Beneficial effects of physical exercise on the osteo-renal Klotho-FGF-23 axis in Chronic Kidney Disease: A systematic review with meta-analysis.

The aim of this study was to investigate the efficacy of physical exercise in chronic kidney disease, describing its impact on the Klotho-FGF23 axis. PubMed, Web of Science and Scopus databases, updated to January 2023, were searched. The present study employed mean difference and a 95% confidence interval (CI) to examine the efficacy of the intervention. Heterogeneity was assessed through inconsistency statistics (I2). Out of the 299 studies identified, a total of 4 randomized controlled trials (RCTs), comprising 272 participants, met the eligibility criteria. Compared with the control group, physical exercise significantly decreased the concentrations of FGF23 (MD: -102.07 Pg/mL, 95% CI: -176.23.47, -27.91 I2= 97%, p = 0.001), and a significantly increased the concentrations of Klotho protein: (MD: 158.82 Pg/mL, 95% CI: 123.33, -194.31, I2 = 0%, p = 0.001). The results of our study indicated that the exercise has a direct relationship with Klotho-FGF23 axis. We can conclude that physical exercise in patients with CKD produces beneficial effects on the pathophysiological components related to this disease, including cardiorespiratory fitness and vascular functions. As observed, both endurance and aerobic physical exercise increase Klotho production and decrease FGF23 levels. Evidence indicates that exercise attenuates the progression of CKD, improves uremic parameters and down-regulates inflammation-related markers.

Fosfatriclaben: Effective dose determination and comparative efficacy assessment with closantel, triclabendazole+ivermectin, triclabendazole+albendazole in artificially infected cattle.

Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days -8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7-100%) and adult parasites (98.9-100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes.

Priorities and challenges in social and healthcare policies for older people living in the Mediterranean basin: A Delphi panel study.

BACKGROUND: Recently, the countries in the Mediterranean basin (which share cultural ties) have been showing a common trend of declining social support for the elderly, with deficiencies in social care models for this demographic. Thus, this Delphi panel study analyzed the gaps in social and integrated care among the participating countries in a European research project. METHODS: This three-round Delphi panel study focused on the European countries of Greece and Spain and the non-European countries of Egypt, Lebanon, and Tunisia. In this project, experts were identified according to their level of expertise in the subject matter, their gender, and their membership in different social groups. Subsequently, they were asked to identify the current situation of social care, set future goals, and locate the gaps regarding the social and healthcare models for older people in the participating countries. The median score (Mdn) and interquartile range (IQR) were calculated to assess the degree of consensus on the different priorities. RESULTS: Among the participating countries, there was a lack of state agreements to maintain social care models, a lack of coordination between public and private institutions to provide social care services, territorial inequalities in terms of access and coverage of rights, and job insecurity for professionals. The desired situation was to integrate social and healthcare services with a person-centered social care model, thus promoting autonomy and empowering users and families in participation and decision-making. CONCLUSIONS: This Delphi study reveals significant disparities in social and healthcare policies for older adults across Mediterranean countries, highlighting shared challenges and specific national needs. European nations like Greece and Spain face fragmented systems, while non-European countries such as Lebanon, Egypt, and Tunisia lack specialized geriatric services and social security. All countries urgently need better professional training, social and economic empowerment of older adults, and integrated national strategies. These findings offer key insights for policymakers to develop equitable, sustainable solutions for aging populations.

May Measurement Month 2021: an analysis of blood pressure screening results from the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2021 (MMM21) blood pressure (BP) campaign to raise awareness of hypertension. The MMM standard protocol designed by the MMM coordinating centre was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken three times, using automated BP apparatus and were either entered via MMM21 app, MMM@Home, and Google Forms or recorded on paper and transferred to Excel spreadsheets by PSH encoders. Hypertension was defined either as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or on antihypertensive medication. A total of 59 655 participated through opportunistic convenience sampling. After multiple imputation, a total of 26 813 (44.9%) participants were identified as having hypertension. Of these, 14 449 (53.9%) were aware and 12 978 (48.4%) were on antihypertensive medication. Of those who were treated, 5644 (43.5%) had controlled BP (<140/90 mmHg) and 7334 (56.5%) were uncontrolled. These latest local data showed that BP awareness is still low with BP control achieved in less than half of treated patients. Continued collaboration is needed to improve BP screening programmes in the country.

Traffic as an Urban Health Determinant: Coverage of the New York City Congestion Pricing Plan on TikTok.

Social listening can provide deeper insight into public sentiment regarding policy proposals, as seen with the congestion pricing initiative in New York City (NYC). The purpose of this study was to assess the content of a sample of TikTok videos related to congestion pricing in NYC. A total of 100 unique videos were extracted from the hashtag #nyccongestionpricing on TikTok and coded for the presence of the following information based on four different areas of focus: video metrics, details about pricing plan, effects of pricing plan, and user-related issues. In total, the 100-video sample received 17,375,818 views, 1,285,610 likes, 89,883 favorites, and 100,634 comments. Only 3 of the 25 content characteristics were present in a majority (> 50) of the videos. These were mentions location (below 60th street of Manhattan) (N = 65), mentions cost (N = 61), and mentions cons of pricing (N = 56). Mentioning location had a significant effect on the views (p = 0.0163) and likes (p = 0.0225) a video received. Mentioning cost had a statistical impact on the views (p = 0.0098), likes (p = 0.0128), favorites (p = 0.0128), and comments (p = 0.0030) that the video received. Mentioning the MTA and benefits of the congestion plan significantly lowered metrics of engagement. Themes that emerged were personal, often negative and tended to focus more on cost to citizens and location, despite the evidence of negative public health impacts. This research can be used as a springboard for future research that examines social listening at the intersection of public health and policy.

Inhibition of Shikimate Kinase from Methicillin-Resistant Staphylococcus aureus by Benzimidazole Derivatives. Kinetic, Computational, Toxicological, and Biological Activity Studies.

Antimicrobial resistance (AMR) is one of the biggest threats in modern times. It was estimated that in 2019, 1.27 million deaths occurred around the globe due to AMR. Methicillin-resistant Staphylococcus aureus (MRSA) strains, a pathogen considered of high priority by the World Health Organization, have proven to be resistant to most of the actual antimicrobial treatments. Therefore, new treatments are required to be able to manage this increasing threat. Under this perspective, an important metabolic pathway for MRSA survival, and absent in mammals, is the shikimate pathway, which is involved in the biosynthesis of chorismate, an intermediate for the synthesis of aromatic amino acids, folates, and ubiquinone. Therefore, the enzymes of this route have been considered good targets to design novel antibiotics. The fifth step of the route is performed by shikimate kinase (SK). In this study, an in-house chemical library of 170 benzimidazole derivatives was screened against MRSA shikimate kinase (SaSK). This effort led to the identification of the first SaSK inhibitors, and the two inhibitors with the greatest inhibition activity (C1 and C2) were characterized. Kinetic studies showed that both compounds were competitive inhibitors with respect to ATP and non-competitive for shikimate. Structural analysis through molecular docking and molecular dynamics simulations indicated that both inhibitors interacted with ARG113, an important residue involved in ATP binding, and formed stable complexes during the simulation period. Biological activity evaluation showed that both compounds were able to inhibit the growth of a MRSA strain. Mitochondrial assays showed that both compounds modify the activity of electron transport chain complexes. Finally, ADMETox predictions suggested that, in general, C1 and C2 can be considered as potential drug candidates. Therefore, the benzimidazole derivatives reported here are the first SaSK inhibitors, representing a promising scaffold and a guide to design new drugs against MRSA.

Characterization of the Effect of N-(2-Methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, Compound 8, against Leishmania mexicana and Its In Vivo Leishmanicidal Activity.

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.

Best practices for iatrogenic anaemia prevention in the intensive care unit: Blood-sparing techniques.

Anaemia is a common issue in patients who are admitted to intensive care units and worsens their condition throughout the stay due to the extraction of blood for diagnostic purposes. It is also well-known that an important amount of the carbon dioxide produced by health services is likely attributable to blood donation, testing and manufacture, storage or distribution of blood components. This must be taken into account to perform nursing interventions consistent with the idea of sustainable health care. In this regard, within patient blood management bundles, with the objective of minimizing the use of blood products, it is recommended to use blood-sparing techniques: small volume tubes (SVT) or closed-blood sampling devices (CBSD). Published studies before 2014 (excepting two more recent ones) have shown that by themselves, both techniques reduce drawn volume but do not decrease haemoglobin reduction and/or need of transfusion. Given the lack of cost-effectiveness studies, it may be easier to implement the use of CBSD as it does not require prior consensus on the discard volume or adaptations in the processing of laboratory tests, as is the case with SVT.

Pathophysiologic Implications and Therapeutic Approach of Klotho in Chronic Kidney Disease: A Systematic Review.

The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho. The purpose of this systematic review was to determine if there are biological and nutraceutical therapies that increase the expression of Klotho and can help prevent complications associated with chronic kidney disease. A systematic literature review was carried out through the consultation of PubMed, Scopus, and Web of Science. Records between the years 2012 and 2022 in Spanish and English were selected. Cross-sectional or prevalence and analytical studies were included that evaluated the effects of Klotho therapy. A total of 22 studies were identified after the critical reading of these selected studies: 3 investigated the association between Klotho and growth factors, 2 evaluated the relationship between the concentration of Klotho and the type of fibrosis, 3 focused on the relationship between vascular calcifications and vitamin D, 2 assessed the relationship between Klotho and bicarbonate, 2 investigated the relationship between proteinuria and Klotho, 1 demonstrated the applicability of synthetic antibodies as a support for Klotho deficiency, 1 investigated Klotho hypermethylation as a renal biomarker, 2 investigated the relationship between proteinuria and Klotho, 4 linked Klotho as an early marker of chronic kidney disease, and 1 investigated Klotho levels in patients with autosomal dominant polycystic kidney disease. In conclusion, no study has addressed the comparison of these therapies in the context of their use with nutraceutical agents that raise the expression of Klotho.

Structure-Based Optimization of Carbendazim-Derived Tubulin Polymerization Inhibitors through Alchemical Free Energy Calculations.

Carbendazim derivatives, commonly used as antiparasitic drugs, have shown potential as anticancer agents due to their ability to induce cell cycle arrest and apoptosis in human cancer cells by inhibiting tubulin polymerization. Crystallographic structures of α/ß-tubulin multimers complexed with nocodazole and mebendazole, two carbendazim derivatives with potent anticancer activity, highlighted the possibility of designing compounds that occupy both benzimidazole- and colchicine-binding sites. In addition, previous studies have demonstrated that the incorporation of a phenoxy group at position 5/6 of carbendazim increases the antiproliferative activity in cancer cell lines. Despite the significant progress made in identifying new tubulin-targeting anticancer compounds, further modifications are needed to enhance their potency and safety. In this study, we explored the impact of modifying the phenoxy substitution pattern on antiproliferative activity. Alchemical free energy calculations were used to predict the binding free energy difference upon ligand modification and define the most viable path for structure optimization. Based on these calculations, seven compounds were synthesized and evaluated against lung and colon cancer cell lines. Our results showed that compound 5a, which incorporates an α-naphthyloxy substitution, exhibits the highest antiproliferative activity against both cancer lines (SK-LU-1 and SW620, IC50 < 100 nM) and induces morphological changes in the cells associated with mitotic arrest and mitotic catastrophe. Nevertheless, the tubulin polymerization assay showed that 5a has a lower inhibitory potency than nocodazole. Molecular dynamics simulations suggested that this low antitubulin activity could be associated with the loss of the key H-bond interaction with V236. This study provides insights into the design of novel carbendazim derivatives with anticancer activity.

The clinical use of computer aided designed/computer aided manufactured titanium nitride coated implant abutments: Surgical and prosthetic considerations-A case series.

OBJECTIVE: To describe the clinical use of nitride-coated titanium CAD/CAM implant abutments in the maxillary esthetic zone in two patients with high esthetic and functional demands and, to highlight the advantages of nitride-coated milled titanium abutments when compared to stock/custom titanium, one-piece monolithic zirconia, and hybrid metal-zirconia implant abutments. CLINICAL CONSIDERATIONS: Due to the inherent mechanical and esthetic clinical challenges, single implant-supported reconstructions in the maxillary esthetic zone are a complex restorative treatment. While CAD/CAM technology has been suggested to enhance and ease implant abutment design and manufacturing, implant abutment material selection remains as a critical decision affecting restoration's long-term clinical outcomes. To date, considering the esthetic disadvantages of conventional titanium implant abutments, the mechanical limitations of one-piece zirconia abutments and the manufacturing time and costs associated with hybrid metal-zirconia abutments, no abutment material can be considered "ideal" for all clinical scenarios. Due to their biocompatibility, biomechanical characteristics (hardness and wear resistance), optical properties (yellow color), and peri-implant soft tissue esthetic integration, the use of CAD/CAM titanium nitride-coated implant abutments has been suggested as a predictable implant abutment material in mechanically challenging but esthetically demanding clinical situations, as the maxillary esthetic zone. CONCLUSIONS: Two patients requiring a combined tooth-implant restorative treatment in the maxillary esthetic zone were treated using CAD/CAM nitride coated titanium implant abutments. The principal advantages of TiN coated abutments include comparable clinical outcomes to stock abutments, optimal biocompatibility, adequate fracture, wear, and corrosion resistance, reduced bacterial adhesion, and excellent esthetic integration with adjacent soft tissues. CLINICAL SIGNIFICANCE: Clinical reports and short term mechanical, biological and esthetic clinical outcomes indicate that CAD/CAM nitride coated titanium implant abutments can represent a predictable restorative alternative to stock/custom and metal/zirconia implant abutments and be considered a clinical relevant option in mechanically challenging but esthetically demanding situations, as often found in the maxillary esthetic zone.

Is caring for pressure ulcers in the intensive care unit in Spain still a challenge? A qualitative study on nurses' perceptions.

BACKGROUND: The incidence of pressure ulcers is an indicator of quality in intensive care units. Due to their frequency and severity, they are identified as a problem of great importance, where the well-being of patients and relatives is compromised, also generating a high healthcare cost. Nurses are primarily responsible for the care of pressure ulcers, however, the existing literature exposes a clear lack of knowledge regarding its prevention and treatment. OBJECTIVES: To explore the attitudes, knowledge and perceived barriers by intensive care nurses regarding pressure ulcers treatment and prevention in a critical care setting. DESIGN: A descriptive qualitative study has been carried out through semi-structured interviews with 22 intensive care nurses from two tertiary university hospitals in Spain. The consolidated criteria for reporting qualitative research (COREQ) guidelines were used to reinforce the methodological approach of the study. FINDINGS: From the collected data, 4 main themes emerged: "lack of specific knowledge about pressure ulcers in intensive care", "continuity of care: the main problem to solve", "teamwork and pressure ulcers: gasping for improvement" and "Skin care as another vital sign". CONCLUSION: Most intensive care nurses consider that they do not have sufficient knowledge regarding pressure ulcers. The nurses' attitudes are positive, however, an ineffective transmission of information and registration regarding ulcers is perceived. Regarding the treatment of pressure ulcers, the lack of continuity of care and updated knowledge/training have been the main barriers. In terms of prevention, the most mentioned barriers have been the clinical condition of the patient and the lack of personnel, despite the level of knowledge.

Development and Pharmacokinetic Evaluation of Two Parenteral Formulations of Albendazole Using Prodrug and Cosolvent Approaches.

Albendazole is a broad-spectrum anthelmintic drug used for parasitic infections. In addition, due to its mechanism of action, it has been studied as an anticancer agent. However, poor and highly variable bioavailability are limiting factors for its use in systemic illnesses. The present study aimed to develop two parenteral formulations of albendazole and to compare its pharmacokinetic profile with the conventional oral administration. Parenteral formulations were developed using two different approaches: a phosphonooxymethylated prodrug and cosolvents. For the albendazole prodrug, once synthetized, its solubility and hydrolysis with alkaline phosphatase were evaluated. A factorial design of experiments was used for the cosolvent formulation. Stability and hemolytic activity were assessed. A pharmacokinetic study was performed on New Zealand rabbits. Both formulations were administered intravenously, and the prodrug was also administered intramuscularly. Results were compared with those obtained after the oral administration of albendazole. A 20,000-fold and 6000-fold increase in albendazole solubility was found with the prodrug and cosolvent formulations, respectively. Both parenteral formulations displayed higher albendazole plasma concentrations for the first 2 h compared with oral administration, even when the oral dose was doubled. The absolute bioavailability of oral albendazole was 15.5% while for the intramuscular administration of the prodrug was 102.6%. Both parenteral formulations showed a significant decrease in the formation of albendazole sulfoxide (ANOVA p<0.05) and allowed greater exposure to albendazole. Albendazole cosolvent parenteral formulation could be a promising option in systemic illnesses considering its ease of preparation and superb pharmacokinetic performance.

Screw-retained internal connection zirconia CAD-CAM abutments in single implant reconstructions: Results of a 1-year prospective case series study.

PURPOSE: To evaluate the clinical and radiographic outcomes of single-tooth implant restorations using one-piece, internally connected, screw-retained, computer-aided design and computer-aided manufactured monolithic zirconia restorations fabricated on regular diameter implants. MATERIAL AND METHODS: Following a 2-stage surgical procedure, 22 implants placed in anterior and posterior areas in 21 partially edentulous patients (mean age of 55 years; 9 males/12 females) were evaluated in terms of plaque index, pocket probing depth, bleeding on probing, level of oral hygiene (OH), signs of mucositis/peri-implantitis, esthetic score (ES), gingival zenith position (GZP), papilla index score, the thickness of peri-implant gingiva, radiographic marginal bone loss, and technical complications. Implants and restorations were prospectively followed from the insertion of the restoration (baseline), up to 12-months post-loading. RESULTS: A 100% implant survival rate resulted after loading; one implant was lost before loading. Clinically, patients performed an adequate OH, and tissues were kept healthy. Probing depth showed a slightly lower value at baseline compared to any follow-up examination (2.26 [0.94] at baseline vs. 2.53 [0.66] mm at 12 months). ES, GZP, and the thickness of the peri-implant gingiva improved throughout the course of the study. Radiographically, average marginal bone level (MBL) was 0.40 (0.40) mm after 1-year follow-up with no differences in average MBL at all time points. Technically, after 1 year of clinical function, neither abutment fracture nor any other serious complications occurred. Hence, prosthetic reconstruction survival rate was 100%. CONCLUSIONS: Clinical outcomes of single-tooth implant restorations using internally connected, screw-retained, computer-aided design and computer-aided manufacturing monolithic zirconia abutments can be considered a reliable treatment alternative after 1-year clinical observation.

Field study on the determination of the effective dose of injectable fosfatriclaben prodrug in sheep naturally infected with Fasciola hepatica.

The aim of the present study was to determine the effective dose of fosfatriclaben through a field study in sheep naturally infected with F. hepatica. Thirty crossbred sheep positive for fluke eggs were selected for inclusion in the trial. On day 0, 5 groups of 6 animals each were formed for treatments: group 1 (G1), G2, and G3 received fosfatriclaben at 4, 6, and 8 mg/kg/IM, respectively. G4 received triclabendazole at 10 mg/kg/PO, and G5 was the untreated control group. Fecal samples of the sheep were analyzed to count the number of fluke eggs to evaluate the percentage of egg reduction. Twenty-one days after treatment, all sheep were humanely euthanized to extract the flukes from the bile ducts. They were counted to assess the percentage of fluke reduction. Fosfatriclaben reduced fluke eggs by 99.6, 99.6, and 100% and flukes by 94.3, 100, and 100%, respectively. Triclabendazole reduced fluke eggs by 95.2% and flukes by 100%. The fosfatriclaben injectable prodrug showed a high fasciolicidal efficacy similar to triclabendazole, with advantages over its predecessor, since only half the dose as compared to triclabendazole was required to remove eggs and flukes in the sheep that were studied.

Titanium Nitride Coated Implant Abutments: From Technical Aspects And Soft tissue Biocompatibility to Clinical Applications. A Literature Review.

PURPOSE: To review the most up to date scientific evidence concerning the technical implications, soft tissue biocompatibility, and clinical applications derived from the use of titanium nitride hard thin film coatings on titanium alloy implant abutments. MATERIALS AND METHODS: A review was performed to answer the following focused question: "What is the clinical reliability of nitride coated titanium alloy abutments?". A MEDLINE search between 1980 and 2021 was performed for investigations pertaining to the clinical use of nitride coated titanium alloy implant abutments (TiN) in case reports, case series, and short- and long-term non/randomized controlled clinical trials. Literature analysis led to addition evaluation of research related to the technical and biological aspects, as well as the physicochemical characteristics of TiN hard thin film coatings and their impact on titanium abutment biocompatibility, mechanical properties, macroscopic surface topography, and optical properties. Therefore, preclinical data from biomechanical and in vitro investigations were also considered as inclusion criteria. RESULTS: The limited number of clinical investigations published made a systematic review and meta-analysis not possible, therefore a narrative review was conducted. TiN coatings have been applied to dental materials and instruments to improve their clinical longevity. Implant abutments are coated with titanium nitride to mask the titanium oxide surface and enhance its surface characteristics providing the TiN abutment surface with a low friction coefficient and a very high chemical inertness. TiN coating is suggested to reduce early bacterial colonization and biofilm formation and enhance fibroblast cell proliferation, attachment and adhesion when compared to Ti controls. Additionally, studies indicate that hard thin film coatings enhance the mechanical properties (hardness and wear resistance) of titanium alloy and appears as a yellow color when deposited on the titanium alloy substrate. To date, clinical investigations show that nitride coated titanium abutments provide promising short-term clinical outcomes. CONCLUSIONS: Published research on nitride-coated abutments is still limited, however, the available biomedical research, mechanical engineering tests, in vitro investigations, and short-term clinical trials have, to date, reported promising mechanical, biological, and esthetic outcomes.

Effectiveness and safety of the Space GlucoseControl system for glycaemia control in caring for postoperative cardiac surgical patients.

BACKGROUND: Hyperglycaemia is a very common complication in post-cardiac surgical patients, and as such, it must be properly managed. For this purpose, the enhanced Model Predictive Control algorithm for glycaemia control has been implemented into a nurse-led device called Space GlucoseControl (SGC) that aims to achieve a safe and effective blood glucose control in a better way than the traditional "paper-based" protocols. PURPOSE: The aim of the study was to know the effectiveness and safety of the SGC in glycaemia control in cardiosurgical adult patients in the immediate postoperative period in the intensive care unit. METHODS: A prospective before-and-after intervention study was conducted. One hundred sixty cardiosurgical adult patients with hyperglycaemia were selected: 80 in the control group from May to November 2018 and 80 in the intervention group (use of the SGC device) from January to December 2019. The primary outcome was the percentage of time within the target range (140-180 mg/dL in the control group and 100-160 mg/dL in the intervention group). RESULTS: The percentage of time within the target range was significantly higher in the SGC group than in the control group (70.5% [58.25-80] vs 54.83% [36.09-75], p < 0.001). The range was also achieved earlier with the SGC (5 [3-6.875] hours vs 7 [4-11] hours; p < 0.05). The first blood glucose value after reaching the target range was higher in the control group, with statistical significance (p < 0.05). There were no hypoglycaemia episodes in the control group. However, during SGC treatment, six episodes of hypoglycaemia occurred, and all of them were nonsevere (mean value = 61 mg/dL). CONCLUSION: The SGC is useful to achieve a faster tight glycaemic control, with a higher percentage of time within the target range, although episodes of nonsevere hypoglycaemia could be observed.

Immunogenicity profile in African green monkeys of a vaccine candidate based on a mutated form of human Interleukin-15.

BACKGROUND: Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based on the recombinant modified human IL-15 (mhIL-15) mixed with the alum adjuvant. A previous study in non-human primates Macaca fascicularis has shown that vaccination induces neutralizing antibodies against native IL-15, without affecting animal behavior, clinical status, or the percentage of IL-15-dependent cell populations. However, the mhIL-15 used as an antigen was active in the IL-2-dependent cytotoxic T-cell line CTLL-2, which could hinder its therapeutic application. The current article evaluated the immunogenicity in African green monkeys of a vaccine candidate based on IL-15 mutant D8SQ108S, an inactive form of human IL-15. RESULTS: IL-15 D8SQ108S was inactive in the CTLL-2 bioassay but was able to competitively inhibit the biological activity of human IL-15. Immunization with 200 µg of IL-15 mutant combined with alum elicited anti-IL-15 IgG antibodies after the second and third immunizations. The median values of anti-IL-15 antibody titers were slightly higher than those generated in animals immunized with 200 µg of mhIL-15. The highest antibody titers were induced after the third immunization in monkeys vaccinated with 350 µg of IL-15 D8SQ108S. In addition, sera from immunized animals inhibited the biological activity of human IL-15 in CTLL-2 cells. The maximum neutralizing effect was observed after the third immunization in sera of monkeys vaccinated with the highest dose of the IL-15 mutant. These sera also inhibited the proliferative activity of simian IL-15 in the CTLL-2 bioassay and did not affect the IL-2-induced proliferation of the aforementioned T-cell line. Finally, it was observed that vaccination neither affects the animal behavior nor the general clinical parameters of immunized monkeys. CONCLUSION: Immunization with inactive IL-15 D8SQ108S mixed with alum generated neutralizing antibodies specific for human IL-15 in African green monkeys. Based on this fact, the current vaccine candidate could be more effective than the one based on biologically active mhIL-15 for treating autoimmune disorders involving an uncontrolled overproduction of IL-15.

Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors.

Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathway and has been validated as a therapeutic target for type 2 diabetes. A wide variety of scaffolds have been included in the structure of PTP1B inhibitors, one of them is the benzimidazole nucleus. Here, we report the design and synthesis of a new series of di- and tri- substituted benzimidazole derivatives including their kinetic and structural characterization as PTP1B inhibitors and hypoglycemic activity. Results show that compounds 43, 44, 45, and 46 are complete mixed type inhibitors with a Ki of 12.6 µM for the most potent (46). SAR type analysis indicates that a chloro substituent at position 6(5), a ß-naphthyloxy at position 5(6), and a p-benzoic acid attached to the linker 2-thioacetamido at position 2 of the benzimidazole nucleus, was the best combination for PTP1B inhibition and hypoglycemic activity. In addition, molecular dynamics studies suggest that these compounds could be potential selective inhibitors from other PTPs such as its closest homologous TCPTP, SHP-1, SHP-2 and CDC25B. Therefore, the compounds reported here are good hits that provide structural, kinetic, and biological information that can be used to develop novel and selective PTP1B inhibitors based on benzimidazole scaffold.

May Measurement Month 2019: an analysis of blood pressure screening results in the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2019 (MMM19) blood pressure (BP) measurement campaign to raise awareness of hypertension especially in those who are not aware of their condition. The MMM19 standard protocol designed by the International Society of Hypertension was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken two to three times, using an automated BP apparatus and were inputted either in the MMM19 app or data were recorded in paper form and manually transferred to Excel spreadsheets by encoders supervised by the PSH. A total of 89 941 participated through opportunistic convenience sampling. After multiple imputation, a total of 47 925 (53.3%) participants had hypertension (≥140/90 mmHg or on antihypertensive medication). Of this number, 31 151 (65%) were aware that they had high BP and 30 120 (62.8%) were on antihypertensive medications. Of the 30 120 participants on antihypertensive medications, only 18 373 (61.1%) had controlled BP (<140/90 mmHg). Being overweight or obese were significant predictors of high BP. Other predictors of high systolic BP and diastolic BP were alcohol intake, smoking, and a previous history of hypertension in pregnancy, while pregnant participants had significantly lower BP. The MMM19 campaign succeeded in raising awareness of high BP in our country, and the opportunistic sampling enhanced a sense of people empowerment by their knowing how easy it is to detect high BP and thereby enabling the prevention of long-term health complications. The higher BP control in the MMM19 hypertensive individuals possibly attests to the success of the previous MMM17 and MMM18 campaigns.