Modulating Helix-preference of an Axially-twisted Molecular Scaffold Through Diastereomeric Salt Formation with Tartaric Acid Stereoisomers.

Herein, we designed a chiral, axially-twisted molecular scaffold (ATMS) using pyridine-2,6-dicarboxamide (PDC) unit as pivot, chiral trans-cyclohexanediamine (CHDA) residues as linkers, and pyrene residues as fluorescent reporters. R,R-ATMS exclusively adopted M-helicity and produced differential response in UV-vis, fluorescence, and NMR upon addition of tartaric acid (TA) stereoisomers allowing naked-eye detection and enantiomeric excess determination. Circular dichroism (CD) profile of R,R-ATMS underwent unique changes during titration with TA stereoisomers - while loss of CD signal at 345 nm was observed with equimolar D-TA and meso-TA, inversion was seen with equimolar L-TA. Temperature increase weakened these interactions to partially recover the original CD signature of R,R-ATMS. 2D NMR studies also indicated the significant structural changes in R,R-ATMS in the solution state upon addition of L-TA. Single crystal X-ray diffraction (SCXRD) studies on the crystals of the R,R-ATMS⊃D-TA salt revealed the interacting partners stacked in arrays and ATMS molecules stabilized by π-π stacking between its PDC and pyrene residues. Contrastingly, tightly-packed supramolecular cages comprised of four molecules each of R,R-ATMS and L-TA were seen in R,R-ATMS⊃L-TA salt, and the ATMS molecules contorted to achieve CH-π interactions between its pyrene residues. These results may have implications in modulating the helicity of topologically-similar larger biomolecules.

CPAK classification cannot be used to determine segmental coronal extra-articular knee deformity.

PURPOSE: While the coronal plane alignment of the knee (CPAK) classification serves as a useful guide in personalising total knee arthroplasty (TKA), the extent of its correlation with segmental coronal extra-articular knee deformities remains uncertain. This study aims to investigate the potential correlation between CPAK matrix groups and segmental coronal extra-articular deformities in prearthritic knees, shedding light on the relationship between these two factors that seems to be both essential to perform personalised TKA. MATERIALS AND METHODS: A radiological assessment of 1240 nonarthritic knees was performed by evaluating lower limb measurements following the protocol established by Paley et al. Subsequently, all knees were classified into their respective CPAK matrix groups. In our quest to discern any correlation between the CPAK matrix groups and the presence of segmental coronal extra-articular knee deformities, nine potential coronal extra-articular deformity phenotype (CEDP) groupswere identified based on medial proximal tibial angle (MPTA) and mechanical lateral distal femoral angle (mLDFA). Neutral values for MPTA and mLDFA were set at 90.0° ± 3.0° and then at 87.0° ± 2.0°. Each CPAK matrix group underwent detailed coronal morphology analysis and then, segmental coronal extra-articular deformities were assessed by comparing them with the CEDP groups. RESULTS: The study revealed a mean hip-knee-ankle angle (HKA) of 178.6° ± 4.4°, mLDFA of 86.9° ± 2.5°, MPTA of 85.4° ± 2.4°, arithmetic HKA of -1.4° ± 3.2° and joint line obliquity of 172.5° ± 3.7°. The varus CPAK groups (I/IV/VII) included 435 patients, the neutral groups (II/V/VIII) comprised 630 patients and the valgus groups (III/VI/IX) had 175 patients. Notably, CPAK matrix groups were not distinctly associated with specific coronal extra-articular deformity phenotype (CEDP) groups. Particularly among the most common CPAK matrix groups (I/II/III/IV/V), there was a significant variation in segmental coronal extra-articular deformity patterns. Moreover, when neutral MPTA/mLDFA values were set at 87.0° ± 2.0°, the CPAK matrix groups exhibited even greater variability in coronal extra-articular deformities. CONCLUSION: The CPAK matrix groups do not exhibit a direct correlation with a specific extra-articular deformity pattern (CEDP), thus rendering them unsuitable for determining segmental coronal extra-articular knee deformities. LEVEL OF EVIDENCE: Level III, retrospective diagnostic study.

Association of antiviral drugs and their possible mechanisms with DRESS syndrome using data mining algorithms.

Antiviral drugs are not known for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The current study aims is to find out the association of antiviral drugs and their possible mechanism with DRESS. Data mining algorithms such as proportional reporting ratio that is, PRR (≥2) with associated χ2  value (>4), reporting odds ratio that is, ROR (≥2) with 95% confidence interval and case count (≥3) were calculated to identify a possible signal. Further, molecular docking studies were conducted to check the interaction of selected antiviral drugs with possible targets. The potential signal of DRESS was found to be associated with abacavir, acyclovir, ganciclovir, lamivudine, lopinavir, nevirapine, ribavirin, ritonavir, and zidovudine among all selected antiviral drugs. Further, subgroup analysis has also shown a potential signal in different age groups and gender. The sensitivity analysis results have shown a decrease in the strength of the signal, however, there was no significant impact on the outcome except for acyclovir. The docking results have indicated the possible involvement of human leukocyte antigen (HLA)*B1502 and HLA*B5801. The positive signal of DRESS was found with selected antiviral drugs except for acyclovir.

The joint line convergence angle (JLCA) correlates with intra-articular arthritis.

PURPOSE: Knees with unicompartmental varus osteoarthritis (OA) usually display a combination of tibiofemoral bony deformity and increased joint line convergence angle (JLCA). The JLCA is a product of intra-articular deformity and lateral soft tissue laxity. This study aims to define the correlation between the JLCA and progression of OA. METHODS: A retrospective radiological analysis of 501 patients, who underwent either high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA), was performed. The preoperative OA grade was reported based on the Ahlbäck and the Kellgren-Lawrence (KL). The hip-knee-ankle angle (HKA), the medial proximal tibial angle (MPTA), the mechanical lateral distal femoral angle (mLDFA) and the joint line convergence angle (JLCA) were recorded. The primary outcome was the relationship between the JLCA values and the OA grade. The secondary outcomes were comparing the JLCA and other alignment parameter values between HTO and UKA groups. RESULTS: A total of 501 (59.3% females n = 297) cases were included, comprising 293 cases of HTO and 208 cases of UKA. Patients had a mean age of 57.63 ± 8.97 years, a mean BMI of 28.37 ± 7.39 kg/m2. Patients with Ahlbäck grade 2 represented 49.3% of all patients (n = 247) and patients with KL grade 3 represented 54.7% of all patients (n = 274). A high JLCA was observed in both groups. The reported mean JLCA in the UKA group was 3.69 ± 2.1°, and in the HTO group was 2.93 ± 1.82. There was a significant association between the increase in the JLCA and the progression of OA based on both the Ahlbäck and KL grades (both p values < 0.001). The mean JLCA in patients with Ahlbäck grades 1 and 4 was 1.48 ± 1.32°, and 7 ± 0.93°, respectively. The mean JLCA in patients with KL grades 1 and 4 was 1.77 ± 1.42°, and 4.89 ± 1.73°, respectively. The mean recorded preoperative HKA angle in the UKA group was 175.06 ± 3.08°, and in the HTO group was 173.26 ± 3.02°, whereas the mean MPTA was 88.63 ± 1.72° for the UKA group and 89.31 ± 2.29° for the HTO group. CONCLUSION: The JLCA progressively increases with osteoarthritis progression in patients with unicompartmental varus knee osteoarthritis. The JLCA can potentially be used as a grading parameter for osteoarthritis progression akin to Ahlbäck and Kellgren-Lawrence grading systems.

Identification of novel signal of clobazam-associated drug reaction with eosinophilia and systemic symptoms syndrome: A disproportionality analysis.

OBJECTIVES: Clobazam is a well-known benzodiazepine used as an anti-anxiety drug as well as an anti-epileptic, particularly for patients who are not responding to first-line treatments. Recent case reports have indicated the association of clobazam with drug reaction with eosinophilia systemic symptoms syndrome (DRESS Syndrome). However, DRESS syndrome is not known to be associated with clobazam. Thus, the main objective of the current study was to identify the potential signal of clobazam-associated DRESS Syndrome. MATERIALS & METHODS: US FDA Adverse event reporting system (US FAERS), pharmacovigilance data 2004Q1-2021Q3 was extracted using OpenVigil 2.1-MedDRA-v24. The Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR) with a Chi-Square value (95% confidence interval), and number of cases (≥3) were used as disproportionality analysis parameters. RESULTS: A total of 141 drug-event combinations were reported and results of disproportionality analysis indicate the positive signal of DRESS syndrome with clobazam. The signal strength was decreased after removing the cases of concomitantly administered drugs (phenytoin, levetiracetam, and valproic acid); however, the association of clobazam with DRESS syndrome remains statistically significant. The subgroup analysis results have shown a greater number of cases in the age group (18-64 years) as compared to other age groups whereas the number of cases in the male and female groups is almost similar. CONCLUSION: The DRESS syndrome is identified as a novel signal with clobazam. However, further causality assessment is required.

MTO1-RESPONDING DOWN 1 (MRD1) is a transcriptional target of OZF1 for promoting salicylic acid-mediated defense in Arabidopsis.

KEY MESSAGE: OZF1 promotes the transcription of MRD1, which is essential for SA-mediated defense against virulent and avirulent bacterial pathogens in Arabidopsis. Salicylic acid (SA) is critical for defense against biotrophic pathogens. A trans-activator protein NPR1 plays significant roles in SA-signaling. However, evidences suggest the existence of NPR1-independent pathways for SA signaling in plants. Previously, we reported Arabidopsis OXIDATION-RELATED ZN-FINGER PROTEIN1 (OZF1) as a positive regulator of NPR1-independent SA-signaling. However, the mechanism or components of OZF1-mediated SA signaling was not known. Through the analysis of differentially expressing genes, we report the identification of MTO1-RESPONDING DOWN 1 (MRD1) as a transcriptional target of OZF1. Expressions of MRD1 and its overlapping gene in Arabidopsis genome, HEI10 increase upon pathogen inoculation in an OZF1-dependent manner. Their mutants are susceptible to both virulent and avirulent bacterial pathogens and show compromised SA-mediated immunity. Overexpression of MRD1 but not the HEI10 rescues the loss-of-resistance phenotype of the ozf1 mutant. OZF1 physically associates at the MRD1 promoter area upon pathogen inoculation. Results altogether support that MRD1 is a transcriptional target of OZF1 for promoting SA-mediated defense in Arabidopsis.

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study.

OBJECTIVE: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs). METHODS: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups. RESULTS: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months). CONCLUSIONS: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections.

Neutral alignment resulting from tibial vara and opposite femoral valgus is the main morphologic pattern in healthy middle-aged patients: an exploration of a 3D-CT database.

PURPOSE: Given the goal of achieving optimal correction and alignment after knee arthroplasty or high tibial osteotomy, literature focusing on the inter-individual variability of the native knee, tibia and femur with regards to the coronal or sagittal alignment is lacking. The aim of this study was to analyse normal angular values in the healthy middle-aged population and determine differences of angular values according to inter-individual features. The first hypothesis was that common morphological patterns may be identified in the healthy middle-aged non-osteoarthritic population. The second hypothesis was that high inter-individual variability exists with regards to gender, ethnicity and alignment phenotype. METHODS: A CT scan-based modelling and analysis system was used to examine the lower limb of 758 normal healthy patients (390 men, 368 women; mean age 58.5 ± 16.4 years) with available data concerning angular values and retrieved from the SOMA database. The hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), posterior distal femoral angle (PDFA), posterior proximal tibial angle (PPTA) and non weight-bearing joint line convergence angle (nwJLCA) were then measured for each patient. Results were analysed for the entire cohort and based on gender, ethnicity and phenotype. RESULTS: The mean HKA was 179.4° ± 2.6°, LDFA: 85.8° ± 2.0°, MPTA: 85.6° ± 2.4°, PDFA: 85.2° ± 1.5°, PPTA: 83.8° ± 2.9° and nwJLCA: 1.09° ± 0.9°. Gender was associated with higher LDFA and lower HKA for men. Ethnicity was associated with greater proximal tibial vara and distal femoral valgus for Asian patients. Patients with an overall global varus alignment had more tibia vara and less femoral valgus than patients with an overall valgus alignment. CONCLUSION: Even if significant differences were found based on subgroup analysis (gender, ethnicity or phenotype), this study demonstrated that neutral alignment is the main morphological pattern in the healthy middle-aged population. This neutrality is the result from tibia vara compensated by an ipsilateral femoral valgus. LEVEL OF CLINICAL EVIDENCE: III, retrospective cohort study.

Highly Crosslinked Polyethylene Can Reduce Wear Rate in THA for High-Demand Patients: A Matched-Paired Controlled Study.

BACKGROUND: The average age of patients benefiting from total hip arthroplasty (THA) has been declining. In addition to pain relief, patients seek to return to physical activity. However, the latter may increase polyethylene wear and therefore the potential risk of early aseptic loosening. The introduction of highly crosslinked polyethylene (HXLPE) has reduced wear rates in the general patient population. The objective of this study was to evaluate the influence of impact sports in patients operated with THA using ceramic-on-conventional polyethylene (cPE) versus ceramic-on-HXLPE, in terms of wear and function, with a minimum of five year follow-up. METHODS: Sixty-eight patients practicing an impact sport (University of California Los Angeles score ≥8) who underwent a primary THA were included: 34 with a ceramic-on-cPE versus 34 with a ceramic-on-HXLPE using the same cementless acetabular and femoral component. Patients were matched-paired by age, sex, BMI, and University of California Los Angeles score. The wear analysis was performed using the IMAGIKA software. The Harris hip score and hip and osteoarthritis outcome score were collected. RESULTS: The linear wear rate was statistically higher (P < .0001) in the cPE group (0.13503 ± 0.0630 mm/year) than in the HXLPE group (0.03059 ± 0.0084 mm/year). Postoperatively, the increase in Harris hip score was calculated at 37.64 for the entire cohort and was comparable in both groups (P = .3674). The hip and osteoarthritis outcome score for pain (P = .0009), daily life activities (P = .0016), and quality of life (P = .0179) were significantly higher in the HXLPE group, with, between groups, a difference inferior to the reported minimal clinical important difference. Three patients exhibited signs of periprosthetic osteolysis in the cPE group, one on the femoral side and two on the acetabular side. None were observed in the HXLPE group. No revision for aseptic loosening was reported in both cohorts. CONCLUSION: Patients partaking in impact sports and receiving a ceramic-on-HXLPE THA demonstrated lower wear and osteolysis rates than those having a ceramic-on-cPE THA, with similar functional results.

Transcriptional signatures modulating shoot apical meristem morphometric and plant architectural traits enhance yield and productivity in chickpea.

Plant height (PH) and plant width (PW), two of the major plant architectural traits determining the yield and productivity of a crop, are defined by diverse morphometric characteristics of the shoot apical meristem (SAM). The identification of potential molecular tags from a single gene that simultaneously modulates these plant/SAM architectural traits is therefore prerequisite to achieve enhanced yield and productivity in crop plants, including chickpea. Large-scale multienvironment phenotyping of the association panel and mapping population have ascertained the efficacy of three vital SAM morphometric trait parameters, SAM width, SAM height and SAM area, as key indicators to unravel the genetic basis of the wide PW and PH trait variations observed in desi chickpea. This study integrated a genome-wide association study (GWAS); quantitative trait locus (QTL)/fine-mapping and map-based cloning with molecular haplotyping; transcript profiling; and protein-DNA interaction assays for the dissection of plant architectural traits in chickpea. These exertions delineated natural alleles and superior haplotypes from a CabHLH121 transcription factor (TF) gene within the major QTL governing PW, PH and SAM morphometric traits. A genome-wide protein-DNA interaction assay assured the direct binding of a known stem cell master regulator, CaWUS, to the WOX-homeodomain TF binding sites of a CabHLH121 gene and its constituted haplotypes. The differential expression of CaWUS and transcriptional regulation of its target CabHLH121 gene/haplotypes were apparent, suggesting their collective role in altering SAM morphometric characteristics and plant architectural traits in the contrasting near isogenic lines (NILs). The NILs introgressed with a superior haplotype of a CabHLH121 exhibited optimal PW and desirable PH as well as enhanced yield and productivity without compromising any component of agronomic performance. These molecular signatures of the CabHLH121 TF gene have the potential to regulate both PW and PH traits through the modulation of proliferation, differentiation and maintenance of the meristematic stem cell population in the SAM; therefore, these signatures will be useful in the translational genomic study of chickpea genetic enhancement. The restructured cultivars with desirable PH (semidwarf) and PW will ensure maximal planting density in a specified cultivable field area, thereby enhancing the overall yield and productivity of chickpea. This can essentially facilitate the achievement of better remunerative outputs by farmers with rational land use, therefore ensuring global food security in the present scenario of an increasing population density and shrinking per capita land area.

ABC Transporter-Mediated Transport of Glutathione Conjugates Enhances Seed Yield and Quality in Chickpea.

The identification of functionally relevant molecular tags is vital for genomics-assisted crop improvement and enhancement of seed yield, quality, and productivity in chickpea (Cicer arietinum). The simultaneous improvement of yield/productivity as well as quality traits often requires pyramiding of multiple genes, which remains a major hurdle given various associated epistatic and pleotropic effects. Unfortunately, no single gene that can improve yield/productivity along with quality and other desirable agromorphological traits is known, hampering the genetic enhancement of chickpea. Using a combinatorial genomics-assisted breeding and functional genomics strategy, this study identified natural alleles and haplotypes of an ABCC3-type transporter gene that regulates seed weight, an important domestication trait, by transcriptional regulation and modulation of the transport of glutathione conjugates in seeds of desi and kabuli chickpea. The superior allele/haplotype of this gene introgressed in desi and kabuli near-isogenic lines enhances the seed weight, yield, productivity, and multiple desirable plant architecture and seed-quality traits without compromising agronomic performance. These salient findings can expedite crop improvement endeavors and the development of nutritionally enriched high-yielding cultivars in chickpea.

Increasing Yttrium-90 Dose Conformality Using Proximal Radioembolization Enabled by Distal Angiosomal Truncation for the Treatment of Hepatic Malignancy.

PURPOSE: To evaluate safety and feasibility of improving radiation dose conformality via proximal radioembolization enabled by distal angiosomal truncation where selective administration was not practical. MATERIALS AND METHODS: Hepatic malignancies treated via angiosomal truncation between January 2017 and March 2019 were retrospectively evaluated. Thirty-three patients (8 women, 25 men; mean age, 62.2 y; range, 36-78 y) underwent 39 treatments. Of treatments, 74.3% (n = 29) were for hepatocellular carcinomas, 10.2% (n = 4) were for cholangiocarcinomas, and 15.4% (n = 6) were for metastatic tumors (1 colorectal adenocarcinoma, 1 pancreatic adenocarcinoma, 3 melanomas, and 1 endometroid carcinoma). Truncation was achieved using temporary embolic devices including a microvascular plug, detachable coil, gelatin slurry, and balloon microcatheter, after which proximal radioembolization was performed. Range of treatment activity was 0.47-5.75 GBq. Technetium-99m macroaggregated albumin and bremsstrahlung single photon emission computed tomography (CT)/CT threshold analysis was conducted to delineate and compare distribution of activity within the treatment angiosome before and after radioembolization. RESULTS: Dosimetric analysis of 14 patients demonstrated a significant reduction in nontarget liver radiation exposure at 5, 20, and 40% thresholds (P = .002, P = .001, and P = .008, respectively). There were no grade 3 or higher adverse events. There was no significant change in Albumin-Bilirubin grade and Eastern Cooperative Oncology Group Performance Status (P = .09 and P = .74) before and 3 months after the procedure. Truncated arteries were patent on subsequent angiography in 11 cases and on MR angiography or CT angiography in 38 of 39 cases. CONCLUSIONS: Proximal radioembolization enabled by distal angiosomal truncation is safe and decreases nontarget parenchymal radioembolization dose in cases not amenable to selective administration.

Presoaking of Semitendinosus Graft With Vancomycin Does Not Alter Its Biomechanical Properties: A Biomechanical In Vitro-Controlled Study Using Graft From Living Donors.

PURPOSE: To compare the biomechanical properties of human semitendinosus graft presoaked with or without vancomycin under a load to failure tensile test. METHODS: Thirty semitendinosus grafts harvested during anterior cruciate ligament reconstruction were included. These were dissected equally into 2 halves and subsequently randomly allocated to a vancomycin group and to a control group. A digital caliper was used to precisely measure each samples thickness, length, and width. For the vancomycin group, samples were presoaked in a solution of 5 mg/mL vancomycin for a duration of 10 minutes and the control group samples were presoaked in a physiological serum equally for 10 minutes. Mechanical testing was performed on a universal testing machine (Instron 5566-A) after a preconditioning of 10 cycles of 1 mm extension and a progression of 10 mm/min to failure for each sample. The stress-strain curve was obtained to determine the elastic modulus (Young's modulus), the ultimate tensile stress, the ultimate tensile elongation (UTE) before failure and the elasticity limit. RESULTS: For the control group, the average Young's modulus value was 4.8 ± 0.8, the average UTS was 25.2 ± 5.2 MPa, the average percentage of UTE was 78 ± 17%, and the average elasticity limit value was 17.3 ± 5.3 MPa. For the vancomycin group, the average Young's modulus value was 4.7 ± 0.9, the average ultimate tensile stress was 24.1 ± 6.1 MPa, the average percentage of UTE was 82 ± 14%, and the average elasticity limit value was 18.5 ± 5.9 MPa. No significant difference was observed between the 2 groups for all investigated parameters. CONCLUSIONS: Presoaking of human semitendinosus graft with vancomycin does not alter its biomechanical properties. CLINICAL RELEVANCE: This study demonstrates that vancomycin presoaking used to prevent post-anterior cruciate ligament reconstruction septic arthritis does not affect immediate biomechanical properties of semitendinosus tendons.

Patient-specific high-tibial osteotomy's 'cutting-guides' decrease operating time and the number of fluoroscopic images taken after a Brief Learning Curve.

PURPOSE: Patient-specific cutting guides (PSCGs) have been advocated to improve the accuracy of deformity correction in opening-wedge high-tibial osteotomies (HTO). It was hypothesized that PSCGs for HTO would have a short learning curve. Therefore, the goals of this study were to determine the surgeons learning curve for PSCGs used for opening-wedge HTO assessing: the operating time, surgeons comfort levels, number of fluoroscopic images, accuracy of post-operative limb alignment and functional outcomes. METHODS: This prospective cohort study included 71 consecutive opening-wedge HTO with PSCGs performed by three different surgeons with different experiences. The operating time, the surgeon's anxiety levels evaluated using the Spielberger State-Trait Anxiety Inventory (STAI), the number of fluoroscopic images was systematically and prospectively collected. The accuracy of the postoperative alignment was defined by the difference between the preoperative targeted correction and the final post-operative correction both measured on standardized CT-scans using the same protocol (ΔHKA, ΔMPTA, ΔPPTA). Functional outcomes were evaluated at 1 year using the different sub-scores of the KOOS. Cumulative summation (CUSUM) analyses were used to assess learning curves. RESULTS: The use of PSCGs in HTO surgery was associated with a learning curve of 10 cases to optimize operative time (mean operative time 26.3 min ± 8.8), 8 cases to lessen surgeon anxiety levels, and 9 cases to decrease the number of fluoroscopic images to an average of 4.3 ± 1.2. Cumulative PSCGs experience did not affect accuracy of post-operative limb alignment with a mean: ΔHKA = 1.0° ± 1.0°, ΔMPTA = 0.5° ± 0.6° and ΔPPTA = 0.4° ± 0.8°. No significant difference was observed between the three surgeons for these three parameters. There was no statistical correlation between the number of procedures performed and the patient's functional outcomes. CONCLUSION: The use of PSCGs requires a short learning curve to optimize operating time, reduce the use of fluoroscopy and lessen surgeon's anxiety levels. Additionally, this learning phase does not affect the accuracy of the postoperative correction and the functional results at 1 year. LEVEL OF EVIDENCE: II: prospective observational study.

Contralateral preoperative templating of lower limbs' mechanical angles is a reasonable option.

PURPOSE: In cases where the femur or tibia exhibits abnormal mechanical angulation due to degenerative changes or fracture, the contralateral leg is often used to complete preoperative templating. The aim of this study was to determine the degree of asymmetry between knee joints in healthy individuals and to determine whether it is affected by differing demographic parameters. METHODS: A CT scan-based modelling and analysis system was used to examine the lower limb of 233 patients (102 males, 131 women; mean age 61.2 ± 15.2 years, mean body mass index 24.9 ± 4.4 kg/m2) The hip-knee angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), posterior proximal tibial angle (ppta) and posterior distal femoral angle (PDFA) were then calculated for each patient. Results were then analysed to calculate femoral symmetry based on absolute differences (AD) and percentage asymmetry (%AS) using a previously validated method. RESULTS: Our results do not demonstrate any considerable asymmetry (percentage of asymmetry > 2%) for all the anatomical parameters analysed: HKA (mean AD = 1.5°; mean AS % = 0.8, n.s), MPTA (AD = 1.1°; AS % = 1.3, n.s), PPTA (AD = 1.4°; AS % = 1.0, n.s), LDFA (AD = 1.2 mm; AS % = 1.4, n.s) and PDFA (AD = 0.9°; AS % = 1.0, n.s). Gender and ethnicity were not associated with significantly higher AD asymmetry. A significant correlation of AD asymmetry was observed between BMI and HKA, BMI and MPTA, and between patients' age and the MPTA. CONCLUSION: This data demonstrate that there is a non-statistically significant mechanical angle asymmetry between the two lower limbs. In cases where contralateral templating is used, such asymmetry will induce minimal (if any) clinical differences. LEVEL OF EVIDENCE: IV.

A protective hinge wire, intersecting the osteotomy plane, can reduce the occurrence of perioperative hinge fractures in medial opening wedge osteotomy.

PURPOSE: A recent study reported that positioning a K-wire to intersect the cutting plane at the theoretical lateral hinge location increases the lateral hinge's resistance to fracture during the opening of opening wedge high tibial osteotomy (OWHTO). The purpose of this study was to evaluate the clinical relevance of the use of this K-wire and its benefits in terms of lateral hinge protection during OWHTO in daily practice. METHODS: A retrospective comparative study identified 206 patients who underwent OWHTO from January 2014 to December 2017. Among these patients, 71 had an additional K-wire (HK + group), whereas 135 did not (HK- group). The subjects meeting the inclusion criteria were included in a matched pairing process, which identified 60 patients in the HK + group and 60 patients in the HK- group. Mean follow-up time was 2.3 ± 1.0 years (range 2-4.2). Radiographic outcomes were evaluated with intraoperative and postoperative fluoroscopic imaging and with CT imaging at 6 weeks post OWHTO surgery. The knee osteoarthritis outcomes score (KOOS) was used and time needed to return to work and any kind of sports was collected. RESULTS: Thirty six patients (30%) were found to have a LHF. Among these patients, 26 (72%) did not have an additional K-wire positioned at their theoretical lateral hinge location (HK- group) during the procedure. LHF rate for patients without additional K-wire group (HK-) was 43.3%, whereas it was 16.7% for the patients with an additional K-wire (HK +) [Odd ratio 3.8 95% CI 1.6-8.3; p = 0.005]. The mean time to return to work, return to any kind of sports, and bone union was significantly shorter for HK + group (p < 0.05). CONCLUSION: This study demonstrated that during OWHTO, positioning a K-wire intersecting the cutting plane at the theoretical lateral hinge location reduced the number of intraoperative lateral hinge fractures. LEVEL OF EVIDENCE: III retrospective case-control study.

Adding a protective K-wire during opening high tibial osteotomy increases lateral hinge resistance to fracture.

PURPOSE: It was hypothesized in this in-vitro study that positioning a K-wire intersecting the cutting plane at the theoretical lateral hinge location would limit the cut depth and help preserve the lateral hinge during the opening of the osteotomy. Objectives were (1) to compare the mechanical resistance of the hinge and the protective effect of leaving the K-wire during the opening procedure (2) to check if the K-wire would limit the depth of the osteotomy. METHODS: An ex-vivo mechanical study, testing 5 pairs of fresh-frozen tibias, was designed. CT-scan based Patient-specific cutting guides were obtained to define the cutting plane and the location of the K-wire at the hinge, using standardized 3D planning protocol. In each pair, OWHTO was performed either with or without the K-wire. To evaluate the hinge's resistance to fracture, the specimens were rigidly fixed at the proximal tibia and a direct load was applied on the free tibial diaphysis to open the osteotomy. The maximum load at breakage, maximum permissible displacement and maximal angulation of the osteotomy before hinge failure was measured. To assess the preservation of an unscathed hinge (protected by the K-wire), the distance from the end of the osteotomy cut to the lateral tibial cortical was measured in mm. RESULTS: The maximum load to hinge breakage in the K-wires PsCG knees compared to the control group (48.3 N vs 5.5 N, p = 0.004), the maximum permissible displacement (19.8 mm vs 7.5 mm, p = 0.005) and the maximal angulation of the osteotomy before hinge breakage (9.9° vs 2.9°, p = 0.002) were all statistically superior in the K-wires PsCG knees compared to the control group. A mean distance of 10 ± 1 mm between cut-bone (saw-print) and lateral hinge cortical bone was found post-performing the osteotomy and the hinge failing. CONCLUSION: The maximum load to breakage and the maximum permissible displacement were, respectively, 880% and 260% higher during the opening of the OWHTO in using K-wires compared to the non-K-wire control group. This confirms the mechanical advantage of using a K-wire for both stabilization and protecting the Hinge during OWHTO. This comparative cadaveric study shows an improvement of the lateral hinges resistance to failing during the opening of the osteotomy. This can be achieved by the placement of a K-wire intersecting the cutting plane at the theoretical location of the lateral hinge.

One-Step Assembly of Fluorescence-Based Cyanide Sensors from Inexpensive, Off-The-Shelf Materials.

We report a simple and versatile approach to assemble sensitive and selective fluorescence "turn-on" sensors for cyanide by combining three off-the-shelf materials; namely fluorescent dye, 1-vinyl imidazole polymer, and cupric chloride. The cyanide-sensing species is a non-fluorescent fluorophore-polymer-Cu2+ complex; which forms as a result of the imidazole polymer's ability to bind both fluorophore and fluorescence quencher (Cu2+). Cyanide removes Cu2+ from these complexes; thereby "turning-on" sensor fluorescence. These sensors are water-soluble and have a detection limit of ~2.5 µM (CN-) in water. Our ternary complex-based sensing approach also enables facile emission tuning; we demonstrate the convenient, synthesis-free preparation of blue and green-emitting sensors using distyrylbiphenyl and fluorescein fluorophores, respectively. Furthermore; these ternary complexes are easily immobilized using agarose to create cyanide-sensing hydrogels; which are then used in a simple; novel microdiffusion apparatus to achieve interference-free cyanide analysis of aqueous media. The present study provides an inexpensive approach for portable; interference-free cyanide detection.

Segmental Ileal Dilatation Presenting with Neonatal Intestinal Obstruction.

Segmental ileal dilatation is an uncommon cause of neonatal intestinal obstruction. This report highlights a rare combination of abnormal distribution of muscles in the muscularis propria and partial loss of interstitial cells of Cajal as causative factors for segmental intestinal dilatation.