a retrospective cohort study, 38 patients (40 Achilles tendons) who received double-row repairs between November 2012 and December 2016 were evaluated. In addition to demographic information, preoperative pain scores and symptom duration were recorded. Perioperative and postoperative records were reviewed, and telephone interviews were conducted to assess patient satisfaction, functional status, postoperative pain, and information regarding surgical complications. At a mean follow-up of 32.5 months, 35 (92.1%) patients reported satisfaction with the outcome. Decreased pain levels were reported in 38 (95%) ankles, with 21 (52.5%) ankles being rated pain-free postoperatively. Of the patients working prior to surgery, 20 (95.2%) were able to return to normal work duties, and all 11 (100%) patients who engaged in sports preoperatively were able to return to the same level of activity. Two patients developed postoperative infections, one of which required operative debridement. No Achilles avulsions were encountered. No significant differences were noted between the 2 operative techniques. Considering the available biomechanical data, along with high patient satisfaction rates and low rate of complications, double-row repair offers a viable option for recalcitrant insertional Achilles tendinopathy.

M.tb-Rv2462c of Mycobacterium tuberculosis Shows Chaperone-like Activity and Plays a Role in Stress Adaptation and Immunomodulation.

Mycobacterium tuberculosis (M.tb)-encoded factors protect it against host-generated stresses and support its survival in the hostile host environment. M.tb possesses two peptidyl-prolyl cis-trans isomerases and a probable trigger factor encoded by Rv2462c which has an FKBP-like PPIase domain. PPIases are known to assist the folding of peptidyl-prolyl bonds and are involved in various cellular processes important for bacterial survival in host-generated stresses. In this study, we aim to functionally characterize Rv2462c of M.tb. Our data suggest that the trigger factor of M.tb exhibits chaperone activity both in vitro and in vivo. Heterologous expression of M.tb-Rv2462c locus into Mycobacterium smegmatis enhanced its survival within macrophages, adaptation to oxidative stress and biofilm formation. M.tb-trigger factor has strong immunomodulatory potential and modifies the cytokine profile of the host towards the proinflammatory axis.

Through the Lens of Scientific Racism: Patient Race Should Not Be Included in the Oral Presentation.

Medical students are taught to include the patient demographics of age and gender in the oral presentation; the inclusion of race is controversial. Epidemiology demonstrates that race, as a social determinant of health, can be a risk factor for disease. However, race, as a social construct, is not a biological cause for disease. In the USA, the relationship between race and health is stained by a long history of scientific racism, and the misuse of science does not rest in our past. Given the complexity and persistence of scientific racism, race should not be included in the oral presentation.