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Background and Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (E m ) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative E m is mainly set by two pore domain potassium (K 2P ) channels, of which the TASK-1 has been extensively investigated., Experimental Approach: Ion channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods. Intracellular [Ca 2+ ] was monitored using fluorescent microscopy. Pulmonary BP and vascular tone measurements were also performed ex vivo using a rat PAH model., Key Results: TREK-1 was the most abundantly expressed K 2P in hPASMCs of healthy donors and idiopathic(I) PAH patients. Background K + -current was similar in hPASMCs for both groups and significantly enhanced by the TREK activator ML-335. In donor hPASMCs, siRNA silencing or pharmacological inhibition of TREK-1 caused depolarisation, reminiscent of the electrophysiological phenotype of idiopathic PAH. ML-335 hyperpolarised donor hPASMCs and normalised the E m of IPAH hPASMCs. A close link was found between TREK-1 activity and intracellular Ca 2+ -signalling using a channel activator, ML-335, and an inhibitor, spadin. In the rat, ML-335 relaxed isolated pre-constricted pulmonary arteries and significantly decreased pulmonary arterial pressure in the isolated perfused lung., Conclusions and Implications: These data suggest that TREK-1is a key factor in E m setting and Ca 2+ homeostasis of hPASMC, and therefore, essential for maintenance of a low resting pulmonary vascular tone. Thus TREK-1 may represent a new therapeutic target for PAH., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Fracture of the lateral tubercle of the posterior process of the talus (Shepherd fracture) is an uncommon injury seen in sport. It is secondary either to indirect trauma on the plantarflexed foot or to high-impact direct trauma. The fracture can be missed with conventional X-rays and therefore advanced imaging methods such as CT scans are usually warranted for management planning. There is a low threshold towards surgical management in the displaced or comminuted case as the delayed functional outcome with conservative treatment is frequently sub-optimal with long-term pain, degenerative changes and non-union. In this regard, recent years saw an increasing interest in the role of minimally invasive approaches for Shepherd´s fracture treatment, such as arthroscopic reduction and internal fixation (ARIF)., Case Report: We present a case of a 27-year-old white male professional football player from Serbia who had Shepard fracture and successfully managed with arthroscopic osteosynthesis. The technical approach is detailed with posterior ankle arthroscopy offering the advantages of a minimally invasive approach with low morbidity and a rapid return to regular sporting activities., Conclusion: The utilization of the 2-port arthroscopic approach this method enables the direct observation of the articular surface along with the corresponding fracture lines, thereby affording the surgeon the chance to achieve accurate reduction via a minimally invasive soft tissue aperture. We advocate that Arthroscopic reduction and internal fixation (ARIF) is a reliable method for the fixation of Shepherd's fracture in the hands of experienced ankle arthroscopists., (© 2024. The Author(s).)

Dietary interventions that modulate the brown adipose tissue (BAT) thermogenic activity could represent a promising therapy for metabolic disorders. In order to examine if dietary walnuts intake regulates the expression of BAT thermogenic markers levels in healthy and metabolically challenged (fructose fed) animals, rats were initially divided into the control and fructose-fed groups. After nine weeks, these groups were subdivided into the one kept on the original regimens and the other supplemented with walnuts. High-fructose diet resulted in an increased relative BAT mass and no change in UCP1 content, while the walnut supplementation increased the amount of UCP1 in BAT, but did not affect 5-HT, NA, DHPG content and DHPG/NA ratio regardless of the diet. Moreover, the CD36 levels were increased following the walnut consumption, unlike FATP1, GLUT1, GLUT4, and glycogen content which remained unchanged. Additionally, the BAT levels of activated IR and Akt were not affected by walnut consumption, while ERK signaling was decreased. Overall, we found that walnut consumption increased UCP1 and CD36 content in the BAT of both control and metabolically challenged rats, suggesting that FFAs represent the BAT preferred substrate under the previously described circumstances. This further implies that incorporating walnuts into the everyday diet may help to alleviate some symptoms of the metabolic disorder., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/Objectives : Due to their high frequency, common risk factors, and similar pathogenic mechanisms, musculoskeletal disorders (MSDs) are more likely to occur with other chronic illnesses, making them a "component disorder" of multimorbidity. Our objective was to assess the prevalence of multimorbidity and to identify the most common clusters of diagnosis within multimorbidity states, with the primary hypothesis that the most common clusters of multimorbidity are MSDs. Methods : The current study employed data from a population-based 2019 European Health Interview Survey (EHIS). Multimorbidity was defined as a ≥2 diagnosis from the list of 17 chronic non-communicable diseases, and to define clusters, the statistical method of hierarchical cluster analysis (HCA) was performed. Results : Out of 13,178 respondents, multimorbidity was present among 4398 (33.4%). The HCA method yielded six multimorbidity clusters representing the most common diagnoses. The primary multimorbidity cluster, which was prevalent among both genders, age groups, incomes per capita, and statistical regions, consisted of three diagnoses: (1) lower spine deformity or other chronic back problem (back pain), (2) cervical deformity or other chronic problem with the cervical spine, and (3) osteoarthritis. Conclusions : Given the influence of musculoskeletal disorders on multimorbidity, it is imperative to implement appropriate measures to assist patients in relieving the physical discomfort and pain they endure. Public health information, programs, and campaigns should be utilized to promote a healthy lifestyle. Policymakers should prioritize the prevention of MSDs by encouraging increased physical activity and a healthy diet, as well as focusing on improving functional abilities.

Background : The external fixation (EF) Ilizarov method, shown to offer efficacy and relative safety, has unique biomechanical properties. Intramedullary nail fixation (IMN) is an advantageous alternative, offering biomechanical stability and a minimally invasive procedure. The aim of this study was to assess outcomes in patients undergoing tibia fracture fixation, comparing the Ilizarov EF and IMN methods in an early phase of IMN implementation in Serbia. Methods: This was a retrospective study including patients with radiologically confirmed closed and open (Gustilo and Anderson type I) tibial diaphysis fractures treated at the Institute for Orthopedic Surgery "Banjica'' from January 2013 to June 2017. The following demographic and clinical data were retrieved: age, sex, chronic disease diagnoses, length of hospital stay, surgical wait times, surgery length, type of anesthesia used, fracture, prophylaxis, mechanism of injury, postsurgical complications, time to recovery, and pain reduction. Pain intensity was measured by the Visual Analog Scale (VAS), a self-reported scale ranging from 0 to 100 mm. Results: A total of 58 IMN patients were compared to 74 patients who underwent Ilizarov EF. Study groups differed in time to recovery ( p < 0.001), length of hospitalization ( p = 0.007), pain intensity at the fracture site ( p < 0.001), and frequency of general anesthesia in favor of intramedullary fixation ( p < 0.001). A shorter surgery time ( p < 0.001) and less antibiotic use ( p < 0.001) were observed when EF was used. Additionally, we identified that the intramedullary fixation was a significant predictor of pain intensity. Conclusions: The IMN method offers faster recovery and reduced pain intensity in comparison to EF, while the length of surgery predicted the occurrence of any complication.

Background: The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ accumulation and dyshomeostasis have shown a key role in AD onset, leading to excitatory/inhibitory imbalance, the impairments of synaptic plasticity and oscillatory activity, and memory deficits. Despite the higher prevalence of Alzheimer's disease (AD) in women compared to men, the possible sex difference is scarcely explored and the information from amyloidosis transgenic mice models is contradictory. Thus, given the lack of data regarding the early stages of amyloidosis in female mice, the aim of this study was to systematically characterize the effect of an intracerebroventricular (icv.) injection of Aβ 1-42 on hippocampal-dependent memory, and on associated activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse, in both male and female mice., Methods: To do so, we evaluated long term potentiation (LTP) with ex vivo electrophysiological recordings as well as encoding and retrieval of spatial (working, short- and long-term) and exploratory habituation memories using Barnes maze and object location, or open field habituation tasks, respectively., Results: Aβ 1-42 administration impaired all forms of memory evaluated in this work, regardless of sex. This effect was displayed in a long-lasting manner (up to 17 days post-injection). LTP was inhibited at a postsynaptic level, both in males and females, and a long-term depression (LTD) was induced for the same prolonged period, which could underlie memory deficits., Conclusions: In conclusion, our results provide further evidence on the shifting of LTP/LTD threshold due to a single icv. Aβ 1-42 injection, which underly cognitive deficits in the early stages of AD. These long-lasting cognitive and functional alterations in males and females validate this model for the study of early amyloidosis in both sexes, thus offering a solid alternative to the inconsistence of amyloidosis transgenic mice models., (© 2023. Society for Women's Health Research and BioMed Central Ltd.)

Purpose: A key part of kinematic alignment (KA) and functional alignment (FA) is to restore the natural femoral joint line, in particular the medial joint line. KA is known to reproduce the femoral joint line accurately; however, direct comparisons with other surgical techniques such as FA are currently lacking. The purpose of this study was to evaluate differences of alignment parameters in KA and FA techniques with a special focus given to the femoral joint line., Methods: We performed a retrospective radiological analysis of pre- and postoperative long leg radiographs of 221 consecutive patients with varus or neutral leg alignment, who underwent primary total knee arthroplasty (TKA) procedures from 2018 to 2020. Patients were assigned to one of four groups: (1) FA: image-based robotic-assisted TKA, (2) FA: imageless robotic-assisted TKA, (3): restricted KA: 3D cutting block-assisted (patient-specific instruments, PSI) TKA, (4): unrestricted KA: calipered technique. Patients' radiographs were (re)-analyzed for overall limb alignment, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), as well as medial and lateral femoral joint line alteration. Statistical significance was determined using unpaired t testing (FA vs. KA group) and one-way ANOVA (subgroup analyses)., Results: Comparisons of KA vs. FA, as well as individual subgroups of KA and FA did not show any differences in the accuracy of medial joint line reconstruction (< 2 mm, p = 0.384, p = 0.744, respectively) and LDFA alteration (< 2°, p = 0.997, 0.921, respectively). Correction of MPTA (3.4° vs. 2.2°) and lateral femoral joint line (2.1 mm vs. 1.5 mm) was higher for FA and FA subgroups compared to KA and KA subgroups (both p < 0.001)., Conclusion: Kinematic and functional alignments showed a comparable accuracy in reconstruction of the medial femoral joint line and femoral joint line orientation. Increased correction of MPTA and lateral femoral joint line was recorded with FA techniques., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

The risk-benefit profile of anti-Aβ monoclonal antibodies (mAbs) in Alzheimer's disease (AD) remains unclear, especially concerning their safety and overall effects on AD progression and cognitive function. Here, we investigated cognitive, biomarker and side effects of anti-Aβ mAbs in large phase III randomized placebo-controlled clinical trials (RCTs) in sporadic AD. The search was performed on Google Scholar, PubMed and ClinicalTrials.gov by applying Jadad score to evaluate the methodological quality of the reports. Studies were excluded if they scored < 3 on Jadad scale or if they analyzed less than 200 sporadic AD patients. We followed PRISMA guidelines and DerSimonian-Laird random-effects model in R. Primary outcomes were cognitive: AD Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini Mental State Examination (MMSE) and Clinical Dementia Rating Scale-sum of Boxes (CDR-SB). Secondary and tertiary outcomes included biomarkers of Aβ and tau pathology, adverse events, and performance on Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale. The meta-analysis included 14,980 patients in 14 studies and four mAbs: Bapineuzumab, Aducanumab, Solanezumab and Lecanemab. The results of this study suggest that anti-Aβ mAbs statistically improved cognitive and biomarker outcomes, particularly Aducanumab and Lecanemab. However, while cognitive effects were of small effect sizes, these drugs considerably increased risk of side effects such as Amyloid Related Imaging Abnormalities (ARIA), especially in APOE-ε4 carriers. Meta-regression revealed that higher (better) baseline MMSE score was associated with improved ADAS Cog and CDR-SB. In order to improve reproducibility and update the analysis in the future, we developed AlzMeta.app, web-based application freely available at https://alzmetaapp.shinyapps.io/alzmeta/., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023. Published by Elsevier B.V.)

So far, the search for a cure for Alzheimer Disease (AD) has been unsuccessful. The only approved drugs attenuate some symptoms, but do not halt the progress of this disease, which affects 50 million people worldwide and will increase its incidence in the coming decades. Such scenario demands new therapeutic approaches to fight against this devastating dementia. In recent years, multi-omics research and the analysis of differential epigenetic marks in AD subjects have contributed to our understanding of AD; however, the impact of epigenetic research is yet to be seen. This review integrates the most recent data on pathological processes and epigenetic changes relevant for aging and AD, as well as current therapies targeting epigenetic machinery in clinical trials. Evidence shows that epigenetic modifications play a key role in gene expression, which could provide multi-target preventative and therapeutic approaches in AD. Both novel and repurposed drugs are employed in AD clinical trials due to their epigenetic effects, as well as increasing number of natural compounds. Given the reversible nature of epigenetic modifications and the complexity of gene-environment interactions, the combination of epigenetic-based therapies with environmental strategies and drugs with multiple targets might be needed to properly help AD patients., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes., Methods: The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week., Results: Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes., Conclusions: Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Miodrag Lalosevic et al.)

Producing isotactic polypropylene (iPP) homo- and copolymers in a wide composition and property range according to customer demand requires perfect alignment between the process technology, catalyst system and polymer structure. The present review shows this for the Borstar ® PP process, a hybrid process employing liquid bulk and gas phase stages, in an exemplary way. It starts with the process design and continues through two generations of Ziegler-Natta catalyst development history to the design of advanced multimodal random and multiphase copolymers. Essential elements of each of the three areas contributing to performance range are highlighted, and an outlook to future development is given.

Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3-CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABA A -mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3-CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in ageing, affecting around 46 million people worldwide but few treatments are currently available. The etiology of AD is still puzzling, and new drugs development and clinical trials have high failure rates. Urgent outline of an integral (multi-target) and effective treatment of AD is needed. Accumulation of amyloid-β (Aβ) peptides is considered one of the fundamental neuropathological pillars of the disease, and its dyshomeostasis has shown a crucial role in AD onset. Therefore, many amyloid-targeted therapies have been investigated. Here, we will systematically review recent (from 2014) investigational, follow-up and review studies focused on anti-amyloid strategies to summarize and analyze their current clinical potential. Combination of anti-Aβ therapies with new developing early detection biomarkers and other therapeutic agents acting on early functional AD changes will be highlighted in this review. Near-term approval seems likely for several drugs acting against Aβ, with recent FDA approval of a monoclonal anti-Aβ oligomers antibody -aducanumab- raising hopes and controversies. We conclude that, development of oligomer-epitope specific Aβ treatment and implementation of multiple improved biomarkers and risk prediction methods allowing early detection, together with therapies acting on other factors such as hyperexcitability in early AD, could be the key to slowing this global pandemic., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC ® ) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50-6.50 µg/mL (R 2 = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.

G protein-gated inwardly rectifying potassium channels (Kir3/GirK) are important for maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Coupled to numerous G protein-coupled receptors (GPCRs), they mediate the effects of many neurotransmitters, neuromodulators and hormones contributing to the general homeostasis and particular synaptic plasticity processes, learning, memory and pain signaling. A growing number of behavioral and genetic studies suggest a critical role for the appropriate functioning of the central nervous system, as well as their involvement in many neurologic and psychiatric conditions, such as neurodegenerative diseases, mood disorders, attention deficit hyperactivity disorder, schizophrenia, epilepsy, alcoholism and drug addiction. Hence, GirK channels emerge as a very promising tool to be targeted in the current scenario where these conditions already are or will become a global public health problem. This review examines recent findings on the physiology, function, dysfunction, and pharmacology of GirK channels in the central nervous system and highlights the relevance of GirK channels as a worthful potential target to improve therapies for related diseases., Competing Interests: Declaration of Competing Interest All authors state they have no actual or potential conflict of interest including any financial, personal or other relationships with individuals or organizations within three years of initiating the work that could inappropriately influence, or be perceived to influence, the study design or data interpretation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This lecture outlines the various alignment philosophies for total knee arthroplasty (TKA). It is logical that our desire to improve clinical outcomes for TKA involves a more personalized and physiological implantation process that preserves each patient's anatomical features. We will take a deep dive into the kinematic alignment concept by describing its rationale, surgical steps and results. Kinematic implantation of TKA can be done reliably at a low cost and appears to achieve acceptable implant biomechanics. While its short-term clinical results are encouraging, it must be evaluated further. The thresholds for acceptable alignment (indications for restricted kinematic alignment) still need to be specified. LEVEL OF EVIDENCE: V; Expert opinion., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The Glycine max xyloglucan endotransglycosylase/hydrolase (EC 2.4.1.207), GmXTH43, has been identified through RNA sequencing of RNA isolated through laser microdissection of Heterodera glycines-parasitized root cells (syncytia) undergoing the process of defense. Experiments reveal that genetically increasing XTH43 transcript abundance in the H. glycines-susceptible genotype G. max[Williams 82/PI 518671] decreases parasitism. Experiments presented here show decreasing XTH43 transcript abundance through RNA interference (RNAi) in the H. glycines-resistant G. max[Peking/PI 548402] increases susceptibility, but it is unclear what role XTH43 performs. The experiments presented here show XTH43 overexpression decreases the relative length of xyloglucan (XyG) chains, however, there is an increase in the amount of those shorter chains. In contrast, XTH43 RNAi increases XyG chain length. The experiments show that XTH43 has the capability to function, when increased in its expression, to limit XyG chain extension. This outcome would likely impair the ability of the cell wall to expand. Consequently, XTH43 could provide an enzymatically-driven capability to the cell that would allow it to limit the ability of parasitic nematodes like H. glycines to develop a feeding structure that, otherwise, would facilitate parasitism. The experiments presented here provide experimentally-based proof that XTHs can function in ways that could be viewed as being able to limit the expansion of the cell wall., Competing Interests: The authors have declared that no competing interests exist.

Background: The study aimed to examine the effect of early hyperglycemia on the morbidity/mortality of very low birth weight premature infants., Methods: This retrospective study included all premature infants with gestational age ≤32 gestational weeks, hospitalized at the Department of Intensive Neonatal Care, Clinical Center Kragujevac, during the period 2017-2019. Hyperglycemia was defined as glycemia of ≥12 mmol/l in one measurement, or > 10 mmol/l in two measurements, at repeated intervals of 2-4 hours. Glycemia was determined from capillary blood, using a gas analyzer of Gem Premier 3000, during the first 7 days of life. Continuous intravenous insulin infusion was administered after ineffective glucose restriction at glycemic values of > 14 mmol/l., Results: Patients with normoglycemia (41/72 (56.94%)) and hyperglycemia (31/72 (43.06%)) did not differ in gender, gestational age, mode of delivery and antenatal administration of steroids, while birth weight had a tendency to be lower in the hyperglycemic group (p=0.052). Hyperglycemia was significantly associated with a low APGAR score at the fifth minute (p=0.048), necrotizing enterocolitis (p=0.011), and shorter duration of mechanical ventilation (p=0.006). Hyperglycemia was associated with significantly more frequent fatal outcomes (35.5%) when compared with the normoglycemic group (4.9%). Accordingly, these patients required inotropic (r=0.036) and insulin therapy (r < 0.001) more often. Retinopathy of prematurity, bronchopulmonary dysplasia and sepsis did not correlate with hyperglycemia in our study. Intraventricular hemorrhage of the first degree was more often associated with normoglycemia in premature infants on prolonged mechanical ventilation while more severe intracranial hemorrhage was more common in the hyperglycemic group but did not result in statistical significance due to the small number of patients., Conclusions: Monitoring glucose levels in the blood of very low birth weight premature infants is clinically important because abnormalities in glucose homeostasis can have serious short-term and long-term consequences.

A thorough understanding of microbial communities in the gut of lower termites is needed to develop target-specific and environmentally benign wood protection systems. In this study, the bacterial community from Reticulitermes virginicus was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) spanning the V3 and V4 regions. Prior to library preparation, the termites were subjected to five treatments over an 18-day period: three groups were fed on wood treated with 0.5% chitosan, 25% acetic acid, or water, the fourth group was taken directly from the original collection log, and the fifth group was starved. Metagenomic sequences were analyzed using QIIME 2 to understand the treatments' effects on the dynamics of the gut bacteria. Four dominant phyla were detected: Bacteroidetes (34.4% of reads), Firmicutes (20.6%), Elusimicrobia (15.7%), and Proteobacteria (12.9%). A significant effect of chitosan treatment was observed in two phyla; Firmicutes abundance was significantly lower with chitosan treatment when compared to other groups, while Actinobacteria was lower in unexposed and starved termites. The results suggest that chitosan treatment not only affects the structure of the microbial community in the gut, but other treatments such as starving also cause shifts in termite gut communities.

In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid- β (A β ) peptides have been shown to play a causal role. Among different A β species, A β 25-35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble A β forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of A β 25-35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. A β 25-35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in A β 25-35 amyloidosis model.

Lignin is a complex phenolic biopolymer found mainly in the secondary cell walls of vascular plants, where it contributes to mechanical strength, water conduction, and plant defence. We studied the lignin of eastern leatherwood (Dirca palustris) because this slow-growing woody shrub is known for its flexible stems. Various analytical techniques and microscopy methods were employed to examine the composition and distribution of lignin and structural polysaccharides in leatherwood xylem in comparison with trembling aspen (Populus tremuloides) and white spruce (Picea glauca). We found that leatherwood has low overall levels of lignin, a high syringyl lignin content, and a unique distribution of lignin. Most remarkably, the cell corners and middle lamellae remain unlignified in mature xylem. These findings help explain the flexibility of leatherwood and also call into question the classical model of lignification, which purports that lignin polymerization begins in the cell corners and middle lamellae. This atypical lignification regime vividly illustrates the diversity in plant secondary cell wall formation that abounds in nature and casts leatherwood as a new model for the study of lignin biogenesis., (© 2019 The Authors New Phytologist © 2019 New Phytologist Trust.)

The feasibility of using β-cyclodextrin (βCD) as an eco-friendly carrier of boric acid for the protection of strand-based wood composites against decay fungi was evaluated. The formation of a βCD-boric acid (βCD-B) complex was confirmed by the appearance of the boron-oxygen bond by using attenuated total reflection-Fourier transform infrared spectroscopy. Chemical shifts of around 6.25 and 1.41 ppm were also observed in 1 H Nuclear Magnetic Resonance (NMR) and 11 B NMR spectra, respectively. The βCD-B preservatives at two levels (5 and 10 wt.%) were uniformly blended with southern pine strands that were subsequently sprayed with polymeric methylene diphenyl diisocyanate (pMDI) resin. The blended strands were formed into a loose mat by hand and consolidated into 25 × 254 × 12 mm oriented strand boards (OSB) using a hot-press. The OSB panels were cut to end-matched internal bonding (IB) strength and fungal decay resistance test specimens. The vertical density profiles (VDPs) of the IB specimens were measured using an X-ray based density profiler and the specimens with statistically similar VDPs were selected for the IB and decay tests. The IB strength of the treated specimens was lower than the control specimens but they were above the required IB strength of heavy-duty load-bearing boards for use in humid conditions, specified in the BS EN 300:2006 standard. The reduced IB of preservative-treated OSB boards could be explained by the destabilized resin upon the addition of the βCD-B complex, as indicated by the differential scanning calorimetry (DSC) results. The resistance of the OSB panels against two brown-rot fungi (i.e., G. trabeum or P. placenta ) was evaluated before and after accelerated leaching cycles. The treated OSBs exposed to the fungi showed an average mass loss of lower than 3% before leaching, while the untreated OSBs had 49 and 35% mass losses due to decay by G. trabeum or P. placenta , respectively. However, upon the leaching, the treatment provided protection only against G. trabeum to a certain degree (average mass loss of 15%). The experimental results suggest that protection efficacy against decay fungi after leaching, as well as the adhesion of the OSB strands, can be improved by increasing the amount of pMDI resin.

Background: Chitosan is a derivative form of chitin, which is the major component of exoskeletons of arthropods and the cell walls of fungi. The antimicrobial activity of chitosan against lepidopterans, aphids, fungi and bacteria has been extensively investigated, but only one report on the termiticidal effect of chitosan on termites has been published. In this study, we examined the termiticidal activity of chitosan by exposing single colonies of Reticulitermes flavipes (Kollar) and Reticulitermes virginicus Banks to wood treated with six different concentrations of chitosan solutions. Termite mortality and percent mass loss of wood samples after exposure to termites for 4 weeks were calculated., Results: High termite mortality (≥ 94%) occurred during exposure of R. flavipes termites to chitosan-treated wood with ≥38 mg g -1 treatment concentrations (≥ 2% chitosan), while <50% termite mortality was observed at lower treatment concentrations (11-15 mg g -1 ; 0.5% and 1% chitosan). For R. virginicus, 100% mortality was observed at all levels of treatment concentrations. A decrease in the percent mass loss of the wood sample was apparent in samples treated with solutions with an increasing chitosan concentration, with a significant difference (P < 0.05) between lower and higher treatment concentrations. Treatment retention in wood samples upon leaching was also determined and showed retention levels of between 0 and 30 mg g -1 chitosan retention., Conclusion: This study investigated the exposure of subterranean termites to chitosan as a wood preservative. The results show that chitosan treatments at sufficiently high loadings could protect wood against termites, preferably under non-leaching conditions. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

We report the preparation of lignin-based rigid polyurethane (RPU) foams from surface functionalized kraft lignin via a simple and environmentally benign process. Lignin was functionalized with polyisocyanate at 80 °C for 1 h, the resulting lignin-polyisocyanate prepolymer was confirmed by increased viscosity and Fourier-transform infrared spectroscopy (FTIR). The RPU foams containing up to 30% surface functionalized lignin as a substitute for petroleum-based polyols exhibited comparable thermal and mechanical properties to conventional RPU foams. The lignin-based RPU foams prepared from surface functionalization outperformed RPU foams without the surface functionalization, showing up to 47% and 45% higher specific compressive strength and modulus, respectively, with a 40% lignin substitution ratio. Thermal insulation and temperature-stability of the two types of the foams were comparable. The results indicate that the surface functionalization of lignin increases reactivity and homogeneity of the lignin as a building block in RPU foams. The life cycle assessment for the lignin-based RPU foams shows that the surface functionalization process would have overall lesser environmental impacts when compared with the traditional manufacturing of RPU foams with synthetic polyols. These findings suggest the potential use of surface functionalized lignin as a sustainable core material replacement for synthetic polyols in building materials.

Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen index, but not free estrogen index, insulin levels, or body mass index, negatively correlated with the endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data suggest that increased androgen availability in PCOS is associated with metformin-sensitive transcriptional downregulation of endometrial autophagy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Various targeted disease-specific therapeutics are currently approved, demonstrating a survival benefit over therapy with interferon-alpha (IFN-α) in patients with metastatic renal cell carcinoma (mRCC). Temsirolimus, a highly specific inhibitor of the mammalian target of rapamycin (mTOR), improves the overall and progression-free survival of high-risk patients with mRCC. The purpose of this study was to estimate the effects of temsirolimus on several laboratory parameters and to report the potential adverse events (AEs) in patients with mRCC., Methods: This research was a controlled, open, prospective and partly retrospective randomized study that included 60 patients up to 65 years of age, divided into the experimental and control group, each containing 30 patients. Patients in the experimental group were treated with temsirolimus. The control group comprised patients in the same stage of disease, treated with IFN-α. The effect of therapy in both groups was monitored during the first year of administration., Results: The overall incidence of AEs was 40% in both groups. Sixteen laboratory parameters were analyzed and the total number of deviations from the reference range was 263 in the experimental group and 229 in the control group. The total number of AEs regarding patient general clinical condition in the experimental group was 193 (asthenia 53.3%, urinary infection 43.3% and pyrexia 40%) and 175 in the control group (pyrexia 76.7%, asthenia 50% and tremor 50%)., Conclusion: Monitoring the renal function parameters during the temsirolimus administration has proved that the therapy had no significant influence on the remaining kidney function. By evaluating the AEs we concluded that there was no significant difference in the number of AEs of all grades between the groups, while the laboratory parameters and physical status deterioration differed qualitatively.

Introduction: High incidences of benign prostatic hyperplasia and lower urinary tract symptoms have a high socioeconomic importance. There are several published studies which have proved the efficiency of phosphodiesterase type 5 inhibitors in treatment of benign prostatic hyperplasia and lower urinary tract symptoms. However, more studies are needed to make this therapy the standard option for treating benign prostatic hyperplasia and lower urinary tract symptoms. This study was aimed at exploring changes in International Prostate Symptom Score, post voiding residuum and maximal urine flow in benign prostatic hyperplasia and lower urinary tract symptoms patients treated by sildenafil for benign prostatic hyperplasia and lower urinary tract symptoms. Matcrial and Methods. This study, which was conducted as a prospective:controlled, opened, randomized study, included 30 patients with benign prostatic hyperplasia and lower urinary tract symptoms. Research was conducted at the Department of Urology, Clinical Center of Vojvodina (November 2011 till November 2012). The inclusion criteria were as following: >45 years of age, International Prostate Symptom Score >3, prostatic specific antigen < l0, normal urinalysis. The patients were periodically tested for International Prostate Symptom Score, maximal urine flow, and post voiding residuum., Results: Statistically significant changes were found in all pprameters: mean International Prostate Symptom Score value improved from 12.8 to 8.6 (32.8% change), mean post voiding residuum value decreased from 49.4 ml to 40.2 ml (186% change), mean maximal urine flow value increased from 11.8 mI/s to 12.8 mI/s (8.5% change)., Conclusion: Treatment of benign prostatic hyperplasia and lower urinary tract symptoms with a continuous low dose of sildenatil seems to be a good treatment choice for the patients with mild to moderate benign prostatic hyperplasia and lower urinary tract symptoms, especially in the patients with concomitant erectile dysfunction. The authors are aware that their study is limited by a small number of patients. Since there are not too many studies on this topic, they believe that their study will contribute to the determination of place and role of this treatment approach.

It is broadly recognized that chemokine-activated neutrophils play a crucial role in the inflammation and disruption of lung tissue observed in several acute and chronic lung diseases. Since glycosaminoglycan side chains of proteoglycans act as chemokine co-receptors in inflammation, we have used a CXCL8-based dominant-negative mutant, dnCXCL8, to displace neutrophil-related chemokines in murine lungs using models of lung inflammation. Treatment with dnCXCL8 resulted in a dose-dependent reduction of neutrophil counts in bronchoalveolar lavage (BAL) of mice exposed to lipopolysaccharide after intravenous, subcutaneous and intratracheal administration. A strong and significant therapeutic effect was achieved already at a dose of 40 µg/kg of dnCXCL8. A similar dose response, but showing a broader spectrum of reduced inflammatory cells and soluble inflammatory markers, was observed in a murine model of tobacco smoke (TS)-induced lung inflammation. The broad spectrum of reduced inflammatory cells and markers can be due to the strong inhibition of neutrophil extravasation into the lung parenchyma, and/or to a relatively broad protein displacement profile of dnCXCL8 which may compete not only with wtCXCL8 for glycosaminoglycan-binding but possibly also with other related glycosaminoglycan-binding pro-inflammatory chemokines. Overall our results demonstrate that antagonizing CXCL8/glycosaminoglycan binding reduces lung inflammation as well as associated lung tissue damage due to LPS and TS and may therefore be a new therapeutic approach for lung pathologies characterized by a neutrophilic inflammatory phenotype., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: A key barrier that limits the full potential of biological processes to create new, sustainable materials and fuels from plant fibre is limited enzyme accessibility to polysaccharides and lignin that characterize lignocellulose networks. Moreover, the heterogeneity of lignocellulosic substrates means that different enzyme combinations might be required for efficient transformation of different plant resources. Analytical techniques with high chemical sensitivity and spatial resolution that permit direct characterization of solid samples could help overcome these challenges by allowing direct visualization of enzyme action within plant fibre, thereby identify barriers to enzyme action., Results: In the current study, the high spatial resolution (about 30 nm) of scanning transmission X-ray microscopy (STXM), and the detection sensitivity (ppm) of time-of-flight secondary ion mass spectrometry (ToF-SIMS), were harnessed for the first time to investigate the progression of laccase, cellulase and xylanase activities through wood samples, and to evaluate complementary action between lignin-modifying and polysaccharide-degrading enzymes. In particular, complementary insights from the STXM and ToF-SIMS analyses revealed the key role of laccase in promoting xylanase activity throughout and between plant cell walls., Conclusions: The spatial resolution of STXM clearly revealed time-dependent progression and spatial distribution of laccase and xylanase activities, whereas ToF-SIMS analyses confirmed that laccase promoted protein penetration into fibre samples, leading to an overall increase in polysaccharide degradation. Spectromicroscopic visualizations of plant cell wall chemistry allowed simultaneous tracking of changes to lignin and polysaccharide contents, which provides new possibilities for investigating the complementary roles of lignin-modifying and carbohydrate-active enzymes.