MCP1 Inverts the Correlation between FGF23 and Omega 6/3 Ratio: Is It Also True in Renal Transplantation?

During chronic kidney disease (CKD) progression, an increase in fibroblast growth factor (FGF23) is present. In stage 5, a positive correlation between FGF23 and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) emerges. Hypothesizing that the rising positive correlation between monocyte chemoattractant protein 1 (MCP1) and n-6 in stage 4 could be the cause, we previously explored FGF23 and MCP1's roles in dyslipidemia and cardiovascular risk in CKD. In the present paper, we retraced the study evaluating 40 kidney transplant patients (KTx), a cohort where several factors might modify the previous relationships found. An ELISA and gas chromatography assessed the MCP1, FGF23, and PUFA levels. Despite the FGF23 increase (p < 0.0001), low MCP1 levels were found. A decrease in the n-6/n-3 ratio (p = 0.042 CKD stage 4 vs. 5) lowered by the increase in both n-3 αlinolenic (p = 0.012) and docosapentaenoic acid (p = 0.049) was observed. A negative correlation between FGF23 and the n-6/n-3 ratio in CKD stage 4 (r2 -0.3 p = 0.043) and none with MCP1 appeared. According to our findings, different mechanisms in the relationship between FGF23, PUFAs, and MCP1 in CKD and KTx patients might be present, which is possibly related to the immunosuppressive status of the last. Future research will further clarify our hypothesis.

Manufacturability of functionally graded porous ß-Ti21S auxetic architected biomaterials produced by laser powder bed fusion: Comparison between 2D and 3D metrological characterization.

Functionally graded porous structures (FGPSs) are attracting increasing interest in the manufacture of prostheses that benefit from lower stiffness and optimized pore size for osseointegration. In this work, we explore the possibility of employing FGPSs with auxetic unit cells. Their negative Poisson's ratio was exploited to reduce the loss of connection between prosthesis and bone usually occurring in standard implant loaded under tension and therefore undergoing lateral shrinking. In addition, to further improve osseointegration and mitigate stress shielding effects, auxetic FGPSs were fabricated in this work using a novel ß-Ti21S alloy characterized by a lower Young's modulus compared to traditional α + ß Ti alloys. Specifically, two different auxetic FGPSs with aspect ratio equal to 1.5 and angle θ of 15° and 25° with a relative density (ρr) gradient of 0.34, 0.49, 0.66 and of 0.40, 0.58, 0.75 were designed and printed by laser powder bed fusion. The 2D and 3D metrological characterization of the as-manufactured structures was compared with the design. 2D metrological characterization was carried out using scanning electron microscopy analysis, while for the 3D characterization, X-ray micro-CT imaging was used. An undersizing of the pore size and strut thickness in the as-manufactured sample was observed in both auxetic FGPSs. A maximum difference in the strut thickness of -14 and -22% was obtained in the auxetic structure with θ = 15° and 25°, respectively. On the contrary, a pore undersizing of -19% and -15% was evaluated in auxetic FGPS with θ = 15° and 25°, respectively. Compression mechanical tests allowed to determine stabilized elastic modulus of around 4 GPa for both FGPSs. Homogenization method and analytical equation were used and the comparison with experimental data highlights a good agreement of around 4% and 24% for θ = 15° and 25°, respectively.

Metrological characterization of porosity graded ß-Ti21S triply periodic minimal surface cellular structure manufactured by laser powder bed fusion.

The design of a functionally graded porous structure (FGPS) for use in prosthetic devices is crucial for meeting both mechanical and biological requirements. One of the most commonly used cellular structures in FGPS is the triply periodic minimal surface (TPMS) structure due to its ability to be defined by implicit equations, which allows for smooth transitions between layers. This study evaluates the feasibility of using a novel ß-Ti21S alloy to fabricate TPMS-based FGPS. This beta titanium alloy exhibits low elastic modulus (53 GPa) and good mechanical properties in as-built condition. Two TPMS FGPSs with relative density gradients of 0.17, 0.34, 0.50, 0.66, and 0.83 and unit cell sizes of 2.5 mm and 4 mm were designed and fabricated using laser powder bed fusion (LPBF). The as-manufactured structures were analyzed using scanning electron microscopy (SEM) and X-ray micro-computed tomography (µ-CT), and the results were compared to the design. The analysis revealed that the pore size and ligament thickness were undersized by less than 5%. Compression tests showed that the stabilized elastic modulus was 4.1 GPa for the TPMS with a 2.5 mm unit cell size and 10.7 GPa for the TPMS with a 4 mm unit cell size. A finite element simulation was performed to predict the specimen's elastic properties, and a lumped model based on lattice homogenized properties was proposed and its limitations were explored.

An Insight into the Defects-Driven Plasticity in Ductile Cast Irons.

The microstructure and tensile behavior of two heavy section castings that had chemical compositions typical of GJS400 were investigated. Conventional metallography, fractography, and micro-Computer Tomography (µ-CT) were employed, enabling the quantification of the volume fractions of eutectic cells with degenerated Chunky Graphite (CHG), which was identified as the major defect in the castings. The Voce equation approach was exploited to evaluate the tensile behaviors of the defective castings for integrity assessment. The results demonstrated that the Defects-Driven Plasticity (DDP) phenomenon, which refers to an unexpected regular plastic behavior related to defects and metallurgical discontinuities, was consistent with the observed tensile behavior. This resulted in a linearity of Voce parameters in the Matrix Assessment Diagram (MAD), which contradicts the physical meaning of the Voce equation. The findings suggest that the defects, such as CHG, contribute to the linear distribution of Voce parameters in the MAD. Furthermore, it is reported that the linearity in the MAD of Voce parameters for a defective casting is equivalent to the existence of a pivotal point in the differential data of the tensile strain hardening data. This pivotal point was exploited to propose a new material quality index assessing the integrity of castings.

Frailty in kidney transplantation: a review on its evaluation, variation and long-term impact.

The problem of frailty in kidney transplantation is an increasingly discussed topic in the transplant field, partially also generated by the multiple comorbidities by which these patients are affected. The criteria currently used to establish the presence and degree of frailty can be rapidly assessed in clinical practice, even in patients with chronic kidney disease (CKD). The main objectives of this work are: (i) to describe the method of evaluation and the impact that frailty has in patients affected by CKD, (ii) to explore how frailty should be studied in the pre-transplant evaluation, (iii) how frailty changes after a transplant and (iv) the impact frailty has over the long term on the survival of renal transplant patients.

Hybrid Ti6Al4V/Silk Fibroin Composite for Load-Bearing Implants: A Hierarchical Multifunctional Cellular Scaffold.

Despite the tremendous technological advances that metal additive manufacturing (AM) has made in the last decades, there are still some major concerns guaranteeing its massive industrial application in the biomedical field. Indeed, some main limitations arise in dealing with their biological properties, specifically in terms of osseointegration. Morphological accuracy of sub-unital elements along with the printing resolution are major constraints in the design workspace of a lattice, hindering the possibility of manufacturing structures optimized for proper osteointegration. To overcome these issues, the authors developed a new hybrid multifunctional composite scaffold consisting of an AM Ti6Al4V lattice structure and a silk fibroin/gelatin foam. The composite was realized by combining laser powder bed fusion (L-PBF) of simple cubic lattice structures with foaming techniques. A combined process of foaming and electrodeposition has been also evaluated. The multifunctional scaffolds were characterized to evaluate their pore size, morphology, and distribution as well as their adhesion and behavior at the metal-polymer interface. Pull-out tests in dry and hydrated conditions were employed for the mechanical characterization. Additionally, a cytotoxicity assessment was performed to preliminarily evaluate their potential application in the biomedical field as load-bearing next-generation medical devices.

How Vaccinations Changed the Outcome of COVID-19 Infections in Kidney Transplant Patients: Single-Center Experience.

Kidney transplant recipients are a vulnerable population at risk of a life-threatening COVID-19 infection with an incidence of death four-times higher than in the general population. The availability of mRNA COVID-19 vaccines has dramatically changed the fate of this infection also within this fragile population. Transplanted patients have an impaired immunological response also to mRNA vaccines. In March 2021, however, we started a vaccination campaign. These preliminary results show that both the incidence of death and of hospitalization dropped from 13% to 2.4% and from 45% to 12.5% compared to the previous outbreaks reported by our group. In univariate analysis, two variables were associated with an increased risk of hospitalization: older age and dyspnea (p = 0.023, p < 0.0001, respectively). In multivariate analysis, dyspnea (p < 0.0001) and mycophenolate therapy (p = 0.003) were independently associated with the risk of hospitalization. The association was even stronger when the two variables were combined (p < 0.0001). Vaccinations did not reduce the incidence of COVID-19 infections among our transplanted patients, but provided certain protection that was associated with a significantly better outcome for this infection.

Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients.

BACKGROUND: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). METHODS: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV-). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). RESULTS: 25(OH)D levels were lower in COV+ than in controls [19(12-26) vs. 23(17-31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5-0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP- [17(8-25) vs. 20(15-26) ng/mL, p = 0.19] and between D+ and D- [14(6-23) vs. 20(14-26) ng/mL, p = 0.22] and had no significant correlation with disease length. CONCLUSIONS: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.

High intensity resistance training as intervention method to knee osteoarthritis.

High intensity resistance training (HI-RT) is a treatment option for Knee Osteoarthritis (KOA). Isotonic machines (leg press, leg extension) are utilized for standardization and reproducibility reasons, but the load used during the protocol is often low, considering that elder people usually have low strength levels, training so with high intensities calculated on low loads. The physiological response of an elder woman trained with high loads on a free weight exercise, the regular barbell deadlift, with a 1 Repetition Maximum (1RM) of 100 kg, can be appreciated in this report, so that for the first time we can see the effect of a one year of high intensity resistance training program on a powerlifting exercise on a 72 year-old woman with KOA. A Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire was administered before starting the training program (T0) and after 1 year of training, as long as a control RX, to evaluate the effect of HI-RT on joint functionality and quality of life.

A 3D-Printed Ultra-Low Young's Modulus ß-Ti Alloy for Biomedical Applications.

The metastable ß-Ti21S alloy is evaluated as a potential candidate for biomedical parts. Near fully dense (99.75 ± 0.02%) samples are additively manufactured (that is, 3D-printed) by laser powder-bed fusion (L-PBF). In the as-built condition, the material consists of metastable ß-phase only, with columnar grains oriented along the building direction. The material exhibits an extremely low Young's modulus (52 ± 0.3 GPa), which was never reported for this type of alloy. The combination of good mechanical strength (σy0.2 = 709 ± 6 MPa, ultimate tensile strength (UTS) = 831 ± 3 MPa) and high total elongation during tensile test (21% ± 1.2%) in the as-built state, that is, without any heat treatment, is close to that of the wrought alloy and comparable to that of heat treated Ti grade 5. The good biocompatibility attested by cytotoxicity tests confirms its great suitability for biomedical applications.

Study of the Compression Behaviour of Ti6Al4V Trabecular Structures Produced by Additive Laser Manufacturing.

The aim of this paper was to investigate the compression properties of several trabecular structures produced by additive laser manufacturing of a Ti6Al4V, having different densities and unit cells. Filling space structures were investigated, with different unit cells characterized by both bending-dominated and stretching-dominated behaviour. The stiffness and yield strength were correlated to relative density according to the Gibson and Ashby model. For a constant porosity, the stiffness and the yield strength varied between two extremes represented by the cubic structure (stretching-dominated deformation) and the cross structure (bending-dominated deformation). The properties of the deformed structures did not differ substantially from those of the regular structures. Only in the cubic structure did distortion enhance the contribution of bending to deformation and both stiffness and strength decreased. Cross structures displayed the highest strength at constant stiffness than the others, since they are characterized by the most favourable orientation of the struts.

An ICT and mobile health integrated approach to optimize patients' education on hypertension and its management by physicians: The Patients Optimal Strategy of Treatment(POST) pilot study.

INTRODUCTION: Uncontrolled hypertension is largely attributed to unsatisfactory doctor's engagement in its optimal management and to poor patients' compliance to therapeutic interventions. ICT and mobile Health solutions might improve these conditions, being widely available and providing highly effective communication strategies. OBJECTIVE: To evaluate whether ICT and mobile Health tools are able to improve hypertension control by improving doctors' engagement and by increasing patients' education and involvement, and their compliance to lifestyle modification and prescribed drug therapy. METHODS: In a pilot study, we have included 690 treated hypertensive patients with uncontrolled office blood pressure (BP), consecutively recruited by 9 general practitioners over 3 months. Patients were alternatively assigned to routine management based on repeated office visits or to an integrated ICT-based Patients Optimal Strategy for Treatment (POST) system including Home BP monitoring teletransmission, a dedicated web-based platform for patients' management by physicians (Misuriamo platform), and a smartphone mobile application (Eurohypertension APP, E-APP), over a follow-up of 6 months. BP values, demographic and clinical data were collected at baseline and at all follow-up visits (at least two). BP control and cardiovascular risk level have been evaluated at the beginning and at the end of the study. RESULTS: 89 patients did not complete the follow-up, thus data analysis was carried out in 601 of them (303 patients in the POST group and 298 in the control group). Office BP control (<;149/90 mmHg) was 40.0% in control group, and 72.3% in POST group at 6 month follow-up. At the same time Home BP control (<;135/85 mmHg average of 6 days) in POST group was 87.5%. CONCLUSION: this pilot study suggests that ICT based tools might be effective in improving hypertension management, implementing positive patients' involvement with better adherence to treatment prescriptions and providing the physicians with dynamic control of patients' home BP measurements, resulting in lesser clinical inertia.

Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression.

BACKGROUND: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation. METHODS: A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation. RESULTS: First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks). CONCLUSION: rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response.