CD40/CD40L expression and its prognostic value in cervical cancer.

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.

[Translated article] Comparative clinical and biomechanical study of different types of osteosynthesis in the treatment of distal femur fractures.

INTRODUCTION AND OBJECTIVES: Distal femoral fractures represent a problem due to their high number of complications. The aim was to compare the results, complications and stability achieved with retrograde intramedullary nailing and the angular stable plate in the treatment of distal femoral diaphyseal fractures. MATERIAL AND METHOD: A clinical and experimental biomechanical study was carried out using finite elements. The results of the simulations allowed us to obtain the main results related to the stability of osteosynthesis. For clinical follow-up data, frequencies were used for qualitative variables, and Fisher's exact test and χ2 test were used to evaluate the significance of the different factors, with the condition of P<.05. RESULTS: In the biomechanical study, the retrograde intramedullar nails demonstrated superiority, obtaining lower values in terms of global displacement, maximum tension, torsion resistance, and bending resistance. In the clinical study, the rate of consolidation of the plates was lower than nails (77% vs. 96%, P=.02). The factor that most influenced the healing of fractures treated with plate were the central cortical thickness (P=.019). The factor that most influenced the healing of nail-treated fractures was the difference between the diameter of the medullary canal and the nail. CONCLUSIONS: Our biomechanical study shows that both osteosynthesis provide sufficient stability, but biomechanically behaves differently. Nails provide greater overall stability being preferable the use of long nails adjusted to the diameter of the canal. Plates form less rigid osteosynthesis, with little resistance to bending.

Comparative clinical and biomechanical study of different types of osteosynthesis in the treatment of distal femur fractures. / Estudio comparativo clínico y biomecánico de distintos tipos de osteosíntesis en el tratamiento de fracturas distales de fémur.

INTRODUCTION AND OBJECTIVES: Distal femoral fractures represent a problem due to their high number of complications. The aim was to compare the results, complications and stability achieved with retrograde intramedullary nailing and the angular stable plate in the treatment of distal femoral diaphyseal fractures. MATERIAL AND METHOD: A clinical and experimental biomechanical study was carried out using finite elements. The results of the simulations allowed us to obtain the main results related to the stability of osteosynthesis. For clinical follow-up data, frequencies were used for qualitative variables, and Fisher's exact test and χ2 test were used to evaluate the significance of the different factors, with the condition of P<.05. RESULTS: In the biomechanical study, the retrograde intramedullar nails demonstrated superiority, obtaining lower values in terms of global displacement, maximum tension, torsion resistance, and bending resistance. In the clinical study, the rate of consolidation of the plates was lower than nails (77% vs. 96%, P=.02). The factor that most influenced the healing of fractures treated with plate were the central cortical thickness (P=.019). The factor that most influenced the healing of nail-treated fractures was the difference between the diameter of the medullary canal and the nail. CONCLUSIONS: Our biomechanical study shows that both osteosynthesis provide sufficient stability, but biomechanically behaves differently. Nails provide greater overall stability being preferable the use of long nails adjusted to the diameter of the canal. Plates form less rigid osteosynthesis, with little resistance to bending.

Influence of plate size and screw distribution on the biomechanical behaviour of osteosynthesis by means of lateral plates in femoral fractures.

Distal femoral fractures are fractures associated with high rates of morbidity and mortality, affecting to three different groups of individuals: younger people suffering high-energy trauma, elderly people with fragile bones and people with periprosthetic fractures around previous total knee arthroplasty. They have been classically treated with conventional plates and intramedullary nails and more recently with locked plates that have increased their indications to more types of fractures. The main objective of the present work is the biomechanical study, by means of finite element simulation, of the stability achieved in the osteosynthesis of femoral fractures in zones 4 and 5 of Wiss, by using locked plates with different plate lengths and different screw configurations, and analysing the effect of screw proximity to the fracture site. A three dimensional (3D) finite element model of the femur from 55-year-old male donor was developed, and then a stability analysis was performed for the fixation provided by Osteosynthesis System LOQTEC® Lateral Distal Femur Plate in two different fracture zones corresponding to the zones 4 and 5 according to the Wiss fracture classification. The study was focused on the immediately post-operative stage, without any biological healing process. The obtained results show that more stable osteosyntheses were obtained by using shorter plates. In the cases of longer plates, it results more convenient disposing screws in a way that the upper ones are closer to fracture site. The obtained results can support surgeons to understand the biomechanics of fracture stability, and then to guide them towards the more appropriate osteosynthesis depending on the fracture type and location.

CD40/CD40L expression and its prognostic value in cervical cancer

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.

Asymptomatic bacteriuria in candidates for active treatment of renal stones: results from an international multicentric study on more than 2600 patients.

The occurrence of asymptomatic bacteriuria concomitant to urolithiasis is an issue for patients undergoing renal stone treatment. Disposing of a preoperative urine culture is essential to reduce the risk of septic events. The endpoint of the study is to report which characteristics of candidates for renal stone treatment are frequently associated with positive urine culture. 2605 patients were retrospectively enrolled from 14 centers; inclusion criteria were age > 18 and presence of a single renal stone 1-2 cm in size. The variables collected included age, gender, previous renal surgery, comorbidities, skin-to-stone distance, stone size, location, density, presence of hydronephrosis. After a descriptive analysis, the association between continuous and categorical variables and the presence of positive urine culture was assessed using a logistic regression model. Overall, 240/2605 patients (9%) had preoperative bacteriuria. Positive urine culture was more frequent in females, patients with previous renal interventions, chronic kidney disease, congenital anomalies, larger stones, increased density. Multivariate analysis demonstrated that previous renal interventions (OR 2.6; 95% CI 1.9-3.4; p < 0.001), renal-related comorbidities (OR 1.31; 95% CI 1.19-1.4; p < 0.001), higher stone size (OR 1.06; 95% CI 1.02-1.1; p = 0.01) and density (OR 1.00; 95% CI 1.0-1.00; p = 0.02) were associated with bacteriuria; male gender and lower caliceal location were inversely related to it. Beyond expected risk factors, such as female gender, other parameters are seemingly favoring the presence of positive urine culture. The awareness of variables associated with bacteriuria allows to assess which individuals are at increased risk of presenting bacteriuria and reduce the rate of septic complications.

Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn's disease patients?

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

Strengthening preparedness against global health threats: A paradigm shift based on One Health approaches.

The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.

Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn's disease patients?

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy.

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.

Biomechanical behavior of retrograde intramedullary nails in distal femoral fractures.

Fractures of the distal femur affect three different groups of individuals: younger people suffering high-energy trauma, elderly people with fragile bones and people with periprosthetic fractures around previous total knee arthroplasty. Main indications of intramedullary nailing are for supracondylar fractures type A or type C of the AO classification. The main objective of the present work is to analyze, by means of FE simulation, the influence of retrograde nail length, considering different blocking configurations and fracture gaps, on the biomechanical behavior of supracondylar fractures of A type. A three dimensional (3D) finite element model of the femur from 55-year-old male donor was developed, and then a stability analysis was performed for the fixation provided by the retrograde nail at a distal fracture with different fracture gaps: 0.5 mm, 3 mm y 20 mm, respectively. Besides, for each gap, three nail lengths were studied with a general extent (320 mm, 280 mm and 240 mm), considering two transversal screws (M/L) at the distal part and different screw combinations above the fracture. The study was focused on the immediately post-operative stage, without any biological healing process. In view of the obtained results, it has been demonstrated new possibilities of blocking configuration in addition to the usual ones, which allows establishing recommendations for nail design and clinical practice, avoiding excessive stress concentrations both in screws, with the problem of rupture and loss of blocking, and in the contact of nail tip with cortical bone, with the problem of a new stress fracture.

Vitality form expression in autism.

The notion of "vitality form" has been coined by Daniel Stern to describe the basic features of action, which may reflect the mood or affective state of an agent. There is general consensus that vitality forms substantiate social interactions in children as well in adults. Previous studies have explored children with Autism Spectrum Disorder (ASD)'s ability in copying and recognizing the vitality forms of actions performed by others. In this paper we investigated, for the first time, how children with ASD express different vitality forms when acting themselves. We recorded the kinematics of ASD and typically developing (TD) children while performing three different types of action with two different vitality forms. There were two conditions. In the what condition we contrasted the three different types of action performed with a same vitality form, while in the how condition we contrasted the same type of action performed with two different vitality forms. The results showed a clear difference between ASD children and TD children in the how, but not in the what, condition. Indeed, while TD children distinguished the vitality forms to be expressed by mostly varying a specific spatiotemporal parameter (i.e. movement time), no significant variation in this parameter was found in ASD children. As they are not prone to express vitality forms as neurotypical individuals do, individuals with ASD's interactions with neurotypical peers could therefore be difficult to achieve successfully, with cascading effects on their propensity to be tuned to their surrounding social world, or so we conjecture. If this conjecture would turn out to be correct, our findings could have promising implication for theoretical and clinical research in the context of ASD.

Gastrointestinal nematode infections in goats: differences between strongyle faecal egg counts and specific antibody responses to Teladorsagia circumcincta in Nera di Verzasca and Alpine goats.

Strongylida are gastrointestinal nematodes (GIN) of greatest importance in small ruminants throughout the world. Differences in resistance and resilience to GIN among goat breeds were reported. This study aims to investigate the mechanism underlying the breed-associated differences using a cosmopolitan (Alpine, AB) and an autochthonous (Nera di Verzasca, NV) goat breed. At first, fifteen goats from the same herd (NV = 7, AB = 8) at day 0 were infected with infective larvae (L3) of mixed GIN. From the 15th day post-infection (DPI), individual parasite egg excretion (faecal egg counts, FEC) was performed on all goats, once per week, until the 63rd DPI. Afterwards, in goats under field conditions (30 AB and 30 NV reared on the same farm), individual faecal and blood samples were collected; FEC-specific antibody and PCV levels were explored. In goats with experimental GIN infection, mean eggs per gram of faeces (EPG) values were consistently lower in NV goats. In goats with natural GIN infection, EPG and prevalence values showed high variability in both breeds; among individual variables, breed had a significant influence on EPG. Further, PCV and anti-T. circumcincta IgA levels were influenced by the breed. Lower PCV values were also associated with higher strongyle EPG in AB goats, and anti-T. circumcincta IgA levels were influenced by both strongyle EPG and breed, with IgA levels being higher in AB vs. NV goats and positively associated with EPG. Neither EPG nor breed had any influence on IgE levels. Both studies on experimental and natural infection confirmed that goats of NV are more resistant to infection with gastrointestinal nematodes.

Cognitive behavioral therapy may have a rehabilitative, not normalizing, effect on functional connectivity in adolescent depression.

BACKGROUND: Whether the differences in brain structure and function, characteristic of adult major depressive disorder (MDD1), are present in adolescent MDD is still unclear, but it has been shown that cognitive behavioral therapy (CBT2) affects resting-state functional connectivity in both adult and adolescent MDD patients, with the claim that CBT has a normalizing effect on MDD-related functional disruption, but this has not been directly tested. METHODS: 128 adolescent MDD patients and 40 adolescent controls were enrolled in the study. We investigated pre-treatment differences in cortical thickness, white matter volume, and resting-state functional connectivity. We also investigated the longitudinal effects of CBT on resting-state functional connectivity, and the relationship between pre-treatment functional disruption and CBT-related changes to resting-state functional connectivity was assessed by the correlation of pre-treatment cross-sectional effects and longitudinal CBT-related effects across multiple brain regions. RESULTS: Patients had greater cortical thickness and white matter volume within fronto-limbic regions of the brain. Patients had greater pre-treatment resting-state functional connectivity within the default-mode, fronto-limbic, central-executive, and salience networks. CBT increased resting-state functional connectivity of the subgenual anterior cingulate and amygdala seeds with predominantly frontal regions. Regions showing the greatest pre-treatment functional disruption showed the weakest CBT-related changes. LIMITATIONS: For ethical reasons, there was no placebo group. CONCLUSIONS: Adolescent MDD is associated with structural and functional differences also seen in adult patients. CBT-related changes in resting-state functional connectivity do not appear to show a normalizing effect, but instead indicate rehabilitative effects on resting-state functional connectivity.

Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study.

OBJECTIVE: To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN: Cohort study. SETTING: ELEMENT Cohort in Mexico City. POPULATION: Pregnant women with singleton births (n = 97). METHODS: We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME: Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS: Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (ß = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (ß = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION: We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT: There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.

The contribution of Latin American research to HPV epidemiology and natural history knowledge.

Our aim was to review the major contributions of studies conducted in different Latin American (LA) countries to the field of human papillomavirus (HPV) epidemiology, natural history, risk of disease, and prevention strategies, mainly in the uterine cervix. Although cytological screening is established in several countries in LA, incidence and mortality rates from cervical cancer (CC) are still extremely high. Finally, data from large cohort studies conducted in LA countries provided seminal data to propose primary and secondary prevention modalities: the HPV vaccine has been introduced in the national immunization programs of several LA countries and multiple screening experiences using HPV testing are under evaluation in the region.

The contribution of Latin American research to HPV epidemiology and natural history knowledge

Our aim was to review the major contributions of studies conducted in different Latin American (LA) countries to the field of human papillomavirus (HPV) epidemiology, natural history, risk of disease, and prevention strategies, mainly in the uterine cervix. Although cytological screening is established in several countries in LA, incidence and mortality rates from cervical cancer (CC) are still extremely high. Finally, data from large cohort studies conducted in LA countries provided seminal data to propose primary and secondary prevention modalities: the HPV vaccine has been introduced in the national immunization programs of several LA countries and multiple screening experiences using HPV testing are under evaluation in the region.

Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: High-frequency ultrasound (HFUS 18-20 MHz) performed on patients with chronic inflammatory demyelinating polyneuropathy (CIDP) shows a focal enlargement, particularly in the proximal segments of upper-arm motor nerves. Ultrahigh frequency ultrasound (UHFUS 30-70 MHz), having a higher spatial resolution, enables a better characterization of nerve structures. The aim of this study was to compare the two ultrasound probes in the evaluation of motor nerve characteristics in CIDP patients. METHODS: Eleven patients with definite or probable CIDP underwent an ultrasound evaluation of median and ulnar nerves, bilaterally. Nerve and fascicle cross-sectional area (CSA), vascularization, and echogenicity were assessed. RESULTS: Nerve and fascicle CSA were increased in the proximal segments, especially in the median nerve, in 9/11 patients and in 10/11 patients at the HFUS and UHFUS evaluations, respectively. A statistically significant difference between CSA values obtained with the two probes was found only for fascicle values. UHFUS allowed for a more precise estimation of fascicle size and number than the HFUS. We were able to identify nerve vascularization in 4/11 patients at UHFUS only. CONCLUSION: UHFUS gives more detailed information on the changes in the internal nerve structure in CIDP patients. In particular, it permits to better characterize fascicle size and morphology, and to have a precise estimation of their number. Its frequency range also allows to evaluate nerve vascularization. SIGNIFICANCE: Ultrasound evaluation could become an adjunctive diagnostic tool for CIDP. Further studies are needed to validate the examined parameters as biomarkers for the evaluation and follow-up of CIDP patients.