Effects of space allowance on patterns of activity in group-housed dairy calves.

With increasing use of social housing for dairy calves, there is a need to refine housing management practices that influence animal behavior and may affect welfare. Our aim was to assess the effect of pen space allowance on activity patterns and pen space use. Holstein heifer calves were group-housed (n = 6 pens; 5 calves/pen) at 14 d ± 2.8 d of age (mean ± SD). After a 7-d adaptation, each pen was exposed to 3 different space allowances (3.7, 4.6, and 5.6 m2/calf) in a random order, according to a replicated Latin square design with three 7-d periods (period 1, d 22-28; period 2, d 29-35; and period 3, d 36-42). Calves were provided milk replacer (12 L/d) ad libitum via an automated milk feeder and gradually weaned over 10 d, beginning at 48 ± 3 d of age. Using leg-based accelerometers (HOBO Pendant G data logger, Onset Computer Corp., Pocasset, MA), we obtained data describing standing time, standing bout frequency, and standing bout duration. Daily pen-level average standing time (6.5 h/d; SE = 0.27) did not differ between treatments. However, with greater space allowance, calves had more frequent standing bouts (22.6 vs. 20.3 bouts/d; 5.6 vs. 3.7 m2/calf; SE = 0.96) of shorter duration. To assess effects of space allowance on within-pen individual variability, we calculated the coefficient of variation for daily activity outcomes at the pen level and intra-class correlation coefficients for hourly standing time, by pen and day. The coefficient of variation for standing behavior outcomes decreased with increasing space allowance, and the intraclass correlation for hourly standing time increased, suggesting that increasing space allowance reduced individual variability and may promote more synchronous rest. Finally, we qualitatively assessed use of pen space using motion heat maps generated using computer vision from video recorded of each pen from 0800 to 1200 h on d 6 and 7 of each experimental period for each pen. These images suggest that calves preferentially used space near the perimeter of the pen, but space was used more uniformly when space allowance is restricted. Overall, these results suggest that lower space allowances may restrict patterns of activity at the pen level and reduce behavioral synchrony.

Strategic framework for the Spanish Society of Internal Medicine 2025-2029 executive summary to guarantee a person cantered care in a high value National Health System.

AIMS: To design a strategic framework for the policy and activity of the Spanish Society of Internal Medicine (SEMI). METHODS: Expert consensus. Participation through expert committees and consultation the proposals of strategic lines to the internists. RESULTS: The SEMI's slogan was changed to "the comprehensive care for the ill person", defining seven strategic lines: Contributing to the transformation of the health system; participating in university teaching; guaranteeing a comprehensive healthcare to the ill person; providing to internal medicine residents and internists with the competences to practice in 21st century healthcare; promoting the research and the generation of scientific evidence in internal medicine; incorporating technological innovation and digital tools; positioning SEMI as a reference institution for healthcare policy. CONCLUSIONS: SEMI proposes to be a key player in the transformation of the Spanish healthcare system.

Breed variability in the cellular mediated immune response to experimental Neospora caninum infection in heifers.

Protozoan parasite Neospora caninum causes abortion in infected cattle while others remain asymptomatic. Host immunity plays a critical role in the outcome of bovine neosporosis. Despite extensive research, there is a critical gap in therapeutic and preventive measures, and no effective vaccines are available. Both beef and dairy cattle can suffer from N. caninum-induced abortions, but cumulative evidence suggests a breed susceptibility being higher in dairy compared with beef breeds. It has been established that the response to N. caninum infection primarily involves a cell-mediated immune response (CMIR) regulated by T-helper type 1 (Th1) cells and specific cytokines. The delayed-type hypersensitivity (DTH) skin test has been used to measure the ability of livestock to generate CMIR, in the context of breeding for disease resistance and as a method for diagnosis of several diseases. In this study, we evaluated the immune response triggered by an N. caninum-induced DTH skin test between Holstein - a dairy breed intensively selected- and Argentinean Creole heifers - a beef breed with minimal genetic selection- to assess differences in CMIR following experimental N. caninum infection. The immune response, measured through skinfold thickness and histological and immune molecular analysis, revealed variations between the breeds. Our study found an increased CMIR in Argentinean Creole heifers compared to Holstein heifers. Differential gene expression of key cytokines was observed at the DTH skin test site. Argentinean Creole heifers exhibited elevated IFN-γ, IL-12, IL-10, and IL-4, while Holstein heifers only showed higher expression of IL-17. This finding could underscore genetic diversity in response to neosporosis, which could be used in breeding cattle strategies for disease resistance in cattle populations.

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis.

Importance: Precise estimation of a patient's drug metabolism capacity is important for antiseizure dose personalization. Objective: To quantify the differences in plasma concentrations for antiseizure drugs associated with variants of genes encoding drug metabolizing enzymes. Data Sources: PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to September 30, 2023, without language restrictions. Study Selection: Two reviewers performed independent study screening and assessed the following inclusion criteria: appropriate genotyping was performed, genotype-based categorization into subgroups was possible, and each subgroup contained at least 3 participants. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for data extraction and subsequent quality, validity, and risk-of-bias assessments. The results from the included studies were pooled with random-effect meta-analysis. Main Outcomes and Measures: Plasma concentrations of antiseizure drugs were quantified with the dose-normalized area under the concentration-time curve, the dose-normalized steady state concentration, or the concentrations after a single dose at standardized dose and sampling time. The ratio of the means was calculated by dividing the mean drug plasma concentrations of carriers and noncarriers of the pharmacogenetic variant. Results: Data from 98 studies involving 12 543 adult participants treated with phenytoin, valproate, lamotrigine, or carbamazepine were analyzed. Studies were mainly conducted within East Asian (69 studies) or White or European (15 studies) cohorts. Significant increases of plasma concentrations compared with the reference subgroup were observed for phenytoin, by 46% (95% CI, 33%-61%) in CYP2C9 intermediate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI, 4%-20%) in CYP2C9 intermediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12% (95% CI, 3%-22%) in CYP3A5 poor metabolizers. Conclusions and Relevance: This systematic review and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were associated with a clinically relevant increase in phenytoin plasma concentrations, several pharmacogenetic variants were associated with statistically significant but only marginally clinically relevant changes in valproate and carbamazepine plasma concentrations, and numerous pharmacogenetic variants were not associated with statistically significant differences in plasma concentrations of antiseizure drugs.

Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: Focus on antipsychotics.

BACKGROUND: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialised tools are used. Three tools have been proven useful to personalise drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. METHODS: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 45 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). RESULTS: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. CONCLUSION: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry.

Seventy years of pheochromocytomas and paragangliomas in Argentina. The FRENAR database.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.

Measures of Suicidal Thoughts and Behaviors in Children and Adolescents: A Systematic Review and Recommendations for Use in Clinical and Research Settings.

Empirically supported measures of suicidal thoughts and behaviors (STBs) are needed to serve as reference outcomes for suicide risk screening tools and to monitor severity and treatment progress in children and adolescents with STBs. The present paper systematically reviewed existing measures of STBs in youth and studies evaluating their psychometric properties and clinical utility. Measures were then evaluated on reliability, validity, and clinical utility. Sixteen articles (20 independent samples) were found with psychometric data with youth samples for eight measures. Interview-based measures were found to have the strongest psychometric support and clinical utility. Significant limitations exist for all self-report measures due to inherent characteristics of these measures that cannot be remedied through additional psychometric study. There is an urgent need for the development and validation of new self-report measures of STBs, particularly for preadolescent children, sexual and gender minority youth, and racial/ethnic minority youth.

Vitamin A Status Modulates Epithelial Mesenchymal Transition in the Lung: The Role of Furin.

Vitamin A deficiency (VAD) induced TGF-ß hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-ß, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT and furin are induced in VAD rats. Furthermore, furin expression continues to increase much more markedly after treatment of VAD rats with RA. In control rats and cell lines, an acute RA treatment induced a significant increase in furin expression, concomitant with changes in EMT markers. A ChIP assay demonstrated that RA directly regulates furin transcription. These results emphasize the importance of maintaining vitamin A levels within the physiological range since both levels below and above this range can cause adverse effects that, paradoxically, could be similar. The role of furin in EMT is discussed.

Understanding limb necrotizing infections: A comprehensive approach.

INTRODUCTION: Necrotizing soft tissue infections (NSTI) are increasing, posing a significant risk of morbidity and mortality. Due to nonspecific symptoms, a high index of suspicion is crucial. Treatment involves a multidisciplinary approach, with broad-spectrum antibiotics, early surgical debridement, and life support. This study analyzes the characteristics, demographics, complications, and treatment of NSTI in a hospital in Madrid, Spain. METHODS: A retrospective observational study was conducted, including all surgically treated NSTI patients at our center from January 2016 to December 2022, examining epidemiological and clinical data. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) was prospectively calculated for all patients. RESULTS: Twenty-two patients (16 men, 6 women, mean age 54.8) were included. Median time from symptom onset to emergency room visit was 3.5 days. All reported severe treatment-resistant pain; sixteen had fever exceeding 37.8°C (72.7%). Skin lesions occurred in twelve (54.5%), and thirteen had hypotension and tachycardia (59.1%). Treatment involved resuscitative support, antibiotherapy, and radical debridement. Median time to surgery was 8.25h. Intraoperative cultures were positive in twenty patients: twelve Streptococcus pyogenes, four Staphylococcus aureus, one Escherichia coli, and four polymicrobial infection. In-hospital mortality rate was 22.73%. CONCLUSIONS: We examined the correlation between our results, amputation rates and mortality with LRINEC score and time to surgery. However, we found no significant relationship unlike some other studies. Nevertheless, a multidisciplinary approach with radical debridement and antibiotic therapy remains the treatment cornerstone. Our hospital stays, outcomes and mortality rates align with our literature review, confirming high morbimortality despite early and appropriate intervention.

[Prevalence, knowledge and control of arterial hypertension in vulnerable neighborhoods of Argentina: A Cross-sectional Study]. / Estudio de prevalencia, conocimiento y control de la hipertensión arterial en barrios vulnerables de Argentina.

INTRODUCTION: Hypertension (HTN) represents the primary individual risk factor, contributing significantly to the global burden of cardiovascular diseases (CVD). In our country, epidemiological research has highlighted substantial variations in the prevalence of these risk factors across different populations. However, there is a lack of epidemiological studies assessing exclusive cardiovascular risk factors within vulnerable neighborhoods characterized by extremely limited economic resources, sociocultural challenges, and inadequate healthcare access. METHODS: A multicenter cross-sectional observational study was conducted among individuals residing in economically deprived and marginalized communities, including informal settlements and underprivileged neighborhoods. Simple random sampling of households was employed. Blood pressure measurements, anthropometric assessments, and epidemiological, economic, and sociocultural questionnaires were administered. Results encompass prevalence rates, awareness levels, and blood pressure control across diverse regions. Logistic regression was utilized to identify independent variables influencing primary outcomes. RESULTS: A total of 989 participants were analyzed. The overall prevalence of hypertension was 48.2%. About 82% had a body mass index (BMI) >25. Approximately 45.3% had less than 6 years of formal education. Independent association was established between education levels below 6 years and higher hypertension prevalence. Among hypertensive individuals, 44% were unaware of their condition, with only 17.2% achieving control, correlated with having health insurance and a higher educational background. Merely 24% were receiving combined therapy. CONCLUSION: The prevalence of hypertension within vulnerable neighborhoods is alarmingly high, surpassing rates in other social strata. Knowledge, treatment, and control levels of hypertension are suboptimal, comparable to other populations. Inadequate use of combination therapy was observed. This study underscores the urgent need for targeted interventions addressing cardiovascular risk factors in poor areas to mitigate the burden of CVD.

Current level of evidence for improvement of antidepressant efficacy and tolerability by pharmacogenomic-guided treatment: A Systematic review and meta-analysis of randomized controlled clinical trials.

The aim of the study was to assess the clinical utility of currently available pharmacogenomic (PGx) tools compared with treatment as usual (TAU), using a meta-analysis of dichotomous and continuous antidepressant efficacy and tolerability data from previously published clinical trials. MEDLINE, clinicaltrial.gov, EU Clinical Trials Register, WHO ICTRP and CENTRAL were systematically searched; of the 962 results originally reviewed, 15 trials were included. Antidepressant efficacy was quantified by relative and absolute changes in symptom severity after eight weeks of treatment and by response and remission rates, while tolerability was estimated by the rate of study discontinuation for any reason. In the PGx-guided patients, symptom severity reduced by an average of 31.0% after eight weeks of treatment, compared to an average reduction of 26.8% in the TAU group. Accordingly, PGx-guided patients experienced a greater reduction in symptom severity of 3.4% (95%CI: 1.6-5.3%), which corresponded to a reduction in the Hamilton Depression score of 0.75 (0.30-1.21), a 37% (15-63%) higher remission rate, and an 18% (5-33%) higher response rate compared with TAU patients, while no difference was observed in discontinuation rate between groups. Notably, the majority of associations lost statistical significance when restricting the dataset to low risk of bias studies, while certain funnel plots suggested a potential publication bias favoring the reporting of statistically significant results. In summary, PGx tools marginally enhance antidepressant efficacy, but not antidepressant tolerability; thus, additional research and advancement of PGx tools are needed to improve integration of PGx in clinical pharmacotherapy of depression.

Chronic inflammation is associated with worsening working memory performance: Preliminary evidence from a diverse, longitudinal cohort of adolescents and young adults.

Many depressed individuals experience cognitive difficulties that persist when depression is in remission. Inflammation is hypothesized to play a role in cognitive dysfunction in depression; however, many aspects of this relationship are not well characterized. The current study examined whether inflammation is associated with specific cognitive deficits in individuals with a history of depression and with progressively worsening working memory over time. Adolescents who participated in a prospective, longitudinal study of adolescent-onset depression were recruited to complete a follow-up cognitive assessment. The sample was comprised of 82 participants (52.4% female; 37.8% white; 42.7% low socioeconomic status) who were aged 22.61 years (SD = 1.50) at the time of the follow-up cognitive assessment. Prior to the follow-up cognitive assessment, they had completed an average of 6.24 (SD = 1.80) prior annual assessments over 6.24 years (SD = 2.08) as part of the parent longitudinal study in which C-reactive protein (CRP), depressive symptoms, and working memory were assessed repeatedly. First, using linear regression, we tested whether individuals exhibiting inflammation (CRP ≥3 mg/L) at multiple timepoints and a history of likely depression (Children's Depression Inventory ≥19) exhibited differentially worse executive functioning, episodic memory, or psychomotor speed. Second, using hierarchical linear modeling, we tested whether the combination of inflammation and likely past depression was associated with poorer working memory over time. Chronic inflammation was associated with worsening working memory over time, but no significant associations were observed in cross-sectional analyses. These preliminary data indicate that chronic inflammation may lead to progressive decline in working memory over time.

Orbital myositis in a patient with Crohn's disease: A case report of two episodes.

PURPOSE: To describe a case report of a 34 years-old patient with Crohn's Disease and two episodes of Ocular Myositis. METHODS: The research methodology employed in this study consisted of a retrospective review of the patient's complete medical history. RESULTS: Crohn's Disease is a chronic inflammatory bowel disorder known to be associated with a wide range of extraintestinal manifestations. Ocular abnormalities, such as episcleritis and uveitis, are commonly observed. However, orbital myositis is an extremely rare ocular extraintestinal manifestations characterized by acute ocular pain that worsens with eye movements and is often accompanied by diplopia. In this case report, we present the case of a 34-year-old woman with a confirmed diagnosis of Crohn's Disease, who experienced two episodes of acute orbital pain exacerbated by ocular movements and diplopia. The diagnosis was established through clinical evaluation and radiologic imaging, with confirmation after a good response to systemic corticosteroids. She responded favorably to systemic corticosteroid therapy on both episodes, and no additional treatment was required. As of now, she remains stable without any ocular sequelae. CONCLUSION: It is important to note that orbital myositis is an uncommon ocular manifestation associated with Crohn's Disease, and prompt recognition and management are crucial to achieve successful outcomes.

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4 months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2 years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative haemoglobin decrease of 3.08±1.08g/dl, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4 months). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study. / Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4month). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

A Weight of Evidence approach to support the assessment of the quality of Manila clam farming sites in a coastal lagoon.

Aquaculture productivity in coastal lagoons is endangered by a complex interplay of anthropogenic and environmental factors, amplified by the effects of climate change in these sensitive areas. To reach a more comprehensive assessment of farming sites quality, a quantitative Weight of Evidence approach (QWoE) is applied for the first time to data collected at four Manila clam (R. philippinarum) farming sites in the Venice lagoon (Italy). This included sediment quality, chemical bioaccumulation, and biological responses. Results revealed a greater hazard for sites closer to the open sea. In these areas, the combination of sediment characteristics and a higher frequency of salinity and temperature stress could explain the alterations measured at a transcriptional and biomarker level. The findings demonstrate that a QWoE approach that integrates multiple sources of evidence should also include physicochemical conditions in order to better understand the impacts of human activities and other stressors on clam aquaculture productivity.

Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

The theory of thermoelasticity with a memory-dependent dynamic response for a thermo-piezoelectric functionally graded rotating rod.

By laminating piezoelectric and flexible materials during the manufacturing process, we can improve the performance of electronic devices. In smart structure design, it is also important to understand how the functionally graded piezoelectric (FGP) structure changes over time when thermoelasticity is assumed. This is because these structures are often exposed to both moving and still heat sources during many manufacturing processes. Therefore, it is necessary to conduct theoretical and experimental studies of the electrical and mechanical characteristics of multilayer piezoelectric materials when they are subjected to electromechanical loads and heat sources. Since the infinite speed of heat wave propagation is a challenge that classical thermoelasticity cannot address, other models based on extended thermoelasticity have been introduced. For this reason, the effects of an axial heat supply on the thermomechanical behavior of an FGP rod using a modified Lord-Shulman model with the concept of a memory-dependent derivative (MDD) will be explored in this study. The exponential change of physical properties in the direction of the axis of the flexible rod will be taken into account. It was also assumed that there is no electric potential between the two ends of the rod while it is fixed at both ends and thermally isolated. Applying the Laplace transform method, the distributions of the physical fields under investigation were calculated. The obtained results were compared to those in the corresponding literature with varying heterogeneity values, kernel functions, delay times, and heat supply speeds. It was discovered that the studied physical fields and the dynamic behavior of the electric potential are weakened by increasing the inhomogeneity index.

Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome.

Background: cardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications. Case presentation: the patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth. Conclusion: this paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

Characterization of the C6D7-RBD Human Monoclonal Antibody Specific to the SARS-CoV-2 S Protein Receptor-Binding Domain.

The new coronavirus infection COVID-19 is an acute viral disease that affects primarily the upper respiratory tract. The etiological agent of COVID-19 is the SARS-CoV-2 RNA virus (Coronaviridae family, Betacoronavirus genus, Sarbecovirus subgenus). We have developed a high-affinity human monoclonal antibody, called C6D7-RBD, which is specific to the S protein receptor-binding domain (RBD) from the SARS-CoV-2 Wuhan-Hu-1 strain and exhibits virus-neutralizing activity in a test with recombinant antigens: angiotensin-converting enzyme 2 (ACE2) and RBD.