Ross University School of Medicine

• We designed a multi-epitope-based vaccine candidate against Mycobacterium tuberculosis (MTB) through an in-silico approach . • Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. • Simulations predicted elevated levels of CD4 and CD8, T- lymphocytes, B- lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. • While the construct showed high antigenicity and lacked allergenic or toxic properties, this study demonstrated the potentials of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. Mycobacterium tuberculosis (MTB) remains a global health challenge, necessitating innovative strategies to enhance control and prevention. The emergence of drug-resistant MTB strains underscores the need for advanced tuberculosis (TB) vaccines beyond the Bacillus Calmette-Guérin (BCG). This study used computational approaches to design a multi-epitope MTB vaccine. Conserved antigenic proteins (PE_PGRS, ESAT-6, and CFP-10) were identified via MTB genome analyses from the NCBI database. Cytotoxic T cell (CTL), helper T cell (HTL), and B cell epitopes were predicted using the Immune Epitope Database (IEDB) and assembled with adjuvants and linkers to optimize stability and immunogenicity. The vaccine construct underwent rigorous assessments of epitope mapping, allergenicity, antigenicity, and tertiary structural modeling. Immune simulation and docking with toll-like receptor 4 (TLR4) confirmed strong binding affinity and robust immunological properties. The final construct, consisting of 512 amino acids and a molecular weight of 48,937.61 Da, demonstrated favorable structural and immunological attributes, including 91% of residues in acceptable regions (Ramachandran analysis). Simulations predicted elevated levels of CD4 and CD8 T lymphocytes, B lymphocytes, plasma cells, and natural killer cells in secondary and tertiary immune responses. Additionally, the vaccine was successfully cloned into an Escherichia coli (strain K12) pET-28a (+) plasmid for expression analysis. This study highlights the promise of reverse vaccinology and in-silico methods for designing effective multi-epitope vaccines. While the construct showed high antigenicity and lacked allergenic or toxic properties, further in vivo evaluations are crucial for confirming human efficacy.

To be prepared for future infectious disease epidemics, this paper considers a data-driven approach for determining optimal vaccination strategies for multi-community settings with heterogeneous populations under uncertain social mixing, disease transmission, and vaccine efficacy. Specifically, we derive an integrated chance constraints stochastic programming (ICC-SP) disease spread model for optimal vaccination strategies to prevent epidemics by keeping the uncertain post-vaccination reproduction number below one at a specified level of risk. A vaccination strategy specifies the proportion of individuals in a given household-type and age-group to vaccinate and the intervention level needed to bound the expected excess of the reproduction number above one by an acceptable level of reliability (or risk). The ICC-SP model is data-driven and uses readily available data on census demographics, age-related disease susceptibility and infectivity, virus variants, and vaccine efficacy defined in three ways: vaccination in terms of effectiveness against infection, symptomatic cases, and hospitalization. This data-driven approach incorporates the decision-maker's level of risk to enable public health policy what-if analyses for future epidemics. A case study using the ICC-SP approach based on COVID-19 data was conducted, and the results of the study provide several insights. The study shows, for example, that to control disease outbreaks vaccination strategies must be combined with a specific intervention level. The proportion of the population to vaccinate to prevent epidemics depends on the criterion of vaccine efficacy used and decreases with increasing intervention level. The study also shows that optimal vaccination strategies prioritize the vaccination of specific households and age groups with high combined levels of relative susceptibility and infectivity.

Stereo-electroencephalography (sEEG) is a minimally invasive technique for intracranial monitoring that was traditionally reserved for adults but is increasingly used in very young pediatric patients with drug-resistant epilepsy. The aim of this study was to evaluate its safety, feasibility, and technical considerations in pediatric patients younger than 3 years. The authors reviewed the records of 21 children younger than 3 years who underwent sEEG monitoring at Lucile Packard Children's Hospital between February 2013 and March 2025. Data were collected from patients' clinical records and operative reports. Skull thickness was measured at the thinnest point under electrodes. Primary outcome variables were 1) sEEG-related complications, and 2) electrode placement entry point error (EPE) and target point error (TPE). Twenty-one patients (67% male) had a mean ± SE age at seizure onset of 0.5 ± 0.5 years (range birth-1.6 years). Patients underwent 23 sEEG surgeries at a mean age of 2.2 ± 0.1 years (range 0.9-2.7 years). The Mayfield headframe with the Infinity Support System was used in 65% of cases. Overall, a mean of 19 ± 1 (range 9-27) depth electrodes were placed per patient. In total, 443 electrodes were placed, most often in the frontal (189 electrodes, 43%) and temporal (121 electrodes, 27%) regions. A total of 440 bolts were used, and the most common sizes were 20 mm (68%) and 13 mm (18%); 3 electrodes were placed without bolts. The mean skull thickness at the thinnest point of electrode placement was 2.0 ± 0.1 mm (range 1.5-3.2 mm). For 417 electrodes available for analysis, the mean EPE was 1.9 ± 0.1 mm, and the mean TPE was 2.8 ± 0.1 mm. Aside from a CSF leak from a bolt in 1 patient, there were no complications. The most common procedures included open resection (61% of sEEG cases) and laser ablation (30%). Procedures were performed at a mean of 43 ± 11 days (range 0-150 days) after sEEG removal, with a mean patient age of 2.3 ± 0.1 years (range 1.2-2.9 years). This study supports the safety and feasibility of sEEG in children younger than 3 years, even in those with a skull thickness < 2 mm. Moreover, the authors report the youngest patient in the literature to have undergone sEEG at 11 months, without complications. The minimum skull thickness in which an electrode was successfully secured with a bolt was 1.5 mm. With appropriate technical adaptations, sEEG can be accurately performed in children younger than 3 years.

Introduction: Gastric-type endocervical adenocarcinoma (GTEC) is an uncommon and aggressive variant of endocervical adenocarcinoma, notable for its lack of association with human papillomavirus (HPV). It often presents late in its clinical course, leading to diagnostic challenges as it may mimic other gynecologic malignancies. Case Presentation: This case report details the clinical course of a 63-year-old female patient who presented with a 2-month history of lower abdominal pain, abdominal distention, constipation, and postcoital bleeding. These symptoms are atypical for GTEC, in which patients typically experience a mucus-like or watery vaginal discharge. A comprehensive diagnostic workup revealed elevated serum levels of cancer antigen (CA) 125 and CA 19-9. Cervical and vaginal biopsies subsequently confirmed a diagnosis of moderately differentiated adenocarcinoma, supported by immunohistochemical analysis that demonstrated strong positivity for CK7, CEA31, HIK1083, and HNF1-β, while showing negativity for p16, estrogen receptor, and p53. Despite her relatively short symptomatic clinical course, the patient exhibited signs of advanced disease, characterized by peritoneal carcinomatosis, vaginal involvement, and obstructive uropathy from pelvic mass effect. Conclusion: This patient’s atypical clinical presentation illustrates that GTEC may mimic ovarian-like tumors, resulting in misclassification and diagnostic delay and further underscoring the challenge that HPV-independent tumors such as GTEC pose to current screening strategies and diagnostic frameworks.

The medical field is evolving rapidly, with an increasing focus on technology to address complex medical issues. In the traditional clinical encounter, the physician’s role is often seen as providing one-way technical expertise. However, every patient-physician interaction is a two-way relationship with the potential for reciprocal learning. In the relational model of patient-physician relationships, the patient is more than a passive bystander but also an integral participant and a teacher from whom physicians can learn invaluable insights, such as the interplay of emotional intelligence and the healing process. These insights can add to the heart of the profession beyond purely academic pursuits. From a senior surgical resident’s point of view, we explore the question: What do physicians learn from patients during the therapeutic relationship that extends beyond our technological tools?

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and structural damage. Two primary treatment strategies-step-up therapy and early aggressive DMARD therapy have been widely debated in clinical practice. The step-up approach begins with NSAIDs or corticosteroids, progressing to DMARDs based on disease severity, whereas early aggressive therapy prioritizes immediate DMARD initiation to prevent irreversible joint damage. This comprehensive review evaluates the effectiveness of these strategies by analyzing randomized controlled trials (RCTs), meta-analyses, and cohort studies assessing treatment outcomes, remission rates, and radiographic progression. A literature search was conducted across PubMed, Scopus, and Web of Science, including studies published between 2010 and 2024. Key clinical trials, including TICORA, COBRA, BeSt, and CAMERA, were critically analyzed to assess the comparative benefits and limitations of both treatment approaches. Evidence suggests that early aggressive therapy is associated with higher remission rates, reduced radiographic progression, and improved long-term physical function, whereas the step-up approach often leads to delayed disease control and cumulative joint damage. However, concerns related to treatment adherence, cost-effectiveness, and safety profiles necessitate further investigation. Future research should focus on biomarker-driven personalized treatment strategies, optimizing drug sequencing, and long-term comparative effectiveness studies to refine RA management.

Finding the clinical significance of facial swelling was of utmost importance in this case. Ludwig angina is a life-threatening cellulitis of the floor of the mouth that is mainly due to infectious causes. This particular patient had an atypical presentation except for the facial swelling in which the patient’s non-specific symptoms made it difficult to obtain a diagnosis. Severe edema can make it difficult to intubate the patient; however, our case did not present with any common symptoms such as this. This is why it is of utmost importance to maintain dental/mouth hygiene and maintenance because of complications such as Ludwig angina. Ludwig angina is becoming more common amongst hospitals, but being able to obtain a diagnosis quickly even with atypical symptoms is of top priority for resolution.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, most often diagnosed at an advanced stage, with limited treatment options and poor outcomes. CA 19-9 is the most commonly used biomarker to support the diagnosis and for treatment monitoring of PDAC, but rising levels during treatment usually suggest disease progression. Pseudoprogression, a transient increase in tumor burden or biomarker levels followed by subsequent improvement, has been described in glioblastoma and in cancers treated with immune checkpoint inhibitors (ICIs), but to our knowledge, it has not previously been reported in pancreatic cancer treated with cytotoxic chemotherapy.We describe a 52-year-old man with metastatic PDAC who was treated with FOLFOX due to underlying cardiac comorbidities. Despite rising CA 19-9 levels from 2,344 U/mL at baseline to more than 90,000 U/mL after two months of therapy, the patient experienced clinical improvement, with resolution of abdominal pain, regained appetite, weight recovery, and enhanced performance status. Continued treatment resulted in a subsequent decline and plateau of CA 19-9 levels, consistent with biochemical pseudoprogression. This case represents a unique and previously undocumented phenomenon of pseudoprogression in PDAC under chemotherapy, underscoring the importance of integrating clinical status with biomarker interpretation to avoid premature discontinuation of effective treatment.