University of Puerto Rico at Bayamón

Background Dissecting intracranial aneurysms (DIAs) have been treated through endovascular reconstructive manners, such as flow diverters (FDs) and stent-assisted coiling (SAC). Notably, no robust evidence has compared both approaches. Hence, the authors conducted a meta-analysis to compare their outcomes. Methods PubMed, Embase and Web of Science were searched for studies employing SAC and FD treatment for DIAs. The following outcomes were considered for extraction: procedure-related mortality, total mortality, postoperative and follow-up complete aneurysm occlusion, complications, good clinical outcomes, recurrence, and retreatment. Odds ratio (OR) with random effects was employed for statistical comparison. Results The meta-analysis included 10 studies. A total of 195 and 222 patients were included in the FD and the SAC group, respectively. Stent-assisted coiling had higher postoperative complete aneurysm occlusion rates (OR 0.03; 95% CI 0.01–0.08). Flow diverter retreatment rate was lower, but without statistical significance (OR 0.35; 95% CI 0.11–1.10). No significant differences were found in follow-up complete aneurysm occlusion (OR 1.18; 95% CI 0.35–3.99); total mortality (OR 0.44; 95% CI 0.09–2.08); intraoperative complications (OR 0.30; 95% CI 0.06–1.45); postoperative complication (OR 0.77; 95% CI 0.35–1.70); good clinical outcomes (OR 0.97; 95% CI 0.43–2.20); and recurrence (OR 0.38; 95% CI 0.13–1.10) between the two groups. Conclusion Stent-assisted coiling shows higher postoperative complete aneurysmal occlusion rates, but both techniques achieve similar rates in angiographic follow-up. Flow diverter has lower, but not statistically significant, retreatment rates than SAC. Both techniques have similar complication rates. Future randomized, multicenter, and prospective studies with larger sample sizes are needed for more conclusive findings.

Background Understanding the dynamics of the gut microbiota in sea urchins is crucial for comprehending the ecological balance in marine ecosystems. The gut microbiota plays a vital role in nutrient metabolism, immune system modulation, and pathogen protection. The microbial composition and dynamics of naturally occurring sea urchin Tripneustes ventricosus have yet to be thoroughly investigated. We hypothesized the gut microbiota of T. ventricosus in the Caribbean, varies across life stages and seasons. Methods Thirty-six naturally occurring large individuals and six small individuals (42 animals) were collected from shallow waters on the northeastern coast of Puerto Rico in February and August of 2019. The fecal pellet’s microbiota was characterized by sequencing V4 region of the 16S rRNA gene. Results We found significant differences in the composition of fecal pellet microbiota between seasons and life stages. Phylum Bacteroidota had greater relative abundance in August, while Firmicutes was more dominant in February. Propionigenium and Roseimarinus had greater relative abundance in August, while Candidatus Hepatoplasma, and Kistimonas had greater relative abundance in February. Differences in the gut digest microbiota were not found between small and large urchins, but small urchins displayed a slightly higher diversity and dominance of Bacteroidota and Proteobacteria, while large urchins exhibited a greater relative abundance of Fusobacteria and Desulfobacterota. However, the genera Ferrominas and Propionigenium counts were significantly lower in small individuals. Discussion This is the first report for this species in the Caribbean region and adds to our comprehension of the microbiota of the white sea urchin across collection periods and size classes, highlighting the dynamic nature of the gut microbiota.

The vertebral column plays a central role in primate locomotion and positional behavior. Understanding its evolution, therefore, has the potential to clarify evolutionary processes that have occurred in the primate lineage as well as the specific behaviors of extinct primates. However, to understand primate vertebral anatomy, it is important to determine how much of this anatomy is heritable and how much develops as a response to environmental factors during life. We estimated heritability for vertebral counts as well as typical cervical, thoracic, and lumbar elements from 210 individuals from the pedigreed Cayo Santiago Macaca mulatta skeletal collection. We found moderate heritability of vertebral counts ( h ² = 0.216–0.326), but with strong heritability of the type of variation (e.g., a tendency to meristic or homeotic change) in the vertebral count ( h ² = 0.599), suggesting a possible explanation for high variability in vertebral numbers among the hominoids in particular. The moderate heritability of vertebral count also suggests that vertebral count is an unsuitable metric for estimating the ancestral state for some taxa. We found strong heritability in the morphology of cervical and upper lumbar zygapophyseal facets ( h ² = 0.548–0.550) and the thoracic spinous processes ( h ² = 0.609–0.761), including high heritability of the spinous process angle in the upper thoracic and upper lumbar elements ( h ² = 0.649–0.752). We suggest these are related to maintaining stability in the cervical and lumbar regions, and reducing motion in the thoracic region, respectively. We propose that spinous processes may contain greater phylogenetic information, whereas transverse processes may contain greater information of function ‘in life’. We also found important size effects, suggesting that size is the most heritable component of overall form and largely responsible for intertrait differences. This suggests that it is inappropriate to indiscriminately remove size effects from morphological comparisons.

Introduction In recent decades, Caribbean coral reefs have lost many vital marine species due to diseases. The well-documented mass mortality event of the long-spined black sea urchin Diadema antillarum in the early 1980s stands out among these collapses. This die-off killed over 90% of D. antillarum changing the reefscape from coral to algal-dominated. Nearly 40 years later, D. antillarum populations have yet to recover. In early 2022, a new mortality event of D. antillarum was reported along the Caribbean, including Puerto Rico. Methods This study identifies the gut microbiota changes associated with the D. antillarum during this mortality event. It contrasts them with the bacterial composition of gut samples from healthy individuals collected in 2019 by using 16S rRNA sequencing analyses. Results Notably, the die-off group’s core microbiome resembled bacteria commonly found in the human skin and gut, suggesting potential anthropogenic contamination and wastewater pollution as contributing factors to the 2022 dysbiosis. The animals collected in 2022, especially those with signs of disease, lacked keystone taxa normally found in Diadema including Photobacterium and Propionigenium. Discussion The association between human microbes and disease stages in the long-spined urchin D. antillarum, especially in relation to anthropogenic contamination, highlights a complex interplay between environmental stressors and marine health. While these microbes might not be the direct cause of death in this species of sea urchins, their presence and proliferation can indicate underlying issues, such as immune depletion due to pollution, habitat destruction, or climate change, that ultimately compromise the health of these marine organisms.

In pediatrics, medications are dosed specifically to the weight or body surface area of the growing child. These calculations are imperative to therapeutic dosing and prevention of adverse drug reactions. Dehydration is a common issue in children and similar to medications, fluids require weight-based calculations. There are four phases of rehydration—resuscitative, titration, maintenance, and convalescent. Fluid management takes into account the appropriate fluid rate during each rehydration phase, the estimated degree of dehydration and the desired fluid electrolyte composition. This chapter provides a step-by-step guide that simplifies the basics of medications and fluids for pediatric patients. Calculation examples are included for routine dosing of common medications and fluid management.

Importance Faculty diversity in academic medicine may better prepare the next generation of equity-minded health care practitioners and leaders. Prefaculty development is an emerging concept to support trainees in achieving key knowledge, skills, and experiences to become successful faculty. Objective To outline competencies, with corresponding milestones, to support the academic career development of learners, inclusive of racial, ethnic, sexual, and gender identities minoritized in medicine. Design, Setting, and Participants Using a modified Delphi process, a national working group consisting of 13 members was established. The group used the published literature and listening sessions with diverse stakeholders to draft a set of competencies and milestones in July 2022. Diverse expert panelists reviewed the draft set over 2 rounds between September 2022 and January 2023. The group considered qualitative data to further refine the draft set between rounds. Consensus was reached when competencies and milestones were rated as agree or strongly agree on importance or appropriateness by 75% or greater of expert panelists after the second round. A final set of competencies and milestones was generated in February 2023. Data from round 1 were analyzed in October 2022 and data from round 2 were analyzed in January 2023. Main Outcomes and Measures The development of prefaculty competencies with corresponding milestones by expert panel rankings and comments. Results The national working group consisted of 13 members who represented diversity across racial, ethnic, and gender identities and academic and career tracks. The working group developed an initial set of 36 competencies and corresponding milestones across 12 domains. After 2 rounds, consensus among 46 expert panelists generated a final list of 32 competencies with corresponding milestones across 11 domains. A total of 26 panelists (56.5%) were women, 11 (23.9%) were Black or African American, 17 (37.0%) were Latina/o/x/e, Hispanic, or of Spanish origin, and 10 (21.7%) were White. Competency domains were divided into 2 groups: foundational (academic career choice and professional identity, mentorship, networking, financial skills, diversity and inclusion, personal effectiveness and self-efficacy, and leadership) and focused (education, community engagement, research, and clinical medicine). Consensus for inclusion or elimination of items was greater than 90% between the 2 rounds. Conclusions and Relevance There was consensus among the working group and expert panelists regarding the importance and appropriateness of the competencies and milestones for diverse trainees to successfully obtain faculty positions. Institutions and national organizations can use these competencies as a framework to develop curricula that support diverse learners’ career development toward academia.

Public health concerns about recent viral epidemics have motivated researchers to seek novel ways to understand pathogen infection in native, wildlife hosts. With its deep history of tools and perspectives for understanding the abundance and distribution of organisms, ecology can shed new light on viral infection dynamics. However, datasets allowing deep explorations of viral communities from an ecological perspective are lacking. We sampled 1086 bats from two, adjacent Puerto Rican caves and tested them for infection by herpesviruses, resulting in 3131 short, viral sequences. Using percent identity of nucleotides and a machine learning algorithm (affinity propagation), we categorized herpesviruses into 43 operational taxonomic units (OTUs) to be used in place of species in subsequent ecological analyses. Herpesvirus metacommunities demonstrated long‐tailed rank frequency distributions at all analyzed levels of host organization (i.e., individual, population, and community). Although 13 herpesvirus OTUs were detected in more than one host species, OTUs generally exhibited host specificity by infecting a single core host species at a significantly higher prevalence than in all satellite species combined. We describe the natural history of herpesvirus metacommunities in Puerto Rican bats and suggest that viruses follow the general law that communities comprise few common and many rare species. To guide future efforts in the field of viral ecology, hypotheses are presented regarding mechanisms that contribute to these patterns.

The adolescent population with Down syndrome (DS) appears to show higher levels of body fat and lower levels of cardiorespiratory fitness or muscle strength than their peers without disabilities. There is a need to create physical activity programs to improve these data. The aim of this research was to determine the effects of a 16-week swimming program, strength program, and combined program (swimming and strength training) on body composition and health-related physical fitness on adolescents with DS and to assess whether there are differences in the results of the different training programs. Forty-five adolescents (17 female and 28 male; average age 15.5 [1.53] years) with DS were recruited and randomized to three groups (swim [ n = 15], strength [ n = 15], and combined [ n = 15]). Results showed that the swim group had significant improvements in all health-related physical fitness variables and there was an improvement in some body-composition variables ( p < .05). The strength and combined groups obtained minor improvements in the variables analyzed. In summary, a 16-week swim program consisting of three sessions of 60 min is able to improve levels of body composition and health-related physical fitness in adolescents with DS. The swim training program seems to be more effective in improving body composition and health-related physical fitness than the strength or combined program. These findings could be useful in different special-education centers due to the predisposition shown by the population with DS to this sport modality.

Wind energy production is growing rapidly worldwide in an effort to reduce greenhouse gas emissions. However, wind energy production is not environmentally neutral. Negative impacts on volant animals, such as bats, include fatalities at turbines and habitat loss due to land-use change and displacement. Siting turbines away from ecologically sensitive areas and implementing measures to reduce fatalities are critical to protecting bat populations. Restricting turbine operations during periods of high bat activity is the most effective form of mitigation currently available to reduce fatalities. Compensating for habitat loss and offsetting mortality are not often practiced, because meaningful offsets are lacking. Legal frameworks to prevent or mitigate the negative impacts of wind energy on bats are absent in most countries, especially in emerging markets. Therefore, governments and lending institutions are key in reconciling wind energy production with biodiversity goals by requiring sufficient environmental standards for wind energy projects.

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R‐cembranoid (4R) is a natural compound that inhibits hippocampal pro‐inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild‐type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase‐1, thrombospondin‐1 (THBS1), glial cell‐derived neurotrophic factor (GDNF), and orosomucoid‐2 (ORM2) by western blot. iNOS and arginase‐1 are widely used protein markers of pro‐ and anti‐inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro‐inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro‐inflammatory protein iNOS while increasing arginase‐1 expression, supporting its anti‐inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS‐induced neuroinflammation in mice.

Research has identified the large conductance voltage- and calcium-activated potassium channel (BK) as a key regulator of neuronal excitability genetically associated to behavioral alcohol tolerance. Sensitivity to ethanol at the molecular level is characterized by acute potentiation of channel activity. BK isoforms show variations in alcohol sensitivity and are differentially distributed on the plasma membrane surface in response to prolonged exposure. MicroRNA (MiRNA) targeting of alcohol-sensitive isoforms coupled with active internalization of BK channels in response to ethanol are believed to be key in establishing homeostatic adaptations that produce persistent changes within the plasma membrane of neurons. In fact, microRNA 9 (miR-9) upregulated expression is a key event in persistent alcohol tolerance mediating acute EtOH desensitization of BK channels. The exact nature of these interactions remains a current topic of discussion. To further study the effects of miR-9 on the expression and distribution of BK channel isoforms we designed an experimental model by transfecting human BK channel isoforms ZERO heterologous constructs in human embryonic kidney cells 293 (HEK293) cells respectively expressing 2.1 (miR-9 responsive), 2.2 (unresponsive) and control (no sequence) 3’untranslated region (3’UTR) miRNA recognition sites. We used imaging techniques to characterize the stably transfected monoclonal cell lines, and electrophysiology to validate channel activity. Finally, we used immunocytochemistry to validate isoform responsiveness to miR-9. Our findings suggest the cell lines were successfully transfected to express either the 2.1 or 2.2 version of ZERO. Patch clamp recordings confirm that these channels retain their functionality and immunohistochemistry shows differential responses to miR-9, making these cells viable for use in future alcohol dependence studies.

4R is a tobacco cembranoid that binds to and modulates cholinergic receptors and exhibits neuroprotective and anti-inflammatory activity. Given the established function of the cholinergic system in pain and inflammation, we propose that 4R is also analgesic. Here, we tested the hypothesis that systemic 4R treatment decreases pain-related behaviors and peripheral inflammation via modulation of the alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in a mouse model of inflammatory pain. We elicited inflammation by injecting Complete Freund’s Adjuvant (CFA) into the hind paw of male and female mice. We then assessed inflammation-induced hypersensitivity to cold, heat, and tactile stimulation using the Acetone, Hargreaves, and von Frey tests, respectively, before and at different time points (2.5 h – 8d) after a single systemic 4R (or vehicle) administration. We evaluated the contribution of α7 nAChRs 4R-mediated analgesia by pre-treating mice with a selective antagonist of α7 nAChRs followed by 4R (or vehicle) administration prior to behavioral tests. We assessed CFA-induced paw edema and inflammation by measuring paw thickness and quantifying immune cell infiltration in the injected hind paw using hematoxylin and eosin staining. Lastly, we performed immunohistochemical and flow cytometric analyses of paw skin in α7 nAChR-cre::Ai9 mice to measure the expression of α7 nAChRs on immune subsets. Our experiments show that systemic administration of 4R decreases inflammation-induced peripheral hypersensitivity in male and female mice and inflammation-induced paw edema in male but not female mice. Notably, 4R-mediated analgesia and anti-inflammatory effects lasted up to 8d after a single systemic administration on day 1. Pretreatment with an α7 nAChR-selective antagonist prevented 4R-mediated analgesia and anti-inflammatory effects, demonstrating that 4R effects are via modulation of α7 nAChRs. We further show that a subset of immune cells in the hind paw expresses α7 nAChRs. However, the number of α7 nAChR-expressing immune cells is unaltered by CFA or 4R treatment, suggesting that 4R effects are independent of α7 nAChR-expressing immune cells. Together, our findings identify a novel function of the 4R tobacco cembranoid as an analgesic agent in both male and female mice that reduces peripheral inflammation in a sex-dependent manner, further supporting the pharmacological targeting of the cholinergic system for pain treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12950-023-00373-8.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed after the localized tumor has metastasized, which decreases its survival rate to a grim 3%. Mortality from PDAC is also increasing in Puerto Rico with lower survival rates than in the US. Therefore, it is pivotal to identify viable targets for the late stages of PDAC. The small GTPase Ras is the most mutated oncogene in PDAC. Oncogenic Ras, as well as multiple oncogenic cell surface receptors, activate the related GTPases Rac and Cdc42, which in turn activate p21-activated kinase (PAK) by autophosphorylation (p-PAK), to drive cancer cell invasion, and thus metastasis. Rac and Cdc42 are overexpressed in 21% of PDAC patients and contribute to poor prognosis. To determine the feasibility of treating PDAC with Rac/Cdc42 inhibitors that we are developing, this study aims to identify the p-PAK levels and Rac/Cdc42 expression in PDAC tissue from Puerto Rican patients. The hypothesis is that p-PAK levels, as well as Rac/Cdc42 expression, are selectively elevated in high-grade invasive PDAC. Immunohistochemistry for p-PAK and immunofluorescence for Rac/Cdc42 were conducted in fixed, paraffin-embedded PDAC biopsy samples of Puerto Rican patients. Preliminary results demonstrate that higher p-PAK levels are correlated with stage 3 and stage 4 tissue, and Rac and Cdc42 are expressed in ductal regions of PDAC tissue. Taken together, p-PAK has potential as a diagnostic biomarker for high-grade PDAC and will aid patient stratification in the planned clinical trials for our lead Rac/Cdc42 inhibitor, MBQ-167. Citation Format: Anamaris Torres-Sanchez, Jahdiel Berrios-Rodriguez, Jerry Cruz-Rodriguez, Jasmin Contreras-Santini, Victor Carlo, Suranganie Dharmawardhane. Expression and activity of Rac, Cdc42, and their downstream effector PAK in Puerto Rican pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A007.

Objective This single-centre, retrospective cohort study was conducted to investigate the predictors of early peritoneal dialysis initiation in newborns and young infants undergoing cardiac surgery. Methods There were fifty-seven newborns and young infants. All subjects received peritoneal dialysis catheter after completion of the cardiopulmonary bypass. Worsening post-operative (post-op) positive fluid balance and oliguria (<1 ml/kg/hour) despite furosemide were the clinical indications to start early peritoneal dialysis (peritoneal dialysis +). Demographic, clinical, and laboratory data were collected from the pre-operative, intra-operative, and immediately post-operative periods. Results Baseline demographic data were indifferent except that peritoneal dialysis + group had more newborns. Pre-operative serum creatinine was higher for peritoneal dialysis + group (p = 0.025). Peritoneal dialysis + group had longer cardiopulmonary bypass time (p = 0.044), longer aorta cross-clamp time (p = 0.044), and less urine output during post-op 24 hours (p = 0.008). In the univariate logistic regression model, pre-op serum creatinine was significantly associated with higher odds of being in peritoneal dialysis + (p = 0.021) and post-op systolic blood pressure (p = 0.018) and post-op mean arterial pressure (p=0.001) were significantly associated with reduced odds of being in peritoneal dialysis + (p = 0.018 and p = 0.001, respectively). Post-op mean arterial pressure showed a statistically significant association adjusted odds ratio = 0.89, 95% confidence interval [0.81, 0.96], p = 0.004) with peritoneal dialysis + in multivariate analysis after adjusting for age at surgery. Conclusions In our single-centre cohort, pre-op serum creatinine, post-op systolic blood pressure, and mean arterial pressure demonstrated statistically significant association with peritoneal dialysis +. This finding may help to better risk stratify newborns and young infants for early peritoneal dialysis start following cardiac surgery.

Case Given the rare incidence of sternal nonunion after traumatic injury, literature describing the management of posttraumatic sternal reconstruction is limited. We present a case of a 54-year-old man with a history of traumatic chest wall injury with multiple unsuccessful attempts at sternal repair who presented with chronic sternal nonunion and persistent bone defect. Sternal reconstruction using a vascularized double-barrel free fibula flap with rigid fixation in multiple planes was performed, with confirmed bony union at 6 months. Conclusion This novel approach to sternal nonunion management allowed effective bridging of posttraumatic sternal bone defects while facilitating osseous integration and long-term stabilization.

Background Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is a rare autosomal recessive disorder affecting the formation of the spine, characterized by a complete bilateral fusion of the ribs at the costovertebral junction, producing a “crablike” appearance of the thorax. Despite being declared a core indication for a V-osteotomy vertical expandable prosthetic titanium rib (VEPTR) expansion thoracoplasty of the posterior thorax, the natural history of STD in untreated subjects remains poorly documented. In this study, we report radiographic and pulmonary function findings and Patient-Reported Outcomes Measurement Information System (PROMIS) and 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24) scores for untreated adult subjects with STD to gain insights into the natural history. Methods We identified 11 skeletally mature, untreated subjects with STD. Findings on medical evaluation, demographics, radiographic parameters, pulmonary function, genetic testing results, PROMIS measures, and EOSQ-24 scores were assessed. Results Five male and 6 female subjects (mean age, 32.3 years [range, 15 to 70 years]) with a confirmed STD diagnosis based on radiographs and genetic testing were evaluated. Mean body mass index (BMI) was 24.4 kg/m ² (range, 18 to 38.9 kg/m ² ), and mean thoracic height was 16 cm (range, 12 to 17 cm). Pulmonary function tests (PFTs) showed a mean forced vital capacity (FVC) of 22% of predicted, mean forced expiratory volume in 1 second (FEV1) of 24% of predicted, and FEV1/FVC ratio of 107% of predicted. The mean PROMIS dyspnea score was 40 ± 8 points (range, 27.7 to 52.1 points). The mean total EOSQ-24 score was 77.3 ± 18 points (range, 43.9 to 93.2 points). Conclusions Our study characterizes the natural history of STD in untreated subjects. We confirmed the expected restrictive pattern in pulmonary function, but interestingly, our subjects exhibited better EOSQ scores compared with those reported in neuromuscular populations. PFT results and thoracic height did not correspond to PROMIS and EOSQ scores, questioning the use of those parameters as a surgical indication. We therefore suggest that the STD diagnosis as an absolute indication for VEPTR expansion thoracoplasty surgery be reconsidered. Level of Evidence Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.