Incorporating Anti-racist Principles Throughout the Research Lifecycle: A Position Statement from the Society of General Internal Medicine (SGIM).

Biomedical research has advanced medicine but also contributed to widening racial and ethnic health inequities. Despite a growing acknowledgment of the need to incorporate anti-racist objectives into research, there remains a need for practical guidance for recognizing and addressing the influence of ingrained practices perpetuating racial harms, particularly for general internists. Through a review of the literature, and informed by the Research Lifecycle Framework, this position statement from the Society of General Internal Medicine presents a conceptual framework suggesting multi-level systemic changes and strategies for researchers to incorporate an anti-racist perspective throughout the research lifecycle. It begins with a clear assertion that race and ethnicity are socio-political constructs that have important consequences on health and health disparities through various forms of racism. Recommendations include leveraging a comprehensive approach to integrate anti-racist principles and acknowledging that racism, not race, drives health inequities. Individual researchers must acknowledge systemic racism's impact on health, engage in self-education to mitigate biases, hire diverse teams, and include historically excluded communities in research. Institutions must provide clear guidelines on the use of race and ethnicity in research, reject stigmatizing language, and invest in systemic commitments to diversity, equity, and anti-racism. National organizations must call for race-conscious research standards and training, and create measures to ensure accountability, establishing standards for race-conscious research for research funding. This position statement emphasizes our collective responsibility to combat systemic racism in research, and urges a transformative shift toward anti-racist practices throughout the research cycle.

Iatrogenic Cerebrospinal Fluid Breast Augmentation: Rare Complication of Ventriculoperitoneal Shunts and Management Strategies.

BACKGROUND: Ventriculoperitoneal shunt is one of the most common neurosurgical procedures in the treatment of hydrocephalus. There are reports of migration of the distal catheter to the breast pocket where cerebrospinal fluid then collects and can develop into a pseudocyst. There exist case reports in the literature of patients with prior breast augmentation who present with distal catheter migration from the peritoneal space into the breast tissue. We present a case series of 3 patients with preexisting breast augmentation who returned with unilateral breast enlargement after ventriculoperitoneal shunt. In all 3 patients, the distal catheter migrated out of the peritoneal space and was found to be coiled around the breast prosthesis. Additionally, we offer recommendations for managing these complications and a review of the literature. METHODS: We performed a systematic review without meta-analysis of studies involving management of shunt migration in the setting of preexisting breast implants. We present a case series of 3 patients whom we treated with breast cerebrospinal pseudocyst after migration of the distal catheter into the breast tissue. RESULTS: A total of 17 studies, dating from 2002 to 2022, met our inclusion and exclusion criteria and were selected for full review. Catheter migration occurred between 2 weeks and 9 months of initial shunt placement. All patients presented with unilateral breast enlargement and cerebrospinal fluid pseudocyst formation. All patients underwent revision shunt surgery. Surgical treatment strategies used included reimplantation of the distal catheter into the pleural space or ipsilateral or contralateral peritoneal space or complete removal of the entire shunt system. CONCLUSIONS: Breast-related ventriculoperitoneal shunt complication is a rare entity that is increasingly seen as more patients receive breast augmentation. Breast-related shunt complications most commonly present with cerebrospinal fluid pseudocyst formation in the breast. It is important for neurosurgeons to be aware of an underlying breast implant before placing a ventriculoperitoneal shunt. For patients who have migration of the distal catheter into the breast, a protocol for managing these situations should be followed to ensure no shunt infection and avoidance of future catheter migration complications with subsequent shunt revisions.

Towards a Machine Learning Driven Trust Management Heuristic for the Internet of Vehicles.

The rapid proliferation of the emerging yet promising notion of the Internet-of-Vehicles (IoV) has led to the development of a variety of conventional trust assessment schemes to tackle insider attackers. The primary reliance of these frameworks is on the accumulation of individual trust attributes. While aggregating these influential parameters, weights are often associated with each individual attribute to reflect its impact on the final trust score. It is of paramount importance that such weights be precise to lead to an accurate trust assessment. Moreover, the value of the minimum acceptable trust threshold employed for the identification of dishonest vehicles needs to be carefully defined to avoid delayed or erroneous detection. This paper employs an IoT data set from CRAWDAD by suitably transforming it into an IoV format. This data set encompasses information regarding 18,226 interactions among 76 nodes, both honest and dishonest. First, the influencing parameters (i.e., packet delivery ratio, familiarity, timeliness and interaction frequency) were computed, and two feature matrices were formed. The first matrix (FM1) takes into account all the pairwise individual parameters as individual features, whereas the second matrix (FM2) considers the average of all pairwise computations performed for each individual parameter as one feature. Subsequently, unsupervised learning is employed to achieve the ground truth prior to applying supervised machine learning algorithms for classification purposes. It is worth noting that Subspace KNN yielded a perfect precision, recall, and the F1-score equal to 1 for individual parametric scores, whereas Subspace Discriminant returned an ideal precision, recall, and the F1-score equal to 1 for mean parametric scores. It is also evident from extensive simulations that FM2 yielded more accurate classification results compared to FM1. Furthermore, decision boundaries among honest and dishonest vehicles have also been computed for respective feature matrices.

Ocular Syphilis Mimicking Giant Cell Arteritis.

Syphilis is a rare cause of vision loss that mostly occurs after an infection of the meninges, brain tissue, and parenchyma. Syphilis can mimic auto-immune disease like giant cell arteritis which also manifest as sudden vision loss. Spirochete Treponema pallidum can spread through sexual contact and cause painless ulcers. Spirochetes can disseminate systemically and lead to secondary syphilis. Ocular syphilis can affect all parts of the eye in secondary and tertiary stages. It can present as scleritis, inflammation of the optic nerve, and uveitis. We present the case of a 59- year-old male suffering from severe vision loss in the left eye and headache initially misdiagnosed with giant cell arteritis. He was correctly diagnosed with ocular syphilis after seeing a red macular rash on palms and soles, and was given penicillin G and probenecid. His visual acuity and field of vision improved soon. Ocular syphilis is usually diagnosed late or misdiagnosed and leads to irreversible vision loss. Physicians should keep in mind the possibility of ocular syphilis in patients presenting with a sudden loss of vision and severe headaches.

Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease. Tumors are poorly immunogenic and immunosuppressive, preventing T cell activation in the tumor microenvironment. Here, we present a microbial-based immunotherapeutic treatment for selective delivery of an immunogenic tetanus toxoid protein (TT856-1313) into PDAC tumor cells by attenuated Listeria monocytogenes. This treatment reactivated preexisting TT-specific memory T cells to kill infected tumor cells in mice. Treatment of KrasG12D,p53R172H, Pdx1-Cre (KPC) mice with Listeria-TT resulted in TT accumulation inside tumor cells, attraction of TT-specific memory CD4 T cells to the tumor microenvironment, and production of perforin and granzyme B in tumors. Low doses of gemcitabine (GEM) increased immune effects of Listeria-TT, turning immunologically cold into hot tumors in mice. In vivo depletion of T cells from Listeria-TT + GEM-treated mice demonstrated a CD4 T cell-mediated reduction in tumor burden. CD4 T cells from TT-vaccinated mice were able to kill TT-expressing Panc-02 tumor cells in vitro. In addition, peritumoral lymph node-like structures were observed in close contact with pancreatic tumors in KPC mice treated with Listeria-TT or Listeria-TT + GEM. These structures displayed CD4 and CD8 T cells producing perforin and granzyme B. Whereas CD4 T cells efficiently infiltrated the KPC tumors, CD8 T cells did not. Listeria-TT + GEM treatment of KPC mice with advanced PDAC reduced tumor burden by 80% and metastases by 87% after treatment and increased survival by 40% compared to nontreated mice. These results suggest that Listeria-delivered recall antigens could be an alternative to neoantigen-mediated cancer immunotherapy.

Yield of Muscle Biopsy in Patients with Findings of Myopathy on Electrodiagnostic Testing.

Background The evaluation of neuromuscular diseases includes detailed clinical assessment, blood testing, electrodiagnostic studies (EDS), biopsy, and genetic tests. EDS alone cannot provide a specific diagnosis. Further testing in the form of genetic tests or muscle biopsy (MB) is required. Objective The objective of the study is to evaluate the yield of MB in patients with findings of myopathy on electrodiagnostic testing and assess the factors affecting an abnormal biopsy outcome. Methods Electromyography (EMG)/nerve conduction studies (NCS) performed for suspected myopathy over 5 years from 2011 to 2016, at the neurophysiology department of a tertiary care center in Pakistan, were reviewed. Based on inclusion criteria, records of 58 patients were retrospectively reviewed. Results After an EMG/NCS diagnosis of myopathy, the frequency of MB testing was only 10.1%. The median age of patients was 26.5 years. The clinically suspected diagnosis was categorized into hereditary myopathy (n = 15, 25.9%) and acquired myopathy (n = 18, 31%). The positive predictive value of EMG is 77.2%. Twenty-eight (48.2%) patients had abnormal MB whereas 20 (34.4%) revealed normal findings. Factors significantly influencing an abnormal outcome of biopsy included moderate-to-severe elevation of creatine kinase (>2,000 U/L),presence of denervation changes, and severe myopathy on EMG. Conclusion Even though the overall yield of MB testing may not be very high in our setting due to the unavailability of special techniques and expertise, certain factors can help to improve the diagnostic yield. Clinicians should encourage MB testing, especially in cases with strong clinical, laboratory and electrodiagnostic suspicion, and absence of genetic testing for suspected myopathy.

Outcomes of patients with Guillain Barre Syndrome - Experience from a tertiary care hospital of a developing Asian country and review of regional literature.

Outcomes of Guillain Barre Syndrome (GBS), particularly those require mechanical ventilation have been reported from a number of Asian countries, albeit, scarcely from Pakistan. We conducted this study to determine the short-term outcomes of GBS and compare the results of mechanically ventilated and non-ventilated patients. Case records of patients admitted with GBS during 2011-2016 at a large tertiary care centre of Pakistan were retrospectively reviewed. 216 patients satisfying inclusion criteria were included. Patients were divided into 2 groups based on requirement of MV (MV and non-MV group). Short term outcomes were assessed by Modified Rankin Scale (MRS) at discharge, 2 weeks and 3 months and comparison done between MV and non-MV group. Outcome based on MRS score is categorized as good (MRS = 0-3) or poor (MRS = 4-6). Requirement for MV was noted in 24.5%. MV patients had severe weakness at presentation, longer length of hospital stay (LOS) and higher frequency of in-hospital complications. Overall mortality was 7.9%. Good outcomes at discharge and at 3 months were noted in significantly higher frequency in non-MV group (50.3% and 93.2% respectively) as compared to MV group (11.3% and 33.3% respectively). In MV group, increasing age, areflexia and longer LOS stay were found as independent predictors of poor outcome. Overall outcomes of GBS in our population are comparable to both regional and international studies. However, poor outcomes in MV group are seen in higher frequency in our study. Increasing age, areflexia and longer LOS may predict poor outcome in MV patients.

Pain-Free Blood Glucose Monitoring Using Wearable Sensors: Recent Advancements and Future Prospects.

Keeping track of blood glucose levels non-invasively is now possible due to diverse breakthroughs in wearable sensors technology coupled with advanced biomedical signal processing. However, each user might have different requirements and priorities when it comes to selecting a self-monitoring solution. After extensive research and careful selection, we have presented a comprehensive survey on noninvasive/pain-free blood glucose monitoring methods from the recent five years (2012-2016). Several techniques, from bioinformatics, computer science, chemical engineering, microwave technology, etc., are discussed in order to cover a wide variety of solutions available for different scales and preferences. We categorize the noninvasive techniques into nonsample- and sample-based techniques, which we further grouped into optical, nonoptical, intermittent, and continuous. The devices manufactured or being manufactured for noninvasive monitoring are also compared in this paper. These techniques are then analyzed based on certain constraints, which include time efficiency, comfort, cost, portability, power consumption, etc., a user might experience. Recalibration, time, and power efficiency are the biggest challenges that require further research in order to satisfy a large number of users. In order to solve these challenges, artificial intelligence (AI) has been employed by many researchers. AI-based estimation and decision models hold the future of noninvasive glucose monitoring in terms of accuracy, cost effectiveness, portability, efficiency, etc. The significance of this paper is twofold: first, to bridge the gap between IT and medical field; and second, to bridge the gap between end users and the solutions (hardware and software).

Drug-induced movement disorder and confusion associated with duloxetine.

A 60-year-old woman with major depressive disorder, developed high blood pressure, confusion and dyskinesias of face, neck and jaw, following an increase in her dose of duloxetine. Routine blood tests including toxic, infective and metabolic workup were unremarkable. Cerebrospinal fluid analysis and electroencephalogram were also normal. MRI brain showed bilaterally symmetrical diffusion-restricted areas in deep cerebral white matter. Duloxetine was held on suspicion of drug adverse effect. She had complete resolution of symptoms within 48 hours and resolution of MRI brain changes over 6 weeks. Serotonin norepinephrine reuptake inhibitors such as duloxetine may have the potential to cause drug-induced movement disorders, confusion and high blood pressure and should be used cautiously especially in elderly.

Lymphocytic choriomeningitis virus infection of dendritic cells interferes with TLR-induced IL-12/IL-23 cytokine production in an IL-10 independent manner.

Dendritic cells produce IL-12 and IL-23 in response to viral and bacterial infection and these cytokines are responsible for successful pathogen clearance. How sequential viral and bacterial infections affect the production of IL-12 and IL-23 is currently not known. Our study demonstrates that in dendritic cells infected with Lymphocytic choriomeningitis virus (LCMV), TLR activation with bacterial PAMPs resulted in reduced IL-12 and IL-23 expression compared to non-infected cells. Furthermore, expression of other proinflammatory cytokines, TNF-α and IL-6, were not inhibited under these conditions. We discovered that TLR-induced phosphorylation of p38 was significantly inhibited in LCMV-infected cells. We detected enhanced expression of suppressor of cytokine signalling (SOCS)-3 and IL-10. Yet, neutralizing IL-10 did not restore IL-12/IL-23 expression. Taken together, these results show that virus infection interferes with the magnitude of TLR-mediated inflammatory responses by repressing specific cytokine expression.

MHC Ib molecule Qa-1 presents Mycobacterium tuberculosis peptide antigens to CD8+ T cells and contributes to protection against infection.

A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response. However, it is unclear what precise role(s) HLA-E/Qa-1 play in the immune response to Mtb. In this study, we found that murine Qa-1 can bind and present Mtb peptide antigens to CD8+ T effector cells during aerosol Mtb infection. Further, mice lacking Qa-1 (Qa-1-/-) were more susceptible to high-dose Mtb infection compared to wild-type controls, with higher bacterial burdens and increased mortality. The increased susceptibility of Qa-1-/- mice was associated with dysregulated T cells that were more activated and produced higher levels of pro-inflammatory cytokines. T cells from Qa-1-/- mice also had increased expression of inhibitory and apoptosis-associated cell surface markers such as CD94/NKG2A, KLRG1, PD-1, Fas-L, and CTLA-4. As such, they were more prone to cell death and had decreased capacity in promoting the killing of Mtb in infected macrophages. Lastly, comparing the immune responses of Qa-1 mutant knock-in mice deficient in either Qa-1-restricted CD8+ Tregs (Qa-1 D227K) or the inhibitory Qa-1-CD94/NKG2A interaction (Qa-1 R72A) with Qa-1-/- and wild-type controls indicated that both of these Qa-1-mediated mechanisms were involved in suppression of the immune response in Mtb infection. Our findings reveal that Qa-1 participates in the immune response to Mtb infection by presenting peptide antigens as well as regulating immune responses, resulting in more effective anti-Mtb immunity.

Development of the Abbott RealTime ZIKA assay for the qualitative detection of Zika virus RNA from serum, plasma, urine, and whole blood specimens using the m2000 system.

Zika virus is an arthropod-borne flavivirus that has rapidly developed into a world-wide concern. Discovered in 1947, the virus was relatively obscure until an outbreak occurred in 2007 in the Yap islands and spread eventually to the Americas in 2015. Only 20% of patients infected with Zika virus develop symptoms. However, there can be serious consequences of infection including birth defects in developing fetuses and links to Guillain-Barré syndrome. The swift rise in infections has necessitated the development of diagnostic tests for both the detection of viral RNA and the presence of virus-specific antibodies. Abbott has developed a dual target RT-PCR assay for the detection of Zika virus RNA within serum, plasma, whole blood, and urine using the automated m2000 system for sample extraction to result reporting. The Abbott RealTime ZIKA assay has a limit of detection of 30 copies per mL in serum, 40 copies per mL in plasma and urine, and 120 copies per mL in whole blood and demonstrates high specificity against challenges from closely related infectious agents.

Assessment of Neck Lumps in Relation to Dentistry.

Neck lumps have a varied aetiology, from a benign inflammatory cause to the first presenting sign of a malignancy. Patients may present to primary care complaining of a neck lump or they may be identified as an incidental finding during routine examination. This article highlights a structured approach to the initial assessment including history taking, risk factor assessment and clinical examination. Further investigations undertaken in a secondary care setting, such as ultrasound and guided fine needle aspirations, are then discussed. The common congenital, inflammatory, infective, vascular and neoplastic causes of neck lumps and their management and specialist referral pathway are discussed.

Argument for the conservative management of mandibular ameloblastomas.

Ameloblastoma is a rare, benign, odontogenic tumour that affects the mandible more commonly than the maxilla. Solid or multicytic variants are often resected and the defects reconstructed with a free flap. To establish the outcome after enucleation and application of Carnoy's solution, irrespective of histological subtype, we used the hospital's histology database to identify all the patients treated between 2001 and 2014 by one surgeon. Variables included patients' characteristics, histological subtype, radiological appearance, follow-up period, and incidence of recurrence. A total of 27 patients (13 male) were included, mean age 41 years (range 12-79). Fifteen (56%) had solid multicystic lesions, and there was an overall predominance of the follicular or plexiform variant, or both. Of the 23 preoperative radiographs that were available, 17 lesions were unicystic, 5 multilobular and scalloped with no septa, and one had aggressive features of multilocularity and a poorly defined peripheral margin. The mean duration of follow up was 38 months (range 3-156). Three patients had recurrence at 20, 27, and 35 months postoperatively, and each had repeat enucleation and application of Carnoy's solution. Reconstruction was not necessary, and to date none has recurred. This study shows the potential benefits of conservative surgery and sterilisation of the cystic cavity with Carnoy's solution. Recurrence is low, and with vigilant surveillance, similar repeat procedures have been effective when necessary. A longer follow-up period and larger numbers of patients are now needed to corroborate these findings.

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection.

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or ß2m (ß2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly ß2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules.

Levamisole-Adulterated Cocaine Nephrotoxicity: Ultrastructural Features.

OBJECTIVES: The issue of levamisole-adulterated cocaine is emerging as a rapidly growing public health concern due to an increasing number of reports describing its role in cutaneous vasculitis and agranulocytosis. Of note, levamisole is recognized as a contaminant in 69% of the cocaine used within the United States. METHODS: We describe a patient who was a chronic cocaine user and developed systemic vasculitis characterized by polyarthralgia, bullous skin lesions, agranulocytosis, and antineutrophil cytoplasmic antibody-positive rapidly progressive glomerulonephritis. RESULTS: The skin biopsy specimen demonstrated leukocytoclastic vasculitis. The renal biopsy specimen revealed pauci-immune necrotizing and crescentic glomerulonephritis and unusual deposits with medium electron density composed of granules, microspherules, and rare single fibrils on electron microscopy. CONCLUSIONS: The electron microscopic features of levamisole-adulterated cocaine toxicity are novel findings that are presented for the first time, to our knowledge, in this report.

A Pulse Rate Estimation Algorithm Using PPG and Smartphone Camera.

The ubiquitous use and advancement in built-in smartphone sensors and the development in big data processing have been beneficial in several fields including healthcare. Among the basic vitals monitoring, pulse rate monitoring is the most important healthcare necessity. A multimedia video stream data acquired by built-in smartphone camera can be used to estimate it. In this paper, an algorithm that uses only smartphone camera as a sensor to estimate pulse rate using PhotoPlethysmograph (PPG) signals is proposed. The results obtained by the proposed algorithm are compared with the actual pulse rate and the maximum error found is 3 beats per minute. The standard deviation in percentage error and percentage accuracy is found to be 0.68 % whereas the average percentage error and percentage accuracy is found to be 1.98 % and 98.02 % respectively.

A study on promoter methylation of PTEN in sporadic breast cancer patients from North India.

BACKGROUND: Epigenetic silencing of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through DNA methylation has been implicated in the pathogenesis of breast cancer. Present study investigates the contribution of PTEN promoter methylation and its associated protein expression in sporadic breast cancer patients from North India. METHODS: A total of 360 paired breast carcinoma and adjacent normal tissue samples from 180 sporadic breast cancer patients were included in the present study and examined for PTEN promoter methylation status by methylation-specific polymerase chain reaction. Immunohistochemistry method was used for determining PTEN protein expression. Molecular findings were statistically correlated with various clinicopathological parameters to identify associations of clinical relevance. RESULTS: Presence of PTEN promoter methylation (39.44 %) significantly correlated with its expression downregulation (45.56 %) in breast tumors (P = 0.0001). Furthermore, their interaction with various clinical parameters was evidenced in stratified analysis. Correlation of PTEN promoter methylation with histologically more malignant grade and PTEN expression loss with triple negative tumor status remained significant even after Bonferroni correction (P < 0.003). CONCLUSIONS: Results implicate promoter methylation to be a mechanism partially responsible for PTEN silencing in sporadic breast cancer for North Indian women. Besides, methylation and expression loss of PTEN exhibited promising potential as candidate biomarkers of risk assessment in subcategorized breast tumors with critical pathologic parameters.