HPV and Cervical Cancer: Molecular and Immunological Aspects, Epidemiology and Effect of Vaccination in Latin American Women.

Cervical cancer is primarily caused by Human Papillomavirus (HPV) infection and remains a significant public health concern, particularly in Latin American regions. This comprehensive narrative review addresses the relationship between Human Papillomavirus (HPV) and cervical cancer, focusing on Latin American women. It explores molecular and immunological aspects of HPV infection, its role in cervical cancer development, and the epidemiology in this region, highlighting the prevalence and diversity of HPV genotypes. The impact of vaccination initiatives on cervical cancer rates in Latin America is critically evaluated. The advent of HPV vaccines has presented a significant tool in combating the burden of this malignancy, with notable successes observed in various countries, the latter due to their impact on immune responses. The review synthesizes current knowledge, emphasizes the importance of continued research and strategies for cervical cancer prevention, and underscores the need for ongoing efforts in this field.

Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses.

Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by T cell receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8+ T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8+ T cells that were a source of interferon-gamma (IFN-γ) that could restrict growth of Cryptosporidium. This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (rhoptry protein 1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells, type 1 conventional dendritic cells were required to generate CD8+ T cell responses to these model antigens. These data sets highlight Cryptosporidium effectors as potential targets of the immune system and suggest that crosstalk between enterocytes and type 1 conventional dendritic cells is crucial for CD8+ T cell responses to Cryptosporidium.

Intestinal cDC1s provide IL-12 dependent and independent functions required for CD4+ T cell-mediated resistance to Cryptosporidium.

Cryptosporidium is an enteric pathogen that is a prominent cause of diarrheal disease. Control of this infection requires CD4+ T cells, though the processes that lead to T cell-mediated resistance have been difficult to assess. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to dissect the early events that influence CD4+ T cell priming and effector function. These studies highlight that parasite-specific CD4+ T cells are primed in the draining mesenteric lymph node (mesLN) and differentiate into Th1 cells in the gut, where they mediate IFN-γ-dependent control of the infection. Although type 1 conventional dendritic cells (cDC1s) were not required for initial priming of CD4+ T cells, cDC1s were required for CD4+ T cell expansion and gut homing. cDC1s were also a major source of IL-12 that was not required for priming but promoted full differentiation of CD4+ T cells and local production of IFN-γ. Together, these studies reveal distinct roles for cDC1s in shaping CD4+ T cell responses to enteric infection: first to drive early expansion in the mesLN and second to drive effector responses in the gut.

Meniscectomy is associated with a higher rate of osteoarthritis compared to meniscal repair following acute tears: a meta-analysis.

PURPOSE: Meniscal tears are common and may impair knee function and biomechanics. This meta-analysis compared meniscal repair versus resection in patients with symptomatic meniscal tears in terms of patient-reported outcomes measures (PROMs), joint width, surgical failure, and rate of progression to osteoarthritis (OA) at conventional radiography. METHODS: This study was conducted according to the 2020 PRISMA statement. In August 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. Two reviewers independently performed the analysis and a methodological quality assessment of the included studies. All the clinical investigations which compared repair versus resection of meniscal tears were accessed. RESULTS: Data from 20 studies (31,783 patients) were collected. The mean BMI was 28.28 ± 3.2 kg/m2, and the mean age was 37.6 ± 14.0 years. The mean time elapsed from injury to surgery was 12.1 ± 10.2 months and the mean medial joint width was 4.9 ± 0.8 mm. Between studies comparability at baseline was found in age, women, BMI, time from injury to surgery and length of the follow-up, PROMs, medial joint width, and stage of OA. The resection group demonstrated a greater Lysholm score (P = 0.02). No difference was found in the International Knee Documentation Committee (P = 0.2). Nine studies reported data on the rate of failures at a mean of 63.00 ± 24.7 months. No difference was found between the two groups in terms of persistent meniscal symptoms (P = 0.8). Six studies reported data on the rate of progression to total knee arthroplasty at a mean of 48.0 ± 14.7 months follow-up. The repair group evidenced a lower rate of progression to knee arthroplasty (P = 0.0001). Six studies reported data on the rate of advanced knee OA at a mean of 48.0 ± 14.7 months of follow-up. The repair group evidenced a lower rate of advanced knee OA (P = 0.0001). No difference was found in the mean joint space width (P = 0.09). CONCLUSION: Meniscal repair is associated with a lower progression to knee osteoarthritis at approximately six years of follow-up compared to partial meniscectomy. No difference in PROMs, medial joint width, and failures were evidenced. LEVEL OF EVIDENCE: Level III, meta-analysis.

Novel Fluoroquinolones with Possible Antibacterial Activity in Gram-Negative Resistant Pathogens: In Silico Drug Discovery.

Antibiotic resistance is a global threat to public health, and the search for new antibacterial therapies is a current research priority. The aim of this in silico study was to test nine new fluoroquinolones previously designed with potential leishmanicidal activity against Campylobacter jejuni, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Salmonella typhi, all of which are considered by the World Health Organization to resistant pathogens of global concern, through molecular docking and molecular dynamics (MD) simulations using wild-type (WT) and mutant-type (MT) DNA gyrases as biological targets. Our results showed that compound 9FQ had the best binding energy with the active site of E. coli in both molecular docking and molecular dynamics simulations. Compound 9FQ interacted with residues of quinolone resistance-determining region (QRDR) in GyrA and GyrB chains, which are important to enzyme activity and through which it could block DNA replication. In addition to compound 9FQ, compound 1FQ also showed a good affinity for DNA gyrase. Thus, these newly designed molecules could have antibacterial activity against Gram-negative microorganisms. These findings represent a promising starting point for further investigation through in vitro assays, which can validate the hypothesis and potentially facilitate the development of novel antibiotic drugs.

Impact of Frailty on Emergency Department Encounters for Cardiovascular Disease: A Retrospective Cohort Study.

Data are limited on whether the causes of emergency department (ED) encounters for cardiovascular diseases (CVDs) and associated clinical outcomes vary by frailty status. Using the United States Nationwide ED Sample, selected CVD encounters (acute myocardial infarction [AMI], ischemic stroke, atrial fibrillation [AF], heart failure [HF], pulmonary embolism, cardiac arrest, and hemorrhagic stroke) were stratified by hospital frailty risk score (HFRS). Logistic regression was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ED mortality among the different frailty groups. A total of 8,577,028 selected CVD ED encounters were included. A total of 5,120,843 (59.7%) had a low HFRS (<5), 3,041,699 (35.5%) had an intermediate HFRS (5 to 15), and 414,485 (4.8%) had a high HFRS (>15). Ischemic stroke was the most common reason for the encounter in the high HFRS group (66.9%), followed by hemorrhagic stroke (11.7%) and AMI (7.2%). For the low HFRS group, AF was the most common reason for the encounter (30.2%), followed by AMI (23.6%) and HF (16.8%). Compared with the low-risk group, high-risk patients had a decreased ED mortality and an increased overall mortality across most CVD encounters (p <0.001). The strongest association with overall mortality was observed among patients with a high HFRS admitted for AF (aOR 27.14, 95% CI 25.03 to 29.43) and HF (aOR 13.71, 95% CI 12.95 to 14.51) compared with their low-risk counterparts. In conclusion, patients presenting to the ED with acute CVD have a significant frailty burden, with different patterns of CVD according to frailty status. Frailty is associated with an increased all-cause mortality in patients for most CVD encounters.

Dendritic cell-mediated responses to secreted Cryptosporidium effectors are required for parasite-specific CD8 + T cell responses.

Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8 + T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8 + T cells that were a source of IFN-γ that could restrict growth of Cryptosporidium . This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (ROP1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells (IEC), type I dendritic cells (cDC1) were required to generate CD8 + T cell responses to these model antigens. These data sets highlight Cryptosporidium effectors as targets of the immune system and suggest that crosstalk between enterocytes and cDC1s is crucial for CD8 + T cell responses to Cryptosporidium .

Effect of Injury Patterns on the Development of Complications and Trauma-Induced Mortality in Patients Suffering Multiple Trauma.

Patients that suffer from severe multiple trauma are highly vulnerable to the development of complications that influence their outcomes. Therefore, this study aimed to evaluate the risk factors that can facilitate an early recognition of adult patients at risk. The inclusion criteria were as follows: admission to a level 1 trauma center, injury severity score (ISS) ≥ 16 (severe injury was defined by an abbreviated injury score (AIS) ≥ 3) and ≥18 years of age. Injury- and patient-associated factors were correlated with the development of four complication clusters (surgery-related, infection, thromboembolic events and organ failure) and three mortality time points (immediate (6 h after admission), early (>6 h-72 h) and late (>72 h) mortality). Statistical analysis was performed using a Chi-square, Mann-Whitney U test, Cox hazard regression analysis and binominal logistic regression analysis. In total, 383 patients with a median ISS of 24 (interquartile range (IQR) 17-27) were included. The overall mortality rate (27.4%) peaked in the early mortality group. Lactate on admission significantly correlated with immediate and early mortality. Late mortality was significantly influenced by severe head injuries in patients with a moderate ISS (ISS 16-24). In patients with a high ISS (≥25), late mortality was influenced by a higher ISS, older age and higher rates of organ failure. Complications were observed in 47.5% of all patients, with infections being seen most often. The development of complications was significantly influenced by severe extremity injuries, the duration of mechanical ventilation and length of ICU stay. Infection remains the predominant posttraumatic complication. While immediate and early mortality is mainly influenced by the severity of the initial trauma, the rates of severe head injuries influence late mortality in moderate trauma severity, while organ failure remains a relevant factor in patients with a high injury severity.

Management of transient bone osteoporosis: a systematic review.

INTRODUCTION: Transient bone osteoporosis (TBO) is characterized by persistent pain, loss of function, no history of trauma and magnetic resonance image (MRI) findings of bone marrow edema. SOURCE OF DATA: PubMed, Google scholar, EMABSE and Web of Science were accessed in February 2023. No time constrains were used for the search. AREAS OF AGREEMENT: TBO is rare and misunderstood, typically affecting women during the third trimester of pregnancy or middle-aged men, leading to functional disability for 4-8 weeks followed by self-resolution of the symptoms. AREAS OF CONTROVERSY: Given the limited evidence in the current literature, consensus on optimal management is lacking. GROWING POINTS: This systematic review investigates current management of TBO. AREAS TIMELY FOR DEVELOPING RESEARCH: A conservative approach leads to the resolution of symptoms and MRI findings at midterm follow-up. Administration of bisphosphonates might alleviate pain and accelerate both clinical and imaging recovery.

Evaluation of an electronic clinical decision support system (DeSSBack) to improve low back pain management: a pilot cluster randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a common reason for primary care consultation; yet doctors often find managing it challenging. An electronic decision support system for LBP (DeSSBack) was developed based on an evidence-based risk stratification tool to improve the management of patients with LBP in a Malaysian primary care setting. This pilot study aimed to assess the feasibility, acceptability, and preliminary effectiveness of DeSSBack for the conduct of a future definitive trial. METHODS: A pilot cluster randomized controlled trial (cRCT) with qualitative interviews was conducted. Each primary care doctor was considered a cluster and randomized to either the control (usual practice) or intervention (DeSSBack) group. Patient outcomes including Roland-Morris Disability Questionnaire (RMDQ), Hospital Anxiety and Depression Scale, and a 10-point pain rating scale were measured at baseline and 2-month postintervention. The doctors in the intervention group were interviewed to explore feasibility and acceptability of using DeSSBack. RESULTS: Thirty-six patients with nonspecific LBP participated in this study (intervention n = 23; control n = 13). Fidelity was poor among patients but good among doctors. The RMDQ and anxiety score had medium effect sizes of 0.718 and 0.480, respectively. The effect sizes for pain score (0.070) and depression score were small (0.087). There was appreciable acceptability and satisfaction with use of DeSSBack, as it was helpful in facilitating thorough and standardized management, providing appropriate treatment plans based on risk stratification, improving consultation time, empowering patient-centred care, and easy to use. CONCLUSIONS: A future cRCT to evaluate the effectiveness of DeSSBack is feasible to be conducted in a primary care setting with minor modifications. DeSSBack was found useful by doctors and can be improved to enhance efficiency. TRIAL REGISTRATION: The protocol of the cluster randomized controlled trial was registered at ClinicalTrials.gov (NCT04959669).

Bacterial pathogens and in-hospital mortality in revision surgery for periprosthetic joint infection of the hip and knee: analysis of 346 patients.

INTRODUCTION: The management of periprosthetic joint infections (PJI) of the lower limb is challenging, and evidence-based recommendations are lacking. The present clinical investigation characterized the pathogens diagnosed in patients who underwent revision surgery for  PJI of total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: The present study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The institutional databases of the RWTH University Medical Centre of Aachen, Germany, were accessed. The OPS (operation and procedure codes) 5-823 and 5-821 and the ICD (International Statistical Classification of Diseases and Related Health Problems) codes T84.5, T84.7 or T84.8 were used. All patients with PJI of a previous THA and TKA who underwent revision surgery were retrieved and included for analysis. RESULTS: Data from 346 patients were collected (181 THAs and 165 TKAs). 44% (152 of 346 patients) were women. Overall, the mean age at operation was 67.8 years, and the mean BMI was 29.2 kg/m2. The mean hospitalization length was 23.5 days. 38% (132 of 346) of patients presented a recurrent infection. CONCLUSION: PJI remain a frequent cause for revisions after total hip and knee arthroplasty. Preoperative synovial fluid aspiration was positive in 37%, intraoperative microbiology was positive in 85%, and bacteraemia was present in 17% of patients. Septic shock was the major cause of in-hospital mortality. The most common cultured pathogens were Staph. epidermidis, Staph. aureus, Enterococcus faecalis, and Methicillin-resistant Staph aureus (MRSA). An improved understanding of PJI pathogens is important to plan treatment strategies and guide the choice of empirical antibiotic regimens in patients presenting with septic THAs and TKAs. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

The Impact of Body Mass Composition on Outcome in Multiple Traumatized Patients-Results from the Fourth Thoracic and Third Lumbar Vertebrae: A Single-Center Retrospective Observational Study.

BACKGROUND: Body mass composition (BC) was shown to correlate with outcome in patients after surgery and minor trauma. As BC is assessed using computed tomography (CT) and routinely applied in multiple trauma (MT), this study will help to analyze whether BC variables also correlate with outcome in trauma patients. MATERIALS AND METHODS: Inclusion criteria were MT (Injury Severity Score (ISS) > 15) and whole-body CT (WBCT) scan on admission. Muscle and fat tissue were assessed at the level of the fourth thoracic vertebra (T4) and the third lumbar vertebra (L3) using Slice-O-matic software, version 5.0 (Tomovision, Montreal, QC, Canada). Univariate and multivariate regression models were used with regard to outcome parameters such as duration of ventilation, hospital stay, local (i.e., pneumonia, wound infection) and systemic (i.e., MODS, SIRS) complications, and mortality. RESULTS: 297 patients were included. BC correlated with both the development and severity of complications. Skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at both T4 and L3 correlated positively with the occurrence of systemic infections. Local infections positively correlated with SMI at T4. Low muscle mass and high visceral adipose tissue (VAT) predicted the severity of systemic and local complications. Muscle tissue markers at both T4 and L3 predicted the severity of complications in roughly the same way. Moreover, higher muscle mass at the L3 level was significantly associated with higher overall survival, while SATI at the T4 level correlated positively with hospital stay, length of stay in the ICU, and duration of ventilation. CONCLUSIONS: A lower muscle mass and a high adipose tissue index are associated with a poor outcome in MT. For the first time, it was shown that BC at the fourth thoracic vertebra is associated with comparable results to those found at the third lumbar level.

PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis.

At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.

Mapping Eastern (EEE) and Venezuelan Equine Encephalitides (VEE) among Equines Using Geographical Information Systems, Colombia, 2008-2019.

INTRODUCTION: Eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) viruses are zoonotic pathogens affecting humans, particularly equines. These neuroarboviruses compromise the central nervous system and can be fatal in different hosts. Both have significantly influenced Colombia; however, few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. OBJECTIVE: To describe the temporal-spatial distribution of those viruses in Colombia between 2008 and 2019. METHODS: Retrospective cross-sectional descriptive study, based on weekly reports by municipalities of the ICA, of the surveillance of both arboviruses in equines, in Colombia, from 2008 to 2019. The data were converted into databases in Microsoft Access 365®, and multiple epidemiological maps were generated with the Kosmo RC1®3.0 software coupled to shape files of all municipalities in the country. RESULTS: In the study period, 96 cases of EEE and 70 of VEE were reported, with 58% of EEE cases occurring in 2016 and 20% of EEV cases in 2013. The most affected municipalities for EEE corresponded to the department of Casanare: Yopal (20), Aguazul (16), and Tauramena (10). In total, 40 municipalities in the country reported ≥1 case of EEE. CONCLUSIONS: The maps allow a quick appreciation of groups of neighbouring municipalities in different departments (1° political division) and regions of the country affected by those viruses, which helps consider the expansion of the disease associated with mobility and transport of equines between other municipalities, also including international borders, such as is the case with Venezuela. In that country, especially for EEV, municipalities in the department of Cesar are bordering and at risk for that arboviral infection. there is a high risk of equine encephalitis outbreaks, especially for VEE. This poses a risk also, for municipalities in the department of Cesar, bordering with Venezuela.

Nude and Modified Electrospun Nanofibers, Application to Air Purification.

Air transports several pollutants, including particulate matter (PM), which can produce cardiovascular and respiratory diseases. Thus, it is a challenge to control pollutant emissions before releasing them to the environment. Until now, filtration has been the most efficient processes for removing PM. Therefore, the electrospinning procedure has been applied to obtain membranes with a high filtration efficiency and low pressure drop. This review addressed the synthesis of polymers that are used for fabricating high-performance membranes by electrospinning to remove air pollutants. Then, the most influential parameters to produce electrospun membranes are indicated. The main results show that electrospun membranes are an excellent alternative to having air filters due to the versatility of the process, the capacity for controlling the fiber diameter, porosity, high filtration efficiency and low-pressure drop.

Midterm results after arthroscopic femoral neck osteoplasty combined with labral debridement for cam type femoroacetabular impingement in active adults.

INTRODUCTION: Arthroscopic labral procedures are frequently undertaken in patients with femoroacetabular impingement (FAI). The role of arthroscopic femoral neck osteoplasty is well established, but less is known about labral procedures. This study evaluates the midterm efficacy and feasibility of arthroscopic osteoplasty with concomitant labral debridement for cam impingement in active adults. METHODS: The present study was conducted according to the STROBE Statement. All 108 patients who underwent primary hip arthroscopy for cam type FAI combined with labral debridement were considered. Axial and anteroposterior plain radiographs of the pelvis were obtained preoperatively to identify the cam deformity and assess the presence of osteoarthritis, the lateral centre-edge angle, and the alpha angle. The ROM (flexion, extension, abduction, adduction, and intra/extra rotation) was evaluated. The following PROMs were administered: visual analogic scale (VAS), Tegner Activity Scale, non-arthritic hip score (NAHS), the international Hip Outcome Tool (iHOT-33) overall score, and related subscales: symptoms and functional limitations, sports and recreational activities, job-related concerns, and social, emotional, and lifestyle concerns. RESULTS: At a mean of 2.0 ± 1.1 months, all 108 patients returned to their daily activities with no limitation. At a mean of 2.6 ± 1.4 months, all 108 patients were able to return to sport with no limitation. At 11.9 ± 2.1-month follow-up, no differences were reported in the range of motion compared to baseline: flexion (P = 0.3), extension (P = 0.09), abduction (P = 0.1), adduction (P = 0.3), internal rotation (P = 0.4), and external rotation (P = 0.6). At 72.8 ± 21.7-month follow-up, the mean VAS score was 1.7 ± 3.0, Tegner Activity Scale 3.5 ± 1.4, NAHS 92.1 ± 21.5, iHOT33 83.3 ± 27.2. At a mean of 21.7 ± 15.5 months following the index procedure, 14 of 108 patients had undergone total hip arthroplasty. No further revisions or complications were reported. CONCLUSION: Arthroscopic femoral neck osteoplasty with concomitant labral debridement for cam type of FAI in active adults yields the reliable results, with a rate of progression to total hip arthroplasty of 13% (14 of 108) at 3-year follow-up. All patients returned to their daily activities with no limitation 2 months postoperatively. Within 3 months, all patients returned to sport with no limitations. No complication related to the index procedure was reported, and no further arthroscopic procedures were necessary.

Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development.

The T-box transcription factor T-bet is regarded as a "master regulator" of CD4+ Th1 differentiation and IFN-γ production. However, in multiple models of infection, T-bet appears less critical for CD8+ T cell expansion and effector function. Here, we show that following vaccination with a replication-deficient strain of Toxoplasma gondii, CD8+ T cell expression of T-bet is required for optimal expansion of parasite-specific effector CD8+ T cells. Analysis of the early events associated with T cell activation reveals that the α chain of LFA1, CD11a, is a target of T-bet, and T-bet is necessary for CD8+ T cell upregulation of this integrin, which influences the initial priming of CD8+ effector T cells. We propose that the early expression of T-bet represents a T cell-intrinsic factor that optimizes T-DC interactions necessary to generate effector responses.

Autologous chondrocyte implantation in the knee is effective in skeletally immature patients: a systematic review.

PURPOSE: This systematic review evaluated the efficacy and safety of autologous chondrocyte implantation (ACI) for chondral defects of the knee in skeletally immature patients. Current available data from patients reported outcome measures (PROMs) and complications were collected, analyzed, and discussed. METHODS: This systematic review was conducted according to the PRISMA guidelines. The following databases were accessed in May 2022: PubMed, Google scholar, Embase, and Scopus. All the clinical studies investigating the efficacy of ACI to manage chondral defects of the knee in skeletally immature patients were accessed. Articles treating patients with surgical procedures other than ACI were not eligible, nor were studies with a follow-up shorter than 12 months. RESULTS: Data from 9 studies (251 procedures) were collected. 32% (80 of 251) of patients were females. The mean length of follow-up was 44.2 ± 29.4 (range, 12-115) months. The mean age of the patients was 16.4 ± 0.7 (range, 15-17) years. The Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Document Committee (IKDC) increased of + 41.9/100 (P = 0.003) and + 33.2/100 (P = < 0.0001) points, respectively. The Lysholm Knee Score improved of + 20.6/100 (P = 0.02) points. The Visual Analogue Scale (VAS) for pain reduced of - 3.6/10 (P = 0.004) points. The Tegner scale did not show any statistically significant improvement from baseline to follow-up (P = n.s.). The rate of graft hypertrophy was 12.5% (5 of 40 patients), and the rate of failure 5.6% (8 of 142 patients). CONCLUSION: ACI for chondral defects of the knee is effective to improve PROMs in skeletally immature patients. The safety profile of ACI still remains controversial. LEVEL OF EVIDENCE: III.

ALK1 controls hepatic vessel formation, angiodiversity, and angiocrine functions in hereditary hemorrhagic telangiectasia of the liver.

BACKGROUND AND AIMS: In hereditary hemorrhagic telangiectasia (HHT), severe liver vascular malformations are associated with mutations in the Activin A Receptor-Like Type 1 ( ACVRL1 ) gene encoding ALK1, the receptor for bone morphogenetic protein (BMP) 9/BMP10, which regulates blood vessel development. Here, we established an HHT mouse model with exclusive liver involvement and adequate life expectancy to investigate ALK1 signaling in liver vessel formation and metabolic function. APPROACH AND RESULTS: Liver sinusoidal endothelial cell (LSEC)-selective Cre deleter line, Stab2-iCreF3 , was crossed with Acvrl1 -floxed mice to generate LSEC-specific Acvrl1 -deficient mice ( Alk1HEC-KO ). Alk1HEC-KO mice revealed hepatic vascular malformations and increased posthepatic flow, causing right ventricular volume overload. Transcriptomic analyses demonstrated induction of proangiogenic/tip cell gene sets and arterialization of hepatic vessels at the expense of LSEC and central venous identities. Loss of LSEC angiokines Wnt2 , Wnt9b , and R-spondin-3 ( Rspo3 ) led to disruption of metabolic liver zonation in Alk1HEC-KO mice and in liver specimens of patients with HHT. Furthermore, prion-like protein doppel ( Prnd ) and placental growth factor ( Pgf ) were upregulated in Alk1HEC-KO hepatic endothelial cells, representing candidates driving the organ-specific pathogenesis of HHT. In LSEC in vitro , stimulation or inhibition of ALK1 signaling counter-regulated Inhibitors of DNA binding (ID)1-3, known Alk1 transcriptional targets. Stimulation of ALK1 signaling and inhibition of ID1-3 function confirmed regulation of Wnt2 and Rspo3 by the BMP9/ALK1/ID axis. CONCLUSIONS: Hepatic endothelial ALK1 signaling protects from development of vascular malformations preserving organ-specific endothelial differentiation and angiocrine signaling. The long-term surviving Alk1HEC-KO HHT model offers opportunities to develop targeted therapies for this severe disease.

Adlerian-informed supervision: Protecting counselors from burnout and improving client outcomes in the juvenile justice system.

Mental health professionals working in the juvenile justice system work with clients who have complex mental health needs putting them at increased risk of burnout and vicarious trauma. Clinical supervision can help beginning counselors provide competent services and, at the same time, protect them from burnout. This article shows how supervisors can use an Adlerian-informed supervision method that integrates the Respectfully Curious Inquiry/Therapeutic Encouragement (RCI/TE) framework with the discrimination model of supervision to increase the supervisee's experience of the Crucial Cs. Supervisors can protect supervisees from burnout and vicarious trauma by increasing feelings of connection, significance, competence, and courage. (PsycInfo Database Record (c) 2023 APA, all rights reserved).