The impact of interval cholecystectomy timing after percutaneous transhepatic cholecystostomy on post-operative adverse outcomes.

OBJECTIVE: This study aims to explore how timing of interval of cholecystectomy (IC) after percutaneous transhepatic cholecystostomy tube (PTC) placement impacts post-operative outcomes. METHODS: A retrospective database analysis of New York State SPARCs database of IC between 2005 and 2015. The timing for IC ranged between > 1 week and < 2 years. Patients undergoing this procedure were further divided into quartiles using 4-time intervals; 1-5 weeks (Q1), 5-8 weeks (Q2), 8-12 weeks(Q3), and > 12 weeks(Q4). The study's primary outcome was hospital length of stay (LOS). Secondary outcomes included discharge status, 30-day readmission, 30-day ED visit, and 90-day reoperation, surgery type, complication, and bile duct injury. Multivariable regression models were used to compare patients across the four-time intervals after adjusting for confounding factors. RESULTS: A total of 1038 patients with a history of PTC followed by IC between > 1 week and < 2 years were included in the final analysis. The median time to IC was 7.7 weeks. Q2 and Q3 both had a significantly higher median LOS of 3 days versus Q1 and Q4 at median of 5 days (p < 0.0001). Patients from racial and ethnic minorities (e.g., African Americans and Hispanics) were more likely to get their IC after 12 weeks (p < 0.05). Further, Black patients had a significantly higher median LOS than White, non-Hispanic patients (8 days vs 4 days, p < 0.0001) and were more likely to have open procedure. Multivariable regression analysis identified shorter LOS during Q2 (Ratio, 0.76, 95%, 0.67-0.87, p < 0.0001), and Q3 (Ratio 0.75, 95% CI, 065-0.86, p < 0.0001) compared to those who got their IC in Q4. Similar findings exist when comparing Q2 and Q3 to those receiving treatment during Q1. CONCLUSION: A time interval of 5-12 weeks between PTC and IC was associated with a decreased LOS. This study also suggests the persistence of racial disparities among these patients.

Variations in Discharge Destination Following Severe Traumatic Brain Injury across the United States.

BACKGROUND: Discharge destination after traumatic brain injury (TBI) may be influenced by non-patient factors such as regional or institutional practice patterns. We hypothesized that non-patient factors would be associated with discharge destination in severe TBI patients. METHODS: All patients in the ACS Trauma Quality Improvement Program 2016 data set with severe TBI, defined as head Abbreviated Injury Scale ≥3, were categorized by discharge destination. Logistic regression was used to assess factors associated with each destination; odds ratios and 95% confidence level are reported. Regressions were adjusted for age, gender, race, insurance, GCS, ISS, polytrauma, mechanism, neurosurgical procedure, geographic region, teaching status, trauma center level, hospital size, and neurosurgeon group size. RESULTS: 75,690 patients met inclusion criteria. 51% were discharged to home, 16% to rehab, 14% to SNF, and 11% deceased. Mortality was similar across geographic region, teaching status, and hospital size. Southern patients were more likely to be discharged to home while Northeastern patients were more likely to be discharged to rehab. Treatment by groups of 3 or more neurosurgeons was associated with SNF discharge as was treatment at community or non-teaching hospitals. Patients treated at larger hospitals were less likely to be discharged to rehab and more likely to go to SNF. CONCLUSIONS: Geographic region, neurosurgeon group size, teaching status, and hospital size are significantly associated with variation in discharge destination following severe TBI. Regional and institutional variation in practice patterns may play important roles in recovery for some patients with severe TBI.

Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin.

Macrophage colony-stimulating factor (M-CSF) influences the proliferation and survival of mononuclear phagocytes through the receptor CSF-1R. The adaptor protein DAP12 is critical for the function of mononuclear phagocytes. DAP12-mutant mice and humans have defects in osteoclasts and microglia, as well as brain and bone abnormalities. Here we show DAP12 deficiency impaired the M-CSF-induced proliferation and survival of macrophages in vitro. DAP12-deficient mice had fewer microglia in defined central nervous system areas, and DAP12-deficient progenitors regenerated myeloid cells inefficiently after bone marrow transplantation. Signaling by M-CSF through CSF-1R induced the stabilization and nuclear translocation of beta-catenin, which activated genes involved in the cell cycle. DAP12 was essential for phosphorylation and nuclear accumulation of beta-catenin. Our results provide a mechanistic explanation for the many defects of DAP12-deficient mononuclear phagocytes.

Dysregulation of the Mitochondrial Unfolded Protein Response Induces Non-Apoptotic Dopaminergic Neurodegeneration in C. elegans Models of Parkinson's Disease.

Due to environmental insult or innate genetic deficiency, protein folding environments of the mitochondrial matrix are prone to dysregulation, prompting the activation of a specific organellar stress-response mechanism, the mitochondrial unfolded protein response (UPRMT). In Caenorhabditis elegans, mitochondrial damage leads to nuclear translocation of the ATFS-1 transcription factor to activate the UPRMT After short-term acute stress has been mitigated, the UPRMT is eventually suppressed to restore homeostasis to C. elegans hermaphrodites. In contrast, and reflective of the more chronic nature of progressive neurodegenerative disorders such as Parkinson's disease (PD), here, we report the consequences of prolonged, cell-autonomous activation of the UPRMT in C. elegans dopaminergic neurons. We reveal that neuronal function and integrity decline rapidly with age, culminating in activity-dependent, non-apoptotic cell death. In a PD-like context wherein transgenic nematodes express the Lewy body constituent protein α-synuclein (αS), we not only find that this protein and its PD-associated disease variants have the capacity to induce the UPRMT, but also that coexpression of αS and ATFS-1-associated dysregulation of the UPRMT synergistically potentiate dopaminergic neurotoxicity. This genetic interaction is in parallel to mitophagic pathways dependent on the C. elegans PINK1 homolog, which is necessary for cellular resistance to chronic malfunction of the UPRMT Given the increasingly recognized role of mitochondrial quality control in neurodegenerative diseases, these studies illustrate, for the first time, an insidious aspect of mitochondrial signaling in which the UPRMT pathway, under disease-associated, context-specific dysregulation, exacerbates disruption of dopaminergic neurons in vivo, resulting in the neurodegeneration characteristic of PD.SIGNIFICANCE STATEMENT Disruptions or alterations in the activation of pathways that regulate mitochondrial quality control have been linked to neurodegenerative diseases due in part to the central role of mitochondria in metabolism, ROS regulation, and proteostasis. The extent to which these pathways, including the mitochondrial unfolded protein response (UPRMT) and mitophagy, are active may predict severity and progression of these disorders, as well as sensitivity to compounding stressors. Furthermore, therapeutic strategies that aim to induce these pathways may benefit from increased study into cellular responses that arise from long-term or ectopic stimulation, especially in neuronal compartments. By demonstrating the detrimental consequences of prolonged cellular activation of the UPRMT, we provide evidence that this pathway is not a universally beneficial mechanism because dysregulation has neurotoxic consequences.

Unplanned hospital admissions within 24 h after 53,185 surgical procedures at a U.S. ambulatory surgery center.

BACKGROUND: Unplanned admission after surgery at an ambulatory surgery center (ASC) is an established measure of the quality of care and can affect the patient's experience. Previous studies on this topic are generally dated, focused on a single specialty, or studied 30-day admissions after ambulatory surgery. Few studies have reported admission within 24 h after surgery at an ASC which is a different but important measure of the quality of anesthetic and surgical care. Understanding admissions within 24 h of surgery can identify opportunities for improvement immediately after surgery. Therefore, our study was designed to assess the incidence and risk factors for unplanned hospital admissions within 24 h after surgery performed at a hospital ASC. METHODS: After Institutional Review Board approval, a retrospective analysis was performed on all adult patients who underwent surgery at a US ASC between January 1, 2016, and December 31, 2022. Data were obtained from the hospital's electronic medical record. The study sample was divided into two groups: those with an unplanned hospital admission within 24 h after surgery and those without an unplanned hospital admission. To evaluate risk factors for unplanned hospital admissions, univariate analyses with p value < 0.05 were utilized to identify significant patient variables related to hospital admissions. These variables were further adjusted using a multivariable Firth logistic regression. Descriptive statistics were used to explore the number of patients in different variable categories. RESULTS: Overall, 53,185 cases were identified for the 7-year period. The incidence of unplanned hospital admission over this period was 0.09% (95% CI 0.07-0.1122%; ranging from 0.05 to 0.12% per year. In the multivariable model, surgery duration (OR 1.010, 95% CI 1.007-1.012, p value < 0.0001), peripheral vascular disease (OR 14.489, 95% CI 4.862-43.174, p value < 0.0001), and deep venous thrombosis (OR 5.527, 95% CI 1.909-16.001, p value = 0.0016) were significantly associated with unplanned hospital admission. CONCLUSION: The overall incidence of unplanned hospital admission after surgery at a large tertiary care ambulatory surgery center is very low. This admission rate can also serve as a reference point for future studies and quality improvement initiatives.

Home Medication Regimens Increase in Complexity After Admission for Fall in the Older Trauma Patient.

BACKGROUND: Hospitalization for the older trauma patient is an opportunity to assess polypharmacy. We hypothesized that medication regimen complexity (RxCS) and pain medication prescriptions (PRxs) would increase in older home-going patients admitted for a fall. METHODS: We retrospectively chart reviewed patients ≥45 years old admitted for a fall at a level 1 trauma center who were discharged home with full medication documentation. RxCS was compared pre-admission and post-discharge with Wilcoxon signed-rank tests; opioid and non-opioid PRxs were compared with Fisher's exact test, α = .05. RESULTS: 103 patients met inclusion criteria; 58% were ≥65 years old. RxCS (9 [.5-13] to 11 [4.5-15], P < .01) increased on discharge. Opioid PRx rates increased significantly in all age groups. Non-opioid PRx rates increased significantly for patients <65 but not for patients ≥65. CONCLUSIONS: Admission for a fall was associated with increases in RxCS, while PRx changes were age-dependent. Providers should recognize that admissions for older patients who fall after trauma are underutilized opportunities to address polypharmacy in high-risk patients.

Percutaneous vertebral augmentation for acute traumatic vertebral Fractures: A TQIP database study.

Patients with vertebral fractures may be treated with percutaneous vertebroplasty (VP) and kyphoplasty (KP) for pain relief. Few studies examine the use of VP and KP in the setting of an acute trauma. In this study, we describe the current use of VP/KP in patients with acute traumatic vertebral fractures. All patients in the ACS Trauma Quality Improvement Program (TQIP) 2016 National Trauma Databank with severe spine injury (spine AIS ≥ 3) met inclusion criteria, including patients who underwent PVA. Logistic regression was used to assess patient and hospital factors associated with PVA; odds ratios and 95 % confidence intervals are reported. 20,769 patients met inclusion criteria and 406 patients received PVA. Patients aged 50 or older were up to 6.73 (2.45 - 27.88) times more likely to receive PVA compared to younger age groups and women compared to men (1.55 [1.23-1.95]). Hospitals with a Level II trauma center and with 401-600 beds were more likely to perform PVA (2.07 [1.51-2.83]) and (1.82 [1.04-3.34]) respectively. African American patients (0.41 [0.19-0.77]), isolated trauma (0.64 [0.42-0.96]), neurosurgeon group size > 6 (0.47 [0.30-0.74]), orthopedic group size > 10, and hospitals in the Northeastern and Western regions of the U.S. (0.33 [0.21-0.51] and 0.46 [0.32-0.64]) were less likely to be associated with PVA. Vertebroplasty and kyphoplasty use for acute traumatic vertebral fractures significantly varied across major trauma centers in the United States by multiple patient, hospital, and surgeon demographics. Regional and institutional practice patterns play an important role in the use of these procedures.

Post-Trauma Discharge Instructions: Are We Dropping the Ball?

INTRODUCTION: Complex follow-up plans for polytrauma patients are compiled at the end of hospitalization into discharge instructions. We sought to identify how often patient discharge instructions incorrectly communicated specialist recommendations. We hypothesized that patients with more complex hospitalizations would have more discharge instruction errors (DI-errors). METHODS: We reviewed adult trauma inpatients (March 2017-March 2018), excluding those who left against medical advice or were expected to follow up outside our system. Complex hospitalizations were represented using injury severity (ISS), hospital length of stay (LOS), intensive care unit length of stay (iLOS), and number of consultants (NC). We recorded the type of consultant (surgical or nonsurgical), and consultant recommendations for follow-up. DI-errors were defined as either follow-up necessary but omitted or follow-up not necessary yet present on the instructions. Patients with DI-errors were compared to patients without DI-errors. Groups were compared using Wilcoxon rank sum or chi-square (alpha <.05). RESULTS: We included 392 patients (median age 45 [IQR 26-58], ISS 14 [10-21], LOS 6 [3-11]). 55 patients (14%) had DI-errors. Factors associated with DI-errors included the total number of consultants and use of nonsurgical consultants. ISS, LOS, iLOS, were not associated with DI-errors. CONCLUSION: Common measures of admission complexity were not associated with DI-errors, although the number and type of consultants were associated with DI-errors. Non-surgical specialty consultant recommendations were more likely to be omitted. It is crucial for patients to receive accurate discharge instructions, and systematic processes are needed to improve communication with the patients at discharge.

Symptomatic Colorectal Cancer Is Associated With Stage IV Diagnosis in Two Disparate Populations.

In the United States, individuals of Black/African Ancestry (AA) have a higher incidence and mortality from colorectal cancer (CRC) compared to individuals of White/European Ancestry (EA). In order to develop an approach towards disentangling the complex effects of associated race and socioeconomic factors on CRC outcome, we have conducted a manual chart review of sporadic CRC pathological diagnoses (total n = 334) at an urban public hospital (UH) and a suburban university hospital (SH). There were significant differences between the SH and UH CRC patients with respect to Black/AA race (4.2% vs. 89.1%, p < 0.0001) and Medicaid/Self-pay insurance status (14.9% vs. 85.0%, p < 0.0001). While a higher proportion of newly diagnosed CRC patients presented with metastatic stage 4 CRC at the UH (21%) than the SH (12.5%), only the presence of symptoms was significantly associated with stage 4 CRC (odds ratio, OR 7.94, 95% confidence interval, CI 1.83- 34.54, p = 0.0057) in a multivariable generalized linear model (GLM). The proportion of asymptomatic CRC patients was ~20% at both institutions, suggesting that the UH has contributed to reducing CRC disparities. Initiation of CRC screening at the recommended age at both institutions could reduce the proportion of CRC patients presenting with metastatic spread.

Predictors for Withdrawal of Life-Sustaining Therapies in Patients With Traumatic Brain Injury: A Retrospective Trauma Quality Improvement Program Database Study.

Many patients with severe traumatic brain injuries (TBIs) undergo withdrawal of life-sustaining therapies (WLSTs) or transition to comfort measures, but noninjury factors that influence this decision have not been well characterized. We hypothesized that WLST would be associated with institutional and geographic noninjury factors. All patients with a head Abbreviated Injury Scale score ≥3 were identified from 2016 Trauma Quality Improvement Program data. We analyzed factors that might be associated with WLST, including procedure type, age, sex, race, insurance, Glasgow Coma Scale score, mechanism of injury, geographic region, and institutional size and teaching status. Adjusted logistic regression was performed to examine factors associated with WLST. Sixty-nine thousand fifty-three patients were identified: 66% male, 77% with isolated TBI, and 7.8% had WLST. The median age was 56 years (34-73). A positive correlation was found between increasing age and WLST. Women were less likely to undergo WLST than men (odds ratio 0.91 [0.84-0.98]) and took more time to for WLST (3 vs 2 days, P < .001). African Americans underwent WLST at a significantly lower rate (odds ratio 0.66 [0.58-0.75]). Variations were also discovered based on US region, hospital characteristics, and neurosurgical procedures. WLST in severe TBI is independently associated with noninjury factors such as sex, age, race, hospital characteristics, and geographic region. The effect of noninjury factors on these decisions is poorly understood; further study of WLST patterns can aid health care providers in decision making for patients with severe TBI.

Fracture of a 40-mm BIOLOX Delta Femoral Head.

Ceramic bearing surfaces have gained popularity in total hip arthroplasty as a result of the favorable mechanical properties and low wear rates. Despite the recognition as an attractive articulation, problems such as ceramic head fracture persist. Smaller heads and higher body mass indices are touted as risk factors for ceramic head fracture and are often associated with antecedent trauma. We present a case report of an 83-year-old male with a body mass index of 26.7 kg/m2 who suffered a fracture of a 40-mm ceramic femoral head. This occurred atraumatically 5 years from his index surgery. This patient underwent revision total hip arthroplasty which included debridement of ceramic debris and alteration of the bearing surface with femoral head and polyethylene liner exchange.

Variation in neurosurgical intervention for severe traumatic brain injury: The challenge of measuring quality in trauma center verification.

BACKGROUND: Intracranial pressure monitor (ICPm) procedure rates are a quality metric for American College of Surgeons trauma center verification. However, ICPm procedure rates may not accurately reflect the quality of care in TBI. We hypothesized that ICPm and craniotomy/craniectomy procedure rates for severe TBI vary across the United States by geography and institution. METHODS: We identified all patients with a severe traumatic brain injury (head Abbreviated Injury Scale, ≥3) from the 2016 Trauma Quality Improvement Program data set. Patients who received surgical decompression or ICPm were identified via International Classification of Diseases codes. Hospital factors included neurosurgeon group size, geographic region, teaching status, and trauma center level. Two multiple logistic regression models were performed identifying factors associated with (1) craniotomy with or without ICPm or (2) ICPm alone. Data are presented as medians (interquartile range) and odds ratios (ORs) (95% confidence interval). RESULTS: We identified 75,690 patients (66.4% male; age, 59 [36-77] years) with a median Injury Severity Score of 17 (11-25). Overall, 6.1% had surgical decompression, and 4.8% had ICPm placement. Logistic regression analysis showed that region of the country was significantly associated with procedure type: hospitals in the West were more likely to use ICPm (OR, 1.34 [1.20-1.50]), while Northeastern (OR, 0.80 [0.72-0.89]), Southern (OR, 0.84 [0.78-0.92]), and Western (OR, 0.88 [0.80-0.96]) hospitals were less likely to perform surgical decompression. Hospitals with small neurosurgeon groups (<3) were more likely to perform surgical intervention. Community hospitals are associated with higher odds of surgical decompression but lower odds of ICPm placement. CONCLUSION: Both geographic differences and hospital characteristics are independent predictors for surgical intervention in severe traumatic brain injury. This suggests that nonpatient factors drive procedural decisions, indicating that ICPm rate is not an ideal quality metric for American College of Surgeons trauma center verification. LEVEL OF EVIDENCE: Epidemiological, level III; Care management/Therapeutic level III.

Differences in the transcriptome signatures of two genetically related Entamoeba histolytica cell lines derived from the same isolate with different pathogenic properties.

BACKGROUND: The availability of two genetically very similar cell lines (A and B) derived from the laboratory isolate Entamoeba histolytica HM-1:IMSS, which differ in their virulence properties, provides a powerful tool for identifying pathogenicity factors of the causative agent of human amoebiasis. Cell line A is incapable inducing liver abscesses in gerbils, whereas interaction with cell line B leads to considerable abscess formation. Phenotypic characterization of both cell lines revealed that trophozoites from the pathogenic cell line B have a larger cell size, an increased growth rate in vitro, an increased cysteine peptidase activity and higher resistance to nitric oxide stress. To find proteins that may serve as virulence factors, the proteomes of both cell lines were previously studied, resulting in the identification of a limited number of differentially synthesized proteins. This study aims to identify additional genes, serving as virulence factors, or virulence markers. RESULTS: To obtain a comprehensive picture of the differences between the cell lines, we compared their transcriptomes using an oligonucleotide-based microarray and confirmed findings with quantitative real-time PCR. Out of 6242 genes represented on the array, 87 are differentially transcribed (> or = two-fold) in the two cell lines. Approximately 50% code for hypothetical proteins. Interestingly, only 19 genes show a five-fold or higher differential expression. These include three rab7 GTPases, which were found with a higher abundance in the non-pathogenic cell line A. The aig1-like GTPasesare of special interest because the majority of them show higher levels of transcription in the pathogenic cell line B. Only two molecules were found to be differentially expressed between the two cell lines in both this study and our previous proteomic approach. CONCLUSIONS: In this study we have identified a defined set of genes that are differentially transcribed between the non-pathogenic cell line A and the pathogenic cell line B of E. histolytica. The identification of transcription profiles unique for amoebic cell lines with pathogenic phenotypes may help to elucidate the transcriptional framework of E. histolytica pathogenicity and serve as a basis for identifying transcriptional markers and virulence factors.

Draft Genome Sequences of Staphylococcus Podophages JBug18, Pike, Pontiff, and Pabna.

We report here the draft genome sequences of Staphylococcus bacteriophages JBug18, Pike, Pontiff, and Pabna, which infect and lyse S. epidermidis and S. aureus strains. All bacteriophages belong to the morphological family Podoviridae and constitute attractive candidates for use as whole-phage therapeutics due to their compact genomes and lytic lifestyles.

Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.

Transcriptomic comparison of two Entamoeba histolytica strains with defined virulence phenotypes identifies new virulence factor candidates and key differences in the expression patterns of cysteine proteases, lectin light chains, and calmodulin.

The availability of Rahman, and the virulent HM-1:IMSS strain of E. histolytica, provides a powerful tool for identifying virulence factors of E. histolytica. Here we report an attempt to identify potential virulence factors of E. histolytica by comparing the transcriptome of E. histolytica HM-1:IMSS and E. histolytica Rahman. With phenotypically defined strains, we compared the transcriptome of Rahman and HM-1:IMSS using a custom 70mer oligonucleotide based microarray that has essentially full representation of the E. histolytica HM-1:IMSS genome. We find extensive differences between the two strains, including distinct patterns of gene expression of cysteine proteinases, AIG family members, and lectin light chains.

The need for continuing vigilance: addressing the threat for transmission of blood-borne infectious disease.

As international travel and human encroachment into previously isolated areas have increased, so too has the potential for the emergence of new infectious diseases. Populations likely to be susceptible to new infectious diseases have also increased in size. The past three decades have seen outbreaks of diseases caused by parvoviruses, Nipah virus, circoviruses, and prions. Infectious pathogens such as these are formidable opponents; they can adapt to new hosts or cause variant diseases within new hosts. Many are also resistant to current inactivation techniques. In order to prevent or contain outbreaks, pathogens that emerge must be identified quickly and efficiently; research and ongoing global surveillance are therefore of primary importance. To effectively protect the blood supply and blood-based therapies, this research should include investigations into improved techniques for detection, screening, and viral inactivation, as well as into ways to reduce patient exposure to infectious pathogens via therapeutic agents. The proactive devotion of appropriate resources to infectious disease containment and prevention prior to an epidemic should be perceived as both essential public health policy and cost effective.

Recent progress in vaccines for amebiasis.

The persistence of amebiasis as a global health problem, despite the availability of effective treatment, has led to the search for vaccines to prevent this deadly disease. Recent clinical studies suggest that mucosal immunity could provide some protection against recurrent intestinal infection with E. histolytica, but there is contradictory evidence about protective immunity after amebic liver abscess. Progress in vaccine development has been facilitated by new animal models that allow better testing of potential vaccine candidates and by the application of recombinant technology to vaccine design. Oral vaccines utilizing amebic antigens either co-administered with some form of cholera toxin or expressed in attenuated strains of Salmonella or Vibrio cholera have been developed and tested in animals for mucosal immunogenicity. Although there has been significant progress on a number of fronts, there are unanswered questions regarding the effectiveness of immune responses in preventing disease in man and, as yet, no testing of any of these vaccines in humans has been performed.

The Entamoeba histolytica genome: something old, something new, something borrowed and sex too?

The recent publication of the protozoan parasite Entamoeba histolytica genome provides new insights into eukaryotic evolution, the role of lateral gene transfer in amebic biology and the adaptations required for eukaryotes that reside within the human intestine.

Structural analysis of the acetaldehyde dehydrogenase activity of Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a member of the ADHE enzyme family.

The ADHE family of enzymes are bifunctional acetaldehyde dehydrogenase (ALDH)/alcohol dehydrogenase (ADH) enzymes that probably arose from the fusion of genes encoding separate ALDH and ADH enzymes. Here we have used the Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) enzyme as a prototype to analyze the structure and function of the ALDH domain of ADHE enzymes. We find that the N-terminal domain of EhADH2, encompassing amino acids 1-446, is sufficient for ALDH activity, consistent with the concept that EhADH2, and other members of the ADHE family comprise fusion peptides. In addition, we show, using site directed mutagenesis, that the catalytic mechanism for the ALDH activity appears to be similar to that described for other members of the ALDH extended family.