Outcomes following surgical intervention for acute hemorrhage in severe traumatic brain injury: a review of the National Trauma Data Bank.

OBJECTIVE: Severe traumatic brain injury (TBI) is a public health issue posing significant morbidity and mortality to afflicted patients. While the effect of time to surgery as the primary factor for survival has been extensively studied, long-term dispositional outcomes following intracranial hemorrhage evacuation have not been well described in the literature. Therefore, the aim of this study was to elicit potential prognostic factors in patients presenting with severe TBI that may have a significant impact on discharge disposition. METHODS: The authors searched the National Trauma Data Bank (NTDB) for patients included between 2010 and 2019, solely focusing on those with a Glasgow Coma Scale score ≤ 8, signifying severe TBI, and with associated intracranial hemorrhage treated via surgical intervention. Numerous characteristics were analyzed, including demographics (age, sex, race, ethnicity, payment status), discharge disposition, time to surgery, pupillary response, midline shift (> 5 mm), and postoperative inpatient complications and comorbidities. Disposition included routine discharge to home, discharge to home with home health services (HHSs), discharge to acute inpatient rehabilitation (AIR), discharge to a skilled nursing facility (SNF)/long-term acute care hospital (LTACH), and death. RESULTS: The authors analyzed data on 7308 patients, 69.6% of whom were White and 11.2% of whom were Black. More young Black and Hispanic patients had severe TBI events than their matched elders, whereas more elderly White patients had severe TBI events than their matched younger counterparts. The most common disposition across all ages was SNF/LTACH. Septuagenarians and octogenarians were 12.1 and 21 times more likely, respectively, to die following a severe TBI than their younger counterparts (p < 0.001). Patients aged 18-29 were 1.7 times more likely to be discharged with HHSs (p < 0.001). Minority race/ethnicity groups were less likely to be discharged to AIR. As age increased, a patient's intensive care unit stay increased by 15 days (p < 0.001) and total hospital length of stay increased by 25 days (p < 0.001). CONCLUSIONS: Neurosurgical evacuation of intracranial hemorrhage in severe TBI has variable long-term morbidity. Utilizing the largest collection of trauma data within the United States, the authors present quantitative evidence on discharge disposition. Understanding these tangible points can help neurosurgeons present potential outcomes to patients, promote preventative care, and generate tangible conversations with patients and their family members.

Anomalous, dielectrophoretic transport of molecules in non-electrolytes.

The electric field (E-field) dielectric polarization-based separations mechanism represents a novel method for separating solutions at small length scales. An E-field gradient with a maximum strength of 0.4 MV/m applied across a 10 µm deep channel is shown to increase the concentration inside the low E-field region by ≈ 40% relative to the high E-field region. This concentration change is two orders of magnitude higher than the estimated change predicted using the classical equilibrium thermodynamics for the same E-field. The deviation between the predicted and the experimental results suggests that the change in volumetric E-field energy with solute concentration is insufficient to explain this phenomenon. The study also explores the effect of varying strength of E-field and frequency of supplied voltage on the dielectric polarization-based separation efficiency. While the increase in the former increases the separation efficiency, the increase in the latter reduces the degree of concentration change due to ineffective charging of the electrodes.

Electronic health record interoperability using FHIR and blockchain: A bibliometric analysis and future perspective.

Electronic health records (EHRs) constitute vital statistics, current health condition, ongoing therapies, and patient data; hence, their interoperability could be useful for epidemiologic and clinical research. Fast Healthcare Interoperability Resources (FHIR) and blockchain are currently "in-use" and tested for exchange of such data. The annual scientific production of publications for both FHIR and blockchain shows steady growth. The data interoperability and electronic data interchange have been introduced in the field of EHR in 2020, hence inferring that data interoperability is relatively a new domain. The thematic mapping suggested "interoperability" of EHR is well-developed and important for the structure of the research field.

Thermodynamic Analysis of Capillary and Electric Field Effects on Liquid-Vapor Equilibrium: A Study on the Water-Ethanol Mixture.

This study investigates phase equilibrium manipulation in nonideal mixtures through a combined capillary and external electric field approach. Utilizing thermodynamic principles, an expression is established for estimating the equilibrium liquid mole fraction in a confined system subjected to a localized electric field within a capillary that is filled with a liquid phase in equilibrium with its vapor counterpart. Applied to a water-ethanol system, the model suggests large shifts in the equilibrium liquid mole fraction of water due to the electric field and capillary effects. These findings reveal that while the capillary's influence remains negligible for radii exceeding 10 nm, capillaries of smaller dimensions, when exposed to electric fields of around 300 MV/m, can amplify the equilibrium liquid water mole fraction by up to 55%. This suggests the potential for phase equilibrium control through larger capillaries and lower electric fields, while intriguing complexities arise at very small radii.

Proportion of thyroid cancer and other cancers in the democratic republic of Congo.

BACKGROUND: Cancer diagnosis is increasing around the world and in the Democratic Republic of the Congo (DRC). The proportion of thyroid cancer has increased over the past three decades. There are very few studies on cancer epidemiology, and in particular on thyroid cancer in the DRC. AIM: To establish the most recent proportion of thyroid cancer in the DRC compared to other cancers. METHODS: This is a retrospective and descriptive study of 6106 consecutive cancer cases listed in the pathological registers of 4 Laboratories in the city of Kinshasa. This study included all cancer cases recorded in the registers between 2005 and 2019. RESULTS: From a sample of 6106 patients, including all cancer types, 68.3% cases were female and 31.7% were male. Breast and cervical cancer were the most common types of cancer in women and, prostate and skin cancer were the most common types in men. Thyroid cancer was sixth in proportion in women and eleventh in men compared to all cancers. Papillary carcinoma was the most common of thyroid cancers. Rare cancers such as anaplastic and medullary thyroid carcinomas had a proportion of 7% and 2%, respectively. CONCLUSION: Newer diagnostic tools led to a surge in cancer diagnoses in the DRC. Thyroid cancer has more than doubled its proportion over the last several decades in the country.

Thermodynamic Study of the Electric Field Effect on Liquid-Vapor Mixture at Equilibrium: An Analysis on a Water-Ethanol Mixture.

In this paper, the effect of electric fields on phase equilibria through polarization is investigated. A relation is derived for the chemical potential of a system, where the electric field is localized over a liquid phase mixture in equilibrium with a vapor phase mixture. This relation is then applied to a water-ethanol mixture to explore the effect of polarization-based electric fields on the liquid phase composition. It is observed that the quadratic dependence on electric field strength produces little effect below field strengths of approx. 10 MV/m. However, above this field strength, the mole fraction of water in the liquid phase grows rapidly, increasing by a factor of 8 for a water vapor phase fraction of 0.2 and a field strength of 500 MV/m, which approaches the dielectric breakdown strength of water. Nonetheless, this field strength could be achievable with microfluidic experimental setups.

Dielectric polarization-based separations in an ionic solution.

A novel non-electrophoretic, electric field-based separation mechanism capable of transporting ions based on their dielectric properties is presented here for the first time. Though this polarization-based mechanism behaves similarly to dielectrophoresis, the separation mechanism is remarkably very efficient at small length scales compared to any dielectrophoretic separation mechanism for particles. For an applied electric field of strength as low as ∼0.75 MV m-1 across a 100 µm channel, the working solute - sodium fluorescein - is shown to decrease in its concentration by ≈20% in electric field region relative to the non electric field region. The existing macroscopic theoretical models like electrohydrodynamics and equilibrium thermodynamics are shown to underestimate the concentration change by two orders of magnitude for the same electric field strength. This surprisingly large difference between theory and experimental results suggests that the electric field-based equilibrium thermodynamic model lacks a key physics.

Novel Raman Spectroscopy Method for Solutions in Uniform, High-Strength Electric Field.

A novel method of measuring the influence of high electric fields on the Raman scattering of fluids is introduced, which can help understand various interactions of a fluid with the high electric field. The microfluidic chip can impose highly controlled, uniform electric fields across the measurement volume with blocked electrodes, eliminating spurious reactions at the electrode surface. The developed methodology and the experimental setup are utilized to examine the effect of the electric field on three of the stretching vibrations of ethanol in water-ethanol mixtures with varying concentrations of ethanol and effective electric fields up to 1.0MV/m. The increase in the electric field is seen to broadly decrease the intensity of Raman scattering due to a decrease in the polarizability of the ethanol molecules. Although this effect is uniform for all water-ethanol mixtures, it reduces in mixtures with high weight-fractions of water because of the already reduced polarizability of an ethanol molecule due to hydrogen bonding. The combined effect of hydrogen bonding and increase in temperature due to the alternating high electric field even results in an increase in the magnitude of peak intensity for relatively low-weight fractions of ethanol.

A review of medical device regulations in India, comparison with European Union and way-ahead.

Indian healthcare sector is a fast-growing industry which is expected to reach $280 billion by 2025. Medical devices market in India is one of the top 20 medical device markets in the world. It is currently valued at $5.2 billion and is expected to reach $50 billion by 2025. However, India does not manufacture many devices indigenously and still imports approximately 70% of its medical devices. Manufacturing and monitoring of medical devices are highly regulated activities. In India, there were no specific medical device regulations and devices were regulated under the Drugs and Cosmetics Act, 1940. To fulfill this gap, Central Drug Standard Control Organization released Indian Medical Device Rules, 2017, which are the new regulations for medical devices in India. Keeping pace with the requirements, these were amended as Medical Devices (Amendment) Rules, 2020, which has come into force in April 2020. These rules cover various aspects of device related regulations, including classification, registration, manufacturing and import, labeling, sales, and postmarket requirements, etc. The rules are a positive step and encompass most of the European Union (EU) approval process, which mandates that the devices are safe and performs its intended function. However, with rapid advancements in medical device technology, much is desired in clarity and revamping of the current regulatory system to harmonize standards to be in-line with advanced regulations like EU.

Effects of Frequency and Joule Heating on Height Rise between Parallel Electrodes with AC Electric Fields.

High strength AC electric fields generate a body force on a dielectric medium confined between two electrodes. The body forces are due to two factors. First is the variation in permittivity across an interface such as liquid-air present between the electrodes. The second is a change in the dielectric property of the medium due to a variation in the thermodynamic properties such as temperature. The height rise of a dielectric medium between two electrodes is one of the consequences of these electrical body forces and is used here as a comparatively simple way to study these forces. In an aqueous solution with finite conductivity, the effects of the frequency of the supplied voltage source and the temperature change due to Joule heating on height rise have never been studied in this context. This study focuses on systems where the contributions of surface forces are negligible and highlights the interplay between solution conductivity, applied electric field, and the solution height/temperature behavior. Using a generic thermodynamic model for an aqueous solution under the application of an alternating current electric field, it is shown that for low conductivity solutions the resulting temperature and height rise change weakly with the applied field frequency and strongly with the applied electric field. For higher conductivity solutions, the behavior becomes more complex with respect to the electric field strength. As compared to Pellat's original model, the height rise varies from strongly suppressed to enhanced.

Harmonising terminology with MedDRA for plain language summaries.

Human volunteers are key stakeholders in any clinical research. For inclusiveness it is ethically imperative to ensure data transparency even after the completion of clinical trials. This is also supported by the Declaration of Helsinki, which in a statement of ethical principles, provides guidance to physicians and other participants in medical research involving human volunteers, suggesting that they have the full right to the results of a trial (1).

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels.

A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a recombinant fusion chimera protein, His-tagged PfMSP-Fu24, by producing it as a tag-free recombinant protein. In this study, tag-free recombinant PfMSPFu24 (rFu24) was expressed in Escherichia coli, and the soluble protein was purified using a three-step purification involving ammonium sulphate precipitation followed by 2-step ion exchange chromatography procedures and shown that it was highly immunogenic with the human-compatible adjuvant Alhydrogel. We further investigated two dipeptides, phenylalanine-α, ß-dehydrophenylalanine (FΔF) and Leucine-α, ß-dehydrophenylalanine (LΔF) based hydrogels as effective delivery platforms for rFu24. These dipeptides self-assembled spontaneously to form a highly stable hydrogel under physiological conditions. rFu24 was efficiently entrapped in both the F∆F and L∆F hydrogels, and the three-dimensional (3D) mesh-like structures of the hydrogels remained intact after the entrapment of the antigen. The two hydrogels significantly stimulated rFu24-specific antibody titers, and the sera from the immunized mice showed an invasion inhibitory activity comparable to that of Alhydrogel. Easily synthesized dipeptide hydrogels can be used as an effective antigen delivery platform to induce immune responses.

Antibody Combinations Targeting the Essential Antigens CyRPA, RH5, and MSP-119 Potently Neutralize Plasmodium falciparum Clinical Isolates From India and Africa.

BACKGROUND: Targeting multiple key antigens that mediate distinct Plasmodium falciparum erythrocyte invasion pathways is an attractive approach for the development of blood-stage malaria vaccines. However, the challenge is to identify antigen cocktails that elicit potent strain-transcending parasite-neutralizing antibodies efficacious at low immunoglobulin G concentrations feasible to achieve through vaccination. Previous reports have screened inhibitory antibodies primarily against well adapted laboratory parasite clones. However, validation of the parasite-neutralizing efficacy against clinical isolates with minimal in vitro cultivation is equally significant to better ascertain their prospective in vivo potency. METHODS: We evaluated the parasite-neutralizing activity of different antibodies individually and in combinations against laboratory adapted clones and clinical isolates. Clinical isolates were collected from Central India and Mozambique, Africa, and characterized for their invasion properties and genetic diversity of invasion ligands. RESULTS: In our portfolio, we evaluated 25 triple antibody combinations and identified the MSP-Fu+CyRPA+RH5 antibody combination to elicit maximal parasite neutralization against P. falciparum clinical isolates with variable properties that underwent minimal in vitro cultivation. CONCLUSIONS: The MSP-Fu+CyRPA+RH5 combination exhibited highly robust parasite neutralization against P. falciparum clones and clinical isolates, thus substantiating them as promising candidate antigens and establishing a proof of principle for the development of a combinatorial P. falciparum blood-stage malaria vaccine.

Uncovering the Cyclic AMP Signaling Pathway of the Protozoan Parasite Entamoeba histolytica and Understanding Its Role in Phagocytosis.

Second messenger signaling controls a surprisingly diverse range of processes in several eukaryotic pathogens. Molecular machinery and pathways involving these messengers thus hold tremendous opportunities for therapeutic interventions. Relative to Ca2+ signaling, the knowledge of a crucial second messenger cyclic AMP (cAMP) and its signaling pathway is very scant in the intestinal parasite Entamoeba histolytica. In the current study, mining the available genomic resources, we have for the first time identified the cAMP signal transduction pathway of E. histolytica. Three heptahelical proteins with variable G-protein-coupled receptor domains, heterotrimeric G-proteins (Gα, Gß, and Gγ subunits), soluble adenylyl cyclase, cyclase-associated protein, and enzyme carbonic anhydrase were identified in its genome. We could also identify several putative candidate genes for cAMP downstream effectors such as protein kinase A, A-kinase anchoring proteins, and exchange protein directly activated by the cAMP pathway. Using specific inhibitors against key identified targets, we could observe changes in the intracellular cAMP levels as well as defect in the rate of phagocytosis of red blood cells by the parasite E. histolytica. We thus strongly believe that characterization of some of these unexplored crucial signaling determinants will provide a paradigm shift in understanding the pathogenicity of this organism.

Surface Plasmon Resonance Analysis of the Protein-protein Binding Specificity Using Autolab ESPIRIT.

Direct protein-protein interactions are known to regulate a wide range of cellular activities. To understand these contacts one can employ various experimental methods like Dynamic Light Scattering (DLS), Fluorescence Resonance Energy Transfer (FRET), Isothermal titration calorimetry (ITC), Chemical crosslinking, Co-immunoprecipitation (Co-IP), Surface Plasmon Resonance (SPR) and many more. Among these, SPR stands out as a quick, label-free, reliable, and accurate quantitation technique. We have used SPR to elucidate the linkage between 14-3-3 Protein 3 (EhP3) and the actin cytoskeleton in the protist pathogen Entamoeba histolytica. It allowed us to screen EhP3 binding with several actin-binding/actin regulatory proteins (Coactosin, Actophorin, Twinfilin, Profilin, and Filamin). Our screening results suggested Coactosin as an important interacting partner of EhP3. A complete kinetic analysis indeed confirmed that EhCoactosin binds EhP3 with an affinity constant of 3 µM.

EhP3, a homolog of 14-3-3 family of protein participates in actin reorganization and phagocytosis in Entamoeba histolytica.

The highly conserved proteins of the 14-3-3 family are universal adaptors known to regulate an enormous range of cellular processes in eukaryotes. However, their biological functions remain largely uncharacterized in pathogenic protists comprising of several 14-3-3 protein isoforms. In this study, we report the role of 14-3-3 in coordinating cytoskeletal dynamics during phagocytosis in a professional phagocytic protist Entamoeba histolytica, the etiological agent of human amebiasis. There are three isoforms of 14-3-3 protein in amoeba and here we have investigated Eh14-3-3 Protein 3 (EhP3). Live and fixed cell imaging studies revealed the presence of this protein throughout the parasite phagocytosis process, with high rate of accumulation at the phagocytic cups and closed phagosomes. Conditional suppression of EhP3 expression caused significant defects in phagocytosis accompanied by extensive diminution of F-actin at the site of cup formation. Downregulated cells also exhibited defective recruitment of an F-actin stabilizing protein, EhCoactosin at the phagocytic cups. In addition, mass spectrometry based analysis further revealed a large group of EhP3-associated proteins, many of these proteins are known to regulate cytoskeletal architecture in E histolytica. The dynamics of these proteins may also be controlled by EhP3. Taken together, our findings strongly suggest that EhP3 is a novel and a key regulatory element of actin dynamics and phagocytosis in E. histolytica.

Good publication practice guideline 3: Evolving standards for medical writers.

Publications in peer-reviewed journals as well as oral and poster presentations for scientific conferences comes under the purview of GPP3 guideline. The GPP3 has kept pace with the changes in publication practices and focusses on every burning aspect of publications. The present paper evaluates the purview of GPP3 guideline in context with the evolving role of medical writer (MW) in the present times. A MW plays an important role to in producing high quality authentic documents. The role of professional MW have previously been emphasised upon in previous versions of GPP guidelines, and have been instrumental in acknowledging role of MWs in medical publications and cementing their existence rather than them being termed as 'ghostwriters'. Additionally the paper focuses on evolving publication and research presentation standards with reference to other guidelines. The paper also focusses on clarity on reimbursements which is in contrast to other Acts (Sunshine Act). Most importantly, the expectations from subsequent guidelines are also discussed which may form basis of subsequent GPP guidelines.

Rare case of male breast intraductal papilloma progressing to invasive ductal carcinoma: A radiologic-pathologic correlation.

Although male breast cancer represents only 0.5%-1% of all breast cancer cases in the United States, the incidence of this disease is slowly rising [1]. Because of its extremely low prevalence, screening and treatment guidelines are not well established. Thus, analyzing cases of male breast cancer can accelerate this process. We present a case of a 52-year-old man, initially diagnosed with biopsy-confirmed intraductal papilloma without atypia, who presented 3 years later with progression of this benign lesion to ductal carcinoma in situ and development of de novo invasive ductal carcinoma. This report stresses the importance of symptom detection and risk factor modification with the goal of decreasing the incidence of this disease.

Naturally Acquired Human Antibodies Against Reticulocyte-Binding Domains of Plasmodium vivax Proteins, PvRBP2c and PvRBP1a, Exhibit Binding-Inhibitory Activity.

Background: Crucial gaps in our understanding of Plasmodium vivax reticulocyte invasion and protective immunity have hampered development of vivax vaccines. P. vivax exclusively invades reticulocytes that is mediated by the P. vivax reticulocyte-binding proteins (PvRBPs) specifically PvRBP2c and PvRBP1a. Vivax infections in Duffy-null individuals have suggested the evolution of alternate invasion pathways that may be mediated by the PvRBPs. Thus, PvRBPs appear as potential targets for efficacious P. vivax neutralization. However, there are limited data validating their vaccine efficacy. In the absence of vivax invasion assays, binding-inhibitory activity of antibodies has been reported to be associated with protection and a measure of vaccine potential. Methods: -based analysis was performed of the PvRBP reticulocyte-binding properties and binding-inhibitory activity of specific anti-PvRBP2c/PvRBP1a human antibodies. Results: PvRBP2c and PvRBP1a displayed a distinct reticulocyte-binding specificity, and their specific reticulocyte-binding domains were mapped within their N-terminal regions. Importantly, naturally acquired antibodies against the reticulocyte-binding domains efficaciously blocked reticulocyte binding of native PvRBPs, suggesting that the human immune system produced functional binding-inhibitory antibodies through exposure to vivax malaria. Conclusions: Reticulocyte-binding domains of PvRBP2c/PvRBP1a are targets of naturally acquired binding-inhibitory antibodies, substantiating their promise as candidate antigens against which vaccine-inducible immunity could potentially be boosted through natural infections.