DigitalCommons@The Texas Medical Center
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Multi-omics to Study Chronic Respiratory Diseases and Viral Infections
No full textIntegrating omics layers reveals complex biological systems, unveiling vital insights into chronic respiratory diseases and COVID-19. This holistic approach is crucial for developing more effective treatments and understanding intricate relationships. https://bit.ly/3VKFzJ
RNAi-Based Screen for Pigmentation in Drosophila melanogaster Reveals Regulators of Brain Dopamine and Sleep
No full textThe dopaminergic system has a large role in behavior and neurological disease, and understanding dopamine level regulation in vivo is critical. To identify dopamine regulators, we utilized Drosophila melanogaster cuticle pigmentation, where dopamine is a precursor to melanin. We measured dopamine from known pigmentation mutants (e.g., tan, ebony, black) and performed an RNAi-based screen to identify additional regulators. We found 153 hits, enriched for developmental signaling pathways and mitochondria-associated proteins. From 35 prioritized candidates, 11 affected head dopamine levels. Effects on brain dopamine were mild, even knocking down the rate-limiting synthesis enzyme Tyrosine hydroxylase (TH), suggesting dopamine levels are tightly regulated in the nervous system. We pursued two hits that reduced brain dopamine levels, clueless and mask. Further examination suggests that the mask regulates the transcription of TH and affects dopamine-dependent sleep. In summary, studying genes that affect cuticle pigmentation helped to identify genes that alter dopamine metabolism and a behavioral regulator
The Impact of Structured Family Meetings in the Intensive Care Unit
No full textThe Impact of Structured Family Meetings in the Intensive Care Unit (ICU)
Purpose
Train providers at an academic institution in a large metropolitan area to conduct family meetings using a structured approach and evaluate this intervention\u27s impact on family satisfaction with communication in the ICU.
Background
Inadequate communication between families and healthcare teams leads to lower family satisfaction, heightened feelings of guilt, and diminished capacity for making clinical decisions.
Methodology
VitalTalk training was utilized to improve providers’ communication skills. Structured family meetings were conducted for Surgical and Thoracic ICU patients with an ICU length of stay of \u3e 5 days or a predicted mortality rate over 25% within 5 days of ICU admission, and then every 5-7 days afterward. Patients’ families completed a survey on their satisfaction with communication using part 2 of the FS-ICU 24 survey. Baseline scores were gathered from the Medical and Neurological ICUs.
Results
Ten questions, using a 5-point Likert scale plus one open-ended question, addressed family satisfaction with communication. Based on the Mann-Whitney U test, the post-intervention (n=101) scores were higher than baseline (n=85) for 9 of 10 questions, with statistical significance and a 9.8% mean improvement in family satisfaction. Quantitative and qualitative data revealed a significant convergence in family perceptions post-intervention, with several complementary themes.
Implications
Training providers to conduct “Structured Family Meetings” in the ICU increases family satisfaction with decision-making regarding caring for their critically ill loved one
Brain Death Versus Circulatory Death: How Functional Warm Ischemia and Cold Storage Impact Myocardial Membrane Repair in Human Donor Hearts
No full textThis study compares myocardial injury responses in human donor hearts from donation after brain death (DBD) and donation after circulatory death (DCD), with a focus on myocardial membrane integrity, pyroptosis, and damage. Unlike DCD hearts, which are exposed to varying durations of functional warm ischemic time (fWIT), DBD hearts, which are never subjected to warm ischemia, served as controls. A total of 24 human hearts were procured, consisting of 6 from the DBD group and 18 from the DCD group. All procured hearts were placed in cold normal saline and stored for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h to assess plasma membrane repair proteins (Annexin A1 and Dysferlin), pyroptosis markers [NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, and N-terminal fragment of gasdermin D (GSDMD-NT)], and to evaluate edema and injury scores. Data suggest that DBD hearts maintained stable levels of plasma membrane repair proteins and showed no evidence of pyroptosis activation or significant injury throughout cold storage. In contrast, DCD hearts exhibited profound Annexin A1 depletion, early and progressive pyroptosis, elevated edema, and worsening histopathological injury, directly correlated with fWITs. These findings underscore that warm ischemia is a critical determinant of pyroptotic damage in donor hearts, and highlight the relative resistance of DBD hearts to such injury during preservation. For DCD hearts, strategies to enhance membrane repair capacity and inhibit pyroptosis during the fWIT phase should be the focus to maintain donor heart quality and suitability for transplantation
Real-time Hemodynamic Deterioration Following Polymorphic Ventricular Tachycardia in a Patient with Preexisting AICD Implanted with LVAD
No full textVentricular arrhythmias (VAs) are common in patients with a left ventricular assist device (LVAD), but the literature remains inconclusive regarding the benefits of an automatic implantable cardioverter-defibrillator (AICD) in this population, especially in those with a preexisting device before LVAD implantation. Here, we report the acute hemodynamic consequences of polymorphic ventricular tachycardia in a patient with a preexisting biventricular AICD who was implanted with an LVAD (HeartMate 3). This case underscores the importance of considering AICD placement on a case-by-case basis and highlights the need for a well-designed study to establish its benefit in this population
Cerebellar Deep Brain Stimulation Rescues Purkinje Cell Mitochondrial Density in a Genetic Mouse Model of Cerebellar Ataxia
No full textDeep brain stimulation (DBS) improves motor function in a growing list of movement diseases including Parkinson\u27s disease, dystonia, and tremor. There is evidence that DBS may also be effective in ataxia. It is not known why DBS is effective, but modulating cell activity and conferring neuroprotection are hypothesized to underlie its benefits. Understanding the effects of DBS on neurons is paramount to extending its clinical use in the treatment of various motor and non-motor diseases. Here, we stimulated the cerebellum of Car8 waddles (Car8wdl) mice, given the cerebellum\u27s important role in ataxia pathophysiology. Using transmission electron microscopy, we tested the effects of therapeutic neuromodulation on Purkinje cell subcellular structures, including the mitochondria and their proximity to the endoplasmic reticulum (ER). In the absence of stimulation, we found increased putative mitochondria-ER contacts in Car8wdl Purkinje cells as well as mitochondrial size and density alterations. Low-frequency cerebellar DBS rescued mitochondrial density, but not size or putative contacts in Car8wdl Purkinje cells. Although increased mitochondrial density and sustained ER contact are specific to DBS treatment, they do not determine efficaciousness. These data uncover a mode of intracellular plasticity in Purkinje cells after stimulation, enhancing our mechanistic understanding of DBS for cerebellar disorders
The Impact of Indigenous American-Like Ancestry on the Risk of Acute Lymphoblastic Leukemia in Hispanic/Latino Children
No full textAcute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for non-genetic correlates of ancestry. Contrary to previous findings, we found that global IA-like ancestry was not significantly associated with ALL risk after adjusting for socioeconomic indicators. However, locally at known ALL risk regions, we uncovered that increasing copies of the IA-like haplotype were positively and significantly associated with ALL risk (e.g., the IA-like haplotype had ∼1.33 times the odds of harboring the risk allele compared to non-IA-like haplotypes), but we found no evidence of interaction between genotype and ancestry in relation to ALL. Admixture mapping identified replicable association signals at chr7p12.2 and chr10q21.2, consistent with the benefit of leveraging genetic ancestry in identifying genetic risk loci. Our results suggest that increased risk of ALL in Hispanic/Latino children may be conferred by the higher frequency of risk alleles within IA-like ancestry and that local ancestry-based analyses are robust strategies to elucidate genetic etiology of disease
Purpuric Pityriasis Rosea in a 7-Year-Old Girl: A Rare Variant With Generalized Involvement
No full textA 7-year-old girl presented with a 10-day history of generalized purpura and petechiae. The eruption began with a solitary violaceous macule on the trunk and progressed within 1 week to multiple oval and round dark-red to violaceous purpuric macules, ecchymoses, and petechiae affecting the face, trunk, and extremities. Lesions were distributed parallel to skin cleavage lines with a characteristic “Christmas-tree” pattern on the back (Fig 1). No oropharyngeal lesions were noted on examination, and the patient denied sore throat or oral discomfort. She reported no pruritus, pain, fever, or systemic symptoms