Causes and risk factors for same-day discharge failure after total hip and knee arthroplasty: a meta-analysis.

In recent decades, the trend toward early same-day discharge (SDD) after surgery has dramatically increased. Efforts to develop adequate risk stratification tools to guide decision-making regarding SDD versus prolonged hospitalization after total hip arthroplasty (THA) remain largely incomplete. The purpose of this report is to identify the most frequent causes and risk factors associated with SDD failure in patients undergoing THA and total knee arthroplasty (TKA). A systematic search following PRISMA guidelines of four bibliographic databases was conducted for comparative studies between patients who were successfully discharged on the same day and those who failed. Outcomes of interests were causes and risk factors associated with same-day discharge failure. Odds ratios (OR) were calculated for dichotomous variables, whereas mean differences (MD) were calculated for continuous variables. Meta-analysis was performed using RevMan software. Random effects were used if there was evidence of heterogeneity. Eight studies with 3492 patients were included. The most common cause of SDD failure was orthostatic hypotension, followed by inadequate physical condition, nausea/vomiting, pain, and urinary retention. Female sex was a risk factor for failure (OR 0.77, 95% CI 0.63-0.93), especially in the THA subgroup. ASA score IV (OR 0.33, 95% CI 0.14-0.76) and III (OR 0.72, 95% CI 0.52-0.99) were risk factors, as were having > 2 allergies and smoking patients. General anesthesia increased failure risk (OR 0.58, 95% CI 0.42-0.80), while spinal anesthesia was protective (OR 1.62, 95% CI 1.17-2.24). The direct anterior and posterior approaches showed no significant differences. In conclusion, orthostatic hypotension was the primary cause of SDD failure. Risk factors identified for SDD failure in orthopedic surgery include female sex, ASA III and IV classifications, a higher number of allergies, smoking patients and the use of general anesthesia. These factors can be addressed to enhance SDD outcomes.

Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide.

While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS.

Bilateral abducens and facial nerve palsies following fourth ventriculoperitoneal shunt with laparoscopic-assisted abdominal catheter placement.

Introduction: Hydrocephalus, altering cerebrospinal fluid (CSF) dynamics, affects 175 per 100,000 adults worldwide. Ventriculoperitoneal shunts (VPS) manage symptomatic hydrocephalus, with 125,000 cases annually. Despite efficacy, VPS face complications, necessitating interventions. Research question: "What are the mechanisms and risk factors for bilateral VIth and VIIth lower motor neuron palsies in hydrocephalus patients with a fourth ventriculoperitoneal shunt?" Material and methods: This study details a 36-year-old female with a neonatal meningitis history, multiple shunt replacements, admitted for abdominal pain secondary to pelvic inflammatory disease. An abdominal shunt catheter removal and external ventricular drain placement occurred after consultation with a general surgeon. A cardiac atrial approach and subsequent laparoscopic abdominal approach were performed without complications. Results: After one month, the patient showed neurological complications, including decreased facial expression, gait instability, and bilateral VIth and VIIth lower motor neuron palsies, specifically upgazed and convergence restriction. Discussion: The complication's pathophysiology is discussed, attributing it to potential brainstem herniation from over-drainage of CSF. Literature suggests flexible endoscopic treatments like aqueductoplasty/transaqueductal approaches into the fourth ventricle. Conclusions: This study underscores the need for increased awareness in monitoring neurological outcomes after the fourth ventriculoperitoneal shunt, particularly in cases with laparoscopic-assisted abdominal catheter placement. The rarity of bilateral abducens and facial nerve palsies emphasizes the importance of ongoing research to understand pathophysiology and develop preventive and therapeutic strategies for this unique complication.

Vitamin E Cup Cross-linked Polyethylene in Total Hip Arthroplasty: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The goal of this study was to assess the efficacy and safety of vitamin E cup cross-linked polyethylene (VEPE) liners compared with standard polyethylene (PE) liners in total hip arthroplasty. METHODS: A systematic search of the PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was conducted. The evaluated outcomes were radiological parameters, functional scores (Harris Hip Score, Numeric Rating Scale, and Activity Scale from the University of California), and adverse events. Odds ratios and mean differences (MD) were calculated for the dichotomous and continuous variables. Meta-analysis was done using Review Manager. RESULTS: Seven randomized controlled trials (n = 990) were included. VEPE liners showed markedly lower penetration at the last follow-up (MD, -0.15; 95% confidence interval [CI], -0.18 to -0.11) and penetration rate at last follow-up (MD, -0.01; 95% CI, -0.01 to -0.00) than standard PE liners. However, no notable differences were observed in cup migration, inclination, anteversion, or patient-reported outcomes. The complication rate was not markedly different between the groups (odds ratio, 1.07; 95% CI, 0.42 to 2.73). DISCUSSION: This meta-analysis found that while VEPE demonstrated decreased penetration rates in total hip arthroplasty, no differences were observed in patient outcomes or complications compared with standard PE. However, the clinical relevance of penetration rate reduction remains uncertain, given the short follow-up period.

Adjuvants influence the immune cell populations present at the injection site granuloma induced by whole-cell inactivated paratuberculosis vaccines in sheep.

Vaccination is the most effective tool for paratuberculosis control. Currently, available vaccines prevent the progression of clinical disease in most animals but do not fully protect them against infection and induce the formation of an injection site granuloma. The precise mechanisms that operate in response to vaccination and granuloma development, as well as the effect that adjuvants could trigger, have not been fully investigated. Therefore, this study aimed to investigate the injection site granulomas induced by two inactivated paratuberculosis vaccines, which differ in the adjuvant employed. Two groups of 45-day-old lambs were immunized with two commercially available vaccines-one (n = 4) with Gudair® and the other (n = 4) with Silirum®. A third group (n = 4) was not vaccinated and served as control. The peripheral humoral response was assessed throughout the study by a commercial anti-Mycobacterium avium subspecies paratuberculosis (Map) antibody indirect ELISA, and the cellular immune response was assessed similarly by the IFN-γ release and comparative intradermal tests. The injection site granulomas were measured during the experiment and sampled at 75 days post-vaccination (dpv) when the animals were euthanized. The tissue damage, antigen and adjuvant distribution, and the presence and amount of immune cells were then determined and assessed by immunohistochemical methods. Antibodies against Map antigens; a general macrophage marker (Iba1), M1 (iNOS), and M2 (CD204) macrophages; T (CD3), B (CD20), and γδ T lymphocytes, proteins MHC-II and NRAMP1, and cytokines IL-4, IL-10, TNF, and IFN-γ were employed. Silirum® elicited a stronger peripheral cellular immune response than Gudair®, while the latter induced larger granulomas and more tissue damage at the site of injection. Additionally, adjuvant and Map antigen distribution throughout the granulomatous inflammatory infiltrate, as well as the NRAMP1 cell expression, which is linked to antigen phagocytosis, were highly irregular. In Silirum® induced granulomas, a higher number of MHC-II and TNF-expressing cells and a lower number of M2 macrophages suggested an improved antigen presentation, which could be due to the better antigen distribution and reduced tissue damage induced by this vaccine.

Evaluation of Midodrine Utilization in Patients with Cancer and Heart Failure.

PURPOSE: The purpose of this study was to evaluate safety and cardiovascular outcomes as well as overall survival of cancer patients with concomitant heart failure (HF) treated with midodrine for hypotension. METHODS: Adult patients diagnosed with cancer and HF who were treated with midodrine at a tertiary cancer center from 03/2013 to 08/2021 were identified. Demographic and clinical parameters were collected retrospectively. RESULTS: A total of 85 patients were included with a median age of 68 years (IQR: 60, 74; 33% female and 85% White). Of those, 31% had HFpEF (EF ≥ 50%), 42% HF with mildly reduced EF (HFmrEF; EF 41-49%), and 27% HFrEF (EF ≤ 40%). The most common indication for midodrine use was orthostatic hypotension (49%). Midodrine was continued for at least one month in 57% of the patients. Supine hypertension was the only side effect reported in 6% of patients. No statistically significant changes in NYHA class, guideline-directed medical therapy, cardiac biomarkers (NT-proBNP or troponin T), echocardiographic findings or cardiovascular hospitalizations were observed between patients who continued treatment with midodrine compared to those who stopped using midodrine over a median follow-up of 38 months. In the multivariable cox regression analysis, continuation of midodrine, compared to discontinuation, and use of midodrine for orthostatic hypotension, as opposed to other causes of hypotension, were not associated with an increased risk of mortality (HR 0.41, 95% CI 0.24-0.69, p < .0001; HR 0.34, 95% CI 0.18-0.64, p < .001, respectively). In contrast, elevated creatinine (> 1.3 for males and > 1.1 for females) was associated with an increased risk of mortality (HR 1.83, 95% CI 1.07-3.14). LVEF was not significantly associated with lower or higher risk of mortality. CONCLUSIONS: In our study, midodrine use in patients with cancer and HF was not associated with significant adverse effects, worse cardiovascular outcomes, or increased risk of mortality. Larger, prospective studies are needed to confirm these findings.

Do Patients Treated With an Unplanned Resection for Small Superficial Soft Tissue Sarcomas Have Worse Long-term Survival Than Those Initially Treated With an Oncologic Resection?

BACKGROUND: Histologic grade, size, and depth are well-known prognostic factors in soft tissue sarcomas (STS). Small (< 5 cm) and superficial STS generally have an excellent prognosis when treated with appropriate surgery. However, they are often misdiagnosed and mistreated. We reported that in midterm follow-up (5 to 7 years), patients with unplanned resections of tumors with positive margins who immediately underwent a reoperation with margin-widening re-resection and postoperative radiotherapy had survival comparable to that of patients who were initially treated correctly. In that article, we included STS larger than 5 cm, deep STS, and individuals with local recurrence. However, we wanted to evaluate the impact of unplanned resection on the survival of patients who had STS with the best prognosis, small and superficial STS, with two groups that were as homogeneous as possible. QUESTION/PURPOSE: Do patients with small and superficial STS who underwent an unplanned resection have worse prognosis in the long term than those who were initially treated correctly? METHODS: We exclusively evaluated patients with small (< 5 cm) and superficial (to the deep fascia) STS. We systematically excluded deep STS. Among this subset, we identified 93 patients with superficial STS. We excluded patients with local relapse, metastatic disease, superficial STS of the head or neck, those with insufficient clinical or dosimetric information, and patients with follow-up of less than 2 years. Furthermore, our focus on investigating the most benign and homogeneous STS prompted us to exclude patients with superficial tumors greater than or equal to 5 cm. This selection was driven by the presumed better prognosis associated with smaller tumors, inevitably leading to a smaller pool of patients for direct comparison with patients who had unplanned resections. The initial expectation was to observe similar survival outcomes between cohorts. Between 1990 and 2019, a total of 17 patients underwent surgical treatment at our private, medium-size center. Of those, 29% (5 patients) were lost to follow-up before 2 years without meeting a study endpoint (relapse, metastasis or revision, reoperation, or death), leaving a total of 71% (12 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with surgery alone. During that same period, another 51 patients were referred to us after undergoing an unplanned resection of a lesion that subsequently was determined to be a soft tissue malignancy. Of those, 18% (9 patients) were lost to follow-up before 2 years without meeting a study endpoint, leaving 82% (42 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with re-excision and postoperative radiotherapy. Patients with unplanned resections had an older mean age (51± 5 versus 44 ± 7 years; p = 0.1) and a higher proportion of female patients (58% versus 38%; p = 0.07), but the groups did not differ in terms of largest diameter, histologic type, or tumor location. However, patients with planned resections had a higher proportion of high-grade STS (75% versus 55%; p = 0.07). No metastases were present in either group at diagnosis. We performed a univariate analysis of the groups. We could not perform a multivariate analysis because of the small sample. We compared the groups in terms of local recurrence and all-cause mortality using the Kaplan-Meier survivorship estimator. RESULTS: According to the Kaplan-Meier survivorship estimator, survivorship free from local recurrence at a mean of 20 years of follow-up was better in the planned resection group than in the unplanned resection group (92% [95% CI 63% to 100%] versus 69% [95% CI 54% to 81%]; p = 0.04). Furthermore, overall survivorship at 5 years was higher in the planned resection group than in the unplanned resection group (100% [95% CI 72% to 100%] versus 70% [95% CI 54% to 81%]; p = 0.04). Similarly, the planned resection group exhibited superior survivorship at 20 years of follow-up (100% [95% CI 72% to 100%] versus 62% [95% CI 47% to 75%]; p = 0.01). Metastatic disease was absent in the planned resection group, while it occurred in 12 patients in the unplanned resection group (28% [95% CI 17% to 44%]). CONCLUSION: Unplanned resection for patients with small and superficial STS was associated with a decrease in overall survival in the long term, despite the use of postoperative radiotherapy. An unplanned resection may be an important prognostic factor. Nevertheless, larger and prospective studies are needed to validate our findings. Although small and superficial lumps are usually benign, nonsarcoma surgeons should be aware that some masses may be malignant, and if in doubt, MR imaging, a biopsy before excision, or consultation with or referral to a sarcoma center should be considered before removing the mass. LEVEL OF EVIDENCE: Level III, therapeutic study.

Femoral Neck Preservation and Diaphyseal Invasion Comparing a Calcar-Metaphyseal Short Stem with its Homonymous Standard Femoral Stem. A Radiographic Study.

BACKGROUND: We aim to compare the preoperative planning radiographs of 50 patients in whom both a short stem and its homonymous standard version were programmed, focusing on the preservation of the neck and the invasion of the femoral shaft. The secondary objective was to evaluate the 50 preoperative radiographs with the 50 postoperative radiographs in which the short stem was implanted, measuring the real invasion of the diaphysis and the real preservation of the femoral neck. MATERIAL AND METHODS: We measured cut level at the femoral neck and diaphyseal invasion in 50 preoperative x-rays where an Alteon Neck Preserving Stem (ANPS) was templated and we compared it with 50 preoperative x-rays where an Alteon Taper Wedge Stem (ATWS) was templated. After surgery, we compared both parameters previously measured in the preoperative x-rays with the 50 postoperative radiographs where the short stem was implanted obtaining the real bone preservation at the femoral neck and the real diaphyseal invasion length. RESULTS: For templating comparison, mean bone preservation at the femoral neck was 14.87mm (SD 3.64) for the ANPS group and 9.94mm (SD 8.39) for the ATWS group (p <0.001). The mean diaphyseal bone invasion was 47.21mm (SD 5.89) and 76.77mm (SD 8.39) for ANPS and ATWS respectively (p <0.001). After surgery, the mean postoperative bone preservation at the femoral neck was 15.08mm (SD 3.1) with a mean of 0.17mm (SD 0.51) more preservation in the preoperative group. CONCLUSION: 1. ANPS allow bone preservation with limited diaphyseal invasion when compared with his homonymous ATWS in the preoperative templates. 2. ANPS showed a good correlation between preoperative radiographs and real bone preservation of the femoral neck and invasion of the femoral shaft.

External Validation and Recalibration of a Mortality Prediction Model for Patients with Ischaemic Stroke.

BACKGROUND: Stroke is a highly prevalent disease that can provoke severe disability. We evaluate a predictive model based on the Minimum Basic Data Set (MBDS) compiled by the Spain Health Ministry, obtained for the period 2008-2012 for patients with ischaemic stroke in Spain, to establish the model's validity and to optimise its calibration. The MBDS is the main clinical-administrative database for hospitalisations recorded in Spain, and to our knowledge, no predictive models for stroke mortality have previously been developed using this resource. The main study aim is to perform an external validation and recalibration of the coefficients of this predictive model with respect to a chronologically later cohort. MATERIAL AND METHODS: External validation (testing the model on a different cohort to assess its performance) and recalibration (validation with optimisation of model coefficients) were performed using the MBDS for patients admitted for ischaemic stroke in the period 2016-2018. A cohort study was designed, in which a recalibrated model was obtained by applying the variables of the original model without their coefficients. The variables from the original model were then applied to the subsequent cohort, together with the coefficients from the initial model. The areas under the curve (AUC) of the recalibration and the external validation procedure were compared. RESULTS: The recalibrated model produced an AUC of 0.743 and was composed of the following variables: age (odds ratio, OR:1.073), female sex (OR:1.143), ischaemic heart disease (OR:1.192), hypertension (OR:0.719), atrial fibrillation (OR:1.414), hyperlipidaemia (OR:0.652), heart failure (OR:2.133) and posterior circulation stroke (OR: 0.755). External validation produced an AUC of 0.726. CONCLUSIONS: The recalibrated clinical model thus obtained presented moderate-high discriminant ability and was generalisable to predict death for patients with ischaemic stroke. Rigorous external validation slightly decreased the AUC but confirmed the validity of the baseline model for the chronologically later cohort.

Efficacy and safety of arthroscopy in femoroacetabular impingement syndrome: a systematic review and meta-analysis of randomized clinical trials.

This study aimed to compare the efficacy and safety of arthroscopy with physiotherapy or joint lavage in patients with femoroacetabular impingement (FAI). A meta-analysis using PubMed, Embase, Scopus, and the Cochrane Collaboration Library databases was performed in September 2022. We included studies focusing on patients with FAI who underwent arthroscopic surgery versus those who underwent physiotherapy or arthroscopic lavage. The outcomes were functional scores (iHOT-33 and HOS ADL) and adverse events. Randomized clinical trials were included in the study. The risk of bias in each study was assessed according to Cochrane guidelines for clinical trials. The data were combined using Review Manager version 5.4. (PROSPERO CRD42022375273). Six RCTs were included, from a pool of 839 patients (407 females). The iHOT-33 and HOS ADL scales showed significant differences at 12 months in favor of the arthroscopy group (MD, 10.65; 95% CI 6.54-4.76) and (MD, 8.09; 95% CI 3.11-13.07). MCID was not achieved through arthroscopy in functional variables. The rates of osteoarthritis (OR, 6.18; 95% CI 1.06-36.00) and numbness (OR, 73.73; 95% CI 10.00-43.92) were significantly higher in the arthroscopy group. Arthroscopic surgery showed statistical superiority over the control group without exceeding the MCID in most studies; however, the results might have been influenced by secondary variables. Finally, arthroscopic surgery results in a high rate of conversion to osteoarthritis.

Incidence and risk factors for stroke after hip fracture: a meta-analysis.

Hip fractures represent a high burden and are associated with mortality in up to 30% of the cases. Stroke complications can be devastating and increase mortality and disability in elderly patients. This study aimed to determine the overall incidence and risk factors for stroke in patients with hip fractures. A systematic search of the literature using PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases was carried out. Studies have reported the incidence of stroke in patients > 50 years of age with hip fractures. Data were extracted according to PRISMA guidelines (PROSPERO: CRD42023384742). Data were combined using Review Manager version 5.4. A random-effects model was adopted if a significant heterogeneity was observed. The primary outcome was the incidence of stroke in patients with hip fractures. The secondary outcomes of interest included the influence on the incidence of demographic factors, associated conditions, habits, and analytical parameters. Of the 635 initially retrieved studies, 18 were included, with 256,197 patients. The mean age of the patients ranged from 55 to 84 years old. The overall incidence of stroke in patients with hip fracture was 6.72% (95% CI 4.37-9.07%. The incidence of stroke by region was highest in the American continent (8.09%, 95% CI 3.60-12.58%; P > 0.001). Regarding associated conditions diabetes significantly increased the risk of stroke (OR 1.80, 95% CI 1.41-2.30). Respect to patient characteristics, BMI greater than 24.4 and female gender did not significantly increase the risk of stroke: (OR 1.07, 95% CI 0.74-1.56) and (OR 1.15, 95% CI 0.91-1.46). Lastly, lower albumin concentrations were a risk factor for stroke in patients with hip fracture (MD - 3.18, 95% CI - 4.06 to 2.31). In conclusion, the incidence of stroke after hip fracture was 6.72%. The incidence of stroke increases over time, and the closely associated risk factors are diabetes and low albumin level.

Femoroacetabular Impingement and the Effect of Osteochondroplasty on Hip Osteoarthritis Prevention: The Pandora's Box Opening Process.

OBJECTIVE: This study was conducted to assess the effect of osteochondroplasty on osteoarthritis (OA) prevention, comparing radiological evolution between identical hips from the same patient who had undergone unilateral surgery. DESIGN: We retrospectively reviewed radiological evolution between hips with similar shape from the same patient who had undergone unilateral surgery. In all, 56 FAI patients (112 hips) with a mean age of 42.18 ± 9.16 years and had undergone unilateral arthroscopy treatment have been included. Four independent researchers measured Wiberg, Acetabular and Alpha angles, Extrusion index, and Tönnis classification preoperatively to verify that operated and non-operated hips had the same shape. OA evolution was assessed by joint space width (JSW) in 3 different articular points and Tönnis classification. RESULTS: No preoperative anatomical differences were present between groups (P > 0.05). At the end of follow-up (31.9 months), a decrease of JSW in the 3 points measured was found in OP hips (OP vs. N-OP; P < 0.01). These results were correlated with changes in the proportion of patients who progressed to grade III in Tönnis classification (from 1.3% preoperative to 23.2% at the end of follow-up). CONCLUSIONS: Osteochondroplasty and labrum procedures were not associated with OA prevention. The OP hips showed a faster OA degeneration, which was not seen in the N-OP. These results will encourage hip surgeons to perform further investigations to avoid the "Pandora's Box Opening Process."

Vacuum-assisted birth in maternal lateral posture versus lithotomy. A simulation study.

OBJECTIVE: Maternal lateral postures provide advantages during childbirth. This study aims to investigate the feasibility of assisting vacuum births in maternal lateral postures in a simulation model. STUDY DESIGN: In a simulation model, four obstetricians and four medical students were randomly allocated to perform vacuum-assisted births first in maternal lateral posture or lithotomy. A modification of Aldo Vacca's 5-step technique was developed to assist vacuum-assisted births in lateral posture. The lateral distance, vertical distance, and distance from the cup center to the flexion point were measured for every placement of the cup. RESULTS AND CONCLUSIONS: A total of 128 vacuum-assisted births were performed. The mean distance to the flexion point was 1.15 ± 0.71 cm for the lithotomy posture and 1.31 ± 0.82 cm for the lateral posture (P = 0.127). There were no statistically significant differences in vacuum extractor cup placement accuracy based on maternal posture. Performing vacuum-assisted births in maternal lateral posture is feasible in a simulation model. The technique is easy to learn, and the differences in cup placement between the lateral and lithotomy postures are small.

Monitoring different sources of marine pollution in the Canarian intertidal zone using Anemonia sulcata as a bioindicator.

Sea anemones have often been used as bioindicators of contamination because they are semisessile organisms that rarelly leave their niche, which is why they are conducive to affecting the ecosystem at the local level. The objective of this work is to determine whether the concentrations of heavy metals and trace elements in the anemone Anemonia sulcata vary depending on the source of contamination present. In 2021 seventy specimens were collected at five sampling points and fourteen specimens were collected in each point (Control Zone, Thermal Power Plant, Sewage Pipe, Harbour and Tourism) in 2021, on the island of Tenerife. All the areas studied characterized by a pollution condition had higher concentrations of metals and trace elements than the control area. The anemones from Harbour presented a greater number of metals with a higher concentration than the other study areas.

An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration.

During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 µg/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.

The local skin cellular immune response determines the clinical outcome of sarcoptic mange in Iberian ibex (Capra pyrenaica).

Introduction: Sarcoptic mange, caused by Sarcoptes scabiei, is a disease with implications for wildlife conservation and management. Its severity depends on the host's local skin immune response, which is largely unknown in Iberian ibex (Capra pyrenaica), a mountain ungulate dramatically affected by mange. In this species, the clinical outcome of sarcoptic mange varies among individuals, and the local immune response could be key to controlling the infestation. This study aims to characterize the local cellular immune response and its relationship with the clinical outcome. Methods: Fourteen Iberian ibexes were experimentally infested with S. scabiei and six more served as controls. Clinical signs were monitored, and skin biopsies were collected from the withers at 26, 46, and 103 days post-infection (dpi). The presence and distribution of macrophages (including M1 and M2 phenotypes), T lymphocytes, B lymphocytes, plasma cells, and interleukine 10 were quantitatively evaluated using immunohistochemical techniques. Results: An inflammatory infiltrate that decreased significantly from 26 to 103 dpi was observed in all the infested ibexes. The predominant inflammatory cell population in the skin of the mangy ibexes was formed by macrophages (mainly the M2 phenotype) followed by T lymphocytes, with lower numbers of B lymphocytes and plasma cells. Three clinical courses were identified: total recovery, partial recovery, and terminal stage. The inflammatory infiltrates were less pronounced in the fully recovered ibexes than in those that progressed to the terminal stage throughout the study. Discussion: The results suggest an exacerbated but effective Th1-type cellular immune response controlling mange in Iberian ibex. Furthermore, the local immune response appears to determine the variability of the clinical responses to S. scabiei infestation in this species. This first report on the progression of local skin immune cells is relevant not only for individuals but also for population management and conservation.

Diseases of Iberian ibex (Capra pyrenaica).

Iberian ibex (Capra pyrenaica) is an ecologically and economically relevant medium-sized emblematic mountain ungulate. Diseases participate in the population dynamics of the species as a regulating agent, but can also threaten the conservation and viability of vulnerable population units. Moreover, Iberian ibex can also be a carrier or even a reservoir of pathogens shared with domestic animals and/or humans, being therefore a concern for livestock and public health. The objective of this review is to compile the currently available knowledge on (1) diseases of Iberian ibex, presented according to their relevance on the health and demography of free-ranging populations; (2) diseases subjected to heath surveillance plans; (3) other diseases reported in the species; and (4) diseases with particular relevance in captive Iberian ibex populations. The systematic review of all the information on diseases affecting the species unveils unpublished reports, scientific communications in meetings, and scientific articles, allowing the first comprehensive compilation of Iberian ibex diseases. This review identifies the gaps in knowledge regarding pathogenesis, immune response, diagnostic methods, treatment, and management of diseases in Iberian ibex, providing a base for future research. Moreover, this challenges wildlife and livestock disease and wildlife population managers to assess the priorities and policies currently implemented in Iberian ibex health surveillance and monitoring and disease management.

Involvement of the PRL-PAK1 Pathway in Cancer Cell Migration.

Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution.

Early hematopoiesis is a continuous process in which hematopoietic stem and progenitor cells (HSPCs) gradually differentiate toward specific lineages. Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of HSPCs. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize an enriched population of human HSPCs obtained from young and elderly healthy individuals.Based on their transcriptional profile, we identified changes in the proportions of progenitor compartments during aging, and differences in their functionality, as evidenced by gene set enrichment analysis. Trajectory inference revealed that altered gene expression dynamics accompanied cell differentiation, which could explain aging-associated changes in hematopoiesis. Next, we focused on key regulators of transcription by constructing gene regulatory networks (GRNs) and detected regulons that were specifically active in elderly individuals. Using previous findings in healthy cells as a reference, we analyzed scRNA-seq data obtained from patients with myelodysplastic syndrome (MDS) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2. In addition, the comparison between transcriptional programs and GRNs regulating normal HSPCs and MDS HSPCs allowed identification of regulons that were specifically active in MDS cases such as SMAD1, HOXA6, POU2F2, and RUNX1 suggesting a role of these transcription factors (TFs) in the pathogenesis of the disease.In summary, we demonstrate that the combination of single-cell technologies with computational analysis tools enable the study of a variety of cellular mechanisms involved in complex biological systems such as early hematopoiesis and can be used to dissect perturbed differentiation trajectories associated with perturbations such as aging and malignant transformation. Furthermore, the identification of abnormal regulatory mechanisms associated with myeloid malignancies could be exploited for personalized therapeutic approaches in individual patients.

Our blood contains many different types of cells; red blood cells carry oxygen through the body, platelets help to stop bleeding and a variety of white blood cells fight infections. All of these critical components come from a pool of immature cells in bone marrow, which can develop and specialise into any of these. However, as we get older, these immature cells can accumulate damage, including mutations in specific genes. This increases the risk of diseases such as myelodysplastic syndromes (MDS), a type of cancer in which the cells cannot develop and the patient does not have enough healthy mature blood cells. The changes in gene activity in the immature cells have previously been studied using samples from young and elderly people, as well as individuals with MDS. These studies examined large numbers of cells together, revealing differences between young and elderly people, and individuals with MDS. However, this does not describe how the different types alter their behaviour. To address this, Ainciburu, Ezponda et al. used a technique called single-cell RNA sequencing to study the gene activity in individual immature blood cells. This revealed changes associated with maturation that may account for the different combinations of cell populations in younger and older people. The results confirmed findings from previous studies and suggested new genes involved in ageing or MDS. Ainciburu, Ezponda et al. used these results to create an analytical system that highlights gene activity differences in individual MDS patients that are independent of age-related changes. These results provide new insights that could help further research into the development of MDS and the ageing process. In addition, scientists could study other diseases using this approach of analysing individual patients' gene activity. In future, this could help to personalise clinical decisions on diagnosis and treatment.