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A Primer for Junior Trainees: The Structure, Binding, and Therapeutic Applications of Immunoglobulin G
No full textImmunoglobulin G (IgG) is a central component of the immune system, a vital tool in research and diagnostics, and has become a cornerstone of next-generation therapeutics. Despite their diverse applications in biology and human medicine, all IgGs function by specifically recognizing their target molecules. Its unique structure facilitates a diversity of protein sequence combinations to recognize a diversity of antigen targets. Because of this flexibility, antibodies have been usurped to create novel therapeutics that can promote or prevent protein-protein interactions. This junior trainee review introduces the structure and general binding mechanism of IgG and explores how its form underlies its biological and therapeutic functions. The unique structural and biophysical properties of IgG drive its versatility. Examples of current and emerging IgG therapeutics illustrate how fundamental mechanisms in IgG-protein interactions permit this molecule to be a novel strategy to combat a wide variety of diseases.S.T.A. is funded by the NIH/NIGMS (R35 GM142691) and received start-up funds from the Indiana University School of Medicine and its Precision Health Initiative (PHI)
Prevalence of cough and associated symptoms among pilgrims in large mass gathering event 2024: a cross-sectional study
No full textObjectives: Large mass gathering events significantly increase the risk of infectious disease transmission, particularly respiratory infections, due to unavoidable overcrowding and exposure to airborne pathogens. Therefore, this study aims to assess the prevalence of cough, its duration, and associated symptoms during the religious mass gathering event among pilgrims in the 2024 Hajj season.
Methods: This cross-sectional study was conducted during Hajj in Makkah, Saudi Arabia, in 2024. A face-to-face random interview utilizing a structured questionnaire was employed to collect data from 2,913 pilgrims, who were randomly selected as participants and were at least 18 years old. Baseline demographic data and clinical characteristics were compiled using descriptive statistics. Continuous variables were presented as means and standard deviations, while categorical data were illustrated as counts and percentages.
Results: Among 2913 Hajj pilgrims, the average age was 53.9 ± 11.8 years, and 1,173 (40.4%) reported cough symptoms. The highest prevalence was in the 50-64 age group (60.7%). Chronic diseases were significantly more common in patients with cough (53.3%). Diabetes (357 cases) and hypertension (330 cases) were the most common conditions. Of the 1,173 participants with cough, 10.3% reported no associated symptoms, while sore throat (30.8%) was the most common. Logistic regression confirmed chronic disease, nationality, and age as significant predictors of cough.
Conclusions: A significant number of cough symptoms were reported, with the highest incidence in older adults. Additionally, notable associations were identified between cough and pre-existing health conditions, particularly diabetes mellitus, hypertension, chronic heart disease, and asthma.. Future research should investigate the long-term effects of cough and its related symptoms or use of medications in mass gatherings
Bioactivity and biocompatibility of bioceramic-based pulp capping materials in laboratory and animal models
No full textRecently, premix bioceramic-based pulp capping (BPC) materials have been introduced with desirable properties. However, data regarding the bioactivity and biocompatibility of these materials remain limited. This present study aimed to evaluate the bioactivity and biocompatibility of BPC materials. This study consisted of five experimental groups: Bio C Repair (BCR); BG Multi (BGM); Well pulp ST (WPS); ProRoot MTA (PMTA); and a no capping (NC) group. Measurement of pH, calcium ion (Ca2+) release, and a bioactivity test were performed. An in vivo experiment was conducted on maxillary first molars of Wistar rats with exposed pulp, and pulpal responses were assessed at 1, 3, 7, and 28 days. Immunohistochemical expressions of Nestin, Osteopontin, and DMP-1 were performed. All materials exhibited alkaline pH. BCR exhibited the highest Ca2+ release (p < 0.05). PMTA, BCR, and WPS produced well-formed calcium phosphate depositions. On day 1, BCR, BGM and NC groups showed no to mild inflammatory responses (p < 0.05). On day 3, mild to moderate inflammatory responses was observed in all groups except for the NC group. On day 7, BCR and WPS groups exhibited no to mild inflammatory responses, along with the mineralized tissue layer formation (MTF). On day 28, no inflammatory responses were observed in the BCR, BGM, and WPS groups. Complete and homogenous MTF was identified in all experimental groups except the NC groups. Variable expression of Nestin, Osteopontin, and DMP-1 was noted at different time points. This present study demonstrated that premix BPC materials exhibited favorable bioactivity and biocompatibility and may serve as potential substitutes for PMTA
Predicting Bacterial Vaginosis Development using Artificial Neural Networks
No full textBacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterized by the depletion of protective Lactobacillus spp. and overgrowth of anaerobes. Artificial neural network (ANN) modeling of vaginal microbial communities offers an opportunity for early detection of incident BV (iBV). 16S rRNA gene sequencing and quantitative PCR was performed on longitudinal vaginal specimens collected from participants within 14 days of iBV or from healthy participants to calculate the inferred absolute abundance (IAA) of vaginal bacterial taxa. ANNs were trained using the IAA of vaginal taxa from 420 vaginal specimens to classify individual vaginal specimens as either pre-iBV (collected before iBV onset) or Healthy. Feature importance was assessed to understand how specific vaginal micro-organisms contributed to model predictions. ANN modeling accurately classified >97% of specimens as either pre-iBV or Healthy (sensitivity >96%, specificity >98%) using IAA of 20 vaginal taxa. Model prediction accuracy was maintained when training models using only a few key vaginal taxa. Models trained using only the top five most important features achieved an accuracy of >97%, sensitivity >92%, and specificity >99%. Model predictive accuracy was further improved by training models on specimens from white and black participants separately; using only three feature models achieved an accuracy >96%, sensitivity >91%, and specificity >91%. Feature analysis found that Lactobacillus species L. gasseri and L. jensenii differed in how they contributed to model predictions in models trained with data stratified by race. A total of 420 vaginal specimens were analyzed, providing a robust dataset for model training and validation
Cardioprotective Role of Coronary Collaterals in the Development of Intramyocardial Hemorrhage in ST-Segment Elevation MI Patients
No full textBackground: Intramyocardial hemorrhage (IMH), evident in 40% of revascularized ST-segment elevation myocardial infarction (STEMI) patients, is a lethal determinant of MI size. IMH compromises myocardial salvage and drives major adverse cardiovascular events.
Objectives: We sought to determine whether the presence and extent of coronary collaterals affect development of IMH in STEMI patients.
Methods: The MIRON-CL trial (NCT05898425) enrolled 294 consecutive STEMI patients reperfused via primary percutaneous coronary intervention (PCI). All underwent pre-PCI angiography to determine Rentrop collateral grades (0: none; III: complete). Three days post-PCI cardiac magnetic resonance imaging quantified myocardial area at risk (T2 edema), IMH (T2∗), and MI (late gadolinium enhancement).
Results: Among 294 patients, 124 had IMH and 170 did not. Patients with no collaterals (CL-, Grade 0) had higher IMH (7.41% ± 5.33% left ventricle) than those with collaterals (CL+; Grade I: 5.23% ± 3.21%, II: 3.11% ± 2.78%, III: 2.05% ± 1.89%; P < 0.001). Total area at risk post-PCI was larger in CL- (37.62% ± 15.32% left ventricle) than in CL+ (21.48% ± 13.21%; P < 0.001). Absence of collaterals correlated with larger MI (CL- 38.66% ± 14.63% vs CL+ 19.84% ± 13.72%; P < 0.001) and higher microvascular obstruction (CL- 8.07% ± 6.60% vs CL+ 2.17% ± 2.35%; P < 0.001). Patients without collaterals had a higher adjusted risk of IMH (OR: 5.71; 95% CI: 3.16-10.33; P < 0.0001).
Conclusions: Extent of coronary collaterals is a determinant of IMH in revascularized STEMI. Since IMH is known to drive post-PCI infarct expansion, determination of collateral status has the potential to identify patients at high risk of infarct expansion. For these high-risk patients, novel targeted therapies to reduce IMH, limit post-MI infarct expansion, and improve outcomes should be further explored
Relationships Between Metabolic and Bariatric Surgery and Adverse Kidney Outcomes: An Analysis of a Retrospective Cohort
No full textObjective: Obesity is associated with an increased risk of chronic kidney disease. Metabolic and bariatric surgery (MBS) is currently the most effective intervention for sustained weight loss and may reduce the risk of obesity-associated kidney disease. This study examined the relationships between MBS and adverse kidney outcomes.
Methods: This retrospective cohort analysis included 4322 patients with obesity, with or without type 2 diabetes mellitus (T2D), who underwent MBS, and 30,919 nonsurgical control patients from a large health system within the state of Indiana. A primary kidney composite [≥ 1 estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2, ≥ 1 eGFR measurement with a ≥ 40% decrease from baseline, or kidney failure-related death], as well as secondary and tertiary composite and individual outcomes were assessed. Multivariable Cox regression models with and without inverse propensity of treatment weighting were employed to assess associations between MBS and incidence rate for each kidney outcome compared with nonsurgical controls.
Results: The mean (standard deviation) follow-up duration was 6.1 (4.5) years. MBS was associated with a 53% (HR: 0.47; 95% CI: 0.42, 0.52; p < 0.001) and 48% (HR: 0.52; 95% CI: 0.46, 0.60; p < 0.001) lower incidence of the primary kidney composite outcome in patients with and without T2D, respectively, and 48%-56% lower risks for the secondary and tertiary outcomes, regardless of T2D status, compared to controls.
Conclusions: MBS was associated with markedly lower risks for adverse kidney outcomes in patients with obesity. These results support the potential for MBS as a weight loss intervention to preserve kidney function in patients with obesity, both with and without T2D
Quantitative functional profiling of ERCC2 mutations deciphers cisplatin sensitivity in bladder cancer
No full textTumor gene alterations can serve as predictive biomarkers for therapy response. The nucleotide excision repair (NER) helicase ERCC2 carries heterozygous missense mutations in approximately 10% of bladder tumors, and these may predict sensitivity to cisplatin treatment. To explore the clinical actionability of ERCC2 mutations, we assembled a multinational cohort of 2,012 individuals with bladder cancer and applied the highly quantitative CRISPR-Select assay to functionally profile recurrent ERCC2 mutations. We also developed a single-allele editing version of CRISPR-Select to assess heterozygous missense variants in their native context. From the cohort, 506 ERCC2 mutations were identified, with 93% being heterozygous missense variants. CRISPR-Select pinpointed deleterious, cisplatin-sensitizing mutations, particularly within the conserved helicase domains. Importantly, single-allele editing revealed that heterozygous helicase-domain mutations markedly increased cisplatin sensitivity. Integration with clinical data confirmed that these mutations were associated with improved response to platinum-based neoadjuvant chemotherapy. Comparison with computational algorithms showed substantial discrepancies, highlighting the importance of precision functional assays for interpreting mutation effects in clinically relevant contexts. Our results demonstrate that CRISPR-Select provides a robust platform to advance biomarker-driven therapy in bladder cancer and supports its potential integration into precision oncology workflows
Accessibility audit of the Midwest Chapter of the Medical Library Association
No full textBackground: In 2023, JJ Pionke became President of the Midwest Chapter of the Medical Library Association (MWCMLA). He determined that for his presidential year, he would form a task force to determine the accessibility levels of the chapter and remediate accessibility issues as appropriate.
Case presentation: To accomplish the accessibility audit of the MWCMLA, Pionke formed an Accessibility Task Force that was time limited to one year. Task force meetings were held once a month to keep people accountable and to share out progress and requests for assistance. The task force was broken up into four teams: annual meeting, policy, social media, and website. Task force members could be on more than one team. The goals of each team were generally the same: what are other organizations doing, what do we have already if anything, and develop best practices/policy/etc. as needed.
Conclusions: The teams fulfilled their mandate by creating best practices/guidelines/policies documents. Some accessibility remediation was needed for the chapter website. The task force's findings and materials were shared out among the MWCMLA as well as passed on to the presidents of the other chapters, many of whom had expressed interest in the results
Side-Lying Position Is Associated With Improved Swallow Outcomes When Compared to Semi-Upright Position in Infants With Dysphagia
No full textPurpose: The purpose of this study was to examine the effects of side-lying and semi-upright positions on videofluoroscopic swallow study (VFSS) outcomes in infants with dysphagia.
Method: A cross-sectional, within-subject design was employed. Infants diagnosed with dysphagia and undergoing VFSS as part of standard of care were prospectively identified at a tertiary care academic children's hospital. Both semi-upright and side-lying positions were assessed with thin liquids using identical bottles/nipples across positions. Severity and frequency of penetration/aspiration and pharyngeal swallow timeliness were rated by three speech-language pathologists specialized in the evaluation and management of pediatric dysphagia. Severity of airway invasion was assessed using the Penetration-Aspiration Scale (PAS) and swallow timeliness using a 3-point ordinal scale. Mixed-level modeling was used to compare swallow outcomes across positions to determine if side-lying was associated with decreased severity and frequency of airway invasion and timelier pharyngeal swallow initiation.
Results: Twenty-one infants diagnosed with oropharyngeal dysphagia were included (Mage = 4.3 months, SD = 2.2). Side-lying position was associated with a significant decrease in severity and frequency of penetration/aspiration when compared with semi-upright position (p < .001). Side-lying position was associated with a 91% decrease in the odds of presenting with a more severe PAS rating when compared with semi-upright position (odds ratio = .09, 95% confidence interval = [.03, .21]). Improvements in airway protection in side-lying position were most common in infants with deep penetration/aspiration in semi-upright position. Significantly fewer pharyngeal swallows were initiated at the level of the pyriform sinuses in side-lying position when compared with semi-upright position (p < .001); however, the lowest level of swallow initiation was similar across positions.
Conclusions: Side-lying position in infants with dysphagia was associated with less severe and less frequent penetration/aspiration when compared with semi-upright position. Future research should identify predictors of which infants benefit most from side-lying position, as well as the physiological mechanisms underlying these findings