The Dimorphos ejecta plume properties revealed by LICIACube.

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.

Histological assessment of new bone formation with biomimetic scaffold in posterolateral lumbar spine fusion.

Spinal fusion procedures often require the use of bone grafts (autograft or allograft) to help bone healing and to increase stability. However, the application of autografts is frequently limited by donor site morbidity. In recent years, different synthetic bone substitutes have been introduced in the clinical practice to overcome these limitations. The purpose of this paper is to report a case where a biomimetic, synthetic and osteoconductive bone graft substitute was successfully implanted in a patient during lumbar spine arthrodesis. The case of a 58-year-old female subjected to lumbar spine arthrodesis with bone augmentation is described. The bone graft substitute RegenOss® (Finceramica, Faenza, Italy) was implanted during spinal arthrodesis. The successful bone integration was evaluated by X-rays. After 11 months, the patient underwent a second surgery due to spine imbalance; the debris of the bone graft was therefore collected and analyzed by macroscopic evaluation and by histology. The bone substitute was successfully implanted during a spinal arthrodesis procedure. Histologic evaluation of the removed bone graft debris showed the complete resorption of the implant and the formation of new bone, which was well integrated with the host bone. This bone substitute may represent a safe and effective alternative to autologous bone grafts, avoiding adverse events related to donor-site morbidity.

Histological assessment of new bone formation with biomimetic scaffold in the presence of bone loss in trauma surgery.

Open reduction and internal fixation (ORIF) surgery may require the use of bone grafts (usually allogeneic). In the context of traumatology surgeries, the use of autologous grafts is almost never used and allogeneic grafts are not always available. In recent years, bone substitutes have been introduced in clinical practice to overcome these limitations. The purpose of this paper is to report two cases in which the use of a bone substitute was used to overcome the bone loss during surgeries of ORIF. Two patients, one with a tibial plateau fracture (Schatzker 6) and one with a proximal humerus fracture (Neer 4), underwent ORIF surgery. In both cases, due to a loss of bone stock, a synthetic bone substitute (OrthOss®) was used. One year after surgery, the complete osseointegration of the synthetic bone substitute was seen, both radiologically and histologically. This bone substitute may represent a safe and effective alternative to autologous bone grafts, avoiding adverse events related to donor-site morbidity.

Bilateral THA in the same sitting for avascular necrosis of the head of the femur in sickle cell patient: our African experience.

Sickle cell anemia is protective against the malaria protozoan. The heterozygous form of the disease is not fatal, and may cause musculoskeletal disorders when sickling occurs, and small vessels are occluded. When the head of the femur is involved, this may result in hip arthritis, often bilateral, at a young age. This article describes three patients in whom bilateral total hip arthroplasty (THA) was performed in the context of a humanitarian mission in Togo, Africa.

Periprosthetic joint infection from Mycobacterium Tuberculosis in Togo, Africa.

Mycobacterium Tuberculosis infections are moderately frequent in developing countries. Because of migratory flows, these diseases will always have an increasing prevalence even in those countries that do not usually present these types of cases. Extra-pulmonary tuberculosis often affects the musculoskeletal system. The sites most involved are the spine (Pott's disease) and the large joints, especially hips and knees. We describe a patient with tuberculosis of the hip, who underwent total hip arthroplasty.

One-stage Bilateral Total Hip Arthroplasty in patient with sickle cell disease and previous Girdlestone procedure on the right side: First presentation in Togo.

80% of Sickle Cell Disease cases are estimated to be in Sub-Saharan Africa. It can lead to various acute and chronic complications and osteonecrosis of the femoral head is one of these. Girdlestone procedure is an option to treat osteonecrosis in patients who could not afford arthroplasty. We report here the first case of bilateral total hip arthroplasty in a patient with a previous Girdlestone procedure on the right side and an osteonecrosis of the femoral hip on the left side.

Clinical anatomy of the meniscus in animal models: pros and cons.

Nowadays, despite the possibility to use in vitro or computer models in research, animal models are still essential. Different animal models are available for meniscal repair investigation. Although a unique perfect model for the structure of the human's knee does not exist, the choice of the proper animal model is crucial for a correct research. The principal animal models in the meniscal repair are sheep, goats, pigs and dogs. Each of these has pros and cons for their utilization. Analysing each pro and con is essential for optimizing the choice of the animal model, which depends on the experimental question, avoiding unnecessary waste of resources and minimizing the animal suffering, according to the Russell and Burch's three "Rs" principles (Reduce, Refine and Recycle). In this concise review, we resume the meniscus anatomical features of the main large animals, to help choose the most suitable animal model for subsequent studies on meniscal repair.

Total hip arthroplasty for osteonecrosis of the femoral head in sickle cell disease: a case series from our African experience.

Sickle cell disease causes osteonecrosis (20% to 50% of patients) and collapse of the femoral head that result in secondary osteoarthritis. Total hip arthroplasty (THA) is a valid alternative for these patients. We define the difficulties that can be encountered when undertaking THA in sickle cell disease patients and give advice on how to deal with these technically demanding procedures. We undertook total hip arthroplasty procedures on 12 patients (4 females and 8 males) with osteonecrosis of the femoral head. Two bilateral prostheses were performed. We had only one type of stem, only one type of acetabular cup and only 28 mm cobalt chrome heads. The procedures were performed through either an anterior or a direct lateral approach. The average size of the Cup was 46 (Versafit, Medacta), the average size of the femoral stem was 0 (Amistem, Medacta), the most used size of the modular head was a S. Standard stem that was used in nine patients, while three patients received a lateralizing stem. Three patients had periprosthetic fracture, treated by cerclage. Total hip replacement is an excellent alternative for patients with osteonecrosis from sickle cell disease. The preparation of the acetabulum and the femur is difficult and requires attention, time and appropriate equipment.

Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates.

Pharmacokinetic/pharmacodynamic properties are strongly correlated with the in vivo efficacy of antibiotics. Propargyl-linked antifolates, a novel class of antibiotics, demonstrate potent antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria, including multidrug-resistant Staphylococcus aureus Here, we report our efforts to optimize the pharmacokinetic profile of this class to best match the established pharmacodynamic properties. High-resolution crystal structures were used in combination with in vitro pharmacokinetic models to design compounds that not only are metabolically stable in vivo but also retain potent antibacterial activity. The initial lead compound was prone to both N-oxidation and demethylation, which resulted in an abbreviated in vivo half-life (∼20 minutes) in mice. Stability of leads toward mouse liver microsomes was primarily used to guide medicinal chemistry efforts so robust efficacy could be demonstrated in a mouse disease model. Structure-based drug design guided mitigation of N-oxide formation through substitutions of sterically demanding groups adjacent to the pyridyl nitrogen. Additionally, deuterium and fluorine substitutions were evaluated for their effect on the rate of oxidative demethylation. The resulting compound was characterized and demonstrated to have a low projected clearance in humans with limited potential for drug-drug interactions as predicted by cytochrome P450 inhibition as well as an in vivo exposure profile that optimizes the potential for bactericidal activity, highlighting how structural data, merged with substitutions to introduce metabolic stability, are a powerful approach to drug design.

Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder.

Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates rat fetal brain gene expression (at a time point analogous to the end of the first trimester of human gestation) in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in the ASD cortex later in life and which are canonically known for roles in affecting prenatally late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD cortical transcriptome throughout life and has downstream impact on cell cycle processes. The cap-dependent translation initiation gene, EIF4E, is one of the most MIA-dysregulated of all ASD-associated genes and targeted network analyses demonstrate prominent MIA-induced transcriptional dysregulation of mTOR and EIF4E-dependent signaling. This dysregulation of translation initiation via alteration of the Tsc2-mTor-Eif4e axis was further validated across MIA rodent models. MIA may confer increased risk for ASD by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD.

Chemical and physical influences in bone and cartilage regeneration: a review of literature.

Nowadays several studies demonstrate the influence of chemical and physical stimulation to bone and cartilage exist. The first studies date back to the 50s and for a long time, they did not have a strong impact on clinical practice. In recent times, however, the findings arising from these studies are increasingly used to address clinical problems such as osteoarthritis or non-unions. The aim of this article is to make a review of the literature of the state of the art about physical and chemical influences on bone and cartilage.

Fibula-pro-tibia transfer with external fixator after tibia fracture with extensive bone defect: a case report.

A 27-year-old girl suffered a tibial fracture with an extensive bone defect due to a major trauma. At first, she was treated with a plate with the purpose to obtain a fibula-pro-tibia transfer, without any improvement. At one-year-follow up, a non-union due to mechanical hardware failure was shown by x-ray. Thus, a second surgery was performed: the ipsilateral fibula was tightly wedged between the preserved proximal and distal third of tibia with an external fixator. We report a follow up of 1 year after the reconstruction that allowed a good bone healing and a remodeling with also further ossification of the periosteal sheath of the fibula.

Comparison of early functional outcomes between two different surgical approaches for total hip arthroplasty.

Total Hip Arthroplasty (THA) is considered the most successful treatment for advanced hip osteoarthritis. Different surgical approaches for THA are available and they have shown excellent outcomes in the long-term follow-ups. However, few studies have analyzed the functional outcomes in the first days after a THA surgery. The purpose of this study was to compare the early functional outcomes between two different surgical techniques: a minimally invasive direct anterior approach (mini-DAA) and a postero-lateral approach (PL). Twelve patients for each group were analyzed. Pre- and postoperative (3, 10, 30 and 90 days after surgery) Patient-Reported Outcome Measures (PROMs) were administered: HOOS, HHS, VAS and SF-12-v2 scores. Moreover, comparison between surgical operation time and blood loss were examined. PROMs showed a significant improvement in the SF-12-v2 in the mini-DAA group compared to the PL group at 3 days after surgery: this difference was maintained also after 10 and 30 days. In addition, HOOS and HHS were significantly ameliorated in the mini-DAA group starting 10 days from surgery. In both groups, a physiological pain reduction was observed in the first days after surgery; comparing it to the pre-surgical VAS values, we found a significant improvement in the scores for the mini-DAA group after 30 days. Moreover, we demonstrated a significant reduction in blood loss for the mini-DAA group. Surgical operation times were similar in the two groups; however, the duration of the mini-DAA procedure was shorter compared with the known literature. In this preliminary study, we demonstrated that the minimally invasive direct anterior approach for THA may lead to benefits in the early postoperative time, as it allows for an improvement in functional outcomes, a reduction of postoperative pain, a reduction of hospitalization time and consequent reduction of postoperative complications; therefore, this surgical approach may consent an early return to work and daily activities.

Evaluation of the use of autologous micro-fragmented adipose tissue in the treatment of knee osteoarthritis: preliminary results of a randomized controlled trial.

Articular cartilage injuries are still unsolved due to the limited intrinsic healing potential of this tissue. Unlike other tissues, inflammation in the synovial joint causes perpetual damage and progressively leads to the development of osteoarthritis. Previous in vitro and in vivo studies have demonstrated the efficacy of mesenchymal stem cells isolated from adipose tissue in modulating inflammation. In this study, we analyzed the role of these cells in modifying the pathological microenvironment present in knee osteoarthritis. This is an interventional, prospective, randomized, controlled study. Starting from June 2017, 39 patients with grade III and IV knee osteoarthritis of Kellgren-Lawrence were enrolled, aged between 45 and 75 years, with pain greater than or equal to 6 according to the VAS scale, without ligament instability, with an axial deviation not greater than 10° and with a BMI between 18 and 30. The control group underwent an arthroscopic debridement, while the experimental group underwent an arthroscopic debridement and a subsequent intra-articular injection of autologous micro-fragmented adipose tissue. Patients were evaluated before surgery and at 6 months after the procedure, by radiological analysis (MRI) and functional outcome measures. The main purpose of the study is to evaluate the symptomatic improvement by comparing the functional outcome scores between the two groups. At 6 months after treatment, preliminary results on 39 patients showed pain reduction and functional improvements in the experimental group without a significant difference due to the low number of patients. The radiological and biochemical analyses are still ongoing. To date, the study has not revealed any side effects. These preliminary results demonstrate an encouraging positive trend in the experimental group. Patient recruitment is still ongoing to finalize the statistical analyses and to confirm our hypothesis.

The treatment of low-grade septic non-unions.

Non-union (or pseudoarthrosis) is defined as a fracture that fails to consolidate after 6 months from the trauma. Current conservative treatments consist of biological (i.e. with calcium, Vitamin D) and mechanical stimulation. Moreover, surgical approaches include the use of endomidollar nail osteosynthesis, compression plates that are often associated with bone grafts. External fixation is a valid surgical alternative especially in case of septic non-unions. Indeed, compression-distraction osteosynthesis results in a significant improvement in bone vascularisation and exerts a powerful osteoinductive stimulus on the non-union site. In this review, we will describe a cohort of patients affected by low-grade septic non-unions and treated with external fixation.

Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.

Demyelination patterns in a mathematical model of multiple sclerosis.

In this paper we derive a reaction-diffusion-chemotaxis model for the dynamics of multiple sclerosis. We focus on the early inflammatory phase of the disease characterized by activated local microglia, with the recruitment of a systemically activated immune response, and by oligodendrocyte apoptosis. The model consists of three equations describing the evolution of macrophages, cytokine and apoptotic oligodendrocytes. The main driving mechanism is the chemotactic motion of macrophages in response to a chemical gradient provided by the cytokines. Our model generalizes the system proposed by Calvez and Khonsari (Math Comput Model 47(7-8):726-742, 2008) and Khonsari and Calvez (PLos ONE 2(1):e150, 2007) to describe Baló's sclerosis, a rare and aggressive form of multiple sclerosis. We use a combination of analytical and numerical approaches to show the formation of different demyelinating patterns. In particular, a Turing instability analysis demonstrates the existence of a threshold value for the chemotactic coefficient above which stationary structures develop. In the case of subcritical transition to the patterned state, the numerical investigations performed on a 1-dimensional domain show the existence, far from the bifurcation, of complex spatio-temporal dynamics coexisting with the Turing pattern. On a 2-dimensional domain the proposed model supports the emergence of different demyelination patterns: localized areas of apoptotic oligodendrocytes, which closely fit existing MRI findings on the active MS lesion during acute relapses; concentric rings, typical of Baló's sclerosis; small clusters of activated microglia in absence of oligodendrocytes apoptosis, observed in the pathology of preactive lesions.

Elevated fetal steroidogenic activity in autism.

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.