Binuclear Lantern Complexes of All First-Row 3d Metals Scandium to Zinc: Metal-Metal Bond Lengths and Bond Orders, with Measures of Intrinsic Metal-Metal Bond Strength.

The B3LYP and M06-L functionals with the cc-pVTZ basis set are used to study lantern-type binuclear complexes of all the first-row (3d block) metals scandium to zinc in various low-energy spin states, out of which the ground states are predicted. These complexes are studied as models using mostly the unsubstituted formamidinate ligand. For each metal, metal-metal (MM) bond lengths are related to the formal MM bond orders (zero to five), derived by MO analysis and by electron counting. The predicted ground-state spin multiplicities and MM bond lengths of the model complexes generally agree fairly well with available experimental results on substituted analogues. Finally, values of the formal shortness ratio and Wiberg index for the MM bonds in all of these complexes in all spin states studied are categorized into ranges according to the MM bond orders 0 to 5 in steps of 0.5. The trends shown validate their use in estimating intrinsic metal-metal bond strength regardless of the metal.

Glycan-Reactive Innate-like B Cells and Developmental Checkpoints.

Using an Ig H chain conferring specificity for N-acetyl-d-glucosamine (GlcNAc), we developed transgenic (VHHGAC39 TG) mice to study the role of self-antigens in GlcNAc-reactive B-1 B cell development. In VHHGAC39 TG mice, GlcNAc-reactive B-1 B cell development during ontogeny and in adult bone marrow was normal. However, adult TG mice exhibited a block at transitional-2 immature B cell stages, resulting in impaired allelic exclusion and accumulation of a B cell subset coexpressing endogenous Ig gene rearrangements. Similarly, VHHGAC39 B cell fitness was impeded compared with non-self-reactive VHJ558 B TG cells in competitive mixed bone marrow chimeras. Nonetheless, adult VHHGAC39 mice immunized with Streptococcus pyogenes produce anti-GlcNAc Abs. Peritoneal cavity B cells transferred from VHHGAC39 TG mice into RAG-/- mice also exhibited robust expansion and anti-GlcNAc Ab production. However, chronic treatment of young VHHGAC39 mice with GlcNAc-specific mAbs leads to lower GlcNAc-binding B cell frequencies while increasing the proportion of GlcNAc-binding B1-a cells, suggesting that Ag masking or clearance of GlcNAc Ags impedes maturation of newly formed GlcNAc-reactive B cells. Finally, BCR H chain editing promotes expression of endogenous nontransgenic BCR alleles, allowing potentially self-reactive TG B cells to escape anergy or deletion at the transitional stage of precursor B cell development. Collectively, these observations indicate that GlcNAc-reactive B cell development is sensitive to the access of autologous Ags.

Decarbonylation Products of Binuclear Methylphosphinidene Complexes of Cyclopentadienyliron Carbonyls: Triplet and Quintet Structures Are Favored Energetically over Singlet Structures with Iron-Iron Multiple Bonding.

The structures, energetics, and energetically preferred spin states of methylphosphinidene-bridged binuclear cyclopentadienyliron carbonyl complexes MePFe2(CO)nCp2 (n = 4, 3, 2, and 1) related to the experimentally known (µ-RP)Fe2(µ-CO)(CO)2Cp2 (R = cyclohexyl, phenyl, mesityl, and 2,4,6-tBu3C6H2) complexes have been investigated by density functional theory. Singlet structures having a pyramidal pseudotetrahedral phosphorus environment with 18-electron iron configurations are energetically preferred in the tricarbonyl and tetracarbonyl systems MePFe2(CO)nCp2 (n = 4 and 3) with the lowest energy structures of the tricarbonyl very closely resembling the experimentally determined structures. For the more unsaturated dicarbonyl and monocarbonyl systems MePFe2(CO)nCp2 (n = 2 and 1), higher spin state triplet and quintet structures are energetically preferred over singlet structures. These more highly unsaturated structures can be derived from the lowest energy singlet MePFe2(CO)nCp2 (n = 4, 3) by the removal of carbonyl groups. The iron atoms giving up carbonyl groups in their 16- and 14-electron configurations bear the spin density of the unpaired electrons in the higher spin states. The lowest energy singlet structure of the monocarbonyl MePFe2(CO)Cp2, although a relatively high energy isomer, is unusual among the collection of MePFe2(CO)nCp2 (n = 4, 3, 2, and 1) structures by having both the formal Fe=Fe double bond and the four-electron donor MeP unit with the planar phosphorus coordination required to allow each of its iron atoms to attain the favored 18-electron configuration.

Systematics of stable copper and silver clusters protected by small bite chelating bidentate sulfur and selenium ligands related to their polyhedral cavities: analogies to aliphatic compounds and three-dimensional spherical aromatic systems.

Silver and copper clusters capped by external chelating dithiolate ligands can be classified according to the cavities in their central coinage metal polyhedra. Silver clusters composed exclusively of fused tetrahedra are analogous to simple saturated organic compounds. The only interstitial atom that can be fit into an Ag4 tetrahedron is hydrogen. Silver polyhedra with larger trigonal prismatic or cubic cavities, including highly distorted cubic cavities, can accommodate halide and chalcogenide anions. The still larger 12-vertex icosahedral and cuboctahedral coinage metal cavities can accommodate oxoanions of the types SO32- and SO42- and their heavier congeners or alternatively interstitial coinage or platinum group metals leading to central M'@M12 units. Copper clusters with central cuboctahedra and silver clusters with central icosahedra possessing interstitial metal atoms approximate sphericality and provide examples of electron-rich metal superatoms with an average metal oxidation state of less than +1. Such copper cluster superatoms have two extra electrons corresponding to a filled 1S2 superatomic orbital. The silver cluster superatoms are electron richer with eight extra electrons corresponding to filled 1S2 + 1P6 superatomic orbitals. In these silver clusters seven or eight faces of the central Ag12 icosahedron are capped by additional silver atoms in order to provide these additional electrons.

Reliability of a novel point of care device for monitoring diabetic peripheral neuropathy.

We aimed to assess DPNCheck's reliability for repeated sural nerve conduction (NC) parameters. This post hoc analysis used data from the randomized controlled ACUDPN trial assessing NC of the N. Suralis every eight weeks over a 6-month period in 62 patients receiving acupuncture against diabetic peripheral neuropathy (DPN) symptoms. The reliability of DPNCheck for nerve conduction velocity and amplitude was assessed using intraclass correlation coefficients (ICC) and was calculated using data from single time points and repeated measures design. The results of the NC measurements were correlated with the Total Neuropathy Score clinical (TNSc). Overall, for both nerve velocity and amplitude, the reliability at each measurement time point can be described as moderate to good and the reliability using repeated measures design can be described as moderate. Nerve velocity and amplitude showed weak correlation with TNSc. DPNCheck's reliability results question its suitability for monitoring DPN's progression. Given the limitation of our analysis, a long-term, pre-specified, fully crossed study should be carried out among patients with DPN to fully determine the suitability of the device for DPN progression monitoring. This was the first analysis assessing the reliability of the DPNCheck for DPN progression monitoring using data from multiple collection time points.

Spinal cord protection for thoracoabdominal aortic aneurysm repair: from bench to bedside.

This keynote lecture and corresponding presentation discuss the anatomy and pathophysiology surrounding spinal cord injury in aortic surgery. This article will discuss risk factors and mechanisms for spinal cord injury, including loss of direct and collateral spinal cord perfusion and ischemia-reperfusion injury. This review will examine these elements in both the laboratory and clinical setting, in addition to other neuroprotective strategies applied in clinical practice. Addressing spinal cord injury requires an integrated and considerate approach to simultaneously optimize spinal cord blood flow, promote collateralization and improve ischemic tolerance. Given the catastrophic clinical consequences for both the patient and their caregivers, continuing to investigate and examine spinal cord injury is of the utmost importance.

B-1 B Cell-Derived Natural Antibodies against N-Acetyl-d-Glucosamine Suppress Autoimmune Diabetes Pathogenesis.

Environmental factors and host microbiota strongly influence type 1 diabetes (T1D) progression. We report that neonatal immunization with group A Streptococcus suppresses T1D development in NOD mice by promoting clonal expansion of N-acetyl-d-glucosamine (GlcNAc)-specific B-1 B cells that recognize pancreatic ß cell-derived Ags bearing GlcNAc-containing posttranslational modifications. Early exposure to Lancefield group A cell-wall carbohydrate Ags increased production of GlcNAc-reactive serum Abs and enhanced localization of innate-like GlcNAc-specific B cells to pancreatic tissue during T1D pathogenesis. We show that B-1 B cell-derived GlcNAc-specific IgM engages apoptosis-associated ß cell Ags, thereby suppressing diabetogenic T cell activation. Likewise, adoptively transferring GlcNAc-reactive B-1 B cells significantly delayed T1D development in naive recipients. Collectively, these data underscore potentially protective involvement of innate-like B cells and natural Abs in T1D progression. These findings suggest that previously reported associations of reduced T1D risk after GAS infection are B cell dependent and demonstrate the potential for targeting the natural Ab repertoire in considering therapeutic strategies for T1D.

Crohn's patients and healthy infants share immunodominant B cell response to commensal flagellin peptide epitopes.

About half of patients with Crohn's disease (CD) develop selective serum IgG response to flagellin proteins of the Lachnospiraceae family. Here, we identified a dominant B cell peptide epitope in CD, locating in the highly conserved "hinge region" between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Serum IgG reactive to this epitope is present at an elevated level in adult CD patients and in pediatric CD patients at diagnosis. Most importantly, high levels of serum IgG to the hinge epitope were found in most infants from 3 different geographic regions (Uganda, Sweden, and the USA) at one year of age. This vigorous homeostatic response decrements with age as it is not present in healthy adults. These data identify a distinct subset of CD patients, united by a shared reactivity to this dominant flagellin epitope that may represent failure of a homeostatic response beginning in infancy.

Frozen Elephant Trunk for Acute Type A Dissection: Is Risk from Procedure or Patient Characteristics?

BACKGROUND: The initial goal of acute Type A aortic dissection (ATAAD) repair remains to get the patient off the table safely. More extensive repair is being pushed at the index operation with the frozen elephant trunk (FET) operation, but outcomes are suggested to be worse. However, we hypothesize that the risk associated with the FET in ATAAD is from the patient presenting factors rather than the operation itself. METHODS: A retrospective review of a single institution prospective database from 2015 to 2021 was performed. Two cohorts were created based on the indication for FET: evidence of radiographic malperfusion (n = 44) or clinical malperfusion (n = 31). Data were analyzed for preoperative characteristics, intraoperative characteristics, and postoperative outcomes. Statistical univariate analysis was performed with chi-square analysis and t-tests with significance determined at an alpha level of 0.05. RESULTS: Preoperative characteristics were similar in each group, independent of malperfusion markers. The intraoperative characteristics were similar, except the clinical malperfusion group had more packed red blood cells and cryoprecipitate given. The clinical malperfusion group had longer intensive care unit length of stay (p < 0.001), more postoperative strokes (p < 0.001), more reoperations (p <0.0001), and higher mortality rate (p = 0.0003). CONCLUSION: These data suggest that clinical malperfusion increases the risk of major complications and death. However, full arch replacement with FET in the absence of clinical malperfusion does not appear to add risk to the operation for ATAAD. Patients with increased risk of distal degeneration should be considered for more aggressive replacement to avoid subsequent arch replacement.

Long-term spring through fall capture data of Eptesicus fuscus in the eastern USA before and after white-nose syndrome.

Emerging infectious diseases threaten wildlife populations. Without well monitored wildlife systems, it is challenging to determine accurate population and ecosystem losses following disease emergence. North American temperate bats present a unique opportunity for studying the broad impacts of wildlife disease emergence, as their federal monitoring programs were prioritized in the USA throughout the 20th century and they are currently threatened by the invasive fungal pathogen, Pseudogymnoascus destructans (Pd), which causes white-nose syndrome. Here we provide a long-term dataset for capture records of Eptesicus fuscus (big brown bat) across the eastern USA, spanning 16 years before and 14 years after Pd invasion into North America. These data represent 30,496 E. fuscus captures across 3,567 unique sites. We encourage the use of this dataset for quantifying impacts of wildlife disease and other threats to wildlife (e.g., climate change) with the incorporation of other available data. We welcome additional data contributions for E. fuscus captures across North and Central America as well as the inclusion of other variables into the dataset that contribute to the quantification of wildlife health.

Gasless laparoscopy in rural India-registry outcomes and evaluation of the learning curve.

BACKGROUND: A program of gasless laparoscopy (GL) has been implemented in rural North-East India. To facilitate safe adoption, participating rural surgeons underwent rigorous training prior to independent clinical practice. An online registry was established to capture clinical data on safety and efficacy and to evaluate initial learning curves for gasless laparoscopy. METHODS: Surgeons who had completed the GL training program participated in the online RedCap Registry. Patients included in the registry provided informed consent for the use of their data. Data on operative times, conversion rates, perioperative complications, length of stay, and hospital costs were collected. Fixed reference cumulative sum (CUSUM) model was used to evaluate the learning curve based on operative times and conversion rates published in the literature. RESULTS: Four surgeons from three rural hospitals in North-East India participated in the registry. The data were collected over 12 months, from September 2019 to August 2020. One hundred and twenty-three participants underwent GL procedures, including 109 females (88.6%) and 14 males. GL procedures included cholecystectomy, appendicectomy, tubal ligation, ovarian cystectomy, diagnostic laparoscopy, and adhesiolysis. The mean operative time was 75.3 (42.05) minutes for all the surgeries. Conversion from GL to open surgery occurred in 11.4% of participants, with 8.9% converted to conventional laparoscopy. The main reasons for conversion were the inability to secure an operative view, lack of operating space, and adhesions. The mean length of stay was 3 (2.1) days. The complication rate was 5.7%, with one postoperative death. The CUSUM analysis for GL cholecystectomy showed a longer learning curve for operative time and few conversions. The learning curve for GL tubal ligation was relatively shorter. CONCLUSION: Gasless laparoscopy can be safely implemented in the rural settings of Northeast India with appropriate training programs. Careful case selection is essential during the early stages of the surgical learning curve.

Unraveling the Major Differences between the Trinuclear Cyclopentadienylmetal Carbonyl Chemistry of Cobalt and That of Nickel-A Theoretical Study.

The geometries and energetics of the trinuclear cyclopentadienylmetal carbonyls Cp3M3(CO)n (Cp = η5-C5H5); M = Co, Ni; n = 3, 2, 1, 0) have been investigated by density functional theory. The cobalt and nickel systems are found to be rather different owing to the different electronic configurations of the metal atoms. For cobalt, the small calculated energy separation of 5.0 kcal/mol between the two lowest-energy singlet Cp3Co3(µ3-CO)(µ-CO)2 and Cp3Co3(µ-CO)3 tricarbonyl structures accounts for the experimental results of both isomers as stable species that can be isolated and structurally characterized by X-ray crystallography. The corresponding Cp3Ni3(CO)3 species in the nickel system are predicted not to be viable owing to exothermic CO dissociation to give the experimentally observed very stable Cp3Ni3(µ-CO)2, which is found to be the lowest-energy isomer by a substantial margin of ∼25 kcal/mol. In all of the low-energy Cp3M3(CO)n (n = 2, 1) structures, including that of the experimentally known triplet spin state Cp3Co3(µ3-CO)2, all of the carbonyl groups are face-bridging or face-semi-bridging µ3-CO groups bonded to all three metal atoms of the M3 triangle. In the lowest-energy carbonyl-free Cp3M3 (M = Co, Ni) structures, agostic C-H-M interactions are found using hydrogens of the Cp rings. In addition, the lowest-energy Cp3Ni3 is the only structure among all of the low-energy Cp3M3(CO)n (M = Co, Ni; n = 3, 2, 1, 0) structures in which each Cp ring is a bridging rather than terminal ligand.

Polyhedral Ferraboranes with Iron Carbonyl Vertices: Carbonyl Migration Processes in the Iron Tetracarbonyl Derivatives.

The structures and energetics of the neutral Bn-1Hn-1Fe(CO)x (x = 4, 3) and the dianions [Bn-1Hn-1Fe(CO)3]2- (n = 6-14) have been investigated by density functional theory. The low-energy structures of the tricarbonyl dianions [Bn-1Hn-1Fe(CO)3]2- are all found to have closo deltahedral structures in accordance with their 2n+2 skeletal electrons. The low-energy structures of the neutral tricarbonyls Bn-1Hn-1Fe(CO)3 (n = 6-14) with only 2n skeletal electrons are based on capped (n-1)-vertex closo deltahedra (n = 6, 7, 8) or isocloso deltahedra with a degree 6 vertex for the iron atom. The closo 8- and 9-vertex deltahedra are also found in low-energy Bn-1Hn-1Fe(CO)3 structures relating to the nondegeneracy of their frontier molecular orbitals. Carbonyl migration occurs in most of the low-energy structures of the tetracarbonyls Bn-1Hn-1Fe(CO)4. Thus, migration of a carbonyl group from an iron atom to a boron atom gives closo Bn-2Hn-2(BCO)(µ-H)Fe(CO)3 structures with a BCO vertex and a hydrogen atom bridging a B-B deltahedral edge. In other low-energy Bn-1Hn-1Fe(CO)4 structures, a carbonyl group is inserted into the central n-vertex FeBn-1 deltahedron to give a Bn-1Hn-1(CO)Fe(CO)3 structure with a central (n+1)-vertex FeCBn-1 deltahedron that can be an isocloso deltahedron or a µ3-BH face-capped n-vertex FeCBn-2 closo deltahedron. Other low-energy Bn-1Hn-1Fe(CO)4 structures include Bn-1Hn-1Fe(CO)2(µ-CO)2 structures with two of the carbonyl groups bridging FeB2 faces (n = 6, 7, 10) or Fe-B edges (n = 12) or structures in which a closo Bn-1Hn-1 ligand (n = 6, 7, 10, 12) is bonded to an Fe(CO)4 unit with exclusively terminal carbonyl groups through B-H-Fe bridges.

MHC Tetramers Specifically Identify High- and Low-avidity Donor-specific B Cells in Transplantation Tolerance and Rejection.

BACKGROUND: Although donor-specific antibody pre- and posttransplantation is routinely assessed, accurate quantification of memory alloreactive B cells that mediate recall antibody response remains challenging. Major histocompatibility complex (MHC) tetramers have been used to identify alloreactive B cells in mice and humans, but the specificity of this approach has not been rigorously assessed. METHODS: B-cell receptors from MHC tetramer-binding single B cells were expressed as mouse recombinant immunoglobulin G1 (rIgG1) monoclonal antibodies, and the specificity was assessed with a multiplex bead assay. Relative binding avidity of rIgG1 was measured by modified dilution series technique and surface plasmon resonance. Additionally, immunoglobulin heavy chain variable regions of 50 individual B-cell receptors were sequenced to analyze the rate of somatic hypermutation. RESULTS: The multiplex bead assay confirmed that expressed rIgG1 monoclonal antibodies were preferentially bound to bait MHC class II I-E d over control I-A d and I-A b tetramers. Furthermore, the dissociation constant 50 binding avidities of the rIgG1 ranged from 10 mM to 7 nM. The majority of tetramer-binding B cells were low avidity, and ~12.8% to 15.2% from naive and tolerant mice and 30.9% from acute rejecting mice were higher avidity (dissociation constant 50 <1 mM). CONCLUSIONS: Collectively, these studies demonstrate that donor MHC tetramers, under stringent binding conditions with decoy self-MHC tetramers, can specifically identify a broad repertoire of donor-specific B cells under conditions of rejection and tolerance.

Medicine and the Law.

The South African (SA) medical internship training programme model was recently revised to extend training into the primary care platform. In this article, we reflect on the experiences of training under the new model from an intern perspective. We use these reflections to make recommendations to the Health Professions Council of SA on how to further improve the training model by implementing systems that guide and empower the intern doctor practising at a primary level of care.

C3N2: the missing part of highly stable porous graphitic carbon nitride semiconductors.

Two-dimensional (2D) porous graphitic carbon nitrides (PGCNs) with semiconducting features have attracted wide attention because of built-in pores with various active sites, large surface area, and high physicochemical stability. However, only a few PGCNs have been synthesized, covering a 1.23-3.18 eV band gap. We systematically investigate two new 2D PGCN monolayers, T-C3N2 and H-C3N2, including possible pathways for their experimental synthesis. Based on first-principles calculations, the mechanical, electronic, and optical properties of T-C3N2 and H-C3N2 have been systematically investigated. These two architectural frameworks exhibit contrasting mechanical characteristics owing to their structural differences. Both T-C3N2 and H-C3N2 monolayers are predicted to be intrinsic semiconductors. Exceptionally, the stacking bilayers of T-C3N2 can transform into a rare 2D nodal-line semimetal structure. The narrow bandgap (0.35 eV) of the T-C3N2 monolayer and its extraordinary transformation in the bilayer electronic structure fill the vacancy of PGCNs as electronic devices in the middle/long wave infrared region. C3N2 structures possess ultrahigh anisotropic carrier mobilities (×104 cm2 V-1 s-1) and exceptional absorption coefficients (×105 cm-1) in the near-infrared and visible light regions, suggesting its possible optoelectronic applications. The findings expand the scope of 2D PGCNs and offer guides for their experimental realization.

Chemical Bonding Topology of Metal-Centered Polygonal Wheels: Two-Dimensional Analogues of Metallaboranes Related to Benzene and Cyclopentadienide.

The anion [Au@Ru5(CO)15(µ-CO)4]- has a pentagonal wheel structure that can be derived from a hypothetical pentagonal ruthenium carbonyl cluster Ru5(CO)20 by insertion of a gold atom in the center, thereby splitting the original Ru5 pentagon in Ru5(CO)20 into five AuRu2 triangles. The six electrons used to form 3c-2e bonds in three of the five AuRu2 triangles suggest a relationship to the aromatic sextet of the likewise pentagonal cyclopentadienide anion. Furthermore, the pentagonal wheel framework of [Au@Ru5(CO)15(µ-CO)4]- can be derived from a pentagonal bipyramid, such as that found in the deltahedral borane anion B7H72-, by bringing the two C5 axial vertices together at the center of the equatorial pentagon. Similarly, the hexagonal wheel complexes Ni@P6R6 and Pd@Pd6(µ-N═CtBu2)6 with six triangular faces can be derived from a hexagonal bipyramid, such as that found in the dirhenaborane (η5-Me5C5)2Re2B6H4Cl2, by bringing the two C6 axial vertices together at the center of the equatorial hexagon. A reasonable chemical bonding model for the hexagonal wheel complexes has three-fold symmetry with 3c-2e bonds in three of these six triangular faces analogous to the C═C double bonds in a Kekulé structure of benzene.

A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans.

Seasonal influenza vaccination elicits hemagglutinin (HA)-specific memory B (Bmem) cells, and although multiple Bmem cell populations have been characterized, considerable heterogeneity exists. We found that HA-specific human Bmem cells differed in the expression of surface marker FcRL5 and transcriptional factor T-bet. FcRL5+T-bet+ Bmem cells were transcriptionally similar to effector-like memory cells, while T-betnegFcRL5neg Bmem cells exhibited stem-like central memory properties. FcRL5+ Bmem cells did not express plasma-cell-commitment factors but did express transcriptional, epigenetic, metabolic, and functional programs that poised these cells for antibody production. Accordingly, HA+ T-bet+ Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5+ Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) in vitro. The T-bet+ Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet+ Bmem cells were represented in the secondary ASC response to repeat vaccination, suggesting that this effector-like population predicts influenza vaccine durability and recall potential.

Effect modifiers influencing the periodontal healing of the adjacent second molar following mandibular third molar removal.

DATA SOURCES: Studies were selected, using appropriate key words, from the following databases: Cochrane Central Register of Controlled Trials; Medline (via Pubmed); Scopus/Elsevier; and Embase. A manual search was also conducted of five periodontology and oral and maxillofacial surgery journals. It was not clarified what proportion of studies included were derived from which source. STUDY SELECTION: Inclusion criteria included prospective studies and randomised controlled trials published in English, with a minimum 6-month follow-up reporting on parameters of periodontal healing distal to the mandibular second molar following removal of M3M in human subjects. These parameters included pocket probing depth (PPD) reduction and final depth (FD), clinical attachment loss (CAL) reduction and FD, alveolar bone defect (ABD) change and FD. Given prognostic indictors and interventions were investigated, the studies were screened using PICO and PECO (Population, Intervention, Exposure, Comparison, Outcome). Cohen's kappa statistic measured the level of agreement between 2 selecting authors (0.96 stage 1 screening, 1.00 stage 2 screening). Disagreements were resolved with a tie-breaker 3rd author. Ultimately, from 918 studies, 17 met the inclusion criteria and 14 were included in the meta-analysis. Studies were excluded on the basis of same patient pools, non-representative outcomes of interest, insufficient follow-up period, and unclear results. DATA EXTRACTION AND SYNTHESIS: The 17 studies meeting the inclusion criteria underwent validity assessment and data extraction, including risk of bias analysis. Meta-analysis was performed to calculate mean difference and standard error for each outcome measure. If these were unavailable, a correlation coefficient was calculated. Meta-regression was used on different subgroups to determine factors affecting periodontal healing. For all analyses, statistical significance was determined as p < 0.05. Statistical variability in outcomes beyond the expected was estimated using I2 analyses, with a value >50% indicating significant heterogeneity. RESULTS: The periodontal parameters investigated yielded the following results after meta-analysis: overall PPD reduction of 1.06 mm at 6 months and 1.67 mm at 12 months; final PPD of 3.81 mm at 6 months; CAL change of 0.69 mm at 6 months; final CAL of 4.28 mm at 6 months and 4.37 mm at 12 months; ABD reduction of 2.62 mm at 6 months; ABD of 3.2 mm at 6 months. The authors found no statistically significant effect on periodontal healing from the following confounding factors: age; M3M angulation (specifically, mesioangular impaction); optimisation of periodontal health prior to surgery; scaling and root planing of the distal second molar at the time of surgery; post-operative antibiotics or chlorhexidine prophylaxis. There were statistically significant correlations between baseline PPD and final PPD. There was improved PPD reduction at 6 months with a three-sided flap compared to others, and regenerative materials and bone grafts improved all periodontal parameters. CONCLUSIONS: Although M3M removal results in modest improvement in periodontal health distally of the second mandibular molar, periodontal defects remain onwards of 6 months. There is limited evidence suggesting a three-sided flap is more beneficial than an envelope flap in PPD reduction at 6 months. Regenerative materials and bone grafts result in significant improvements across all periodontal health parameters. The most important predictive factor in final PPD of the distal second mandibular molar is baseline PPD.