Recent publications
Background
Puerto Rico and U.S. Virgin Islands Veterans (PRVs) have faced recurring challenges from hurricanes, earthquakes, and the COVID-19 pandemic. These events combined with prior traumas and social determinants of health (SDoH), may contribute to neuropsychiatric mental health conditions (MHCs) like post-traumatic stress disorder (PTSD) and substance use disorder (SUD) in PRVs affected by SARS-CoV-2.
Methods
To clinically characterize the risk factors for MHCs among SARS-CoV-2 infected PRVs, we examined 839 records (2016–2020) to study SARS-CoV-2 infections and MHCs. Records were assessed for (i) PTSD and SUD using health data at diagnosis; (ii) clinical details pre-hurricanes (control; group 1), during hurricanes (group 2), and pandemic (group 3). Groups 1 and 2 were reviewed in 2020 to gauge exacerbation. Patient Health Questionnaire (PHQ-2/PHQ-9), PTSD checklist (PCL-5), Alcohol Use Disorders Identification Test (AUDIT), SDoH, and other tools were used for clinical evaluation, with the data analyzed using logistic regression.
Results
Health data indicated SARS-CoV-2 infection in 21 PRVs. Earthquakes did not affect the infected PRVs nor did SDoH have any significant impact. Clinical analysis revealed that SUD worsened during hurricanes and exacerbation of all MHCs occurred during the pandemic among SARS-CoV-2 infected PRVs.
Conclusions
These results underscore the fact that the combination of natural disasters like hurricanes and SARS-CoV-2 had synergistically contributed to the deterioration of neuropsychiatric MHCs, therefore warranting equitable MH support.
Despite research and treatment advances in health care, the implementation of research evidence into practice remains a challenge, especially for historically marginalized populations. There have been numerous calls to action to integrate health equity into implementation science frameworks, models, and theories. Yet, progress toward better integration of these approaches has been hampered by the theoretical and aspirational nature of calls to action up to the present time, which poses a challenge as it remains unclear how to specifically move from rhetoric to action. We present three case examples from our work to illustrate how to synergize health equity research and implementation science into our approach to “equity-grounded implementation science” focused on processes and practices located at the intersection of these fields. These three distinct studies focused on reducing mental health inequities in historically marginalized communities, namely, Latino and Black individuals in mainland United States and Puerto Rico. For each study, we describe the study aim, methodology, setting in which activities were carried out, the health equity elements, and the implementation science aspects. We articulate how each study bridged implementation science and health equity research by (a) situating the study activities in community settings; (b) codesigning interventions to ensure their cultural, linguistic, and contextual relevance; and (c) weaving mixed methods and community-engaged approaches to draw community insights. Finally, we illustrate how to address key implementation outcomes in these health equity studies, representing a significant step toward turning rhetoric into actionable solutions for reducing mental health inequities in marginalized communities.
The published manuscript by Taylor & Francis in The Clinical Neuropsychologist on 02.21.2025 is available at: https://doi.org/10.1080/13854046.2025.2469353
Objective: To examine neuropsychology education and training in Puerto Rico (PR) and identify areas of growth within neuropsychology curricula in graduate programs. Method: A survey was conducted among 44 psychology graduate students, 21 psychologists, and 17 neuropsychologists in PR to assess interest in neuropsychology, education and training experiences, training barriers, professional affiliations, awareness of the Houston Conference Guidelines (HCG), knowledge of competitive neuropsychology internships in the United States (US), and attitudes toward neuropsychology training in PR. Comparisons were made to evaluate PR’s alignment with the US HCG standards. Results: Participants were primarily Spanish-English bilinguals completing or with doctoral degrees in clinical psychology. While APA-approved programs in PR offer foundational neuropsychology courses, clinical training opportunities are limited, resulting in few individuals acquiring HCG competencies. Most neuropsychology training occurs in private practice settings. Barriers to HCG training standards include the scarcity of neuropsychology practicums, with students often seeking education and training outside their institutions. The top professional affiliation was with the National Academy of Neuropsychology. Strengths included the number of psychotherapy hours, while research skills and consultation need improvement. Most participants reported inadequate guidance on postdoctoral training and agreed with the recognition of clinical neuropsychology as a sub-specialty in PR, alongside the development of local training guidelines. Conclusions: PR is advancing neuropsychology for a bilingual and bicultural population, but addressing barriers in education and training is essential. Coordinated efforts among educational institutions, the government, and professionals are crucial to enhance neuropsychological practice on the island and contribute to the global neuropsychology community.
Puerto Rico faces a significant health crisis due to the mass migration of physicians to the United States, exacerbating the challenge of achieving the World Health Organisation’s recommended physician-to-population ratio. While economic factors such as higher salaries in the US have been identified as primary drivers, the complexity of this migration wave requires a deeper exploration. This study quantitatively examines the role of push factors, pull factors, and spatial stigmatisation in physician migration from Puerto Rico. Using data from a randomly selected sample of 550 physicians (255 who had migrated to the US and 295 who lived in Puerto Rico), we analyse how perceptions of Puerto Rico’s image and reputation, combined with stigmatisation linked to practicing medicine on the Island, influence migration decisions. Findings highlight that while better economic opportunities in the US are significant, the spatial stigma associated with Puerto Rico’s healthcare system plays a crucial role in the decision to migrate. Policies aimed at curbing physician migration must address not only economic incentives but also the broader socio-cultural perceptions that contribute to the stigmatisation of practicing medicine in Puerto Rico. This study provides insights to inform comprehensive policy solutions to the healthcare crisis in Puerto Rico.
Sleep disorders are characterized by impaired quality, timing, and amount of sleep, resulting in daytime distress and functioning. Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by oto-sino-pulmonary manifestations with multiple comorbidities, including sleep disorders. Background/Objectives: This pilot study aims to assess sleep disorders and neuropsychiatric comorbidities in Puerto Rican patients with the RSPH4A (c.921+3_921+6delAAGT) PCD founder mutation. However, the literature on sleep-related disorders and their neuropsychiatric comorbidities in PCD is limited. Methods: A cohort of fifteen patients with the RSPH4A (c.921+3_921+6delAAGT) founder mutation (six pediatric, nine adults) were evaluated for sleep quality, cognitive, neurodevelopmental history, and mood-related manifestations, followed by diagnostic polysomnography for sleep-disordered breathing and other sleep-related disorder detection. Results: Twelve out of fifteen (12/15, 80%) patients presented with sleep-related disorders, particularly obstructive sleep apnea where the median Pediatric AHI was 1.25/h (IQR: 1.1–1.75/h), T < 90: 0.1 min (IQR: 0–1.9 min) and adult AHI 1.3 (IQR: 0.9–8), T < 90: 0.2 min (IQR: 0–3.5 min). PCD patients also presented complex sleep behaviors, and more than half had sleep-related movement manifestations such as sleep-related Bruxism, PLMS, among others. All pediatric patients with OSA met criteria for an anxiety disorder, with a GAD-7 of 13 (IQR: 10.5–15.8); this association was not clearly seen in adults. Conclusions: Patients with PCD RSPH4A exhibited multiple sleep and neuropsychiatric manifestations, particularly OSA, sleep-related movement disorders and complex sleep behaviors. Further studies are needed to determine if these manifestations result from obstructive breathing, sleep mechanism disruption, or other neurodevelopmental impairment associated with this ciliopathy.
Lung cancer remains the most common malignancy independent of sex. Here, we focused on unraveling the molecular mechanisms of CaS nanoclusters inducing cytotoxicity by investigating DNA damage, the cell cycle, oxidative stress, and cellular repair mechanisms in non-small-cell lung carcinoma (NSCLC) cells compared to healthy lung fibroblasts. Our previous studies have demonstrated the therapeutic potential of calcium sulfide (CaS) nanostructures in skin and breast cancer models, leading to a significant reduction in cancer cell proliferation. However, how CaS nanoclusters enhance their therapeutic effects on cancer cells while minimizing damage to healthy cells remains unknown. Our results show that CaS nanoclusters, once dissociated into Ca2+ and H2S in an acidic microenvironment, selectively allow extracellular calcium to enter, leading to an increase in free calcium entry, triggering oxidative stress and limiting DNA repair mechanisms in NSCLC. Furthermore, CaS nanoclusters selectively arrest NSCLC cells in the G0-G1 and S phases of the cell cycle without affecting healthy cells’ cycles. Here, we also show that the selective effects of CaS nanoclusters on lung adenocarcinoma are less likely to be regulated by intrinsic apoptotic or mitochondrial pathways. They are, rather, caused by an increase in Ca2+ and ROS, causing double-stranded DNA breakages. This selectivity for malignant cells is pH-dependent because it occurs in the acidic microenvironment characteristic of these cells. Overall, this is the first piece of evidence that CaS disrupts genomic stability, prevents the replication of damaged cells, and ultimately influences cell fate decisions such as cell cycle arrest or cell death including mitotic catastrophe and necroptotic simultaneous events.
Background: This case report outlines the clinical workflows for immediate implant placement for both maxillary central incisors and ceramic laminate veneers for the remaining teeth in the smile zone. Methods: The patient’s chief complaint was to improve her smile and address periapical infections with purulent exudate at the apex of her central incisors. Clinical and CBCT evaluations determined that the maxillary central incisors were non-restorable, while the lateral incisors and canines showed signs of incisal wear. Atraumatic extractions were performed for the central incisors, and immediate implants were placed with a 3D-printed surgical guide in conjunction with an autogenous soft tissue grafting procedure. Once the soft tissue between the central incisors was contoured with provisional implant restorations, minimally invasive veneer preparations were performed for porcelain laminate veneers. Final restorations were bonded under dental dam isolation. Results: Single immediate implants for maxillary central incisors can be successfully paired with ceramic laminate veneers on adjacent teeth in the smile zone to replace non-restorable teeth in the esthetic zone. Conclusions: Atraumatic tooth extraction, 3D implant planning with grafting procedures, and minimally invasive ceramic veneers can help in meeting patients’ esthetic and functional expectations. Total isolation using a dental dam maximizes the bonding performance of ceramic restorations.
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Background: Patients with localized unresectable or cisplatin-ineligible urothelial cancer (UC) have limited treatment options. Biomarker identification can guide targeted therapies. In the DUART study, pre-treatment immune cell subsets were significantly linked to disease control. Our planned correlative aim was to evaluate the same biomarkers using post-adjuvant treatment (post-Rx) peripheral blood mononuclear cells (PBMCs). Methods: This was a prospective, multi-institutional study BTCRC-GU15-023. Our N=16 all had valid Post-Rx values and disease control status. Eligibility criteria: >18yrs, advanced/unresectable UC, and available tumor specimen. All received concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in a Phase II study. Blood samples were taken at pretreatment, 12 weeks, and post-Rx. Biomarkers were detected using multicolor flow cytometry-based analysis of PBMCs to detect T lymphocyte subsets and by dimensionality reduction using FlowJo. Correlative objective: Evaluate post-Rx time points for biomarkers that contribute to disease progression or response. Two-sample T-tests were used to study the association. All tests were two-sided and the statistical significance level used was 0.05. Results: Standard flow cytometry analysis revealed a statistically significant increase in ICOS+ CD4 and CD8 T cells in post-Rx samples among patients with progression-free survival at one year. In addition, responder patients (CR/PR/SD, n=12) showed a significant decrease in CD8 central memory T cells compared to progressors (PD, n=4) in post-Rx samples. Although not statistically significant, additional trends were noted, including decreased PD-1+ CD4 T cells in responder patients, decreased CD4 T effector memory RA+ (TEMRA), and increased CD4 naïve T cells in responder patients. There was a slight increase in interferon gamma-producing CD8 T cell subsets in responder patients and a significant decrease in central memory CD8 T cells. tSNE analysis revealed similar trends in the data, including increased naïve CD4 T cells in responder patients and slight increases in some cytokine-producing CD8 T cell subsets. Conclusions: Our small cohort demonstrates some significant differences in post-Rx T cell populations linked to therapy response, and further evaluation in a larger cohort of patients is needed. The identification of predictive biomarkers could help a more personalized therapeutic approach.
Background: Replacing a maxillary central incisor and immediately placing an implant represents a clinical challenge. Methods: This case report demonstrates a full digital workflow to achieve a predictable implant placement and esthetically pleasing restoration for a 35-year-old male patient who suffered a horizontal root fracture after a sports accident. The patient’s treatment included digital implant planning, minimally traumatic tooth extraction, computer-guided implant placement, soft tissue augmentation, and a provisional restoration to contour the augmented gingival tissues. The process began with cone beam computed tomography (CBCT) evaluation and patient consultation on treatment options, with the patient opting for implant therapy. Using a 3D-printed surgical guide, the implant was placed precisely, and a soft tissue graft was used to enhance the gingival architecture and volume. A provisional restoration was designed to support the emergence profile and condition the peri implant soft tissues. A final digital impression was made, and a screw-retained all-ceramic crown was fabricated uneventfully after healing. Results: This digital approach allowed accurate planning and allowed the efficient execution of a technique-sensitive procedure such as immediate implant placement, thus providing an esthetic and functional solution while minimizing treatment time. Conclusions: The case highlights that immediate implant therapy in the esthetic zone requires meticulous planning and execution, and that incorporating advanced digital tools and techniques is required to achieve favorable clinical outcomes.
In 2017, approximately 5 million Americans were living with Alzheimer’s disease (AD), and it is estimated that by 2050 this number could increase to 16 million. In this study, we apply mathematical optimization to approach microarray analysis to detect differentially expressed genes and determine the most correlated structure among their expression changes. The analysis of GSE4757 microarray dataset, which compares expression between AD neurons without neurofibrillary tangles (controls) and with neurofibrillary tangles (cases), was casted as a multiple criteria optimization (MCO) problem. Through the analysis it was possible to determine a series of Pareto efficient frontiers to find the most differentially expressed genes, which are here proposed as potential AD biomarkers. The Traveling Sales Problem (TSP) model was used to find the cyclical path of maximal correlation between the expression changes among the genes deemed important from the previous stage. This leads to a structure capable of guiding biological exploration with enhanced precision and repeatability. Ten genes were selected (FTL, GFAP, HNRNPA3, COX1, ND2, ND3, ND4, NUCKS1, RPL41, and RPS10) and their most correlated cyclic structure was found in our analyses. The biological functions of their products were found to be linked to inflammation and neurodegenerative diseases and some of them had not been reported for AD before. The TSP path connects genes coding for mitochondrial electron transfer proteins. Some of these proteins are closely related to other electron transport proteins already reported as important for AD.
Background
This study examines the long-term effectiveness and safety of the vertical expandable prosthetic titanium rib (VEPTR) device, developed in 1989 to treat early-onset scoliosis (EOS) and thoracic insufficiency syndrome (TIS). Specifically, it assesses VEPTR outcomes over 20 years in a single center, focusing on spine deformity correction, pulmonary function, weight percentile changes, and complication rates.
Methods
A retrospective analysis was conducted on 36 patients from the EOS clinic who underwent VEPTR implantation without prior spine surgery, with at least 2 years of follow-up. Data collected included age, sex, weight, height, BMI, weight percentiles, comorbidities, radiographic parameters, pulmonary function tests, and complications. Weight percentile (WP) was calculated as preoperative WP and last follow-up WP. Coronal and sagittal deformities were measured preoperatively, immediately postimplantation, and at the last follow-up. Pulmonary function tests included forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) and were correlated with weight percentile changes. Complications were classified using established criteria.
Results
The mean age at VEPTR implantation was 86±34 months, with most cases attributed to neuromuscular scoliosis (56%). The initial coronal Cobb angle improved from 59±18 to 32±14 degrees postimplantation but increased to 60±25 at the final follow-up. Sagittal angles showed similar trends. Pulmonary function tests indicated a decline in FVC and FEV1 over time. There was no correlation between weight percentile changes and pulmonary function changes. Complication rates were high, affecting 63% of patients, which included hardware prominence, device migration, and infections as the most common.
Conclusions
Although VEPTR devices initially corrected spinal deformities, their long-term benefits are limited as the correction becomes less pronounced over time. Expected improvement in pulmonary function is not observed. A different approach to treating EOS and TIS is necessary, as the significant complication rates challenge the implants’ effectiveness.
Level of evidence
Level III.
Background
Distinguishing between non-severe and severe dengue is crucial for timely intervention and reducing morbidity and mortality. World Health Organization (WHO)-recommended warning signs offer a practical approach for clinicians but have limited sensitivity and specificity. This study aims to evaluate machine learning (ML) model performance compared to WHO-recommended warning signs in predicting severe dengue among laboratory-confirmed cases in Puerto Rico.
Methods
We analyzed data from Puerto Rico’s Sentinel Enhanced Dengue Surveillance System (May 2012–August 2024), using 40 clinical, demographic, and laboratory variables. Nine ML models, including Decision Trees, K-Nearest Neighbors, Naïve Bayes, Support Vector Machines, Artificial Neural Networks, AdaBoost, CatBoost, LightGBM, and XGBoost, were trained using fivefold cross-validation and evaluated with area under the receiver operating characteristic curve (AUC-ROC), sensitivity, and specificity. A subanalysis excluded hemoconcentration and leukopenia to assess performance in resource-limited settings. An AUC-ROC value of 0.5 indicates no discriminative power, while values closer to 1.0 reflect better performance.
Results
Among the 1708 laboratory-confirmed dengue cases, 24.3% were classified as severe. Gradient boosting algorithms achieved the highest predictive performance, with an AUC-ROC of 97.1% (95% CI: 96.0–98.3%) for CatBoost using the full 40-variable feature set. Feature importance analysis identified hemoconcentration (≥ 20% increase during illness or ≥ 20% above baseline for age and sex), leukopenia (white blood cell count < 4000/mm³), and timing of presentation at 4–6 days post-symptom onset as key predictors. When excluding hemoconcentration and leukopenia, the CatBoost AUC-ROC was 96.7% (95% CI: 95.5–98.0%), demonstrating minimal reduction in performance. Individual warning signs like abdominal pain and restlessness had sensitivities of 79.0% and 64.6%, but lower specificities of 48.4% and 59.1%, respectively. Combining ≥ 3 warning signs improved specificity (80.9%) while maintaining moderate sensitivity (78.6%), resulting in an AUC-ROC of 74.0%.
Conclusions
ML models, especially gradient boosting algorithms, outperformed traditional warning signs in predicting severe dengue. Integrating these models into clinical decision-support tools could help clinicians better identify high-risk patients, guiding timely interventions like hospitalization, closer monitoring, or the administration of intravenous fluids. The subanalysis excluding hemoconcentration confirmed the models’ applicability in resource-limited settings, where access to laboratory data may be limited.
Graphical Abstract
Supplementary Information
The online version contains supplementary material available at 10.1186/s40249-025-01273-0.
Background: In the 6 months following Hurricane Maria the number of people who died from the hurricane was much higher than was initially estimated from death certificates. Disruption of health care services and displacement led to the exacerbation of pre-existing chronic diseases. The objectives of this study were to (1) estimate the excess deaths in Puerto Rico in the 6 months following Maria, (2) identify geographical areas experiencing higher risk of chronic disease mortality following Maria and (3) identify community-level vulnerability characteristics associated with some communities being at higher risk of increased chronic disease mortality after Maria. Methods: Death records were obtained from Puerto Rico’s Department of Health Demographic Registry. Mortality risks per 100 000 were calculated for chronic disease categories and all-cause mortality for the 6 months following Maria and the same months in the year before. Geospatial analysis using Getis–Ord Gi* Statistic was used to determine if mortality clusters of 6 month mortality risk following hurricane Maria by census tract were statistically significant. Multinomial logistic regression was used to model the association between census tract level social vulnerability and being classified as higher or sustained risk of mortality in the 6 months following Hurricane Maria compared to the previous year’s mortality risk. Odds ratios and 95% confidence intervals were estimated to measure associations between social vulnerability and mortality risk. Results: In the 6 months following Maria there were increases in mortality risk for cardiovascular disease, Alzheimer’s, diabetes, sepsis, chronic respiratory disease, hypertension and all-cause mortality. Examining community level characteristics associated with vulnerability to disasters, neighborhoods with higher proportion of people 65 and older, higher proportion of houses being multiunit structures and higher proportion of households with no vehicle, in comparison to other neighborhoods in Puerto Rico,were more likely to have sustained high risk for mortality before and after Maria or increased risk of being a hot spot for chronic disease mortality after Maria.
The mechanisms underlying the pathophysiology of endometriosis, characterized by the presence of endometrium-like tissue outside the uterus, remain poorly understood. This study aimed to identify cell type-specific gene expression changes in superficial peritoneal endometriotic lesions and elucidate the crosstalk among the stroma, epithelium, and macrophages compared to patient-matched eutopic endometrium. Surprisingly, comparison between lesions and eutopic endometrium revealed transcriptional similarities, indicating minimal alterations in the sub-epithelial stroma and epithelium of lesions. Spatial transcriptomics highlighted increased signaling between the lesion epithelium and macrophages, emphasizing the role of the epithelium in driving lesion inflammation. We propose that the superficial endometriotic lesion epithelium orchestrates inflammatory signaling and promotes a pro-repair phenotype in macrophages, providing a new role for complement 3 in lesion pathobiology. This study underscores the significance of considering spatial context and cellular interactions in uncovering mechanisms governing disease in endometriotic lesions.
Case
An active healthy 68-year-old male sustained a bilateral quadriceps tendon rupture while running. He underwent a simultaneous bilateral quadriceps tendon repair in a dual-surgeon approach. The right quadriceps tendon was repaired with a tourniquet, while the left quadriceps tendon tear was repaired without one. Postoperatively, the patient developed deep vein thrombosis in the right leg, which led to a bilateral pulmonary embolism. This case illustrates a potential complication of tourniquet use in patients undergoing quadriceps tendon repairs.
Conclusion
The use of tourniquets in orthopaedic surgeries may be associated with potential risks, such as development of venous thromboembolism including deep vein thrombosis and pulmonary embolism. This case highlights the importance of carefully considering tourniquet use for quadriceps tendon repairs and close postoperative monitoring, early mobility, and thromboprophylaxis to prevent severe complications.
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