Towards unlocking the biocontrol potential of Pichia kudriavzevii for plant fungal diseases: in vitro and in vivo assessments with candidate secreted protein prediction.

BACKGROUND: Plant fungal pathogens cause substantial economic losses through crop yield reduction and post-harvest storage losses. The utilization of biocontrol agents presents a sustainable strategy to manage plant diseases, reducing the reliance on hazardous chemical. Recently, Pichia kudriavzevii has emerged as a promising biocontrol agent because of its capacity to inhibit fungal growth, offering a potential solution for plant disease management. RESULTS: Two novel Pichia kudriavzevii strains, Pk_EgyACGEB_O1 and Pk_EgyACGEB_O2, were isolated from olive brine samples. The microscopic characterization of the strains revealed similar structures. However, there were noticeable differences in their visual morphology. Based on their internal transcribed spacer (ITS) DNA sequences, Pk_EgyACGEB_O1 and Pk_EgyACGEB_O2 strains assigned by GenBank IDs MZ507552.1 and MZ507554.1 shared high sequence similarity (~ 99.8% and 99.5%) with P. kudriavzevii, respectively. Both strains were evaluated in vitro against plant pathogenic fungi. The strains revealed the ability to consistently inhibit fungal growth, with Pk_EgyACGEB_O2 showing higher effectiveness. In addition, both P. kudriavzevii strains effectively controlled grey mold disease caused by B. cinerea in golden delicious apples, suggesting their potential as sustainable and eco-friendly biocontrol agents for post-harvest diseases. Based on a comprehensive bioinformatics pipeline, candidate-secreted proteins responsible for the potent antifungal activity of P. kudriavzevii were identified. A total of 59 proteins were identified as common among the P. kudriavzevii CBS573, SD108, and SD129 strains. Approximately 23% of the secreted proteins in the P. kudriavzevii predicted secretome are hydrolases with various activities, including proteases, lipases, glycosidases, phosphatases, esterases, carboxypeptidases, or peptidases. In addition, a set of cell-wall-related proteins was identified, which might enhance the biocontrol activity of P. kudriavzevii by preserving the structure and integrity of the cell wall. A papain inhibitor was also identified and could potentially offer a supplementary defense against plant pathogens. CONCLUSION: Our results revealed the biocontrol capabilities of P. kudriavzevii against plant pathogenic fungi. The research focused on screening novel strains for their ability to inhibit the growth of common pathogens, both in vitro and in vivo. This study shed light on how P. kudriavzevii interacts with fungal pathogens. The findings can help develop effective strategies for managing plant diseases.

Curcumin assisted green synthesis of silver and zinc oxide nanostructures and their antibacterial activity against some clinical pathogenic multi-drug resistant bacteria.

According to WHO warnings, the antibiotic resistance crisis is a severe health issue in the 21st century, attributed to the overuse and misuse of these medications. Consequently, the dramatic spreading rate of the drug-resistant microbial pathogens strains. The microbiological, biochemical tests and antibiotic sensitivity identified the bacteria's multi-drug resistance (MDR). About 150 different clinical samples were taken from hospitalized patients, both males, and females, ranging from 9 to 68 years. Gram-negative strains were (70.0%), while Gram-positive isolates were (30.0%). Among sixteen antibiotics, antibiotic susceptibility of imipenem was found to be the most efficient drug against most of the Gram-negative and Gram-positive isolates, followed by meropenem, depending on the culture and sensitivity results. All the experimental bacteria showed multidrug-resistant phenomena. In this study, green synthesized silver (Cur-Ag NPs) and zinc oxide (Cur-ZnO NPs) nanoparticles in the presence of curcumin extract. In addition, their physicochemical properties have been characterized using different techniques such as UV-Vis spectroscopy, transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and colloidal properties techniques. Furthermore, curcumin-capped silver nanoparticles (AgNPs) exhibited solid antimicrobial action against the experimental bacterial isolates, except Proteus vulgaris (i.e., P. vulgaris). Curcumin-capped zinc oxide nanoparticles (ZnO NPs) found antimicrobial activity against all tested strains. Finally, the minimum inhibitory concentration exhibited values from 3.9 to 15.6 µg ml-1, which is too small compared to other traditional antibiotics. In addition, the green-synthesized Cur-Ag NPs and Cur-ZnO NPs showed good biocompatibility.

Modeling, Synthesis, and Biological Evaluation of Potential Retinoid-X-Receptor (RXR) Selective Agonists: Analogs of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(4-isobutoxy-3-isopropylphenyl)amino)nicotinic Acid (NEt-4IB).

Five novel analogs of 6-(ethyl)(4-isobutoxy-3-isopropylphenyl)amino)nicotinic acid-or NEt-4IB-in addition to seven novel analogs of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), a FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Bexarotene treatment elicits side-effects by provoking or disrupting other RXR-dependent pathways. Analogs were assessed by the modeling of binding to RXR and then evaluated in a human cell-based RXR-RXR mammalian-2-hybrid (M2H) system as well as a RXRE-controlled transcriptional system. The analogs were also tested in KMT2A-MLLT3 leukemia cells and the EC50 and IC50 values were determined for these compounds. Moreover, the analogs were assessed for activation of LXR in an LXRE system as drivers of ApoE expression and subsequent use as potential therapeutics in neurodegenerative disorders, and the results revealed that these compounds exerted a range of differential LXR-RXR activation and selectivity. Furthermore, several of the novel analogs in this study exhibited reduced RARE cross-signaling, implying RXR selectivity. These results demonstrate that modification of partial agonists such as NEt-4IB and potent rexinoids such as bexarotene can lead to compounds with improved RXR selectivity, decreased cross-signaling of other RXR-dependent nuclear receptors, increased LXRE-heterodimer selectivity, and enhanced anti-proliferative potential in leukemia cell lines compared to therapeutics such as 1.

Analysis of Aneuploidy Spectrum From Whole-Genome Sequencing Provides Rapid Assessment of Clonal Variation Within Established Cancer Cell Lines.

BACKGROUND: The revolution in next-generation sequencing (NGS) technology has allowed easy access and sharing of high-throughput sequencing datasets of cancer cell lines and their integrative analyses. However, long-term passaging and culture conditions introduce high levels of genomic and phenotypic diversity in established cell lines resulting in strain differences. Thus, clonal variation in cultured cell lines with respect to the reference standard is a major barrier in systems biology data analyses. Therefore, there is a pressing need for a fast and entry-level assessment of clonal variations within cell lines using their high-throughput sequencing data. RESULTS: We developed a Python-based software, AStra, for de novo estimation of the genome-wide segmental aneuploidy to measure and visually interpret strain-level similarities or differences of cancer cell lines from whole-genome sequencing (WGS). We demonstrated that aneuploidy spectrum can capture the genetic variations in 27 strains of MCF7 breast cancer cell line collected from different laboratories. Performance evaluation of AStra using several cancer sequencing datasets revealed that cancer cell lines exhibit distinct aneuploidy spectra which reflect their previously-reported karyotypic observations. Similarly, AStra successfully identified large-scale DNA copy number variations (CNVs) artificially introduced in simulated WGS datasets. CONCLUSIONS: AStra provides an analytical and visualization platform for rapid and easy comparison between different strains or between cell lines based on their aneuploidy spectra solely using the raw BAM files representing mapped reads. We recommend AStra for rapid first-pass quality assessment of cancer cell lines before integrating scientific datasets that employ deep sequencing. AStra is an open-source software and is available at https://github.com/AISKhalil/AStra.

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

Identification and utilization of copy number information for correcting Hi-C contact map of cancer cell lines.

BACKGROUND: Hi-C and its variant techniques have been developed to capture the spatial organization of chromatin. Normalization of Hi-C contact map is essential for accurate modeling and interpretation of high-throughput chromatin conformation capture (3C) experiments. Hi-C correction tools were originally developed to normalize systematic biases of karyotypically normal cell lines. However, a vast majority of available Hi-C datasets are derived from cancer cell lines that carry multi-level DNA copy number variations (CNVs). CNV regions display over- or under-representation of interaction frequencies compared to CN-neutral regions. Therefore, it is necessary to remove CNV-driven bias from chromatin interaction data of cancer cell lines to generate a euploid-equivalent contact map. RESULTS: We developed the HiCNAtra framework to compute high-resolution CNV profiles from Hi-C or 3C-seq data of cancer cell lines and to correct chromatin contact maps from systematic biases including CNV-associated bias. First, we introduce a novel 'entire-fragment' counting method for better estimation of the read depth (RD) signal from Hi-C reads that recapitulates the whole-genome sequencing (WGS)-derived coverage signal. Second, HiCNAtra employs a multimodal-based hierarchical CNV calling approach, which outperformed OneD and HiNT tools, to accurately identify CNVs of cancer cell lines. Third, incorporating CNV information with other systematic biases, HiCNAtra simultaneously estimates the contribution of each bias and explicitly corrects the interaction matrix using Poisson regression. HiCNAtra normalization abolishes CNV-induced artifacts from the contact map generating a heatmap with homogeneous signal. When benchmarked against OneD, CAIC, and ICE methods using MCF7 cancer cell line, HiCNAtra-corrected heatmap achieves the least 1D signal variation without deforming the inherent chromatin interaction signal. Additionally, HiCNAtra-corrected contact frequencies have minimum correlations with each of the systematic bias sources compared to OneD's explicit method. Visual inspection of CNV profiles and contact maps of cancer cell lines reveals that HiCNAtra is the most robust Hi-C correction tool for ameliorating CNV-induced bias. CONCLUSIONS: HiCNAtra is a Hi-C-based computational tool that provides an analytical and visualization framework for DNA copy number profiling and chromatin contact map correction of karyotypically abnormal cell lines. HiCNAtra is an open-source software implemented in MATLAB and is available at https://github.com/AISKhalil/HiCNAtra .

Hierarchical discovery of large-scale and focal copy number alterations in low-coverage cancer genomes.

BACKGROUND: Detection of DNA copy number alterations (CNAs) is critical to understand genetic diversity, genome evolution and pathological conditions such as cancer. Cancer genomes are plagued with widespread multi-level structural aberrations of chromosomes that pose challenges to discover CNAs of different length scales, and distinct biological origins and functions. Although several computational tools are available to identify CNAs using read depth (RD) signal, they fail to distinguish between large-scale and focal alterations due to inaccurate modeling of the RD signal of cancer genomes. Additionally, RD signal is affected by overdispersion-driven biases at low coverage, which significantly inflate false detection of CNA regions. RESULTS: We have developed CNAtra framework to hierarchically discover and classify 'large-scale' and 'focal' copy number gain/loss from a single whole-genome sequencing (WGS) sample. CNAtra first utilizes a multimodal-based distribution to estimate the copy number (CN) reference from the complex RD profile of the cancer genome. We implemented Savitzky-Golay smoothing filter and Modified Varri segmentation to capture the change points of the RD signal. We then developed a CN state-driven merging algorithm to identify the large segments with distinct copy numbers. Next, we identified focal alterations in each large segment using coverage-based thresholding to mitigate the adverse effects of signal variations. Using cancer cell lines and patient datasets, we confirmed CNAtra's ability to detect and distinguish the segmental aneuploidies and focal alterations. We used realistic simulated data for benchmarking the performance of CNAtra against other single-sample detection tools, where we artificially introduced CNAs in the original cancer profiles. We found that CNAtra is superior in terms of precision, recall and f-measure. CNAtra shows the highest sensitivity of 93 and 97% for detecting large-scale and focal alterations respectively. Visual inspection of CNAs revealed that CNAtra is the most robust detection tool for low-coverage cancer data. CONCLUSIONS: CNAtra is a single-sample CNA detection tool that provides an analytical and visualization framework for CNA profiling without relying on any reference control. It can detect chromosome-level segmental aneuploidies and high-confidence focal alterations, even from low-coverage data. CNAtra is an open-source software implemented in MATLAB®. It is freely available at https://github.com/AISKhalil/CNAtra.

A pragmatic randomized controlled trial exploring the relationship between pulse number and response to repetitive transcranial magnetic stimulation treatment in depression.

BACKGROUND: Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. In particular, it is unclear whether there is a relationship between elements of the dose of stimulation (i.e., number of pulses) and clinical response. To address one aspect of dose, we conducted a trial comparing standard and high dose versions of high frequency left sided and low frequency right sided rTMS protocols (left standard = 50 trains, left high = 125 trains, right standard = 20 min, right high = 60 min, all per day in a single session). METHOD: 300 patients with treatment resistant depression were enrolled in a four arm randomized controlled trial across a four week time period. The primary outcome assessment was a comparison of response and remission rates on data from the 17-item Hamilton Rating Scale for Depression Rating Scale (HRSD-17). RESULTS: The rate of response exceeded 45% in all groups. There was no significant difference between groups on initial analysis of the primary or secondary outcome measures (response rates: standard left = 52.5%, high left = 47.3%, standard right = 49.1%, high right = 48.4%). There was a greater remission rate with high compared to moderate dose left sided treatment when controlling for illness duration. We also found significant improvements in quality of life across all treatment groups. Illness duration was weakly associated with response. CONCLUSIONS: There was no consistent association between the antidepressant effect of rTMS and the number of TMS pulses provided across the ranges investigated in this study. Increasing TMS pulse number in individual sessions seems unlikely to be a method to substantially improve clinical outcomes, and future research should explore alternative means of improving clinical response. The study was registered on the Australian and New Zealand Clinical Trials Register (ACTRN12612000321842) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362063&isReview=true.

Medial Patellofemoral Ligament Reconstruction in Traumatic Patellar Dislocation without Patellar Fixation.

Acute traumatic patellar dislocation is a common injury, and spontaneous reduction may occur at the time of injury or may be reduced at the field of the accident by someone. It may be associated with osteochondral fractures and rupture of medial patellar stabilizers leading to recurrent patellar instability. The aim of this prospective study was to evaluate the outcomes of medial patellofemoral (PF) ligament (MPFL) reconstruction in recurrent traumatic patellar dislocation. Forty-five patients presented with PF instability as a result of traumatic rupture MPFL with normal patellar tracking underwent MPFL reconstruction without patellar fixation hardware through two parallel transpatellar tunnels and one screw in femoral tunnel. All patients were evaluated clinically preoperatively and at a minimum follow-up of 24 months, and International Knee Documentation Committee (IKDC) and Kujala scores were used to assess the clinical results. All patients were available for evaluation at a minimum of 24 months (up to 36 months). The mean age of these patients at the time of surgery was 22.82 years (range: 18-34 years). All patients gave history of trauma of their knees. Mean IKDC scale showed significant improvement as it rose from 47.17 preoperatively to 77.94 postoperatively, and mean Kujala score rose from 53.88 preoperatively to 86.24 postoperatively (p < 0.001). No recurrence of dislocation was recorded. Only three patients had mild atrophy of thigh and one patient had some difficulty in jumping. Reconstruction of MPFL by this method provides good clinical result in the treatment of PF instability by using autologous graft (semitendinosus and gracilis). Less hardware were used with less complications.

Propolis supplementation improved productivity, oxidative status, and immune response of Barki ewes and lambs.

AIM: The present study was conducted to study the effect of propolis administration on bio-hematological parameters, antioxidant enzyme activities, and productivity of Barki ewes during late pregnancy and lactation under the arid conditions. MATERIALS AND METHODS: Twenty-five pregnant Barki ewes were fed the basal diet (n=12, control) and the basal diet plus propolis (5 g/kg diet, n=13) for 1 month before parturition and continued 2 months after parturition. Milk yield and milk composition, hematological constituents, antioxidant enzyme activities, thyroid hormones, and lambs birth and weaning weights, and antioxidants were determined. RESULTS: Significant (p<0.05) increase in white blood cells in the propolis group compared to control was observed. Mean corpuscular hemoglobin (Hb) (MCH) and corpuscular Hb (MCH concentration %) were decreased (p<0.05) in propolis compared to control group. Milk yield was increased (p<0.05) in the propolis group compared with control and continued to increase with the advancement of lactation. Milk fat and milk total solids increased (p<0.05) in the propolis group than the control. Plasma immunoglobulin A (IgA) was increased (p<0.05) in propolis compared to control with no effect in IgM and IgG. Superoxide dismutase, hydrogen peroxide (HP), and nitric oxide were decreased (p<0.01) in the propolis group compared to control. Weaning weight for lambs born to ewes fed propolis was increased (p<0.05) at week 8 after birth compared with control lambs. Malondialdehyde and HP activities were decreased (p<0.01) in lambs born to propolis ewes compared to control. CONCLUSION: Crude Chinese propolis (5 g/d) supplementation improved milk yield, milk composition, and the antioxidant enzymes in Barki ewes and immune functions, growth performance and antioxidant status in their lambs under arid conditions.

Testing Novel Pyrimidinyl Rexinoids: A New Paradigm for Evaluating Rexinoids for Cancer Prevention.

Rexinoids, selective ligands for retinoid X receptors (RXR), have shown promise in preventing many types of cancer. However, the limited efficacy and undesirable lipidemic side-effects of the only clinically approved rexinoid, bexarotene, drive the search for new and better rexinoids. Here we report the evaluation of novel pyrimidinyl (Py) analogues of two known chemopreventive rexinoids, bexarotene (Bex) and LG100268 (LG268) in a new paradigm. We show that these novel derivatives were more effective agents than bexarotene for preventing lung carcinogenesis induced by a carcinogen. In addition, these new analogues have an improved safety profile. PyBex caused less elevation of plasma triglyceride levels than bexarotene, while PyLG268 reduced plasma cholesterol levels and hepatomegaly compared with LG100268. Notably, this new paradigm mechanistically emphasizes the immunomodulatory and anti-inflammatory activities of rexinoids. We reveal new immunomodulatory actions of the above rexinoids, especially their ability to diminish the percentage of macrophages and myeloid-derived suppressor cells in the lung and to redirect activation of M2 macrophages. The rexinoids also potently inhibit critical inflammatory mediators including IL6, IL1ß, CCL9, and nitric oxide synthase (iNOS) induced by lipopolysaccharide. Moreover, in vitro iNOS and SREBP (sterol regulatory element-binding protein) induction assays correlate with in vivo efficacy and toxicity, respectively. Our results not only report novel pyrimidine derivatives of existing rexinoids, but also describe a series of biological screening assays that will guide the synthesis of additional rexinoids. Further progress in rexinoid synthesis, potency, and safety should eventually lead to a clinically acceptable and useful new drug for patients with cancer.

Anatomic Reconstruction of the Anterior Cruciate Ligament of the Knee With or Without Reconstruction of the Anterolateral Ligament: A Randomized Clinical Trial.

BACKGROUND: Rotational instability of the knee remains an issue after anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to evaluate the subjective and objective outcomes of combined reconstruction of the ACL and anterolateral ligament (ALL) of the knee. The hypothesis was that favorable outcomes can be achieved with this surgical procedure compared with isolated anatomic reconstruction of the ACL. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: One hundred ten patients with a unilateral ACL injury and high-grade pivot shift were randomly assigned to undergo either combined ACL and ALL reconstruction (group A) or isolated ACL reconstruction (group B). Preoperative and postoperative evaluations of the patients were conducted by obtaining history details, recording physical examination findings, measuring knee laxity using the KT-1000 arthrometer, and using validated outcome scores for the knee. P < .05 was considered as the cut-off level of statistical significance. The Fisher exact and Mann-Whitney U tests were used to assess statistical significance. RESULTS: At a mean follow-up of 27 months, 53 and 50 patients in groups A and B, respectively, were available for analysis. No statistically different outcomes were found between the 2 groups except for the KT-1000 arthrometer values. The median KT-1000 arthrometer result for combined ACL and ALL reconstruction was 1.3 mm, while the median result for isolated ACL reconstruction was 1.8 mm ( P < .001). None of the patients (n = 0; 0.0%) who underwent combined ACL and ALL reconstruction had anterior translation of greater than 5 mm at maximum pulling strength compared with their normal knees at final follow-up. On the other hand, 3 (6.0%) patients who underwent isolated ACL reconstruction had anterior translation of more than 5 mm. No serious complications were found in both groups. CONCLUSION: Combined ACL and ALL reconstruction was found to be effective in improving subjective and objective outcomes. Nevertheless, these findings were not significantly superior to isolated ACL reconstruction except for the instrumented knee laxity testing results. This might indicate that ALL reconstruction should not be performed routinely for patients undergoing ACL reconstruction.

Extracorporeal shock wave therapy for the treatment of coccydynia: a series of 23 cases.

BACKGROUND: Coccydynia can lead to significant functional disability and worsening of quality of life if not properly managed. In this study, we aim to assess the outcomes of extracorporeal shock wave therapy in patients with coccydynia. METHODS: A prospective case series study was carried out from January to December 2015. Twenty-three patients, mean age of 38.3 ± 12.1 (range 18-64), were included. The majority were females (13; 56.5%), had pain for at least 6 weeks (17; 73.9%) and had trauma to the sacrococcygeal region (17; 73.9%). They had three sessions (one session per week for three consecutive weeks) of focused shock wave therapy directed to the maximal point of coccygeal tenderness. Numerical pain scale and Oswestry disability index were used to assess outcome. RESULTS: Six (26.1%) patients did not complete the follow-up because of no, or minimal, improvement of their pain. After 6 months of follow-up, the median numerical pain scale significantly decreased from 7.0 ± 4.0 to 2.0 ± 2.0 among the 17 patients with coccydynia (p < 0.001). The median Oswestry disability index improved from 24.0 ± 9.0 before therapy to 8.0 ± 9.0 at final follow-up (p < 0.001). Before treatment, 12 (70.6%) patients had moderate-to-severe disability. In contrast, no patients had severe disability and only one (5.9%) patient had moderate disability at final follow-up (p < 0.001). CONCLUSION: Extracorporeal shock wave therapy had favorable outcomes in treating coccydynia. The majority of patients had partial relief of their pain and disability following this therapy.

Cone Beam Guided Corticotomy Using Piezoelectric Surgery.

OBJECTIVES: This study was designed to compare skeletal and dental angular measurements of orthodontic treatment facilitated by cone beam guided corticotomy to that of conventional orthodontic treatment as well as treatment time. METHODS: Twenty female and male adult orthodontic patients with an age range of 19 to 29 years and suffering from bimaxillary protrusion recommended for first premolars extraction were randomly assigned to one of two groups: The test group was treated with a closed technique of corticotomy -facilitated orthodontics using a piezoelectric device and guided by cone beam radiography. The control group was treated with conventional orthodontic treatment. A fixed orthodontic appliance was used and anchorage was done using miniscrews. Cone beam computed tomography (CBCT) was performed for each patient of the test group. Image analysis was done using On Demand Software where linear and angular measurements were taken to virtually assess the configuration of the six anterior teeth together with the position of the lingual and mental foramen. These measurements were transferred to the study model and a surgical guide was constructed. Corticotomy was performed using the piezotome with the aid of the constructed guide. Orthodontic measurements were recorded pre- and post-treatment including total treatment time for both groups. RESULTS: Using a surgical guide, the surgery was a straightforward procedure. At the end of treatment, by comparing the mean change of skeletal angular measurements between the two groups, the control group showed a significant decrease in the mean of change in the facial angle compared to the test group (p ≤ 0.05). By comparing the mean change of dental angular measurements between the two groups, the test group showed a significant decrease in SN - U1° (angle between the sella-nasion line and the maxillary incisor), and a significant increase in the interincisal angle compared to the control group (p ≤ 0.05). Regarding the total treatment time, the test group showed a significant decrease in the mean total treatment time compared to the control group. CONCLUSION: CBCT provided comprehensive information regarding anatomical relationships and individual patient findings for improved diagnosis and treatment planning. The use of a surgical template guided by the cone beam imaging provided a novel conservative technique that simplified the surgical procedure. Corticotomy-facilitated orthodontics showed marked improvement in some skeletal and dental angular measurements compared to conventional orthodontics in patients with bimaxillary protrusion, as well as a decrease in treatment time.

Intratunnel versus extratunnel autologous hamstring double-bundle graft for anterior cruciate ligament reconstruction: a comparison of 2 femoral fixation procedures.

BACKGROUND: Anatomic double-bundle anterior cruciate ligament (ACL) reconstruction provides excellent results for restoring normal kinematics to the knee. Nevertheless, strong evidence supporting an ideal method for fixation of the ACL graft is lacking. HYPOTHESIS: Intratunnel femoral fixation of the ACL graft via a cross-pin fixation technique would provide better clinical and objective results than the extratunnel femoral fixation with cortical buttons. STUDY DESIGN: Randomized clinical trial; Level of evidence, 2. METHODS: Seventy patients with a unilateral ACL-deficient knee were randomly assigned to 1 of 2 femoral fixation groups. Group A (35 patients) was fixed with 2 bioabsorbable Rigidfix pins, 1 cross-pin per bundle, while group B (35 patients) was secured with 1 EndoButton cortical button per bundle. All femoral tunnels were created via an anteromedial portal, and a bioabsorbable Biointrafix interference screw was used for tibial fixation for both groups. The evaluation of the patients was performed by history details, clinical examination findings, measurement of the joint laxity by KT-1000 arthrometer, and use of validated patient outcome questionnaires. Statistical analysis was carried out with Fisher exact and Mann-Whitney U tests, with P<.05 considered the cutoff level of significance. RESULTS: At a mean follow-up of 30 months, 34 and 32 patients of group A and B, respectively, were available for evaluation. There were no statistically significant differences between the treatment groups regarding the subjective and objective outcomes, except for KT-1000 arthrometer values. The median KT-1000 value of patients in the cross-pin fixation group was 1.30 mm, while the median value in the cortical button fixation group was 1.95 mm (P<.001). Four patients with ACL grafts that were fixed with cortical buttons demonstrated failure of stability via the instrumented knee laxity testing, while patients from the other group had no failures. CONCLUSION: Intratunnel femoral fixation of the double-bundle ACL graft from the cross-pin fixation technique provided better instrumented knee laxity results than did the extratunnel femoral fixation with cortical buttons. Future larger studies comparing these 2 techniques should be conducted to ensure the availability of stronger evidence supporting the findings of this study.

Comparação entre os tempos de procedimento e fluoroscopia e o volume de contraste das vias de acesso radial e femoral em pacientes submetidos a cateterismo cardíaco / Comparison of procedural and fluoroscopy times and contrast volume between radial and femoral access for cardiac catheterization

Introdução: Há controvérsias na literatura quanto às vantagens da via radial para cateterismos diagnósticos comparadas às da via femoral. O objetivo deste estudo foi comparar o acesso pelas vias radial e femoral quanto aos tempos de procedimento e de fluoroscopia, e ao volume de contraste utilizado. Métodos: Estudo observacional, retrospectivo, realizado por meio de análise documental de registros de pacientes submetidos consecutivamente ao cateterismo cardíaco, nos meses de julho de 2012 a dezembro de 2013. Resultados: Foram analisados 192 pacientes, sendo a via radial utilizada em 78,1% dos casos. A idade dos pacientes foi de 63,1 ± 11,9 anos, a maioria era do sexo masculino (55,7%) e 21,4% eram diabéticos. O tempo do procedimento foi menor no grupo radial 12,0 minutos (9,0 a 17,2 minutos) vs. 18,3 minutos (12,0 a 34,5 minutos), p < 0,01. O tempo de fluoroscopia foi de 270,0 segundos (180,0 a 389,5 segundos) vs. 244,0 segundos (175,3 a 705,0 segundos), sem diferença entre os grupos (p = 0,59). O volume de contraste foi menor nos pacientes avaliados por via radial 100,0 mL (75,0 a 117,5 mL) vs. 100,0 mL (80,0 a 150,0 mL), p < 0,01. Conclusões: Em nosso laboratório, que privilegiou a via radial como via de acesso para cateterismos cardíacos, os tempos do procedimento e de fluoroscopia, bem como o volume de contraste, foram menores ou comparáveis aos da abordagem femoral...

Background: There is controversy in the literature about the advantages of the radial vs. femoral access route for diagnostic catheterizations. This study aimed to compare the radial and femoral access for procedural and fluoroscopy times and for contrast volume. Methods: This was an observational, retrospective study based on the records of consecutive patients undergoing cardiac catheterization from July 2012 to December 2013. Results: We evaluated 192 patients and the radial access was used in 78.1% of the cases. Mean age was 63.1 ± 11.9 years, most were male (55.7%) and 21.4% had diabetes. Procedural time was lower in the radial group: 12.0 minutes (9.0 to 17.2 minutes) vs. 18.3 minutes (12.0 to 34.5 minutes), p < 0.01. Fluoroscopy time was 270.0 seconds (180.0 to 389.5 seconds) vs. 244.0 seconds (175.3 to 705.0 seconds), and there was no difference between groups (p = 0.59). Contrast volume was lower in the radial group: 100.0 mL (75.0 to 117.5 mL) vs. 100.0 mL (80.0 to 150.0 mL), p < 0.01. Conclusions: In this laboratory, which favored the radial access for cardiac catheterization, procedural and fluoroscopy times, as well as contrast volume, were lower or comparable to the femoral access...

Equivalent beneficial effects of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in a large randomized trial in treatment-resistant major depression.

Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. Recent studies have produced conflicting results as to whether unilateral rTMS is more or less effective than sequentially applied bilateral rTMS. To address this we conducted a trial comparing sequential bilateral rTMS to right-sided unilateral rTMS using a priming protocol. Patients with treatment-resistant depression (n = 179) were enrolled in a two-arm randomized controlled trial across a 4-wk time period. The primary outcome assessment was the Hamilton Depression Rating Scale. Overall, there was a substantial response rate of >50% (and a 40% remission rate); however, there were no significant differences in clinical response between the two treatment groups. rTMS was well tolerated with a very low discontinuation rate. There was no relationship between response in the current trial and previous response, or non-response, to electroconvulsive therapy. We found no significant differences in clinical response between sequential bilateral rTMS and right-sided unilateral rTMS applied with a priming protocol. The results of this study do not support superior efficacy of bilateral rTMS and instead suggest that other approaches should be explored to increase treatment efficacy.

Surgical management of traumatic knee dislocation with posterolateral corner injury.

PURPOSE: To evaluate the results of our method of surgical treatment of traumatic knee dislocation with injury to the posterolateral corner by use of a standardized protocol. METHODS: Twenty-five consecutive patients presented with a grossly dislocated or reduced knee. Five of these patients were not included in this series. The remaining 20 patients were treated by primary arthroscopic reconstruction. The anterior cruciate ligament (ACL) was reconstructed using gracilis tendon reinforced with artificial ligament (Ligament Augmentation and Reconstruction System [LARS] ligament); the posterior cruciate ligament (PCL) was reconstructed with semitendinosus tendon and reinforced with LARS ligament; and the posterolateral corner was treated using the gracilis and semitendinosus tendons from the uninjured knee. Twenty patients returned for subjective and objective evaluation at a minimum of 24 months after surgery. Early mobilization through continuous and active exercise was started on the fourth day postoperatively. RESULTS: At a mean follow-up of 44 months, the mean Lysholm score was 90 points, the mean score on the survey of daily activities was 90 points, and the sports activities score on the knee outcome survey averaged 80 points. By the rating of Meyers et al. the results were excellent in 6 patients, good in 10 patients, fair in 3 patients, and poor in one patient. The final International Knee Documentation Committee (IKDC) rating was not normal in any knee. The mean loss of extension was 2° (range, 0° to 3°) and loss of flexion was 12° (range, 10° to 15°). CONCLUSIONS: By using the described method of arthroscopically assisted reconstruction of the cruciate ligaments and the posterolateral corner, 80% of the patients had good subjective results and functional stability, and according to the IKDC scale, 45% of knees were nearly normal, 45% were abnormal, and 10% were severely abnormal. No patient's rating returned to normal. LEVEL OF EVIDENCE: Level IV, therapeutic case series.