Synthesis, Optical Characterization in Solution and Solid-State, and DFT Calculations of 3-Acetyl and 3-(1'-(2'-Phenylhydrazono)ethyl)-coumarin-(7)-substituted Derivatives.

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a-d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones (2a-d) were synthesized in 74-65% yields. The UV-Vis data were in the 295-428 nm range. The emission depends on the substituent in position C-7 bearing electron-donating groups. Compounds 1b-d showed good optical properties due to the D-π-A structural arrangement. In compounds 2a-d, there is a quenching effect of fluorescence in solution. However, in the solid, an increase is shown due to an aggregation-induced emission (AIE) effect given by the rotational restraints and stacking in the crystal. Computational calculations of the HOMO-LUMO orbitals indicate high absorbance and emission values of the molecules, and gap values represent the bathochromic effect and the electronic efficiency of the compounds. Compounds 1a-d and 2a-d are good candidates for optical applications, such as OLEDs, organic solar cells, or fluorescence markers.

Cytotoxic Acetogenins from the Roots of Annona purpurea.

Annona purpurea, known in Mexico as "cabeza de negro" or "ilama", belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A-E (1-5). These compounds have an aliphatic chain of 37 carbons with a terminal α,ß unsaturated γ-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) α-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF α,α'-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1-4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM).

Solventless Synthesis of Poly(pyrazolyl)phenyl-methane Ligands and Thermal Transformation of Tris(3,5-dimethylpyrazol-1-yl)phenylmethane.

The solventless synthesis of tris(pyrazolyl)phenylmethane ligands of formula C6H5C(PzR2)3 (R = H, Me), starting from PhCCl3 and 3,5-dimethylpyrazole (PzMe2) or pyrazole (Pz) was performed. The sterically crowded C6H5C(PzMe2)3 is thermally transformed into the bis(pyrazolyl)(p-pyrazolyl)phenylmethane ligand PzMe2-C6H4CH(PzMe2)2. In this compound both PzMe2 rings are linked through the N-atom to the methine C-atom. At higher temperatures, the binding mode of PzMe2 changes from N1 to C4. All transformations occurred via quinonoid carbocation intermediates that undergo an aromatic electrophilic substitution on the 4-position of PzMe2. Reaction conditions were established to obtain five tris(pyrazolyl)phenylmethane ligands in moderate to good yields. ¹H- and 13C-NMR spectroscopy and X-ray diffraction of single crystals support the proposed structures.

Solid state structure and solution thermodynamics of three-centered hydrogen bonds (O∙∙∙H∙∙∙O) using N-(2-benzoyl-phenyl) oxalyl derivatives as model compounds.

Intramolecular hydrogen bond (HB) formation was analyzed in the model compounds N-(2-benzoylphenyl)acetamide, N-(2-benzoylphenyl)oxalamate and N1,N2-bis(2-benzoylphenyl)oxalamide. The formation of three-center hydrogen bonds in oxalyl derivatives was demonstrated in the solid state by the X-ray diffraction analysis of the geometric parameters associated with the molecular structures. The solvent effect on the chemical shift of H6 [δH6(DMSO-d6)-δH6(CDCl3)] and Δδ(ΝΗ)/ΔT measurements, in DMSO-d6 as solvent, have been used to establish the energetics associated with intramolecular hydrogen bonding. Two center intramolecular HB is not allowed in N-(2-benzoylphenyl)acetamide either in the solid state or in DMSO-d6 solution because of the unfavorable steric effects of the o-benzoyl group. The estimated ΔHº and ΔSº values for the hydrogen bonding disruption by DMSO-d6 of 28.3(0.1) kJ·mol-1 and 69.1(0.4) J·mol-1·K-1 for oxalamide, are in agreement with intramolecular three-center hydrogen bonding in solution. In the solid, the benzoyl group contributes to develop 1-D and 2-D crystal networks, through C-H∙∙∙A (A = O, π) and dipolar C=O∙∙∙A (A = CO, π) interactions, in oxalyl derivatives. To the best of our knowledge, this is the first example where three-center hydrogen bond is claimed to overcome steric constraints.

Evaluation of Mis-Selection of End Vertebrae and Its Effect on Measuring Cobb Angle and Curve Length in Adolescent Idiopathic Scoliosis.

Background: The Cobb angle is critical in assessing adolescent idiopathic scoliosis (AIS) patients. This study aimed to evaluate the error in selecting the upper- and lower-end vertebrae on AIS digital X-rays by experienced and novice observers and its correlation with the error in measuring the Cobb angle and determining the length of the scoliotic curves. Methods: Using the TraumaMeter v.873 software, eight raters independently evaluated 68 scoliotic curves. Results: The error percentage in the upper-end vertebra selection was higher than for the lower-end vertebra (44.7%, CI95% 41.05-48.3 compared to 35%, CI95% 29.7-40.4). The mean bias error (MBE) was 0.45 (CI95% 0.38-0.52) for the upper-end vertebra and 0.35 (CI% 0.69-0.91) for the lower-end vertebra. The percentage of errors in the choice of the end vertebrae was lower for the experienced than for the novices. There was a positive correlation (r = 0.673, p = 0.000) between the error in selecting the end vertebrae and determining the length of the scoliotic curves. Conclusions: We can conclude that errors in selecting end vertebrae are common among experienced and novice observers, with a greater error frequency for the upper-end vertebrae. Contrary to the consensus, the accuracy of determining the length of the scoliotic curve is limited by the Cobb method's reliance on the correct selection of the end vertebrae.

Molecular structure and selective theophylline complexation by conformational change of diethyl N,N'-(1,3-phenylene)dicarbamate.

The receptor ability of diethyl N,N'-(1,3-phenylene)dicarbamate (1) to form host-guest complexes with theophylline (TEO) and caffeine (CAF) by mechanochemistry was evaluated. The formation of the 1-TEO complex (C12H16N2O4·C7H8N4O2) was preferred and involves the conformational change of one of the ethyl carbamate groups of 1 from the endo conformation to the exo conformation to allow the formation of intermolecular interactions. The formation of an N-H...O=C hydrogen bond between 1 and TEO triggers the conformational change of 1. CAF molecules are unable to form an N-H...O=C hydrogen bond with 1, making the conformational change and, therefore, the formation of the complex impossible. Conformational change and selective binding were monitored by IR spectroscopy, solid-state 13C nuclear magnetic resonance and single-crystal X-ray diffraction. The 1-TEO complex was characterized by IR spectroscopy, solid-state 13C nuclear magnetic resonance, powder X-ray diffraction and single-crystal X-ray diffraction.

Ethanolic Extract of Salvia officinalis Leaves Affects Viability, Survival, Migration, and the Formation and Growth of 3D Cultures of the Tumourigenic Murine HPV-16+-Related Cancer Cell Line.

Salvia officinalis (SO) is one of the most widely used plants in traditional medicine worldwide. In the present study, the effect of an ethanolic extract of S. officinalis leaves on hallmarks of cancer of HPV-16-positive cancer tumorigenic cells, TC-1, was analyzed in vitro. Phytochemical and spectroscopic analysis were performed. Additionally, the extract's flavonoid content, reducing iron, and antioxidant capacity were determined. In regard to the in vitro tests, the cytotoxic activity and its effect on the replicative capacity and on the cell migration of TC-1 cells were analyzed by viability and clonogenic, survival, and wound healing assays. The effect of a pre-treatment or treatment on 3D culture formation, growth, and reversion capacity was also examined. The results of the phytochemical analysis allowed the detection of tannins, saponins, steroids, and flavonoids. The flavonoids content was found to be 153.40 ± 10.68 µg/mg of extract. Additionally, the extract exhibited an antioxidant capacity and a ferric-reducing capacity of around 40% compared to the ascorbic acid. Thin layer chromatographic (TLC) analysis and spectroscopic tests showed the presence of compounds similar to quercetin and catechin flavonoids in the extract. In the in vitro assays, the SO extract induced in a concentration-dependent way changes in cell morphology, the decrease of cell viability, survival, and migration. At a concentration of 125 µg/mL, the extract inhibited spheroid formation, reduced their growth, and affected their reversion to 2D. Ethanolic extract of S. officinalis leaves had inhibitory effects on hallmarks of the cancer line HPV-16+. This suggests that the phytochemicals present in it may be a source of chemotherapeutics against cervical cancer.

NMR structural study of the prototropic equilibrium in solution of Schiff bases as model compounds.

An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

Helical supramolecular assembly of N2,N2')bis[3-(morpholin-4-yl)propyl]-N1,N1'-(1,2-phenylene)dioxalamide dimethyl sulfoxide monosolvate.

In the title compound, C(24)H(36)N(6)O(6)·C(2)H(6)OS, the carbonyl groups are in an antiperiplanar conformation, with O=C-C=O torsion angles of 178.59 (15) and -172.08 (16)°. An intramolecular hydrogen-bonding pattern is depicted by four N-H...O interactions, which form two adjacent S(5)S(5) motifs, and an N-H...N interaction, which forms an S(6) ring motif. Intermolecular N-H...O hydrogen bonding and C-H...O soft interactions allow the formation of a meso-helix. The title compound is the first example of a helical 1,2-phenylenedioxalamide. The oxalamide traps one molecule of dimethyl sulfoxide through N-H...O hydrogen bonding. C-H...O soft interactions give rise to the two-dimensional structure.

Crystal structure and characterization of the sulfamethazine-piperidine salt.

Sulfamethazine [N1-(4,6-dimethylpyrimidin-2-yl)sulfanilamide] is an antimicrobial drug that possesses functional groups capable of acting as hydrogen-bond donors and acceptors, which make it a suitable supramolecular building block for the formation of cocrystals and salts. We report here the crystal structure and solid-state characterization of the 1:1 salt piperidinium sulfamethazinate (PPD+·SUL-, C5H12N+·C12H13N4O2S-) (I). The salt was obtained by the solvent-assisted grinding method and was characterized by IR spectroscopy, powder X-ray diffraction, solid-state 13C NMR spectroscopy and thermal analysis [differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)]. Salt I crystallized in the monoclinic space group P21/n and showed a 1:1 stoichiometry revealing proton transfer from SUL to PPD to form salt I. The PPD+ and SUL- ions are connected by N-H+...O and N-H+...N interactions. The self-assembly of SUL- anions displays the amine-sulfa C(8) motif. The supramolecular architecture of salt I revealed the formation of interconnected supramolecular sheets.

Integration of Square Fiducial Markers in Patient-Specific Instrumentation and Their Applicability in Knee Surgery.

Computer technologies play a crucial role in orthopaedic surgery and are essential in personalising different treatments. Recent advances allow the usage of augmented reality (AR) for many orthopaedic procedures, which include different types of knee surgery. AR assigns the interaction between virtual environments and the physical world, allowing both to intermingle (AR superimposes information on real objects in real-time) through an optical device and allows personalising different processes for each patient. This article aims to describe the integration of fiducial markers in planning knee surgeries and to perform a narrative description of the latest publications on AR applications in knee surgery. Augmented reality-assisted knee surgery is an emerging set of techniques that can increase accuracy, efficiency, and safety and decrease the radiation exposure (in some surgical procedures, such as osteotomies) of other conventional methods. Initial clinical experience with AR projection based on ArUco-type artificial marker sensors has shown promising results and received positive operator feedback. Once initial clinical safety and efficacy have been demonstrated, the continued experience should be studied to validate this technology and generate further innovation in this rapidly evolving field.

The Use of Human Sterilized Crushed Tooth Particles Compared with BTCP Biomaterial and Empty Defects in Bone Formation inside Critical Rabbit Calvaria Sites.

This study aimed to assess the bone regeneration of critical-size defects in rabbit calvaria filled with freshly crushed extracted teeth, comparing them with BTCP biomaterial and empty sites. Materials and methods: Twenty-one female New Zealand rabbits were used in this study. Two critical-size defects 6 mm in size were created in the skull bone, each with a 3 mm separation between them. Three experimental groups were evaluated: Group A (human sterilized crushed teeth granules alone), Group B (Bioner Bone, Bioner Sitemas Implantológicos), and Group C (unfilled defects). The animals were sacrificed at 4 and 8 weeks. Evaluation of the samples involved histological and histomorphometric analyses with radiographic evaluation. The histological evaluation showed a higher volume reduction in Group A compared with Group B (p < 0.05) and Control. Group A showed the highest values for cortical closure and bone formation around the particles, followed by Group B and Group C (p < 0.05). Within the limitations of this animal study, we can conclude that the use of human tooth particles leads to increased bone formation and reduced connective tissue in critical-size defects in rabbit calvaria when compared to BTCP biomaterial. The calvarial model is a robust base for the evaluation of different biomaterials.

Indolealkylamines in the venom of the scorpion Thorellius intrepidus.

Scorpions are a group of arthropods that strike fear in many people due to their severe medical symptoms, even death, caused by their venomous stings. Even so, not all scorpion species contain harmful venoms against humans but still have valuable bioactive molecules, which could be used in developing new pharmaceutical leads for treating important diseases. This work conducted a comprehensive analysis of the venom from the scorpion Thorellius intrepidus. The venom of T. intrepidus was separated by size exclusion chromatography, and four main fractions were obtained. Fraction IV (FIV) contained small molecules representing over 90% of the total absorbance at 280 nm. Analysis of fraction FIV by RP-HPLC indicated the presence of three main molecules (FIV.1, FIV.2, and FIV.3) with similar UV absorbance spectra profiles. The molecular masses of FIV.1, FIV.2, and FIV.3 were determined, resulting in 175.99, 190.07, and 218.16 Da, respectively. Further confirmation through 1H-NMR and 13C-NMR analyses revealed that these molecules were serotonin, N-methylserotonin, and bufotenidine. These intriguing compounds are speculated to play a pivotal role in self-defense and increasing venom toxicity and could also offer promising biotechnological applications as small bioactive molecules.

Tracking SARS-CoV-2 introductions in Mozambique using pandemic-scale phylogenies: a retrospective observational study.

BACKGROUND: From the start of the SARS-CoV-2 outbreak, global sequencing efforts have generated an unprecedented amount of genomic data. Nonetheless, unequal sampling between high-income and low-income countries hinders the implementation of genomic surveillance systems at the global and local level. Filling the knowledge gaps of genomic information and understanding pandemic dynamics in low-income countries is essential for public health decision making and to prepare for future pandemics. In this context, we aimed to discover the timing and origin of SARS-CoV-2 variant introductions in Mozambique, taking advantage of pandemic-scale phylogenies. METHODS: We did a retrospective, observational study in southern Mozambique. Patients from Manhiça presenting with respiratory symptoms were recruited, and those enrolled in clinical trials were excluded. Data were included from three sources: (1) a prospective hospital-based surveillance study (MozCOVID), recruiting patients living in Manhiça, attending the Manhiça district hospital, and fulfilling the criteria of suspected COVID-19 case according to WHO; (2) symptomatic and asymptomatic individuals with SARS-CoV-2 infection recruited by the National Surveillance system; and (3) sequences from SARS-CoV-2-infected Mozambican cases deposited on the Global Initiative on Sharing Avian Influenza Data database. Positive samples amenable for sequencing were analysed. We used Ultrafast Sample placement on Existing tRees to understand the dynamics of beta and delta waves, using available genomic data. This tool can reconstruct a phylogeny with millions of sequences by efficient sample placement in a tree. We reconstructed a phylogeny (~7·6 million sequences) adding new and publicly available beta and delta sequences. FINDINGS: A total of 5793 patients were recruited between Nov 1, 2020, and Aug 31, 2021. During this time, 133 328 COVID-19 cases were reported in Mozambique. 280 good quality new SARS-CoV-2 sequences were obtained after the inclusion criteria were applied and an additional 652 beta (B.1.351) and delta (B.1.617.2) public sequences were included from Mozambique. We evaluated 373 beta and 559 delta sequences. We identified 187 beta introductions (including 295 sequences), divided in 42 transmission groups and 145 unique introductions, mostly from South Africa, between August, 2020 and July, 2021. For delta, we identified 220 introductions (including 494 sequences), with 49 transmission groups and 171 unique introductions, mostly from the UK, India, and South Africa, between April and November, 2021. INTERPRETATION: The timing and origin of introductions suggests that movement restrictions effectively avoided introductions from non-African countries, but not from surrounding countries. Our results raise questions about the imbalance between the consequences of restrictions and health benefits. This new understanding of pandemic dynamics in Mozambique can be used to inform public health interventions to control the spread of new variants. FUNDING: European and Developing Countries Clinical Trials, European Research Council, Bill & Melinda Gates Foundation, and Agència de Gestió d'Ajuts Universitaris i de Recerca.

Synthesis and in vitro antioxidant activity evaluation of 3-carboxycoumarin derivatives and QSAR study of their DPPH• radical scavenging activity.

The in vitro antioxidant activities of eight 3-carboxycoumarin derivatives were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazil (DPPH•) radical scavenging activity method. 3-Acetyl-6-hydroxy-2H-1-benzopyran-2-one (C1) and ethyl 6-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate (C2) presented the best radical-scavenging activity. A quantitative structure-activity relationship (QSAR) study was performed and correlated with the experimental DPPH• scavenging data. We used structural, geometrical, topological and quantum-chemical descriptors selected with Genetic Algorithms in order to determine which of these parameters are responsible of the observed DPPH• radical scavenging activity. We constructed a back propagation neural network with the hydrophilic factor (Hy) descriptor to generate an adequate architecture of neurons for the system description. The mathematical model showed a multiple determination coefficient of 0.9196 and a root mean squared error of 0.0851. Our results shows that the presence of hydroxyl groups on the ring structure of 3-carboxy-coumarins are correlated with the observed DPPH• radical scavenging activity effects.

(E)-4-Hy-droxy-2-{[(2-phenyl-eth-yl)iminium-yl]meth-yl}phenolate.

The title Schiff base compound, C(15)H(15)NO(2), crystallized as the iminium-phenolate zwitterion. The H atom is localized on the imine N atom, forming a strong intra-molecular hydrogen bond with the phenolate O atom, and giving rise to an S(6) ring motif. The mol-ecule has an E conformation about the C=N bond. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains propagating along [010]. There are also C-H⋯O inter-actions present.

Crystal structures of cocrystals of 2,7-dihydroxynaphthalene with isoniazid and piracetam.

Cocrystals of 2,7-dihydroxynaphthalene (DHN, or naphthalene-2,7-diol) with isoniazid (pyridine-4-carbohydrazide) (INH), denoted DHN-INH [C10H8O2·C6H7N3O, (I)], and piracetam [2-(2-oxopyrrolidin-1-yl)acetamide] (PIR), denoted DHN-PIR [C10H8O2·C6H10N2O2, (II)], were obtained by the solvent-assisted grinding method and characterized by IR spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. Cocrystal (I) crystallized in the triclinic space group P-1 and showed a 2:2 stoichiometry. DHN and INH molecules are connected by O-H...N(pyridine) and O-H...N(hydrazide) hydrogen bonds. Cocrystal (II) crystallized in the space group Pca21 with a 1:1 stoichiometry. DHN and PIR molecules are connected by O-H...O=C hydrogen bonds. The supramolecular architecture of cocrystal (I) showed interlinked supramolecular tapes; meanwhile, in cocrystal (II), interlinked supramolecular sheets were observed.

Reliability of the posterior condylar offset.

The posterior condylar offset (PCO) has been proposed as a determinant of a postoperative range of motion after total knee arthroplasty, although there is no consensus. This study aimed to demonstrate the error introduced by forcing the femoral rotation to overlap both condyles for the "true" lateral X-ray projection for the PCO measurement. We hypothesize that the angular discrepancy between the posterior femoral cortical reference plane and the posterior condylar axis plane due to rotation invalidates the acquisition of reliable measurements on X-rays. We have measured the PCO in 50 "true" lateral X-rays and compared it with the medial and lateral condyles PCO's assessed on a computed tomography-scan-based three-dimensional (3D) model of each knee. PCO based on the 3D imaging differed significantly between the medial (25.8 ± 3.67 mm) and lateral (16.59 ± 2.92 mm) condyle. Three-dimensional PCO values differ significantly from those determined in the radiographic studies. Also, the mean values of the medial and lateral condyle PCO measurements differed significantly (p < 0.001) with all PCO measurements on radiographs. We have identified a difference between the posterior cortical plane and the posterior condylar axis projections, both on the axial plane with a mean value of 11.23° ± 3.64°. Our data show an interplane discrepancy angle between the posterior femoral diaphyseal cortical and the posterior condylar axis plane (due to the femur's necessary rotation to overlap both condyles) may invalidate the 2D X-ray PCO assessment as a reliable measurement.

Use of the Xiaomi Mi Band for sleep monitoring and its influence on the daily life of older people living in a nursing home.

Background: Lower quantity and poorer sleep quality are common in most older adults, especially for those who live in a nursing home. The use of wearable devices, which measure some parameters such as the sleep stages, could help to determine the influence of sleep quality in daily activity among nursing home residents. Therefore, this study aims to analyse the influence of sleep and its changes concerning the health status and daily activity of older people who lived in a nursing home, by monitoring the participants for a year with Xiaomi Mi Band 2. Methods: This is a longitudinal study set in a nursing home in [Details omitted for double-anonymized peer reviewed]. The Xiaomi Mi Band 2 will be used to measure biomedical parameters and different assessment tools will be administered to participants for evaluating their quality of life, sleep quality, cognitive state, and daily functioning. Results: A total of 21 nursing home residents participated in the study, with a mean age of 86.38 ± 9.26. The main outcomes were that sleep may influence daily activity, cognitive state, quality of life, and level of dependence in activities of daily life. Moreover, environmental factors and the passage of time could also impact sleep. Conclusions: Xiaomi Mi Band 2 could be an objective tool to assess the sleep of older adults and know its impact on some factors related to health status and quality of life of older nursing homes residents. Trial Registration: NCT04592796 (Registered 16 October 2020) Available on: https://clinicaltrials.gov/ct2/show/NCT04592796.

Computed Tomography-Based Patient-Specific Instrumentation Loses Accuracy with Significant Varus Preoperative Misalignment.

Patient-specific instrumentation (PSI) has been introduced to simplify and make total knee arthroplasty (TKA) surgery more precise, effective, and efficient. We performed this study to determine whether the postoperative coronal alignment is related to preoperative deformity when computed tomography (CT)-based PSI is used for TKA surgery, and how the PSI approach compares with deformity correction obtained with conventional instrumentation. We analyzed pre- and post-operative full length standing hip-knee-ankle (HKA) X-rays of the lower limb in both groups using a convention > 180 degrees for valgus alignment and < 180 degrees for varus alignment. For the PSI group, the mean (± SD) pre-operative HKA angle was 172.09 degrees varus (± 6.69 degrees) with a maximum varus alignment of 21.5 degrees (HKA 158.5) and a maximum valgus alignment of 14.0 degrees. The mean post-operative HKA was 179.43 degrees varus (± 2.32 degrees) with a maximum varus alignment of seven degrees and a maximum valgus alignment of six degrees. There has been a weak correlation among the values of the pre- and post-operative HKA angle. The adjusted odds ratio (aOR) of postoperative alignment outside the range of 180 ± 3 degrees was significantly higher with a preoperative varus misalignment of 15 degrees or more (aOR: 4.18; 95% confidence interval: 1.35-12.96; p = 0.013). In the control group (conventional instrumentation), this loss of accuracy occurs with preoperative misalignment of 10 degrees. Preoperative misalignment below 15 degrees appears to present minimal influence on postoperative alignment when a CT-based PSI system is used. The CT-based PSI tends to lose accuracy with preoperative varus misalignment over 15 degrees.