Neurological symptoms in pediatric abusive head trauma: Multi-center data for clinical forensic medicine.

Central nervous system-associated lesions can frequently be found in abusive head trauma (AHT) cases. Since there are frequently no visible signs of injury on the body surface, the diagnosis of AHT can be challenging. In particular, if the affected child shows only isolated neurological symptoms, these are often misinterpreted as a minor illness.

Temporal development of subdural collections in infants with confessed abusive head trauma: a forensic neuroimaging study.

Objectives: Estimating the age of injury in pediatric abusive head trauma (AHT) is a challenging task but potentially valuable for the identification of perpetrators. The aims of the study are (1) to describe the temporal development of different imaging features of subdural collections (SDCs), and (2) to provide novel age-diagnostic reference data for forensic-radiological expert reports.

Methods: Using a multi-center approach and a 10-year study period, serial neuroimaging studies of 13 comprehensively investigated AHT cases (8 CT and 26 MRI scans) were analyzed regarding several subdural imaging parameters (SDC appearances, entities, components, and associated findings).

ELISA-R: an R-based method for robust ELISA data analysis.

Enzyme-linked immunosorbent assay (ELISA) is a technique to detect the presence of an antigen or antibody in a sample. ELISA is a simple and cost-effective method that has been used for evaluating vaccine efficacy by detecting the presence of antibodies against viral/bacterial antigens and diagnosis of disease stages. Traditional ELISA data analysis utilizes a standard curve of known analyte, and the concentration of the unknown sample is determined by comparing its observed optical density against the standard curve.

Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen [bedaquiline-pretomanid-linezolid (BPaL)] during the first 3 weeks of treatment at human equivalent doses.

Use of Multiple Pharmacodynamic Measures to Deconstruct the Nix-TB Regimen in a Short-Course Murine Model of Tuberculosis.

A major challenge for tuberculosis (TB) drug development is to prioritize promising combination regimens from a large and growing number of possibilities. This includes demonstrating individual drug contributions to the activity of higher-order combinations. A BALB/c mouse TB infection model was used to evaluate the contributions of each drug and pairwise combination in the clinically relevant Nix-TB regimen (bedaquiline-pretomanid-linezolid [BPaL]) during the first three weeks of treatment at human equivalent doses.

Blood taken immediately after fatal resuscitation attempts yields higher quality DNA for genetic studies as compared to autopsy samples.

Background: The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable for high-throughput DNA sequencing (NGS).

Mucosal exposure to non-tuberculous mycobacteria elicits B cell-mediated immunity against pulmonary tuberculosis.

Bacille Calmette-Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTMs) are opportunistic pathogens present ubiquitously in the environment.

Fractures and skin lesions in pediatric abusive head trauma: a forensic multi-center study.

Abusive head trauma (AHT) and its most common variant, the shaken baby syndrome (SBS), are predominantly characterized by central nervous system-associated lesions. Relatively little data are available on the value of skeletal and skin injuries for the diagnosis of SBS or AHT. Thus, the present study retrospectively investigated 72 cases of living children diagnosed with the explicit diagnosis of SBS during medico-legal examinations at three German university institutes of legal medicine.

Fundamentals of Capillary Electrophoretic Migration and Separation of SDS Proteins in Borate Cross-Linked Dextran Gels.

Recent progress in the development and production of new, innovative protein therapeutics require rapid and adjustable high-resolution bioseparation techniques. Sodium dodecyl sulfate capillary gel electrophoresis (SDS-CGE) using a borate (B) cross-linked dextran (D) separation matrix is widely employed today for rapid consistency analysis of therapeutic proteins in manufacturing and release testing. Transient borate cross-linking of the semirigid dextran polymer chains leads to a high-resolution separation gel for SDS-protein complexes.

A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model.

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation.

Proteomic Profiling of IgG1 Producing CHO Cells Using LC/LC-SPS-MS: The Effects of Bioprocessing Conditions on Productivity and Product Quality.

The biopharmaceutical market is dominated by monoclonal antibodies, the majority of which are produced in Chinese hamster ovary (CHO) cell lines. Intense cell engineering, in combination with optimization of various process parameters results in increasing product titers. To enable further improvements in manufacturing processes, detailed information about how certain parameters affect cellular mechanisms in the production cells, and thereby also the expressed drug substance, is required.

Abusive head trauma in court: a multi-center study on criminal proceedings in Germany.

The shaken baby syndrome (SBS) is a common variant of abusive head trauma (AHT) in infants and toddlers. Data on the legal outcome of such cases are still sparse. By means of a retrospective multi-center analysis, 72 cases of living children diagnosed with SBS/AHT from three German university institutes of legal medicine were identified.

BCG-Prime and boost with Esx-5 secretion system deletion mutant leads to better protection against clinical strains of Mycobacterium tuberculosis.

Although vaccination with BCG prevents disseminated forms of childhood tuberculosis (TB), it does not protect against pulmonary infection or Mycobacterium tuberculosis (Mtb) transmission. In this study, we generated a complete deletion mutant of the Mtb Esx-5 type VII secretion system (Mtb Δesx-5). Mtb Δesx-5 was highly attenuated and safe in immunocompromised mice.

Acquisition of High-Quality Spectral Flow Cytometry Data.

Flow cytometry allows the visualization of physical, functional, and/or biological properties of cells including antigens, cytokines, size, and complexity. With increasingly large flow cytometry panels able to analyze up to 50 parameters, there is a need to standardize flow cytometry protocols to achieve high-quality data that can be input into analysis algorithms. Without this clean data, algorithms may incorrectly categorize the cell populations present in the samples.

Cyto-Feature Engineering: A Pipeline for Flow Cytometry Analysis to Uncover Immune Populations and Associations with Disease.

Flow cytometers can now analyze up to 50 parameters per cell and millions of cells per sample; however, conventional methods to analyze data are subjective and time-consuming. To address these issues, we have developed a novel flow cytometry analysis pipeline to identify a plethora of cell populations efficiently. Coupled with feature engineering and immunological context, researchers can immediately extrapolate novel discoveries through easy-to-understand plots.

Multi-Omics Reveals Impact of Cysteine Feed Concentration and Resulting Redox Imbalance on Cellular Energy Metabolism and Specific Productivity in CHO Cell Bioprocessing.

Chinese hamster ovary (CHO) cells are currently the primary host cell lines used in biotherapeutic manufacturing of monoclonal antibodies (mAbs) and other biopharmaceuticals. Cellular energy metabolism and endoplasmic reticulum (ER) stress are known to greatly impact cell growth, viability, and specific productivity of a biotherapeutic; but the molecular mechanisms are not fully understood. The authors previously employed multi-omics profiling to investigate the impact of a reduction in cysteine (Cys) feed concentration in a fed-batch process and found that disruption of the redox balance led to a substantial decline in cell viability and titer.

[On the quality of the external post-mortem examination in cases of fatal head trauma : A comparison of death certificate and forensic autopsy].

Background: In Germany it is required by law that basically every type of physician needs to be capable of executing a correct external post-mortem examination of a corpse. In recent years, numerous investigations on external post-mortem examinations repeatedly reported systematic mistakes and erroneous procedures in various clinical and medicolegal case groups. Accordingly, the completion of death certificates is frequently performed incorrectly.

Updating the risk profile of fatal head trauma: an autopsy study with focus on age- and sex-dependent differences.

Fatal head trauma (FHT) represents one of the most frequent causes of death diagnosed in forensic pathology. However, profound statistic autopsy data on FHT is still sparse. Therefore, the purpose of this study was to investigate the circumstances and injury patterns of FHT with particular focus on age and sex, and additionally, to describe a recent risk profile of FHT.

Molecular autopsy and family screening in a young case of sudden cardiac death reveals an unusually severe case of FHL1 related hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a prevalence of about 1:200. It is characterized by left ventricular hypertrophy, diastolic dysfunction and interstitial fibrosis; HCM might lead to sudden cardiac death (SCD) especially in the young. Due to low autopsy frequencies of sudden unexplained deaths (SUD) the true prevalence of SCD and especially of HCM among SUD remains unclear.

Understanding Subdural Collections in Pediatric Abusive Head Trauma.

Life-threatening physical abuse of infants and toddlers is frequently correlated with head injuries. A common variant of the abusive head trauma is the shaken baby syndrome. The present review article sheds light on subdural collections in children with abusive head trauma and aims at providing a recent knowledge base for various medical disciplines involved in diagnostic procedures and legal proceedings.

Multi-Omics Study on the Impact of Cysteine Feed Level on Cell Viability and mAb Production in a CHO Bioprocess.

There is continual demand to maximize CHO cell culture productivity of a biotherapeutic while maintaining product quality. In this study, a comprehensive multi-omics analysis is performed to investigate the cellular response to the level of dosing of the amino acid cysteine (Cys) in the production of a monoclonal antibody (mAb). When Cys feed levels are insufficient, there is a significant decrease in protein titer.

Complementary middle-down and intact monoclonal antibody proteoform characterization by capillary zone electrophoresis - mass spectrometry.

High-resolution capillary zone electrophoresis - mass spectrometry (CZE-MS) has been of increasing interest for the analysis of biopharmaceuticals. In this work, a combination of middle-down and intact CZE-MS analyses has been implemented for the characterization of a biotherapeutic monoclonal antibody (mAb) with a variety of post-translational modifications (PTMs) and glycosylation structures. Middle-down and intact CZE separations were performed in an acidified methanol-water background electrolyte on a capillary with a positively charged coating (M7C4I) coupled to an Orbitrap mass spectrometer using a commercial sheathless interface (CESI).