Combinatorial therapies for spinal cord injury repair.

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Social Inclusion for People with Intellectual Disability and on the Autism Spectrum through Assistive Technologies: Current Needs and Future Priorities.

CONTEXT: Contemporary technologies, such as mainstream and specialised Assistive Technologies (ATs), are seen as effective. However, there is a noticeable gap between technological progress and the ability to customise these technologies to meet the unique needs and characteristics of neurodivergent individuals, particularly those on the Autism Spectrum and people with Intellectual Disability (pwID). PURPOSE: The goal of this study is to investigate the present requirements and future priorities acknowledged by specialists in the field regarding the progress of social inclusion for this population, making use of ATs. METHODS AND RESULTS: A qualitative survey involving 24 international experts, and its respective thematic analysis reveals challenges in social inclusion, emphasizing communication and physical accessibility, awareness gaps, and stigma. Concurrently, issues surrounding ATs include limited access, insufficient training, and a lack of awareness and skills, with individuals, and families being inadequately involved. CONCLUSION AND IMPLICATIONS: The study proposes strategies for overcoming these challenges, with a focus on accessibility, awareness, skills, family involvement, and customization. Identified research needs encompass scientific development, inclusive approaches, and changes in technological development paradigms.

Customization and Accessibility of Assistive Technologies (ATs): The research emphasizes the critical gap between existing ATs and their alignment with the needs of people with Intellectual Disability (pwID) and those on the autism spectrum. This is crucial for rehabilitation since its effectiveness is based on the consideration of individual requirements. In this sense, the present study involves enhancing the adaptability of technologies to support varied communication styles and learning abilities, thereby promoting greater independence and participation in daily activities, also through rehabilitation.Policy and Infrastructure Development: In an innovative manner, the study points out the systemic challenges, including inadequate policies and lack of support infrastructure, that hinder the effective use of ATs. For rehabilitation practices to be impactful, there is a need for policy reform and infrastructure development that prioritizes the provision and integration of ATs into education, employment, and community living. This includes ensuring funding for AT acquisition, creating inclusive educational and work environments, and improving public spaces to accommodate the needs of pwID and on the autism spectrum.Involvement of Individuals and Families in the AT Development Process: The paper highlights the limited involvement of individuals with ID and on the autism spectrum, and their families, in the process of developing and selecting ATs. Therefore, an important implication for rehabilitation is the need to adopt a person-centred approach that actively involves these individuals and their families in decision-making processes and, whenever possible, in co-creation processes. This approach ensures that AT solutions are better suited to the users' preferences, challenges, and daily life contexts, thereby enhancing the effectiveness of technological aids in supporting social inclusion and autonomy.Adoption of Qualitative, In-Depth Methods in AT Research: The adoption of qualitative research methods in disability and health research significantly contributes to the development of human-centred, context-driven, and personalized technologies and rehabilitation strategies.

Vector Competence of Aedes aegypti from São Tomé and Príncipe for West Nile Virus Transmission.

The global distribution of Aedes aegypti mosquitoes, particularly in tropical regions, poses a significant public health risk due to their apparent ability to transmit arboviruses such as West Nile virus (WNV). This study aimed to evaluate the vector competence of Ae. aegypti from São Tomé and Príncipe (STP) for the transmission of the WNV PT6.39 strain, considering its potential role as a bridge vector in a region where Culex quinquefasciatus would be the main vector. Aedes aegypti mosquitoes were collected, reared, and experimentally infected with WNV, with viral dissemination and transmission potential assessed 7, 14, and 21 days post infection (dpi). The results showed an increasing trend in infection rates, from 5% at 7 dpi to 35% at 21 dpi, with corresponding dissemination rates of 0%, 100%, and 43%. The transmission rates also increased from 0% at 7 dpi to 67% at 21 dpi, with a maximum transmission efficiency of 10% observed at the final time point. Although Ae. aegypti from STP demonstrated the potential to transmit WNV, the overall transmission efficiency remained relatively low. These findings provide necessary insights into the vector competence of Ae. aegypti in this region, highlighting the importance of continued monitoring and targeted vector control measures to mitigate the risk of potential WNV outbreaks.

Characterization of the microbiome of Aedes albopictus populations in different habitats from Spain and São Tomé.

The mosquito microbiome significantly influences vector competence, including in Aedes albopictus, a globally invasive vector. Describing the microbiome and Wolbachia strains of Ae. albopictus from different regions can guide area-specific control strategies. Mosquito samples from Spain and São Tomé were analyzed using 16S rRNA gene sequencing and metagenomic sequencing. Wolbachia infection patterns were observed by sex and population. Female mosquitoes were blood-fed, a factor considered in analyzing their microbiota. Results revealed a dominance of dual Wolbachia infections, strains A and B, in the microbiome of both populations of Ae. albopictus, especially among females. Both populations shared a core microbiome, although 5 and 9 other genera were only present in Spain and São Tomé populations, respectively. Genera like Pelomonas and Nevskia were identified for the first time in Aedes mosquitoes. This study is the first to describe the Ae. albopictus bacteriome in Spain and São Tomé, offering insights for the development of targeted mosquito control strategies. Understanding the specific microbiome composition can help in designing more effective interventions, such as microbiome manipulation and Wolbachia-based approaches, to reduce vector competence and transmission potential of these mosquitoes.

The extent of postpartum cardiac reverse remodeling is reflected in urine proteome.

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.

Environmental conditions affect the nutritive value and alkaloid profiles of Lupinus forage: Opportunities and threats for sustainable ruminant systems.

The identification of crops that simultaneously contribute to the global protein supply and mitigate the effects of climate change is an urgent matter. Lupins are well adapted to nutrient-poor or contaminated soils, tolerate various abiotic stresses, and present relevant traits for acting as ecosystem engineers. Lupins are best studied for their seeds, but their full foraging potential needs further evaluation. This study evaluated the effects of location and sowing date on forage production, proximate composition, and the detailed mineral and alkaloid profiles of three species of Lupinus (L. albus cv. Estoril, L. angustifolius cv. Tango, and L. luteus cv. Cardiga). Sowing date and location and their interaction with the plant species significantly affected the vast majority of measured parameters, emphasizing the effects of climate and soil conditions on these crops. The relatively high crude protein and in vitro digestibility support the potential of the lupin species studied as sustainable forage protein sources in diets for ruminant animals. The content of individual essential macro and trace elements was below the maximum tolerable levels for cattle and sheep. Lupanine, smipine, and sparteine were the most abundant quinolizidine alkaloids in L. albus cv. Estoril, lupanine, and sparteine in L. angustifolius cv. Tango, and lupinine, gramine, ammodendrine, and sparteine in L. luteus cv. Cardiga. Based on the maximum tolerable levels of total quinolizidine alkaloid intake, the dietary inclusion of forages of L. albus cv. Estoril and L. angustifolius cv. Tango does not pose a risk to the animals, but the high alkaloid content of L. luteus cv. Cardiga may compromise its utilization at high levels in the diet. Overall, the results reveal a high potential for lupins as protein forage sources well adapted to temperate regions and soils with lower fertility, with a relevant impact on livestock sustainability in a climate change era.

Agronomic, Nutritional Traits, and Alkaloids of Lupinus albus, Lupinus angustifolius and Lupinus luteus Genotypes: Effect of Sowing Dates and Locations.

Lupins (Lupinus spp.) are legumes with high relevance for the sustainability of agricultural systems as they improve the soil quality, namely, through the fixation of atmospheric nitrogen, and have good adaptability to different climates and soil conditions. Besides, they possess high nutritive value, especially due to the high protein content of the seeds. Nevertheless, the plants' productivity and metabolism can be influenced by the genotype, the edaphoclimatic conditions, and the sowing practices. In this work, the effect of edaphoclimatic conditions and sowing dates on the productivity, nutritional factors, and alkaloids of the seeds of L. albus cv. Estoril, L. angustifolius cv. Tango, and L. luteus cv. Cardiga was evaluated. High variability in the seeds and protein productions, nutritional traits, and alkaloid content related to the species was observed, along with a significant effect of the location. Lupinus albus cv. Estoril showed a good compromise between productivity and low alkaloid content, being an interesting genotype for food and feed use in the conditions of this trial.

High-Value Compounds in Papaya By-Products (Carica papaya L. var. Formosa and Aliança): Potential Sustainable Use and Exploitation.

BACKGROUND: Food waste is a global and growing problem that is gaining traction due to its environmental, ethical, social, and economic repercussions. Between 2022 and 2027, the worldwide papaya market is expected to have a huge increase, meaning a growth in organic waste, including peels and seeds. Thus, this study evaluated the potential use of peels and seeds of two mature papaya fruits as a source of bioactive compounds, converting these by-products into value-added products. Proximate analysis (AOAC methods), mineral content (ICP-MS), free sugars (HPLC-ELSD), fatty acid composition (GC-FID), vitamin E profile (HPLC-DAD-FLD), and antioxidant activity (DPPH and FRAP assays) were evaluated. RESULTS: Both by-products showed high total protein (20-27%), and dietary fiber (32-38%) contents. Papaya peels presented a high ash content (14-16%), indicating a potential application as a mineral source. 14 fatty acids were detected, with α-linolenic acid (30%) as the most abundant in the peels and oleic acid (74%) in the seeds. Both by-products showed high antioxidant activity. CONCLUSION: Papaya by-products display great potential for industrial recovery and application, such as formulation of new functional food ingredients.

The Peptide Antibiotic Corramycin Adopts a ß-Hairpin-like Structure and Is Inactivated by the Kinase ComG.

The rapid development of antibiotic resistance, especially among difficult-to-treat Gram-negative bacteria, is recognized as a serious and urgent threat to public health. The detection and characterization of novel resistance mechanisms are essential to better predict the spread and evolution of antibiotic resistance. Corramycin is a novel and modified peptidic antibiotic with activity against several Gram-negative pathogens. We demonstrate that the kinase ComG, part of the corramycin biosynthetic gene cluster, phosphorylates and thereby inactivates corramycin, leading to the resistance of the host. Remarkably, we found that the closest structural homologues of ComG are aminoglycoside phosphotransferases; however, ComG shows no activity toward this class of antibiotics. The crystal structure of ComG in complex with corramycin reveals that corramycin adopts a ß-hairpin-like structure and allowed us to define the changes leading to a switch in substrate from sugar to peptide. Bioinformatic analyses suggest a limited occurrence of ComG-like proteins, which along with the absence of cross-resistance to clinically used drugs positions corramycin as an attractive antibiotic for further development.

Effects of taurine, cysteine and melatonin as antioxidant supplements to the freezing medium of Prochilodus brevis sperm.

Cryopreservation consist of a set of methods to preserve cells and tissues by drastically reducing the temperature. Among some undesired effects, cryopreservation might generate reactive oxygen species that lead to an increase of oxidative stress, causing damage to cells. This study aimed to test taurine, cysteine, and melatonin on the freezing of Prochilodus brevis sperm and assess its effects on post-thawed sperm quality. Sperm was collected and seven pools were formed (n = 7). They were diluted (1:9) in standard medium (5% glucose, 10% dimethyl sulfoxide and 5% egg yolk) supplemented or not (control) with taurine (0.3, 1.0, 3.16 or 10.0 mM), cysteine (0.3, 1.0, 3.16 or 10.0 mM) or melatonin (0.6, 1.12, 2.0 or 3.56 mM). Post-thawed sperm was evaluated for kinetic (total motility, velocities, and percentage of rapid cells), morphology and membrane and DNA integrity. Differences were found when melatonin was used as an antioxidant. For the variables rapid sperm and sperm velocities, 3.56 mM melatonin presented higher results than the control (melatonin 0 mM). Melatonin 2 mM was similar to 3.56 mM on rapid sperm, average path velocity (VAP) and curvilinear velocity (VCL). No difference was found between concentration 0 mM (control) and taurine treatments. As for cysteine, 0.3 mM presented the best results for rapid sperm than 10 mM, and higher VCL and VAP than 1 mM. Melatonin 3.56 mM presented higher results on kinetic parameters (rapid motility, VCL, VSL and VAP) than other tested antioxidants. Therefore, melatonin 3.56 mM is recommended to be added to the sperm freezing medium of P. brevis.

Finding unveiled: Culex thalassius (Diptera: Culicidae), a new mosquito species emerges in the Cabo Verde archipelago.

Mosquito-borne diseases can pose significant burdens. In many countries, they pose a risk to national economies and the well-being of humans and animals. To mitigate this, mosquito surveillance is crucial to assess the real and potential transmission of mosquito-borne diseases. Between 2020 and 2023, mosquito larvae were collected from both indoor and outdoor breeding sites in urban and rural areas of 4 municipalities of Santiago and Boavista Islands in Cabo Verde. Mosquitoes were identified morphologically and by polymerase chain reaction-based techniques that targeted the mitochondrial cytochrome C oxidase subunit I sequence. During this period, 6,825 breeding sites were assessed, and of 8,094 mosquito specimens screened, 194 specimens of Culex thalassius were identified for the first time in the country in 4 municipalities of Santiago and Boavista Islands. This new finding highlights the importance of including entomological surveillance in health systems. Although this species has only been detected on a few islands, it is important to continuously monitor it to determine its distribution, spread/dispersal, density, and potential involvement in pathogen transmission.

Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

Authors' Response.

Dear Editor, We would like to thank Dr. Madias for his valuable comment on our original article entitled "QT interval prolongation in Takotsubo Syndrome: a frightening feature with no major prognostic impact" published in Monaldi Archives for Chest Disease on December 6, 2023...

Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2+ macrophages and a cellular response orchestrated by these cells. CCR2-/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2-/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV.

The impact of echocardiographic indexation to evaluate cardiac reverse remodeling throughout pregnancy and postpartum.

INTRODUCTION AND OBJECTIVES: Echocardiography guidelines suggest normalizing left ventricular (LV) volumes and mass (LVM) to body size. During pregnancy, continuous weight variation impacts on body surface area (BSA) calculation, limiting the longitudinal analysis of cardiac remodeling (CR) and reverse remodeling (RR) variables. Our aim was to identify the most common indexing methodologies in the literature on pregnant populations through a systematic review; and, to compare four scaling methods: (i) none (absolute values); (ii) indexing to the BSA before pregnancy; (iii) allomeric indexing; and (iv) indexing to BSA measured at the same day of cardiac assessment, using an illustrative example. METHODS: We performed a systematic review of CR and RR during pregnancy and post-partum, using two databases. We included studies reporting longitudinal echocardiographic analysis of cardiac chamber volumes in humans. We used a prospective cohort study of healthy pregnant women who underwent four echocardiographic evaluations during pregnancy and postpartum, as an illustrative example. RESULTS: Twenty-seven studies were included, most studies indexed to BSA measured at each evaluation moment (n=21). Within-subjects design was the most reported to analyse longitudinal data (n=17). Indexation to the pre-pregnancy BSA or application of allometric indexes revealed a higher effect than BSA measured at each evaluation and an equal effect to not indexing using within-subjects design. The within-subjects designs also revealed a higher effect size value than the between-subjects design for longitudinal analysis of LVM adaptations during pregnancy and postpartum. CONCLUSION(S): This study concludes that indexation methods do not impact the clinical interpretation of longitudinal echocardiographic assessment but highlights the need to harmonize normalization procedures during pregnancy.

QT interval prolongation in Takotsubo syndrome: a frightening feature with no major prognostic impact.

Despite the frequent and often severe repolarization abnormalities seen in Takotsubo syndrome (TTS), the underlying mechanism of life-threatening arrhythmias is incompletely understood, and the risk remains uncertain. TTS is considered a potential cause of acquired long QT syndrome; however, there is no robust evidence that QT prolongation has a major prognostic impact on these patients' outcomes. Our aim was to assess the prevalence and clinical implications of acquired long QT during TTS events and compare in-hospital and long-term outcomes between patients with and without corrected QT interval (QTc) prolongation. This is a retrospective cohort study that included 113 patients admitted to our tertiary care hospital with a diagnosis of TTS. The cohort was divided into two groups: a long QTc group (QTc≥460 milliseconds in any electrocardiogram at admission or during hospitalization) and a normal QTc group. Baseline characteristics, occurrences during hospitalization, and outcome data were obtained from the revision of medical registries and hospital visits. Of the 113 patients, 107 (94.7%) were female. The mean age was 67.6±11.7 years. QTc prolongation was found in 38%. Demographic characteristics, relevant chronic medication, prevalence of cardiovascular risk factors, and other comorbidities were similar between the groups, except for history of atrial fibrillation, which was more common in the long QTc group. Syncope was more prevalent in the long QTc group. In-hospital complications were not statistically different between patients with long and normal QTc (48.8% versus 44.2%, p=0.637), including ventricular arrhythmias and complete atrioventricular block (both 4.7% versus 1.4%, p=0.556). In-hospital mortality was 0.9%, corresponding to one patient in the long QTc group. The mean follow-up time was 4.8±3.8 years. 5-year all-cause mortality and the occurrence of the composite endpoint of major adverse cardiac and cerebrovascular events did not differ between the groups (p=0.511 and p=0.538, respectively). Our study found no association between prolonged QTc interval during TTS events and adverse prognosis, since in-hospital and long-term outcomes were similar between the groups. Our findings suggest that, although QT prolongation is usually a frightening feature on ECG, this repolarization abnormality during the acute phase has no major prognostic implications in the TTS population.

Surgical Strategies for Tuberculous Spondylodiscitis With Severe Osteoporosis: A Case Illustrating the Challenges of Delayed Intervention.

Tuberculous spondylodiscitis (Pott's spine) is a complex extrapulmonary manifestation of tuberculosis (TB) that poses significant medical challenges, characterized by vertebral destruction affecting approximately 2% of all TB cases. The management of this condition involves a multidisciplinary approach, with surgical intervention indicated for specific cases, including those with neurological complications, spinal instability, and kyphosis. We report a case of a 49-year-old female with a confirmed diagnosis of tuberculous spondylodiscitis who had undergone eight months of tuberculostatic therapy. She was referred for neurosurgical consultation due to uncontrollable axial pain, despite favorable clinical and imaging responses, which had rendered her immobile for six months. Imaging revealed a complete collapse of the L5 vertebral body, and a complementary dual x-ray absorptiometry (DEXA) scan demonstrated severe osteoporosis. A two-stage surgical approach was chosen to address her condition, involving corpectomy through an anterior approach, followed by lumbopelvic stabilization. Postoperative recovery was uneventful, with progressive improvement in pain and mobility. This case highlights the challenges of managing tuberculous spondylodiscitis and underscores the significance of early detection to prevent complications like severe osteoporosis. In this case, delayed referral for surgery following an extended period of immobility added complexity to an already difficult case. The severe osteoporosis, with a t-score of -5.7, had a substantial impact on surgical planning, leading to a more robust approach to arthrodesis with substantial lumbopelvic instrumentation in order to mitigate the risks associated with implant failure. This case shows that timely intervention and a comprehensive multidisciplinary approach are essential for the effective management of tuberculous spondylodiscitis, especially in cases complicated by severe osteoporosis.

Hypothermic machine perfusion for uterus transplantation.

OBJECTIVE: To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context. DESIGN: This video article shows all the technical details of using the HMP for uterine transplantation. SETTING: University. ANIMALS: Porcine model. INTERVENTION: Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient. MAIN OUTCOME MEASURES: The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus. RESULTS: This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients. CONCLUSION: Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.

Clinical, hematological, biochemical, and histopathological evaluations in domestic cats (Felis catus) infected by Leishmania infantum.

A high frequency of feline leishmaniasis has been reported in several countries. However, much information about disease progression in cats still needs to be clarified. This study aimed to verify the occurrence of clinicopathological changes in cats infected with Leishmania infantum. A total of 60 cats were divided into three groups of 20 animals each: control, suspects, and infected. All 60 cats underwent blood count and biochemical analyses. Serum samples from 20 animals with leishmaniasis were also used to diagnose feline immunodeficiency virus and feline leukemia virus. A total of five of the infected animals underwent necropsy for a histopathological study. The main clinical findings in cats with leishmaniasis were lymphadenomegaly (65%), alopecia (55%), ulcerative skin lesions and weight loss (40%), skin nodules (25%), a significant reduction in red blood cells (p=0.0005) and hematocrit (p=0.0007), hyperplasia in spleen 4/5(80%), presence of Leishmania in the spleen 2/5(40%), hepatitis 3/5(60%), liver degeneration 4/5(80%) and inflammatory nephropathy 3/5(60%). It was concluded that cats with leishmaniasis presented significant clinical, hematological, and histopathological alterations compatible with L. infantum infection. The observation of lymphadenomegaly, weight loss, skin lesions and low concentration of red blood cells, contributes significantly to the diagnosis and analysis of progression of feline leishmaniasis.