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.

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.

Fracture resistance of bonded CAD/CAM restorations with standard or extended preparations.

The purpose of this study was to evaluate the fracture resistance of teeth with standard or extended mesio-occlusodistal (MOD) preparations after restoration with bonded computer-aided design/computer-aided manufacturing (CAD/CAM) materials. Standard or extended MOD cavities were prepared in 60 of 70 extracted, caries-free third molars. In the standard MOD preparations (n = 30), 4.5- mm buccal and lingual/palatal wall thickness remained, and proximal boxes extended 1.0 mm coronal to the cementoenamel junction. In the extended MOD preparations (n = 30), the buccal and lingual/palatal walls were reduced to a thickness of 3.0 mm. A CAD/CAM acquisition unit was used to scan 20 standard and 20 extended preparations. Subsequently, 10 standard and 10 extended preparations were restored with milled lithium disilicate, and 10 of each type were restored with resin nanoceramic. Ten of each preparation type were left unrestored (negative control). An additional 10 third molars were neither prepared nor restored (positive control). After thermocycling and cyclic loading, specimens were fractured in a material testing device. Although bonded CAD/CAM restorations reinforced the tooth structure, the mean fracture loads were significantly lower (P < 0.05) in teeth with restored extended preparations (2642.4 [SD 479.4] N) than in teeth with restored standard preparations (3376.6 [SD 817.9] N). The type of CAD/CAM restorative material did not significantly affect the fracture load. Practitioners should consider covering the cusps with a CAD/CAM restorative material to reduce the potential for fracture in preparations with reduced cuspal thickness, especially in patients with heavier occlusion or functional loads.

Translucency and strength of high-translucency monolithic zirconium oxide materials.

The purpose of this study was to evaluate the translucency and strength of highly translucent monolithic zirconia ceramic materials recently introduced to the market. Four monolithic zirconium oxide materials promoted as having high translucency (BruxZir Shaded 16, BruxZir HT, Lava Plus, and inCoris TZI C) were compared to a high-translucency, lithium disilicate monolithic glass-ceramic material (IPS e.max CAD HT). To evaluate translucency, the materials were sectioned into 0.5-, 1.0-, 1.5-, and 2.0-mm-thick specimens; all were sintered and polished. Translucency parameters were calculated with a spectrophotometer. To evaluate flexural strength and modulus, the ceramic materials were sectioned to create beams and fractured in a universal testing machine. The lithium disilicate had significantly greater translucency than the zirconia materials at each thickness. In general, the translucencies of the zirconia materials were similar at each thickness. However, at the manufacturers' recommended minimal thicknesses, 0.5-mm specimens of BruxZir Shaded 16, inCoris TZI C, and Lava Plus were more translucent than the 1.0-mm-thick specimens of IPS e.max CAD HT. Translucency significantly decreased for each material at each increase in thickness. The flexural strengths of the zirconia materials were similar to each other and significantly greater than that of IPS e.max CAD HT. Flexural moduli were more variable. Of the zirconia materials, BruxZir Shaded 16 had an overall better combination of translucency, strength, and modulus.

Subcellular localisation of pMEK has a different prognosis in locally advanced head and neck cancer treated with concomitant radiochemotherapy.

BACKGROUND: MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy. METHODS: Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67. RESULTS: Sixty-six percent of patients were positive for pMEK expression in the nucleus and 41 % in cytoplasm. On univariate analysis, high nuclear pMEK was predictive of worse 5y-DFS and 5y-OS, with a trend to significance (26 % vs. 41 %, p = 0.09; 36 % vs. 47 %, p = 0.07). High cytoplasmic pMEK was predictive of better 5-y OS and 5-y DFS outcomes (61 % vs. 27 %, p = 0.01; 46 % vs. 22 %, p = 0.02). On multivariate analysis, low cytoplasmic pMEK and high nuclear pMEK predicted worse DFS and OS (p = 0.01; p = 0.04 and p = 0.02; p = 0.02 respectively). CONCLUSIONS: Subcellular localisation of pMEK has different prognosis in locally advanced head and neck cancer treated with radiochemotherapy.

Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

IncA/C Plasmid Carrying bla(NDM-1), bla(CMY-16), and fosA3 in a Salmonella enterica Serovar Corvallis Strain Isolated from a Migratory Wild Bird in Germany.

A Salmonella enterica serovar Corvallis strain was isolated from a wild bird in Germany. This strain carried the IncA/C2 pRH-1238 plasmid. Complete sequencing of the plasmid was performed, identifying the blaNDM-1, blaCMY-16, fosA3, sul1, sul2, strA, strB, aac(6')-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, and merA genes, which confer clinically relevant resistance to most of the antimicrobial classes, including ß-lactams with carbapenems, fosfomycin, aminoglycosides, co-trimoxazole, tetracyclines, and macrolides. The strain likely originated from the Asiatic region and was transferred to Germany through the Milvus migrans migratory route.

Microtensile bond strength of lithium disilicate to zirconia with the CAD-on technique.

PURPOSE: Recently, a novel technique was introduced to combine lithium disilicate and zirconia into one restoration. The purpose of this study was to compare the microtensile bond strength of veneering ceramic to a zirconia core in two techniques: the e.max® CAD-on technique and the Press-on technique. MATERIALS AND METHODS: Group A was prepared by veneering sintered zirconia blocks (e.max® ZirCAD) with lithium disilicate blocks (e.max® CAD) using the CAD-on technique according to manufacturer's instructions. Group B was prepared by taking sintered e.max® ZirCAD blocks and veneering them with fluorapatite glass-ceramic (e.max® ZirPress) using the Press-on technique according to manufacturer's instructions. Each block was loaded in a dynamic cyclic loading machine. The blocks were then sectioned into 1 × 1 mm(2) beams (n = 43) using a precision saw, thermocycled, and loaded in tension until failure on a universal testing machine. A mean and standard deviation were determined per group. Data were analyzed using an unpaired t-test (α = 0.05). RESULTS: The mean microtensile bond strengths were 44.0 ± 13.8 MPa for the CAD-on technique and 14.9 ± 8.8 MPa for the Press-on technique. Significant differences were found between the two groups (p = 2.7E-19). CONCLUSIONS: The CAD-on technique (lithium disilicate/zirconia) resulted in greater microtensile bond strength than the Press-on technique (fluorapatite glass-ceramic/zirconia).

Assessment of the performance of algorithms for cervical cancer screening: evidence from the Ludwig-McGill cohort study.

OBJECTIVE: There are currently multiple tests available for cervical cancer screening and the existing screening policies vary from country to country. No single approach will satisfy the specific needs and variations in risk aversion of all populations, and screening algorithms should be tailored to specific groups. We performed long term risk stratification based on screening test results and compared the accuracy of different tests and their combinations. METHODS: A longitudinal cohort study of the natural history of HPV infection and cervical neoplasia enrolled 2462 women from a low-income population in Brazil. The interviews and cervical screening with cytology and HPV DNA testing were repeated according to a pre-established protocol and the subjects were referred for colposcopy and biopsy whenever high grade lesions were suspected. We compared the specificity, sensitivity and predictive values of each screening modality. Long term risk stratification was performed through time-to-event analyses using Kaplan-Meier analysis and Cox regression. RESULTS: The best optimization of sensitivity and specificity was achieved when using dual testing with cytology and HPV DNA testing, whereby the screening test is considered positive if either component yields an abnormal result. However, when allowing 12months for the detection of lesions, cytology alone performed nearly as well. Risk stratification revealed that HPV DNA testing was not beneficial for HSIL cases, whereas it was for ASCUS and, in some combinations, for negative and LSIL cytology. CONCLUSION: Our results suggest that some high risk populations may benefit equally from cytology or HPV DNA testing, and may require shorter intervals between repeat testing.

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.

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.

[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.

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.

Increased plasma levels of total homocysteine but not asymmetric dimethylarginine in Hispanic subjects with ischemic stroke FREC-VI sub-study.

BACKGROUND AND PURPOSE: Despite sharing some metabolic and pathological mechanisms, the reported association between total homocysteine (tHcy), asymmetric dimethylarginine (ADMA) and stroke remains controversial, particularly in Hispanic populations from developing countries in which genetic, socioeconomic, and nutritional factors are different to those described in developed countries. Our objectives were to determine the relationships of these factors to stroke and to each other independent of other cardiovascular risk factors, and to explore potential sex differences. METHODS: This national (Colombia) multicenter case-control study included 238 cases and 238 controls to evaluate traditional and emerging risk factors for ischemic stroke including tHcy and ADMA plasma levels. RESULTS: The median plasma levels of tHcy were 8.48 µM for controls and 10.01 µM for cases (P<0.0001). Plasma levels of tHcy between 12 and 50µM were considered moderate hyperhomocysteinemia (HtHcy). There were no differences in plasma ADMA concentration between groups (P=0.40). Plasma levels of ADMA and creatinine were not correlated (P=0.47). After adjusting for confounding factors, the presence of HtHcy was strongly associated with stroke (OR 8.97; P<0.0001). The adjusted association between HtHcy and stroke in men (OR 9.98) was comparable to that in women (OR 8.98) (P=0.41). CONCLUSIONS: In this Hispanic population, with relatively normal renal function, plasma levels of tHcy but not ADMA were associated with stroke independent of other cardiovascular risk factors.

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.

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.

Persistence and clearance of HPV from the penis of men infected and non-infected with HIV.

Due to high rates of human papillomavirus (HPV) infection, the incidence of intraepithelial neoplasia and anal cancer, most studies concerning HPV in men seropositive for HIV have focused on the anal canal. Few studies have targeted the penile region in HIV-infected men. A total of 72 men seropositive for HIV and 72 men seronegative for HIV were followed-up for 6 months, and their penile exfoliated cells were tested for HPV DNA. There were no significant differences between the HIV-positive and HIV-negative men in persistence (respectively, 69.5% vs. 66.9%), clearance (respectively, 15.3% vs. 23.1%), and those men never infected with HPV during the four follow-up visits (15.2% for HIV-positive vs. 20% for HIV-negative). High-risk HPV types were detected more frequently in penile smears from men infected with HIV, while, in HIV-seronegative men, the low-risk HPV types were more abundant (P = 0.001). Multiple infections with both high- and low-risk HPV types were significantly more frequent in HIV-seropositive compared to those who were HIV-seronegative (P = 0.0004). The attendance rates at follow-up visits were 86%, 78%, and 58% in months 1, 2, and 6, respectively, for men infected with HIV and 93%, 72%, and 60% for the HIV-negative group. It is concluded that HIV infection can be considered a risk factor for clearance and persistence of HPV. Multiple infections with different types of HPV including high-risk HPVs are frequent in men who are infected with HIV.