Cross-cultural adaptation and validation of the KOOS, JR questionnaire for assessing knee osteoarthritis in Spanish-speaking patients.

PURPOSE: The present study aims to translate, adapt and validate a Spanish version of the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR), including a reliability and validity analysis in patients with knee osteoarthritis (OA). METHODS: This study conducted a prospective validation study following the six stages of the "Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures". Psychometric testing was conducted in patients with knee osteoarthritis. Subjects answered the Spanish KOOS, JR (S-KOOS, JR) and a validated Spanish Oxford Knee Score (S-OKS). Retest was conducted at 10 days. Acceptability, floor and ceiling effect, internal consistency (Cronbach's α), reproducibility (mixed-effect model coefficient [MEMC]) and construct validity (Spearman's correlation; p = 0.05) were assessed. RESULTS: Forty-one patients (mean age: 65.6 ± 5.39; 48.8% female) participated in the study. All patients (100%) answered both scores during the first assessment and 38 (92.7%) during the second assessment. All patient-reported outcomes measures were answered completely (100%). The S-KOOS, JR resulted in 100% acceptability when answered. There were no ceiling or floor effects detected. The Cronbach's α for the S-KOOS, JR was 0.927 and its MEMC was 0.852 (CI 95% 0.636-1.078). The Spearman's correlation between the S-KOOS, JR and the S-OKS was 0.711 (CI 0.345-0.608; p < 0.001) and 0.870 (CI 0.444-0.651; p < 0.001) for the first and second assessments, respectively. CONCLUSION: The S-KOOS, JR has very high internal consistency and reproducibility, with a high correlation with the S-OKS; it is a reliable and valid instrument for characterising Spanish-speaking patients suffering from knee OA. LEVEL OF EVIDENCE: IV.

Vancomycin Presoaking of Hamstring Autografts in Anterior Cruciate Ligament Reconstruction Is Associated With Higher Magnetic Resonance Imaging Graft Signal Without Influencing Clinical Outcome.

PURPOSE: To present the clinical and imaging results of a series of patients undergoing anterior cruciate ligament reconstruction with vancomycin presoaking of the hamstring autograft compared with patients in the immediate period prior, when no vancomycin was used. METHODS: This was a retrospective sequential series of patients with anterior cruciate ligament reconstruction using either a graft protocol with no vancomycin presoaking (group 1, January 2013 to October 2015) or a graft protocol with vancomycin presoaking (group 2, November 2015 to December 2018). Lysholm and International Knee Documentation Committee scores were obtained at a minimum 24-month follow-up. Graft ruptures were recorded. Between 6 and 12 months' follow-up, magnetic resonance imaging (MRI) was obtained to evaluate graft healing and integration. RESULTS: There were 102 patients (72% male patients), with 40 in group 1 (mean age, 32.2 years) and 62 in group 2 (mean age, 32.3 years). A graft rupture occurred in 5 patients (13%) in group 1 and 6 patients (10%) in group 2 (P = .65). The median Lysholm score was 95 points (interquartile range [IQR], 86-100 points) in group 1 and 95 points (IQR, 90-100 points) in group 2 (P = .37). The median International Knee Documentation Committee score was 93 points (IQR, 82-99 points) in group 1 and 94 points (IQR, 86-99 points) in group 2 (P = .22). MRI evaluation of integration showed that 87 patients (90%) had no synovial fluid at the tunnel-graft interface, without a difference between groups (P = .24). On the basis of graft signal appearance, hyperintense grafts were found in 45 patients (46%); isointense, 45 (46%); and hypointense, 7 (7%). Group 1 had a higher prevalence of hypointense grafts, whereas group 2 had a higher prevalence of hyperintense and isointense grafts (P = .003). CONCLUSIONS: Vancomycin presoaking of hamstring grafts increased the number of hyperintense and isointense grafts on MRI. Additionally, more hypointense grafts were noted when vancomycin was not used, suggesting the presence of more mature grafts in the non-vancomycin group. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Postoperative Infection After Anterior Cruciate Ligament Reconstruction: Prevention and Management.

Because septic arthritis after anterior cruciate ligament reconstruction is an uncommon complication, information on prevention strategies has not been extensively studied. Recommendations that can be made from the available evidence are as follows: (1) prophylactic intravenous antibiotics should be given preoperatively; (2) patellar tendon autograft use decreases the possibility of a postoperative infection; and (3) vancomycin presoaking of grafts is strongly recommended, especially when performing hamstring autograft anterior cruciate ligament reconstruction. When septic arthritis presents after anterior cruciate ligament reconstruction, early management is crucial to allow a satisfactory outcome. Accordingly, early clinical suspicion is the most important factor to achieve a timely diagnosis. The treatment of choice is arthroscopic lavage with intravenous antibiotic treatment. Graft retention, when possible, is important for obtaining better functional results.

Effective In Vitro Control of Two Phytopathogens of Agricultural Interest Using Cell-Free Extracts of Pseudomonas fluorescens and Chitosan.

A biofungicide is a natural product that can be derived from various sources such as, among others, microorganisms, higher plants, animal products, phytochemicals, semiochemicals, and antagonist microorganisms. One of the most important approaches for the production of biofungicides is the combination of biocontrol agents. This study showed the inhibition growth of Alternaria alternata and Fusarium solani treated with cell-free extracts of P. fluorescens. Using thin-layer chromatography and plate assays it was also demonstrated that the cell-free extracts of P. fluorescens contained siderophores and derivates of 4-diacetylphloroglucinol and phenazine. Moreover, the combination of cell-free extracts of P. fluorescens and chitosan [50-1.5% (v/v)] had a synergistic effect since they notably inhibited the mycelial growth of A. altenata and F. solani. Various morphological alterations to the mycelia and conidia of the treated fungi as a result of this combination were also observed. The present study could be a starting point to control other fungal phytopathogens using different cell-free extracts and chitosan as biocontrol agents.

Nanosystems Applied to HIV Infection: Prevention and Treatments.

Sexually-transmitted infections (STIs) are a global health concern worldwide as they cause acute diseases, infertility, and significant mortality. Among the bacterial, viral, and parasitic pathogens that can be sexually transmitted, human immunodeficiency virus (HIV) has caused one of the most important pandemic diseases, which is acquired immune deficiency syndrome (AIDS). 32.7 million people have died from AIDS-related illnesses since the start of the epidemic. Moreover, in 2019, 38 million people were living with HIV worldwide. The need to deal with this viral infection becomes more obvious, because it represents not only a problem for public health, but also a substantial economic problem. In this context, it is necessary to focus efforts on developing methods for prevention, detection and treatment of HIV infections that significantly reduce the number of newly infected people and provide a better quality of life for patients. For several decades, biomedical research has been developed allowing quick solutions through the contribution of effective tools. One of them is the use of polymers as vehicles, drug carrier agents, or as macromolecular prodrugs. Moreover, nanosystems (NSs) play an especially important role in the diagnosis, prevention, and therapy against HIV infection. The purpose of this work is to review recent research into diverse NSs as potential candidates for prevention and treatment of HIV infection. Firstly, this review highlights the advantages of using nanosized structures for these medical applications. Furthermore, we provide an overview of different types of NSs used for preventing or combating HIV infection. Then, we briefly evaluate the most recent developments associated with prevention and treatment alternatives. Additionally, the implications of using different NSs are also addressed.

Phenylpropanoids Are Connected to Cell Wall Fortification and Stress Tolerance in Avocado Somatic Embryogenesis.

Somatic embryogenesis (SE) is a valuable model for understanding the mechanism of plant embryogenesis and a tool for the mass production of plants. However, establishing SE in avocado has been complicated due to the very low efficiency of embryo induction and plant regeneration. To understand the molecular foundation of the SE induction and development in avocado, we compared embryogenic (EC) and non-embryogenic (NEC) cultures of two avocado varieties using proteomic and metabolomic approaches. Although Criollo and Hass EC exhibited similarities in the proteome and metabolome profile, in general, we observed a more active phenylpropanoid pathway in EC than NEC. This pathway is associated with the tolerance of stress responses, probably through the reinforcement of the cell wall and flavonoid production. We could corroborate that particular polyphenolics compounds, including p-coumaric acid and t-ferulic acid, stimulated the production of somatic embryos in avocado. Exogen phenolic compounds were associated with the modification of the content of endogenous polyphenolic and the induction of the production of the putative auxin-a, adenosine, cellulose and 1,26-hexacosanediol-diferulate. We suggest that in EC of avocado, there is an enhanced phenylpropanoid metabolism for the production of the building blocks of lignin and flavonoid compounds having a role in cell wall reinforcement for tolerating stress response. Data are available at ProteomeXchange with the identifier PXD019705.

Orthopedic surgery residents' perception of online education in their programs during the COVID-19 pandemic: should it be maintained after the crisis?

Background and purpose - During the COVID-19 pandemic, most of the teaching centers in Chile have shifted to online resources. We decided to do a survey on orthopedic residents regarding this type of education to assess for strengths and weaknesses of digital education in orthopedic programs.Methods - A survey was performed targeting 110 orthopedic residents belonging to different training programs around the country. 100 residents completed the survey.Results - 86% stated that their programs are using online education. When asked in detail, 86% had been involved in webinars, 28% had received online presentations, 12% had participated in online tests, and 7% had evaluated patients. Webinars were rated (1 = very unsatisfactory, 10 = very satisfactory) with a mean grade of 8.1 (1-10), online presentations 7.3 (1-10), online tests 3.8 (1-8), and online patient evaluations 2.9 (1-9). When asked if, after the end of the pandemic, they would continue using the online modalities, 82% would continue attending webinars, 72% would continue watching online presentations, 27% would continue performing online tests, and 33% of the residents would continue performing online evaluations of patients.Interpretation - Even though resident evaluation of online activities is positive, face-to-face theoretical activities are still valued as a necessary complement for orthopedic residency education.

Regioselective Photocycloaddition of Saccharin Anion to π-Systems: Continuous-Flow Synthesis of Benzosultams.

Saccharin is a versatile scaffold to build up different heterocycles with relevance in asymmetric catalysis, agricultural chemistry, medicinal chemistry, and so forth. Here, we report a photochemical strategy to obtain seven-membered ring benzosultams in one step, using saccharin anion as starting material. The reaction can be improved in a photoflow reactor and its scope was evaluated. Furthermore, computational study at the CASPT2//CASSCF level of theory was also performed to rationalize the involved mechanism.

Flocculation and Expression of FLO Genes of a Saccharomyces cerevisiae Mezcal Strain with High Stress Tolerance.

Mezcal is a distillate produced by spontaneous fermentation of the must obtained from stalks of Agave spp. plants that are cooked and pressed. Agave must contains a high amount of fructose and phenolic compounds, and fermentation usually occurs under stressful (and uncontrolled) environmental conditions. Yeasts capable of growing under such conditions usually display advantageous biological and industrial traits for stress tolerance such as flocculation. In this study, seven Saccharomyces cerevisiae strains isolated from mezcal must were exposed to temperatures ranging between 10 and 40 °C, and to different sugar sources (fructose or glucose). Yeasts grown in fructose increased their stress tolerance, determined by colony count in a microdrop assay, under low temperature (10 °C) compared to the growth at 40 °C on solid cultures. The most stress-tolerant mezcal strain (Sc3Y8) and a commercial wine (Fermichamp) strain, used as control, were grown under fermentation conditions and exposed to long-term temperature stress to determine their performance and their potential for flocculation. Compared to glucose, fermentation on fructose increased the metabolite accumulation at the end of culture, particularly at 40 °C, with 2.3, 1.3 and 3.4 times more glycerol (8.6 g/L), ethanol (43.6 g/L) and acetic acid (7.3 g/L), respectively. Using confocal microscopy analysis, we detected morphological changes such as aggregation and wall recognition at the level of budding scars in yeast, particularly in the Sc3Y8 strain when it was exposed to 40 °C. The analysis confirmed that this mezcal strain was positive for flocculation in the presence of Ca2+ ions. Analysis of FLO1, FLO5 and FLO11 gene expression implicated in flocculation in both Saccharomyces strains showed a strong transcriptional induction, mainly of the FLO5 gene in the mezcal Sc3Y8 strain.

Five-Strand Hamstring Autograft Versus Quadruple Hamstring Autograft With Graft Diameters 8.0 Millimeters or More in Anterior Cruciate Ligament Reconstruction: Clinical Outcomes With a Minimum 2-Year Follow-Up.

PURPOSE: To compare the outcomes of 2 groups of patients undergoing anterior cruciate ligament (ACL) reconstruction: the first with a quadrupled semitendinosus gracilis (ST-G) autograft larger than 8 mm diameter and the second with a 5-strand ST-G autograft larger than 8 mm due to an insufficient diameter graft harvesting. METHODS: This was a retrospective study with 70 patients divided into 2 groups. Inclusion criteria included ACL ruptures of less than 3 months, ST-G ACL reconstructions, and final (4-strand or 5-strand) graft size larger than 8 mm. Exclusion criteria included multiligament knee injuries, meniscal or chondral pathology, ACL re-ruptures, inflammatory joint disease, or other procedures in the knee. RESULTS: Group A comprised 33 patients with a quadruple ST-G graft, and group B comprised 37 patients with an insufficient graft diameter (<8 mm) in which a 5-strand graft was used. Mean age in group A was 29.7 (range 17-52) years and in group B was 30.6 (range 13-53) years (P = .78). Average follow-up in group A was 32.2 (range 24-48) months and in group B was 30.35 (range 24-48) months (P = .75). Average graft diameter in group A was 8.5 mm (range 8-10) and in group B when the graft was measured as quadruple was 7.2 mm (range 6.5-7.5) and 9.2 mm (range 8-10) when it was converted to 5-strand (P = .00596). Group A had 3 (9%) re-ruptures, and group B had 2 (5.4%) (P = .55). The average postoperative Lysholm score in group A was 93.3 (range 71-100) and in group B was 97.1 (range 80-100) (P = .79). Mean postoperative International Knee Documentation Committee in group A was 91 (range 75.9-100) and in group B was 96.8 (range 82-100) (P = .18). CONCLUSIONS: In our study, the 5-strand hamstring autograft in ACL reconstruction was clinically comparable with the quadruple autograft larger than 8 mm. The differences in re-rupture and clinical outcomes were not statistically significant between the 2 groups, suggesting that it is a valid option when we have a graft of insufficient diameter. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Is There Any Correlation Between Short-Term MRI And Mid-Term Clinical Resultsin Patients Undergoing An Osteochondral Autograft In The Knee?

Thirthy three patients (mean age 32 years) undergoing OA were retrospectively evaluated. All patients had MRI at mean 6.6 months. Lysholm, International Knee Documentation Committee (IKDC), and Tegner scores. The aim is to evaluate Magnetic Resonance Imaging (MRI) in patients who underwent an Osteochondal Autograft (OA) and correlate them with their clinical results-evaluated at mean followup of 28 months (12-88). Tegner Pre-operatively: 6.6, Post-operative: 7.4 (p<0.001). Mean Lysholm: 87, mean IKDC: 86. MRI: complete filling of the lesion in 25 (75.7%) patients, complete integration of the graft in 5 (15.1%) and intact repair tissue in 22 (66.6%. Positive correlation between the degree of repair and filling of the defect and higher Lysholm and IKDC (p<0.05). There is a minor association between short-term MRI and mid-term clinical results after an OA being the degree of repair and filling of the chondral defect the only parameters correlated with patient´s evolution.

Making maxillary barbels with a proximal-distal gradient of Wnt signals in matrix-bound mesenchymal cells.

The evolution of specific appendages is made possible by the ontogenetic deployment of general cell signaling pathways. Many fishes, amphibians and reptiles have unique skin appendages known as barbels, which are poorly understood at the cellular and molecular level. In this study, we examine the cell arrangements, cell division patterns, and gene expression profiles associated with the zebrafish maxillary barbel, or ZMB. The earliest cellular organization of the ZMB is an internal whorl of mesenchymal cells in the dermis of the maxilla; there is no epithelial placode, nor any axially-elongated epithelial cells as expected of an apical ectodermal ridge (AER). As the ZMB develops, cells in S-phase are at first distributed randomly throughout the appendage, gradually transitioning to a proliferative population concentrated at the distal end. By observing ZMB ontogenetic stages in a Wnt-responsive transgenic reporter line, TCFsiam, we identified a strongly fluorescent mesenchymal cell layer within these developing appendages. Using an in vitro explant culture technique on developing barbel tissues, we co-localized the fluorescent label in these cells with the mitotic marker EdU. Surprisingly, the labeled cells showed little proliferation, indicating a slow-cycling subpopulation. Transmission electron microscopy of the ZMB located these cells in a single, circumferential layer within the barbel's matrix core. Morphologically, these cells resemble fibroblasts or osteoblasts; in addition to their matrix-bound location, they are identified by their pancake-shaped nuclei, abundant rough endoplasmic reticulum, and cytoplasmic extensions into the surrounding extracellular matrix. Taken together, these features define a novel mesenchymal cell population in zebrafish, the "TCF(+) core cells." A working model of barbel development is proposed, in which these minimally mitotic mesodermal cells produce collagenous matrix in response to ectodermally-derived Wnt signals deployed in a proximal-distal gradient along the appendage. This documents a novel mechanism of vertebrate appendage outgrowth. Similar genetic signals and cell behaviors may be responsible for the independent and repeated evolution of barbel structures in other fish species.

Platelet-rich plasma use in anterior cruciate ligament surgery: systematic review of the literature.

PURPOSE: To systematically review the current literature for evidence that would substantiate the use of platelet-rich plasma (PRP) in the treatment of anterior cruciate ligament (ACL) ruptures. METHODS: We performed a systematic search in PubMed and Embase of studies written in the English and Spanish languages that compared the use of PRP with a control group in patients with ACL injuries assessing graft-to-bone healing, graft maturation, and/or clinical outcomes and were randomized controlled trials or prospective cohort studies. RESULTS: Eleven studies fulfilled the inclusion criteria, comprising 516 patients (266 ACL reconstructions using PRP and 250 ACL reconstructions without PRP). Six studies reported a statistically significant difference (4 studies) or tendency toward faster graft maturation in the platelet group (2 studies). One study found no differences. Regarding tunnel healing/widening, 1 study showed faster healing in the PRP group and 5 studies showed no differences between the 2 groups. Considering clinical outcomes, 1 study showed better clinical outcomes with PRP use and 5 studies showed no benefits with the use of PRP. CONCLUSIONS: Concerning ACL graft maturation, there is promising evidence that the addition of PRP could be a synergic factor in acquiring maturity more quickly than grafts with no PRP, with the clinical implication of this remaining unclear. Regarding tunnel healing, it appears that there is not an improvement with the addition of PRP. There is no proof that clinical outcomes of ACL surgery are enhanced by the use of PRP. LEVEL OF EVIDENCE: Level III, systematic review of Level I through III studies.

IAA-producing rhizobacteria from chickpea (Cicer arietinum L.) induce changes in root architecture and increase root biomass.

Rhizobacteria promote and have beneficial effects on plant growth, making them useful to agriculture. Nevertheless, the rhizosphere of the chickpea plant has not been extensively examined. The aim of the present study was to select indole-3-acetic acid (IAA) producing rhizobacteria from the rhizosphere of chickpea plants for their potential use as biofertilizers. After obtaining a collection of 864 bacterial isolates, we performed a screen using the Salkowski reaction for the presence of auxin compounds (such as IAA) in bacterial Luria-Bertani supernatant (BLBS). Our results demonstrate that the Salkowski reaction has a greater specificity for detecting IAA than other tested auxins. Ten bacterial isolates displaying a wide range of auxin accumulation were selected, producing IAA levels of 5 to 90 µmol/L (according to the Salkowski reaction). Bacterial isolates were identified on the basis of 16S rDNA partial sequences: 9 isolates belonged to Enterobacter, and 1 isolate was classified as Serratia. The effect of BLBS on root morphology was evaluated in Arabidopsis thaliana. IAA production by rhizobacteria was confirmed by means of a DR5::GFP construct that is responsive to IAA, and also by HPLC-GC/MS. Finally, we observed that IAA secreted by rhizobacteria (i) modified the root architecture of A. thaliana, (ii) caused an increase in chickpea root biomass, and (iii) activated the green fluorescent protein (GFP) reporter gene driven by the DR5 promoter. These findings provide evidence that these novel bacterial isolates may be considered as putative plant-growth-promoting rhizobacteria modifying root architecture and increasing root biomass.

A high-throughput screening assay to identify bacterial antagonists against Fusarium verticillioides.

A high-throughput antagonistic assay was developed to screen for bacterial isolates capable of controlling the maize fungal phytopathogen Fusarium verticillioides. This assay combines a straightforward methodology, in which the fungus is challenged with bacterial isolates in liquid medium, with a novel approach that uses the plant lectin wheat germ agglutinin (WGA) coupled to a fluorophore (Alexa-Fluor® 488) under the commercial name of WGA, Alexa Fluor® 488 conjugate. The assay is performed in a 96-well plate format, which reduces the required laboratory space and streamlines quantitation and automation of the process, making it fast and accurate. The basis of our assay is that fungal biomass can be assessed by WGA, Alexa Fluor® 488 conjugate staining, which recognizes the chitin in the fungal cell wall and thus permits the identification of potential antagonistic bacteria that inhibit fungal growth. This principle was validated by chitin-competition binding assays against WGA, Alexa Fluor® 488 conjugate; confocal laser microscopy confirmed that the fluorescent WGA, Alexa Fluor® 488 conjugate binds to the chitin of the fungal cell wall. The majority of bacterial isolates did not bind to the WGA, Alexa Fluor® 488 conjugate. Furthermore, including washing steps significantly reduced any bacterial staining to background levels, even in the rare cases where bacterial isolates were capable of binding to WGA. Confirmatory conventional agar plate antagonistic assays were also conducted to validate our technique. We are now successfully employing this large-scale antagonistic assay as a pre-screening step for potential fungal antagonists in extensive bacteria collections (on the order of thousands of isolates).

Return to sports in female athletes after anterior cruciate ligament reconstruction: A systematic review and metanalysis.

IMPORTANCE: Return to sport (RTS) is considered an indicator of successful recovery after anterior cruciate ligament reconstruction (ACLR). In recent years, there has been major interest in documenting RTS following anterior cruciate ligament (ACL) injury. Despite women being at increased risk for ACL injuries and a global increase in women's participation in sports, research has not adequately focused on female athletes. OBJECTIVE: The purpose of this study is to conduct a systematic review and meta-analysis evaluating the RTS rate in female athletes after ACLR. We hypothesize that most of the female athletes can RTS. EVIDENCE REVIEW: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Electronic databases (PubMed, Embase, and Epistemonikos) were searched for articles reporting RTS rates and contextual data in female athletes. The following search terms were used: "anterior cruciate ligament reconstruction" OR "ACL reconstruction" AND "female" OR "women" AND "return to sports" OR "return to play" to retrieve all relevant articles published between 2003 and 2023. A quality assessment of the included studies was conducted. FINDINGS: Fifteen articles were included, reporting on 1456 female athletes participating in pivoting sports. The included studies comprised 9 cohorts, 1 case-control study, 2 case series, 2 descriptive epidemiology studies, and 1 observational study. Eight out of fifteen studies focused solely on elite-level athletes. The participants had a mean age of 23.13 years. Soccer was the most prevalent sport among the participants, accounting for 49.7% of all athletes included. All 15 studies reported an RTS rate, yielding a meta-proportion of 69% [95% CI, 58-80%] for RTS. Nine articles reported the average time to RTS, which was 10.8 months [95% CI, 8.7-12.8 months]. CONCLUSIONS: This systematic review demonstrates that a majority of female athletes (69 â€‹%) can RTS participation at an average of 10.8 months, however, the available information is insufficient, and quantitative data and reasons for not returning to play are lacking. Future studies should establish return-to-play criteria in this population and determine reasons for not returning to play. LEVEL OF EVIDENCE: III.

Specific considerations in female patients with patellar instability: current concepts.

Prior literature suggests that patellofemoral instability (PFI) is significantly more prevalent in women than in men. This higher prevalence is commonly attributed to anatomical differences between sexes, particularly with patellofemoral alignment. These differences encompass a higher rate of trochlear dysplasia (TD), patella alta, an increased Q angle, and soft tissue imbalances. In recent years, worse outcomes have been reported in female patients after patellofemoral stabilization surgery using medial patellofemoral ligament reconstruction (MPFLr) alone or in combination with a tibial tubercle osteotomy (TTO), for this reason an "à la carte" plan (addressing the individuals anatomical risk factors) could be more appropriate for female patients.

Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.

Dravet syndrome is a severe genetic epilepsy primarily caused by de novo mutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications. Preclinical Dravet syndrome animal models are a valuable tool to identify candidate anti-seizure medications for these patients. Among these, scn1lab mutant zebrafish, exhibiting spontaneous seizure-like activity, are particularly amenable to large-scale drug screening. Thus far, we have screened more than 3000 drug candidates in scn1lab zebrafish mutants, identifying valproate, stiripentol, and fenfluramine e.g. Food and Drug Administration-approved drugs, with clinical application in the Dravet syndrome population. Successful phenotypic screening in scn1lab mutant zebrafish is rigorous and consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behaviour and (ii) an electrophysiology-based assay, using in vivo local field potential recordings, to quantify electrographic seizure-like events. Historically, nearly 90% of drug candidates fail during translation from preclinical models to the clinic. With such a high failure rate, it becomes necessary to address issues of replication and false positive identification. Leveraging our scn1lab zebrafish assays is one approach to address these problems. Here, we curated a list of nine anti-seizure drug candidates recently identified by other groups using preclinical Dravet syndrome models: 1-Ethyl-2-benzimidazolinone, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays in scn1lab mutant zebrafish identified only 1-Ethyl-2-benzimidazolinone, chlorzoxazone and lisuride. However, second-stage local field potential recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of anti-seizure medications.

Early Postoperative Results in Robotic-Arm-Assisted Total Knee Replacement versus Conventional Technique: First Latin American Experience.

Early results with robotic-arm-assisted total knee arthroplasty (TKA) are encouraging; nevertheless, literature might be unrepresentative, as it comes mostly from American, European, and Asian countries. There is limited experience and no comparative clinical reports in Latin America, a region of mainly low- and middle-income countries with limited access to these promising technologies. This study aims to compare the early postoperative results of the first Latin American experience with robotic-arm-assisted TKA versus conventional TKA. A cohort study was performed, including 181 consecutive patients (195 knees) with advanced symptomatic knee osteoarthritis (OA) undergoing primary TKA between March 2016 and October 2019. The cohort included 111 consecutive patients (123 knees) undergoing conventional TKA, followed by 70 consecutive patients (72 knees) undergoing robotic-arm-assisted TKA. The same surgical team (surgeon 1 and surgeon 2) performed all procedures. Patients with previous osteotomy, posttraumatic OA, and revision components were not considered. The same anesthetic and rehabilitation protocol was followed. The investigated clinical outcomes (for the first 60 postoperative days) were: surgical tourniquet time, time to home discharge, time to ambulation, postoperative daily pain (Visual Analog Scale), opioid use, range of motion, blood loss, complications, and postoperative mechanical axis. The early clinical postoperative results of this first Latin American comparative experience of robotic-arm-assisted TKA versus conventional technique showed lower opioids requirements and faster functional recovery of ambulation in those patients operated with the robotic system; nevertheless, surgical times were higher, without differences in total postoperative complications and other clinical outcomes.

Navigation in anterior cruciate ligament reconstruction: State of the art.

Computer navigation (CN) for anterior cruciate ligament (ACL) surgery has been used mainly for two purposes: to enhance the accuracy of tunnel position and to evaluate the kinematics of the ACL reconstruction (ACLR) and the stability achieved by different surgical techniques. Many studies have shown that navigation may improve the accuracy of anatomical tunnel orientation and position during ACL reconstructive surgery compared with normal arthroscopic tunnel placement, especially regarding the femoral side. At the same time, it has become the gold-standard method for intraoperative knee kinematic assessment, as it permits a quantitative multidirectional knee joint laxity evaluation. CN in ACL surgery has been associated with diverse problems. First, in most optic systems additional skin incisions and drill holes in the femoral bone are required for fixation of a reference frame to the femur. Second, additional radiation exposure and extra medical cost to the patient for preoperative planning are usually needed. Third, CN, due to additional steps, has more opportunities for error during preoperative planning, intraoperative registration, and operation. Fourth, soft tissues, including the skin and subcutaneous tissues, are usually not considered during the preoperative planning, which can be a problem for kinematic and stability assessment. Many studies have concluded that ACLR using a CN system is more expensive than conventional surgery, it adds extra time to the surgery and it is not mitigated by better clinical outcomes. This, combined with costs and invasiveness, has limited the use of CN to research-related cases. Future technology should prioritize less invasive intra-operative surgical navigation.