Disposition, outcomes, and lengths of stay due to bupropion overdose at a tertiary care center with a medical toxicology service.

INTRODUCTION: Bupropion is an antidepressant with unique mechanisms of action leading to a narrow therapeutic window. Parallel to increasing indications, there is an increasing number of overdoses and fatalities attributable to bupropion overdose. Due to the serious effects of a bupropion overdose including arrhythmias and early or delayed seizures, these patients necessitate prolonged monitoring with high levels of medical care. In the setting of a tertiary care center with a medical toxicology consult service, our institution is heavily relied upon to manage these patients. This study was performed to provide clarity on the resources used, lengths-of-stay, and treatments provided for these patients. METHODS: All patients at a tertiary care center with an oral bupropion overdose and a medical toxicology consult less than 24 h after the ingestion were included between July 15, 2017 and October 14, 2021. Chart review was performed to determine lengths-of-stay, the unit of disposition, treatments provided, and outcomes. RESULTS: A total of 73 cases were identified with 36 bupropion-only ingestions. Most cases were transferred from outside facilities, developed seizures, had QRS prolongation; and almost a third required intubation. The vast majority were admitted to an ICU and received GABA-A agonists. A median of 1.47 days per case was spent in the ED or ICU. There was an average of 41.9 ED or ICU bed-days per year and 68.5 non-psychiatric bed-days per year occupied by a patient after a bupropion overdose at a single center. CONCLUSIONS: Bupropion overdose necessitates high resource utilization which we believe will increase with the expanding indications for its use.

Flecainide poisoning and prolongation of elimination due to alkalinization.

BACKGROUND: Flecainide is a 1C antidysrhythmic that is primarily used for ventricular tachycardia or premature ventricular contractions when other treatment is ineffective. It has a very narrow therapeutic window which may cause death in a double dose and requires inpatient initiation for cardiac monitoring. Despite established pharmacokinetic data from flecainide in therapeutic dosing, there is negligible data on flecainide toxicokinetics after an intentional overdose. Due to the inherent differences in pharmacokinetic and toxicokinetic principles, rarely can the peak effect or elimination half-life accurately be applied to the poisoned patient after an overdose. In overdose, flecainide can cause a variety of fatal dysrhythmias which may require sodium bicarbonate for stabilization but also may reduce the renal elimination of flecainide, meaning the life-saving treatment may prolong the time of toxicity. CASE REPORT: We present a case of an acute ingestion of flecainide with a known time of ingestion and known amount of ingestion who experienced subsequent life-threatening effects which required endotracheal intubation, sodium bicarbonate, aggressive electrolyte repletion, and multiple days in an intensive care unit. RESULTS: Serial serum and urine samples revealed a prolonged toxic serum concentration of flecainide. CONCLUSION: These results demonstrate the change in elimination kinetics of flecainide in the setting of urinary alkalization which is evident through prolonged morphologic changes present on serial electrocardiograms.

A Fatal Colchicine Ingestion With Antemortem Blood Concentration.

ABSTRACT: Although there are multiple therapeutic uses for colchicine, it is particularly dangerous in the setting of overdose due to an irreversible mechanism of action combined with a narrow therapeutic window. Colchicine is an antimitotic agent that binds tubulin and inhibits microtubule polymerization. This produces a predictable sequence of toxicity beginning with gastrointestinal effects with progression to multiorgan system dysfunction. Unfortunately, there are no specific antidotes for colchicine toxicity after organ injury has occurred, which can lead to tragic consequences. Despite the recognized toxicity, it is exceedingly rare to find a case in the medical literature with a confirmed time of ingestion, amount ingested, data from longitudinal examinations, and laboratory assessments, with a quantitative blood colchicine concentration. We present a case of acute colchicine overdose of 18 mg (approximately 0.25 mg/kg) with subsequent multiorgan failure and death with an antemortem blood colchicine concentration of 14 ng/mL at 18.5 hours after ingestion.

Prehospital end-tidal CO2 as an early marker for transfusion requirement in trauma patients.

OBJECTIVE: Below normal end-tidal carbon dioxide measurement (ETCO2) is associated with worse outcomes in sepsis and trauma patients as compared to patients with normal ETCO2. We sought to determine if ETCO2 can be used in the prehospital setting to predict transfusion requirement, operative hemorrhage control, or mortality in the first 24 h after admission for trauma. METHODS: This is a retrospective cohort study at a suburban, academic Level 1 Trauma Center. Patients were sequentially identified as prehospital trauma alerts from a single EMS system which requires, per policy, ETCO2 for all traumas. One year of prehospital data was collected and paired with hospital trauma registry data. Comparisons were made between ETCO2 values for patients who required transfusion, operative blood loss control, or who died, and those who did not. RESULTS: Two hundred thirty-five trauma patients were transported via the study EMS system, of which 105 (44.7%) had documented ETCO2 values. Patient mean age was 60 (SD24) years with 59 (56.2%) male. Three patients were intubated prehospital and seven were intubated in the trauma bay. Mean prehospital ETCO2 for those who needed transfusion, surgery, or died (n = 11) was 25.7 (9.1) compared to 30.6 (7.8) for those who did not (p = 0.049). Optimal cutoff for our population was EtCO2 ≤ 27 with a sensitivity of 72.7% (95% CI 32-93) and specificity of 72.2% (62-81). CONCLUSION: Below normal ETCO2 values were associated with increase need for transfusion, operative intervention, and death. Further study is warranted to determine if ETCO2 outperforms other predictors of severe trauma.

The Experience of Pain and Pain Tool Preferences of Hospitalized Youth.

BACKGROUND: An accurate holistic pediatric pain assessment is necessary for quality pain management. Evidence continues to be published indicating inadequacies in pediatric pain management. It is important for clinicians to consider the pain assessment process while caring for youth. AIM: The purpose of this study was to understand the pain experience through focused interviews and to explore how youth use, interpret and understand self-report pain assessment tools including their tool preferences. DESIGN: A qualitative descriptive study using a research developed semi-structured interview guide was conducted with 40 hospitalized youth, 10-17 years (M: 13yr; S.D. 2.4); 21 (52.5%) female on a medical inpatient unit. Interview questions focused on: current pain experience; pain related symptoms; evaluation of pain treatment and preferences for select pain assessment tools: 0-10 Numeric Rating Scale, The Oucher, Faces Pain Scale-Revised, and Adolescent Pediatric Pain Tool (APPT). SETTING: Large tertiary and quaternary care pediatric hospital located in northeastern United States. PARTICIPANTS/SUBJECTS: Hospitalized youth, 10-17 years of age. RESULTS: Analysis of transcribed interviews yielded 3 themes: My Pain Now, Pain Treatment Expectations, and Telling Healthcare Providers about My Pain. Additionally, pain tools preference, assessment frequency, and discussion of how behavior, activity level, and pain expression was different for each youth. APPT was the preferred pain assessment tool. Descriptive words such as sharp, throbbing, and aching were identified most often. Youth identified that activity and pain level often do not match. CONCLUSIONS: Because pain is multi-dimensional, assessing each dimension (quality, location, intensity, and meaning) is key to thorough assessment. Results provide insight into youth preferences influencing clinical practice such as offering options for interventions and having a voice in the pain management process. All nurses caring for children should discuss available pain tools preferably before the child is in pain and assure the child knows how to use the tool.

Resting Stage of Plankton Diversity from Singapore Coastal Water: Implications for Harmful Algae Blooms and Coastal Management.

Resting strategies of planktonic organisms are important for the ecological processes of coastal waters and their impacts should be taken into consideration in management of water bodies used by multiple industries. We combined different approaches to evaluate the importance of resting stages in Singapore coastal waters. We used molecular approaches to improve the knowledge on Singapore biodiversity, we sampled and extracted cysts from sediments to evaluate the density of resting stages in Johor Strait, and we compared systematically information on Singapore planktonic biodiversity to existing published information on resting stages from these reported organisms. This is the first study evaluating the importance of resting stages in Singapore waters. Above 120 species reported in Singapore are known to produce resting stages though no previous work has ever been done to evaluate the importance of these strategies in these waters. The results from the resting stage survey confirmed 0.66 to 5.34 cyst g-1 dry weight sediment were present in the Johor Strait suggesting that cysts may be flushed by tidal currents into and out of the strait regularly. This also suggest that the blooms occurring in Singapore are likely due to secondary growth of Harmful Algae Bloom species in the water rather than from direct germination of cysts from sediment. Finally, we discuss the importance of these resting eggs for three main national industries in Singapore (shipping, marine aquaculture and provision of drinking water through seawater desalination). We argue that this study will serve as a baseline for some of the future management of Singapore waters.

Angiotensinogen import in isolated proximal tubules: evidence for mitochondrial trafficking and uptake.

The renal proximal tubules are a key functional component of the kidney and express the angiotensin precursor angiotensinogen; however, it is unclear the extent that tubular angiotensinogen reflects local synthesis or internalization. Therefore, the current study established the extent to which angiotensinogen is internalized by proximal tubules and the intracellular distribution. Proximal tubules were isolated from the kidney cortex of male sheep by enzymatic digestion and a discontinuous Percoll gradient. Tubules were incubated with radiolabeled 125I-angiotensinogen for 2 h at 37°C in serum/phenol-free DMEM/F12 media. Approximately 10% of exogenous 125I-angiotensinogen was internalized by sheep tubules. Subcellular fractionation revealed that 21 ± 4% of the internalized 125I-angiotensinogen associated with the mitochondrial fraction with additional labeling evident in the nucleus (60 ± 7%), endoplasmic reticulum (4 ± 0.5%), and cytosol (15 ± 4%; n = 4). Subsequent studies determined whether mitochondria directly internalized 125I-angiotensinogen using isolated mitochondria from renal cortex and human HK-2 proximal tubule cells. Sheep cortical and HK-2 mitochondria internalized 125I-angiotensinogen at a comparable rate of (33 ± 9 vs. 21 ± 10 pmol·min-1·mg protein-1; n = 3). Lastly, unlabeled angiotensinogen (100 nM) competed for 125I-angiotensinogen uptake to a greater extent than human albumin in HK-2 mitochondria (60 ± 2 vs. 16 ± 13%; P < 0.05, n = 3). Collectively, our data demonstrate angiotensinogen import and subsequent trafficking to the mitochondria in proximal tubules. We conclude that this pathway may constitute a source of the angiotensinogen precursor for the mitochondrial expression of angiotensin peptides.

Evidence for a mitochondrial angiotensin-(1-7) system in the kidney.

Evidence for an intracellular renin-angiotensin system (RAS) in various cell organelles now includes the endoplasmic reticulum, nucleus, and mitochondria (Mito). Indeed, angiotensin (ANG) AT1 and AT2 receptor subtypes were functionally linked to Mito respiration and nitric oxide production, respectively, in previous studies. We undertook a biochemical analysis of the Mito RAS from male and female sheep kidney cortex. Mito were isolated by differential centrifugation followed by a discontinuous Percoll gradient and were coenriched in Mito membrane markers VDAC and ATP synthase, but not ß-actin or cathepsin B. Two distinct renin antibodies identified a 37-kDa protein band in Mito; angiotensinogen (Aogen) conversion was abolished by the inhibitor aliskiren. Mito Aogen was detected by an Aogen antibody to an internal sequence of the protein, but not with an antibody directed against the ANG I N terminus. ANG peptides were quantified by three direct RIAs; mitochondrial ANG II and ANG-(1-7) contents were higher compared with ANG I (23 ± 8 and 58 ± 17 vs. 2 ± 1 fmol/mg protein; P < 0.01, n = 3). 125I-ANG I metabolism primarily revealed the formation of 125I-ANG-(1-7) in Mito that reflects the endopeptidases neprilysin and thimet oligopeptidase. Last, immunoblot studies utilizing the ANG-(1-7)/Mas receptor antibody revealed the protein in isolated Mito from sheep renal cortex. Collectively, the current data demonstrate that Mito actively metabolize the RAS precursor protein Aogen, suggesting that ANG-(1-7) may be generated within Mito to establish an intramitochondrial RAS tone and contribute to renal mitochondrial function.

An angiotensin-(1-7) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme.

Angiotensin 1-7 [ANG-(1-7)] is expressed within the kidney and exhibits renoprotective actions that antagonize the inflammatory, fibrotic, and pro-oxidant effects of ANG II. We previously identified an peptidase that preferentially metabolized ANG-(1-7) to ANG-(1-4) in the brain medulla and cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. J Neurochem 130: 313-323, 2014); thus the present study established the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1-7) to ANG-(1-4) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells. The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390; human HK-2 cells expressed subnanomolar sensitivity (IC50 = 0.5 nM) and the highest specific activity (123 ± 5 fmol·min(-1)·mg(-1)) compared with the tubules (96 ± 12 fmol·min(-1)·mg(-1)) and cortex (107 ± 9 fmol·min(-1)·mg(-1)). The peptidase was purified 41-fold from HK-2 cells; the activity was sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1-7) and its endogenous analog [Ala(1)]-ANG-(1-7) (alamandine) were preferentially hydrolyzed by the peptidase compared with ANG II, [Asp(1)]-ANG II, ANG I, and ANG-(1-12). Although the ANG-(1-7) peptidase and insulin-degrading enzyme (IDE) share similar inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked differences in substrate specificity, which suggest these peptidases are distinct. We conclude that an ANG-(1-7) peptidase is expressed within the renal proximal tubule and may play a potential role in the renal renin-angiotensin system to regulate ANG-(1-7) tone.

Coral-the world's most diverse symbiotic ecosystem.

Zooxanthellate corals (i.e. those harbouring Symbiodinium) are the main builders of the world's shallow-water marine coral reefs. They represent intimate diverse symbioses between coral animals, single-celled photosynthetic dinoflagellates (Symbiodinium spp.), other microscopic eukaryotes, prokaryotes and viruses. Crabs and other crustaceans, worms, sponges, bivalves and hydrozoans, fishes, sea urchins, octopuses and sea stars are itinerant members of these 'rainforests of the sea'. This review focuses on the biodiversity of scleractinian coral animals and their best studied microscopic epi- and endosymbionts. In relation to coral-associated species diversity, Symbiodinium internal transcribed spacer region sequence types tally 10(2) -10(3) or up to ~15 different operational taxonomic units (OTUs, or putative species at the 97% sequence identity level; this cut-off was chosen based on intragenomic sequence diversity observed in monoclonal cultures) and prokaryotes (mostly bacterial) total 10(2) -10(4) OTUs. We analysed all publically accessible 16S rRNA gene sequence data and found Gammaproteobacteria were extremely abundant, followed by Alphaproteobacteria. Notably, Archaea were poorly represented and 'unassigned OTUs' were abundant in data generated by high-throughput DNA sequencing studies of corals. We outline and compare model systems that could be used in future studies of the coral holobiont. In our future directions, we recommend a global coral sampling effort including substantial attention being paid to method of coral tissue acquisition, which compartments (mucus, tissue, skeleton) to explore, broadening the holobiont members considered and linking biodiversity with functional investigations.

The ins and outs of angiotensin processing within the kidney.

The kidney is a key target organ for bioactive components of the renin-angiotensin system (RAS); however, various renal cells such as the tubular epithelium contain an intrinsic RAS. The renal RAS can be functionally divided into ANG II-AT1 receptor and ANG-(1-7)-AT7/Mas receptor arms that functionally oppose one another. The current review considers both extracellular and intracellular pathways that potentially govern the formation and metabolism of angiotensin peptides within the renal proximal tubules.

Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm.

INTRODUCTION: Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. MATERIALS AND METHODS: A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. RESULTS: One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. DISCUSSION: Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. CONCLUSIONS: Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

The rising threat of peyssonnelioid algal crusts on coral reefs.

For more than a century, coral reefs have been exposed to increasing anthropogenic disturbances that have profoundly altered their community structure. These perturbations continue to challenge coral reefs in new ways as ecological paradigms are recast in the Anthropocene Epoch1. In recent decades, macroalgal blooms have blighted Caribbean reefs2, but the appearance of aggressive peyssonnelioid algal crusts (PAC) that are rapidly increasing in abundance to become dominant members of the benthos on Caribbean and Indo-Pacific reefs is a novel phenomenon in tropical seas3. By pre-empting vacant space, overgrowing corals, deterring the settlement of coral larvae, and favouring a phase transition from coral to algae4, PAC are likely to accelerate the decline in dominance of corals on global reefs (Figure 1).

Inter-comparison of marine microbiome sampling protocols.

Research on marine microbial communities is growing, but studies are hard to compare because of variation in seawater sampling protocols. To help researchers in the inter-comparison of studies that use different seawater sampling methodologies, as well as to help them design future sampling campaigns, we developed the EuroMarine Open Science Exploration initiative (EMOSE). Within the EMOSE framework, we sampled thousands of liters of seawater from a single station in the NW Mediterranean Sea (Service d'Observation du Laboratoire Arago [SOLA], Banyuls-sur-Mer), during one single day. The resulting dataset includes multiple seawater processing approaches, encompassing different material-type kinds of filters (cartridge membrane and flat membrane), three different size fractionations (>0.22 µm, 0.22-3 µm, 3-20 µm and >20 µm), and a number of different seawater volumes ranging from 1 L up to 1000 L. We show that the volume of seawater that is filtered does not have a significant effect on prokaryotic and protist diversity, independently of the sequencing strategy. However, there was a clear difference in alpha and beta diversity between size fractions and between these and "whole water" (with no pre-fractionation). Overall, we recommend care when merging data from datasets that use filters of different pore size, but we consider that the type of filter and volume should not act as confounding variables for the tested sequencing strategies. To the best of our knowledge, this is the first time a publicly available dataset effectively allows for the clarification of the impact of marine microbiome methodological options across a wide range of protocols, including large-scale variations in sampled volume.

Comparison of two guideline-concordant antimicrobial combinations in elderly patients hospitalized with severe community-acquired pneumonia.

OBJECTIVE: Two of the guideline-concordant therapies for severe community-acquired pneumonia are either a beta-lactam and fluoroquinolone or beta-lactam and macrolide. However it is unclear if there is a benefit for one vs. the other for elderly patients with severe community-acquired pneumonia. DESIGN: A retrospective population-based cohort study of patients with community-acquired pneumonia. SETTING: Patients admitted to an intensive care unit of any Department of Veterans Affairs hospital during 5-yr period. PATIENTS: We included only those patients>65 yrs of age admitted to the intensive care unit with community-acquired pneumonia who received either beta-lactam+fluoroquinolone or beta-lactam+macrolide antibiotic therapy for pneumonia. INTERVENTION: Not applicable. MEASUREMENTS: We used multilevel regression models to examine the effect of beta-lactam+fluoroquinolone vs. beta-lactam+macrolide on each of the outcomes after adjusting for potential confounders using propensity scores. MAIN RESULTS: The cohort consisted of 1,989 patients: 98.5% male and a mean age of 74 yrs. For treatment, 44% of subjects received beta-lactam+fluoroquinolone and 56% received beta-lactam+macrolide. Unadjusted 30-day mortality was 27% for beta-lactam+fluoroquinolone and 24% for beta-lactam+macrolide (p=.11). In the multilevel models, the use of beta-lactam+fluoroquinolone was not significantly associated with 30-day mortality (odds ratio 1.05, 95% confidence interval 0.85-1.30). However, the use of beta-lactam+fluoroquinolone was significantly associated with increased mean length of stay (incidence rate ratio 1.30, 95% confidence interval 1.27-1.33). CONCLUSIONS: We found no significant difference for 30-day mortality but did demonstrate an association with increase in length of stay associated with the use of beta-lactam + fluoroquinolone. Randomized controlled trials are needed to determine the most effective antibiotics regimes for patients with severe pneumonia.

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019.

BACKGROUND: There are two Food and Drug Administration (FDA)-approved antivenoms available for rattlesnake envenomations in the United States: the equine-derived F (ab')2 product sold with the brand name Anavip (F (ab')2 AV) and the ovine-derived Fab product sold with the brand name Crofab (FabAV). OBJECTIVE: To compare the clinical outcomes of rattlesnake envenomation patients treated either with FabAV or F (ab')2AV or a combination of these. METHODS: This is a retrospective chart review of all human rattlesnake envenomations requiring antivenom reported to one regional poison control center in 2019. Patients were categorized as receiving F (ab')2 AV, FabAV, or a combination of both. Baseline characteristics included demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation. RESULTS: There were a total of 123 patients requiring antivenom. Of these, 57 (46.3%) received FabAV, 53 (43.1%) received F (ab')2 AV, and 13 (10.6%) received a combination of these. Those receiving F (ab')2 AV were younger, with an average age of 40.8 (±25.0) years versus 51.3 (±19.9) years (p = 0.0161) for those receiving FabAV. Time between envenomation and antivenom administration, ASSS, and the percentage of those with coagulopathy at presentation were otherwise similar. Patients treated with F (ab')2 AV or FabAV received a similar total number of vials [16.0 vials (±6.1) vs 14.5 vials (±5.4), p = 0.189], but patients treated with F (ab')2 AV were more frequently given additional doses [31 patients (58.5%) vs. 22 FabAV patients (38.6%), p = 0.0051]. In patients with outpatient follow-up for 2 weeks, fewer patients treated with F (ab')2 AV developed late coagulopathy [5 patients (11.1%) vs 22 FabAV patients (48.9%), p = 0.0004]. Adverse events were generally mild and uncommon with no difference in frequency between patients who received either antivenom (2 F (ab')2 AV patients vs 4 FabAV patients, p = 0.6637). CONCLUSIONS: Other than patient age, we found no significant difference in the baseline demographics, time between envenomation and administering antivenom, an abbreviated snakebite severity score (ASSS), and the presence of coagulopathy at presentation between patients receiving F (ab')2 AV or FabAV. Patients receiving F (ab')2 AV were more likely to be given an additional dose beyond the minimum typical treatment course, but less likely to develop late coagulopathy. Adverse events were uncommon and generally mild whether patients received either antivenom.

An unusual microbiome characterises a spatially-aggressive crustose alga rapidly overgrowing shallow Caribbean reefs.

Several species of crustose coralline algae (CCA) and their associated microbial biofilms play important roles in determining the settlement location of scleractinian corals on tropical reefs. In recent decades, peyssonnelid algal crusts (PAC) have become spatial dominants across large areas of shallow Caribbean reefs, where they appear to deter the recruitment of scleractinians. Our genetic investigations of PAC in St. John, US Virgin Islands, amplifying the large-subunit ribosomal RNA and psbA protein D1 marker genes, revealed them to be identical to Ramicrusta textilis previously reported overgrowing corals in Jamaica. Specimens of PAC sampled from the Honduras were likewise identical, confirming that this crustose alga inhabits the easternmost and westernmost regions of the Caribbean. We also analysed 16S rDNA tag amplicon libraries of the biofilms associated with PAC and sympatric CCA, which is favoured for coral settlement. Our results show that the microbial communities on PAC (vs. CCA) are characterized by significantly lower numbers of the epibiotic bacterial genus Pseudoalteromonas, which facilitates the recruitment and settlement of marine invertebrates. From these data, we infer that PAC are therefore unlikely to be attractive as settlement sites for coral larvae. Given the significant ecological change anticipated on these reefs due to increasing cover of PAC, there is an urgent need to further investigate competitive interactions between PAC and scleractinian corals, and elucidate the role of PAC and their associated microbiomes in accentuating phase shifts from coral to algae on tropical reefs.

Points & Pearls: Pediatric community-acquired pneumonia: diagnosis and management in the emergency department

Worldwide, pneumonia is the most common cause of death in children aged < 5 years. Distinguishing viral from bacterial causes of pneumonia is paramount to providing effective treatment but remains a significant challenge. For patients who can be managed with outpatient treatment, the utility of laboratory tests and radiographic studies, as well as the need for empiric antibiotics, remains questionable. This issue reviews viral and bacterial etiologies of community-acquired pneumonia in pediatric patients, offers guidance for obtaining historical information and interpreting physical examination findings, discusses the utility of various diagnostic techniques, and provides recommendations for the treatment of previously healthy and medically fragile children. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice.]

Effects of exercise training on cardiac function and myocardial remodeling in post myocardial infarction rats.

To test the hypothesis that early exercise training after myocardial infarction (MI) could preserve cardiac function, alleviate left ventricular (LV) remodeling and induce a protective effect on morphology, male Sprague-Dawley rats underwent coronary ligation or sham operation, and were assigned to 3 groups: Sham, sedentary MI (SedMI), and exercise MI (ExMI). We measured the changes in collagen volume fraction, matrix metalloproteinase (MMP) 1, tissue inhibitor matrix metalloproteinase 1 (TIMP-1), angiotensin II receptor type 1 (AT1), and angiotensin converting enzyme (ACE) at gene and protein levels after 8 weeks of exercise training. Cardiac functions were determined by echocardiographic and hemodynamic measurements. Early exercise training after MI had no effect on LV wall thinning. Cardiac function was significantly preserved in the ExMI group in comparison to the SedMI group. The collagen volume fraction in the ExMI group was significantly lower than in the SedMI group. Compared to the SedMI group, the ExMI group showed a markedly decrease at both the gene and protein levels in TIMP-1 (P<0.05). No significant differences were found in MMP-1 among the three groups. MMP-1/TIMP-1 ratio in the ExMI group was significantly higher than in the SedMI group. In addition, the expression of AT1 protein in the ExMI group was significantly lower than in the SedMI group. Furthermore, both ACE mRNA expression and ACE binding in the ExMI group are significantly decreased compared to the SedMI group. Our results suggest that early exercise training after MI reduces TIMP-1 expression, improves the balance between MMPs and TIMPs, and mitigates the expressions of ACE and AT1 receptor. These improvements, in turn, attenuate myocardial fibrosis and preserve post-MI cardiac function.