Homicide Manner-of-Death Classification in Arrest-Related Death.

ABSTRACT: Multiple studies have documented various factors that influence or determine forensic pathologist classification of manner of death. There do not appear to be any published studies on manner of death classification specifically regarding arrest-related deaths (ARDs). The goal of this study was to consider a large body of cases of nonfirearm ARDs to analyze the homicide classification with regards to numerous decedent and practitioner (medical examiner/coroner [ME/C]) variables. We analyzed 1145 US autopsy reports from the years 2006-2020, inclusive, and considered decedent variables of age, ethnicity, height, weight, body mass index, toxicology, and mention of a conducted electrical weapon and ME/C influence variables of gender, country region, and year. We found that the homicide classification likelihood increased by a factor of 1.04-1.05 per year, 1.34-1.37 for a female medical examiner, and 1.4-1.5 going from Southern states to Western states. There is an increasing trend for ME/C to label nonfirearm ARDs as homicides in the United States. The homicide classification is more common in Western states and less common in Southern states, and it was more common with a female ME/C.

Effects of Discontinuation of Weekly Surveillance Testing on Methicillin-Resistant Staphylococcus aureus in the NICU.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major cause of serious morbidity and mortality in the neonatal intensive care unit (NICU). There is no clear consensus on infection control measures. Some approaches to MRSA colonization management may be burdensome with unclear benefits. The objective of this study was to determine if stopping weekly MRSA surveillance with active detection and contact isolation (ADI) was associated with a change in infection rate. STUDY DESIGN: This is a retrospective cohort study of infants admitted to two affiliated NICUs. The ADI cohort infants received weekly nasal MRSA cultures and were placed in contact isolation if MRSA colonized for the duration of their hospitalization. The No Surveillance cohort infants were only placed in isolation if there was active MRSA infection or if MRSA colonization was identified incidentally. The rates of infection were determined between the cohorts. RESULTS: There were 8,406 neonates representing 193,684 NICU days in the comparison period. In the ADI cohort, MRSA colonization occurred in 3.4% of infants and infection occurred in 29 infants (0.4%). There were no differences between cohorts in the percent of infants with a MRSA infection at any site (0.5 vs. 0.5%, p = 0.89), rate of MRSA infections per 1,000 patient-days (0.197 vs. 0.201, p = 0.92), rate of bloodstream infections (0.12 vs. 0.26%, p = 0.18), or in the overall mortality rate (3.7 vs. 3.0% p = 0.13). ADI represented an annual cost of $590,000. CONCLUSION: The rates of MRSA infection did not change when weekly ADI was discontinued and was associated with a decrease in cost and resource utilization. KEY POINTS: · Placing MRSA-colonized infants in contact isolation is a common practice.. · Data are limited with respect to efficacy in the NICU.. · This study provides evidence that active detection and contact isolation for MRSA colonization may not be beneficial..

Pneumatic Impedance of Spit Socks and N95 Masks: The Applicability to Death Investigation.

INTRODUCTION: Restrained subjects often spit on law enforcement and corrections officers and medical responders. Based on the droplet-transmitted risk of COVID-19, such spitting could be considered a potentially life-threatening assault. Officers commonly use "spit socks" over the head and neck of spitting subjects to reduce this risk. The pneumatic impedance of such socks has not been published, so this remains an open issue for arrest-related death investigation. METHODS: We purchased samples of 3 popular spit sock models, 3 insect-protecting "bug" socks and hats, 3 N95 masks, a standard 3-ply surgical mask, and a common dust mask. We used a BTmeter model BTN8468 digital anemometer, an HTI model HT-1890 digital manometer, and an AC Infinity Cloudline model S6 inline controllable fan to measure air flow versus pressure drop. We compared the curves graphically and also calculated a pneumatic pseudo-impedance by dividing the pressure drop by the air velocity. RESULTS: The spit and bug socks allowed nearly maximum airflow with minimal pressure (≤1 mm Hg), whereas none of the masks allowed greater than 2 m/s of airflow at maximum pressure of 3 mm Hg. All of the spit and bug masks were grouped together with the lowest pneumatic impedances, whereas all of the N95 masks were grouped together with the highest values. The dust mask and surgical mask were in between with the dust mask closer to the spit and bug masks, whereas the surgical mask was closer to the N95 masks in impedance. CONCLUSIONS: Commonly used spit socks offer nearly zero resistance to breathing. The highest resistance spit sock was still 100 times better than the best N95 mask for airflow during inhalation. Our results do not support the occasional hypothesis that spit socks might contribute to an arrest-related death.

Confusion between firearms and electrical weapons as a factor in police shootings.

Conducted electrical weapons (CEW) have risks including trauma associated with uncontrolled falls, probes penetrating the eye, and fume ignition. A lesser-known risk is weapon-confusion error with officers mistakenly discharging their firearm when they intended to deploy their electrical weapon. We searched for incidents of possible weapon confusion with the TASER® brand CEWs via open-source media, litigation filings, and a survey of CEW law enforcement master instructors. We found 19 incidents of possible CEW weapon confusion in law enforcement field uses from January 2001 to April 2021. We eliminated a case as not meeting our criteria for probable weapons confusion leaving 18 cases, thus giving a demonstrated CEW discharge risk of 3.9 per million with confidence limits (2.4-6.2 per million) by Wilson score interval. Ipsilateral carry of the weapons was historically correlated with increased risk vs. contralateral carry. Officer gender was not a predictor of weapon confusion. The psychological issues behind weapon confusion under stress are discussed. The concurrent carry of electrical weapons and firearms presents a very small but real risk of injury and death from confusion between an electrical weapon and a firearm.

Police shootings after electrical weapon seizure: homicide or suicide-by-cop.

PURPOSE: Risks of handheld electrical weapons include head impact trauma associated with uncontrolled falls, ocular probe penetration injuries, thermal injuries from the ignition of volatile fumes, and weapon confusion police-involved shooting. There is also an uncommon but critical risk of a shooting after a subject gained control of an officer's electrical weapons. METHODS: The authors searched for police shooting incidents involving loss of control of TASER® weapons via open-source media reports, crowd-sourced internet sites, litigation filings, and a survey of Axon law-enforcement master instructors. RESULTS: The authors report 131 incidents of subjects attempting to or gaining control of an officer's electrical weapon from 2004 to 2020, 53 of which resulting in a shooting. These incidents demonstrated a risk of 11.8 shootings per million electrical weapon discharges (95% confidence limits of 9.0 to 15.1 per million by Wilson score interval). CONCLUSIONS: The use of electrical weapons presents a rare but real risk of injury and death from a shooting following a subject's attempts to gain control of the weapon.

Use of the RAM Cannula with Early Bubble Continuous Positive Airway Pressure Requires Higher Pressures: Clinical and In vitro Evaluations.

OBJECTIVE: Early bubble continuous positive airway pressure (bCPAP) in the delivery room (DR) reduces early intubation, mechanical ventilation, and bronchopulmonary dysplasia. The RAM cannula, adopted for ease of patient care, is a high resistance nasal interface that, when used with bCPAP, only transmits a portion of set pressures and attenuates the bubble effects. This study aimed to review early bCPAP pressures and bCPAP failure with the RAM cannula interface over a 6-year period. STUDY DESIGN: Retrospective, single-center study of infants delivered <1,250 g from 2013 to 2018 (n = 735) begun on bCPAP in the DR with the RAM cannula. In vitro testing of bCPAP pressure transmission was also performed for multiple nasal interfaces and nasal occlusion percentages. RESULTS: The percentage of infants intubated in the DR decreased over time (59 to 42%), while the average bCPAP pressure increased from 5.3 to 6.8 cmH2O. A total of 355 infants (48%) were admitted to the neonatal intensive care unit (NICU) from the DR on BCPAP. The failure rate for bCPAP in NICU within 72 hours decreased from 45 to 24% as the maximum CPAP increased from 5.8 to 7.6 cmH2O. Pneumothorax rates did not change. CPAP pressure transmission decreased with all sizes of the RAM cannula. CONCLUSION: When utilizing the RAM cannula for bCPAP, higher CPAP levels were associated with decreases in DR intubations and CPAP failure within the first 72 hours. If clinicians choose to use the RAM cannula for bCPAP, they will need higher set pressures to achieve lung inflation and the beneficial oscillatory effect will be diminished. KEY POINTS: · The transmission of the pressure oscillations from bubble CPAP is diminished with the RAM cannula.. · Increasing set CPAP pressures was associated with a decreased delivery room intubation rate and a decreased CPAP failure rate within 72 hours.. · Clinicians using the RAM cannula for bCPAP will need to increase pressures to obtain adequate lung inflation or change to a nasal interface designed for bCPAP..

Onlay Patellofemoral Arthroplasty in Patients With Isolated Patellofemoral Arthritis: A Systematic Review.

BACKGROUND: Patellofemoral arthroplasty (PFA) for isolated patellofemoral osteoarthritis (OA) remains controversial due to variable postoperative outcomes and high failure rates. Second-generation (2G) onlay prostheses have been associated with improved postoperative outcomes. This systematic review was performed to assess the current overall survivorship and functional outcomes of 2G PFA. METHODS: A search was performed using PubMed, Cochrane Library, EMBASE, and Google Scholar. Thirty-three studies published in the last 15 years (2005-2020) were included; of these 22 studies reported patient-reported outcome measures. Operative and nonoperative complications were analyzed. Pooled statistical analysis was performed for survivorship and functional scores using Excel 2016 and Stata 13. RESULTS: The mean age of the patients was 59.7. When analyzing all studies, weighted survival at mean follow-up of 5.52 was 87.72%. Subanalysis of studies with minimum 5 years of follow up showed a survival of 94.24%. Fifteen studies reported Oxford Knee Score with a weighted mean postoperative Oxford Knee Score of 33.59. Mean American Knee Society Score pain was 79.7 while mean American Knee Society Score function was 79.3. The most common operative complication was OA progression for all implants. The percentage of revisions and conversions reported after analyzing all studies was 1.37% and 7.82% respectively. CONCLUSION: Safe and acceptable results of functional outcomes and PFA survivorship can result from 2G PFAs at both short and mid-term follow-up for patients with isolated patellofemoral OA. However, long-term follow-up outcomes are still pending for the newer implants. More extensive studies using standardized functional outcomes and long-term cost benefits should be evaluated.

Surfactant and budesonide for respiratory distress syndrome: an observational study.

BACKGROUND: In preterm infants on moderately high ventilator support, the addition of budesonide to surfactant lowered bronchopulmonary dysplasia (BPD) rates by 20% without increased morbidity or mortality. The aim of this cohort comparison was to determine the safety and efficacy of the combination in infants with milder respiratory distress syndrome (RDS). METHODS: In August 2016 we began administering budesonide (0.25 mg/kg) mixed with surfactant (Survanta 4 mL/kg) to all infants ≤ 1250 g who failed CPAP and required intubation. Infants were compared to a historical cohort (2013-2016) who received surfactant alone. RESULTS: BPD or death did not change between the historical surfactant cohort (71%, n = 294) and the budesonide cohort (69%, n = 173). Budesonide was associated with a decrease in the need for continued mechanical ventilation, severe BPD type II or death (19-12%), grade III BPD or death (31-21%), and the median gestational age at discharge was 1 week earlier. Histologic chorioamnionitis was associated with decreased budesonide effects. Secondary morbidities (NEC, IVH, ROP, Sepsis) were similar. CONCLUSION: Overall BPD rates remained unchanged with the addition of budesonide. Budesonide was associated with decreased severity of BPD, decreased mechanical ventilation use, earlier discharge, and similar short-term outcomes.

Interhospital Transport of Infants on Bubble Continuous Positive Airway Pressure via Ground and Air.

OBJECTIVE: The purpose of this study was to evaluate the use of a respiratory protocol for the interhospital transport of infants with respiratory distress on bubble continuous positive airway pressure (bCPAP) and provide information on the safety of bCPAP during transport via ground and helicopter. METHODS: We evaluated a retrospective cohort study of neonates (gestational age 22-41 weeks) transported to our level 4 neonatal intensive care unit (NICU) before (n = 529) and after implementing (n = 540) protocols for increasing bCPAP and intubation criteria. Infants were evaluated for intubation before transport, the safety of transport, and the need for intubation shortly after arrival in the NICU. RESULTS: After initiating the protocols, less infants received mechanical ventilation, and more infants received bCPAP for transport via ground and helicopter. Upon arrival to the NICU, infants using the protocols had lower fraction of inspired oxygen and higher continuous positive airway pressures, and similar numbers required intubations in the first 12 hours. There were no differences in the rate of pneumothoraces. CONCLUSIONS: bCPAP can be used on both ground and helicopter transport of very small infants. Respiratory protocols decreased mechanical ventilation during transport without increasing the need for intubation within 12 hours of arrival.

Self-Assembled Anion-Binding Cryptand for the Selective Liquid-Liquid Extraction of Phosphate Anions.

The ligands L1 and L2 form trinuclear self-assembled complexes with Cu2+ (i.e. [(L1 )2 Cu3 ]6+ or [(L2 )2 Cu3 ]6+ ) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions.

The catalytic mechanism for aerobic formation of methane by bacteria.

Methane is a potent greenhouse gas that is produced in significant quantities by aerobic marine organisms. These bacteria apparently catalyse the formation of methane through the cleavage of the highly unreactive carbon-phosphorus bond in methyl phosphonate (MPn), but the biological or terrestrial source of this compound is unclear. However, the ocean-dwelling bacterium Nitrosopumilus maritimus catalyses the biosynthesis of MPn from 2-hydroxyethyl phosphonate and the bacterial C-P lyase complex is known to convert MPn to methane. In addition to MPn, the bacterial C-P lyase complex catalyses C-P bond cleavage of many alkyl phosphonates when the environmental concentration of phosphate is low. PhnJ from the C-P lyase complex catalyses an unprecedented C-P bond cleavage reaction of ribose-1-phosphonate-5-phosphate to methane and ribose-1,2-cyclic-phosphate-5-phosphate. This reaction requires a redox-active [4Fe-4S]-cluster and S-adenosyl-L-methionine, which is reductively cleaved to L-methionine and 5'-deoxyadenosine. Here we show that PhnJ is a novel radical S-adenosyl-L-methionine enzyme that catalyses C-P bond cleavage through the initial formation of a 5'-deoxyadenosyl radical and two protein-based radicals localized at Gly 32 and Cys 272. During this transformation, the pro-R hydrogen from Gly 32 is transferred to the 5'-deoxyadenosyl radical to form 5'-deoxyadenosine and the pro-S hydrogen is transferred to the radical intermediate that ultimately generates methane. A comprehensive reaction mechanism is proposed for cleavage of the C-P bond by the C-P lyase complex that uses a covalent thiophosphate intermediate for methane and phosphate formation.

Eye injury from electrical weapon probes: Mechanisms and treatment.

PURPOSE: While generally reducing morbidity and mortality, TASER® electrical weapons have risks associated with their usage, including burn injuries and head and cervical trauma associated with uncontrolled falls. The primary non-fatal complications appear to be significant eye injury but no analysis of the mechanisms or suggested treatments has been published. METHODS: We used a biomechanical model to predict the risk of eye injury as a function of distance from the weapon muzzle to the eye. We compared our model results to recently published epidemiological findings. We also describe the typical presentation and suggest treatment options. RESULTS: The globe rupture model predicted that a globe rupture can be expected (50% risk) when the eye is within 6 m of the muzzle and decreases rapidly beyond that. This critical distance is 9 m for lens and retinal damage which is approximately the range of the most common probe cartridges. Beyond 9 m, hyphema is expected along with a perforation by the dart portion of the probe. Our prediction of globe rupture out to 6 m (out of a typical range of 9 m) is consistent with the published risk of enucleation or unilateral blindness being 69 ±â€¯18%, with an eye penetration. CONCLUSIONS: Significant eye injury is expected from a penetration by an electrical weapon probe at close range. The risk decreases rapidly at extended distances from the muzzle. Not all penetrating globe injuries from electrical weapon probes will result in blindness.

Medical Simulation as a Vital Adjunct to Identifying Clinical Life-Threatening Gaps in Austere Environments.

BACKGROUND: Maternal mortality and morbidity are major causes of death in low-resource countries, especially those in Sub-Saharan Africa. Healthcare workforce scarcities present in these locations result in poor perioperative care access and quality. These scarcities also limit the capacity for progressive development and enhancement of workforce training, and skills through continuing medical education. Newly available low-cost, in-situ simulation systems make it possible for a small cadre of trainers to use simulation to identify areas needing improvement and to rehearse best practice approaches, relevant to the context of target environments. METHODS: Nurse anesthetists were recruited throughout Sierra Leone to participate in simulation-based obstetric anesthesia scenarios at the country's national referral maternity hospital. All subjects participated in a detailed computer assisted training program to familiarize themselves with the Universal Anesthesia Machine (UAM). An expert panel rated the morbidity/mortality risk of pre-identified critical incidents within the scenario via the Delphi process. Participant responses to critical incidents were observed during these scenarios. Participants had an obstetric anesthesia pretest and post-test as well as debrief sessions focused on reviewing the significance of critical incident responses observed during the scenario. RESULTS: 21 nurse anesthetists, (20% of anesthesia providers nationally) participated. Median age was 41 years and median experience practicing anesthesia was 3.5 years. Most participants (57.1%) were female, two-thirds (66.7%) performed obstetrics anesthesia daily but 57.1% had no experience using the UAM. During the simulation, participants were observed and assessed on critical incident responses for case preparation with a median score of 7 out of 13 points, anesthesia management with a median score of 10 out of 20 points and rapid sequence intubation with a median score of 3 out of 10 points. CONCLUSION: This study identified substantial risks to patient care and provides evidence to support the feasibility and value of in-situ simulation-based performance assessment for identifying critical gaps in safe anesthesia care in the low-resource settings. Further investigations may validate the impact and sustainability of simulation based training on skills transfer and retention among anesthesia providers low resource environments.

Aminofutalosine Synthase: Evidence for Captodative and Aryl Radical Intermediates Using ß-Scission and SRN1 Trapping Reactions.

Aminofutalosine synthase (MqnE) is a radical SAM enzyme involved in the menaquinone biosynthetic pathway. In this communication, we propose a novel mechanism for this reaction involving the addition of the adenosyl radical to the substrate double bond to form a captodative radical followed by rearrangement and decarboxylation to form an aryl radical anion which is then oxidized by the [4Fe-4S]+2 cluster. Consistent with this proposal, we describe the trapping of the captodative radical and the aryl radical anion using radical triggered C-Br fragmentation reactions. We also describe the trapping of the captodative radical by replacing the vinylic carboxylic acid with an amide.

An Aerodigestive Approach to Laryngeal Clefts and Dysphagia Using Injection Laryngoplasty in Young Children.

PURPOSE OF REVIEW: Our objective is to summarize the presentation, diagnosis, and management of mild laryngeal clefts in children. We focus on deep interarytenoid notches (DIN), a subclassification of type 1 laryngeal clefts (LC1), and review the literature and our multidisciplinary experience utilizing injection laryngoplasty (IL). RECENT FINDINGS: DIN is a mild form of LC1 and is considered a normal anatomical variant. Recent cohort studies demonstrate IL to be a safe, low-risk, and efficacious treatment of LC1, but few studies focus on DIN. We present results from two aerodigestive clinic (ADC) pilot studies at our institution, in patients 1-3 years old, with DIN-related dysphagia and aspiration (DA). Feeding, respiratory-related symptom scores, and aspiration/penetration assessed on modified barium swallow (MBS) significantly improved following combined IL and feeding therapy using a thickener weaning protocol (TWP). Subgroup analysis reveals combined IL and TWP to be particularly effective in patients with severe baseline DA. Multidisciplinary aerodigestive evaluation and management with IL and feeding therapy focused on weaning levels of thickener is emerging as a novel and effective approach for treatment of DIN-related DA in young children. Further comparative, prospective trials investigating effects of IL and feeding therapy are required to validate results.

Intermediates in the transformation of phosphonates to phosphate by bacteria.

Phosphorus is an essential element for all known forms of life. In living systems, phosphorus is an integral component of nucleic acids, carbohydrates and phospholipids, where it is incorporated as a derivative of phosphate. However, most Gram-negative bacteria have the capability to use phosphonates as a nutritional source of phosphorus under conditions of phosphate starvation. In these organisms, methylphosphonate is converted to phosphate and methane. In a formal sense, this transformation is a hydrolytic cleavage of a carbon-phosphorus (C-P) bond, but a general enzymatic mechanism for the activation and conversion of alkylphosphonates to phosphate and an alkane has not been elucidated despite much effort for more than two decades. The actual mechanism for C-P bond cleavage is likely to be a radical-based transformation. In Escherichia coli, the catalytic machinery for the C-P lyase reaction has been localized to the phn gene cluster. This operon consists of the 14 genes phnC, phnD, …, phnP. Genetic and biochemical experiments have demonstrated that the genes phnG, phnH, …, phnM encode proteins that are essential for the conversion of phosphonates to phosphate and that the proteins encoded by the other genes in the operon have auxiliary functions. There are no functional annotations for any of the seven proteins considered essential for C-P bond cleavage. Here we show that methylphosphonate reacts with MgATP to form α-D-ribose-1-methylphosphonate-5-triphosphate (RPnTP) and adenine. The triphosphate moiety of RPnTP is hydrolysed to pyrophosphate and α-D-ribose-1-methylphosphonate-5-phosphate (PRPn). The C-P bond of PRPn is subsequently cleaved in a radical-based reaction producing α-D-ribose-1,2-cyclic-phosphate-5-phosphate and methane in the presence of S-adenosyl-L-methionine. Substantial quantities of phosphonates are produced worldwide for industrial processes, detergents, herbicides and pharmaceuticals. Our elucidation of the chemical steps for the biodegradation of alkylphosphonates shows how these compounds can be metabolized and recycled to phosphate.

Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG.

The azinomycins are a family of potent antitumor agents with the ability to form interstrand cross-links with DNA. This study reports on the unusual biosynthetic formation of the 5-methyl naphthoate moiety, which is essential for effective DNA association. While sequence analysis predicts that the polyketide synthase (AziB) catalyzes the formation of this naphthoate, 2-methylbenzoic acid, a truncated single-ring product, is formed instead. We demonstrate that the thioesterase (AziG) acts as a chain elongation and cyclization (CEC) domain and is required for the additional two rounds of chain extension to form the expected product.

Do trauma center levels matter in older isolated hip fracture patients?

BACKGROUND: Younger, multi-trauma patients have improved survival when treated at a trauma center. Many regions now propose that older patients be triaged to a higher level trauma centers (HLTCs-level I or II) versus lower level trauma centers (LLTCs-level III or nondesignated TC), even for isolated injury, despite the absence of an established benefit in this elderly cohort. We therefore sought to determine if older isolated hip fracture patients have improved survival outcomes based on trauma center level. METHODS: A retrospective cohort of 1.07 million patients in The Nationwide Emergency Department Sample from 2006-2010 was used to identify 239,288 isolated hip fracture patients aged ≥65 y. Multivariable logistic regression was performed controlling for patient- and hospital-level variables. The main outcome measures were inhospital mortality and discharge disposition. RESULTS: Unadjusted logistic regression analyses revealed 8% higher odds of mortality (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.00-1.16) and 10% lower odds of being discharged home (OR, 0.90; 95% CI, 0.80-1.00) among patients admitted to an HLTC versus LLTC. After controlling for patient- and hospital-level factors, neither the odds of mortality (OR, 1.06; 95% CI, 0.97-1.15) nor the odds of discharge to home (OR, 0.98; 95% CI, 0.85-1.12) differed significantly between patients treated at an HLTC versus LLTC. CONCLUSIONS: Among patients with isolated hip fractures admitted to HLTCs, mortality and discharge disposition do not differ from similar patients admitted to LLTCs. These findings have important implications for trauma systems and triage protocols.

Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity.

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 µM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

l-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota.

A previously unknown metabolic pathway for the utilization of l-galactose was discovered in a prevalent gut bacterium, Bacteroides vulgatus. The new pathway consists of three previously uncharacterized enzymes that were found to be responsible for the conversion of l-galactose to d-tagaturonate. Bvu0219 (l-galactose dehydrogenase) was determined to oxidize l-galactose to l-galactono-1,5-lactone with kcat and kcat/Km values of 21 s(-1) and 2.0 × 10(5) M(-1) s(-1), respectively. The kinetic product of Bvu0219 is rapidly converted nonenzymatically to the thermodynamically more stable l-galactono-1,4-lactone. Bvu0220 (l-galactono-1,5-lactonase) hydrolyzes both the kinetic and thermodynamic products of Bvu0219 to l-galactonate. However, l-galactono-1,5-lactone is estimated to be hydrolyzed 300-fold faster than its thermodynamically more stable counterpart, l-galactono-1,4-lactone. In the final step of this pathway, Bvu0222 (l-galactonate dehydrogenase) oxidizes l-galactonate to d-tagaturonate with kcat and kcat/Km values of 0.6 s(-1) and 1.7 × 10(4) M(-1) s(-1), respectively. In the reverse direction, d-tagaturonate is reduced to l-galactonate with values of kcat and kcat/Km of 90 s(-1) and 1.6 × 10(5) M(-1) s(-1), respectively. d-Tagaturonate is subsequently converted to d-glyceraldehyde and pyruvate through enzymes encoded within the degradation pathway for d-glucuronate and d-galacturonate.