Dysregulation of the angiotensin-II Type-I receptor (AT1R) and its pathway was reported to associate with poor-prognosis in several malignancies, including colorectal-cancer (CRC). We have explored the therapeutic-potential of targeting AT1R using valsartan, and its pharmacological-interaction with Fluorouracil (5-FU) in CRC. Anti-proliferative function was evaluated in 2-/3-dimensional cells and in vivo models. Anti-proliferative, anti-migratory, apoptotic function and effect on cell-cycle was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing test, and Fluorescence-activated cell sorting (FACS), respectively, while gene-expression was determined at mRNA/protein levels. By histogical analysis and measuring of oxidative/antioxidant markers, we evaluated the anti-inflammatory properties of valsartan. Valsartan suppressed cell-growth and impacted the anti-tumor-activities of 5-FU by apoptosis-induction. Valsartan inhibited the cells migration by perturbation of Matrix metalloproteinase (MMP1). Furthermore, valsartan inhibited tumor-growth and metastasis, and this was more notable in valsartan/5-FU combination-treated-group. The mechanism was plausible to be via the induction of Reactive-oxygen-species (ROS) and down-regulation of Superoxide-dismutase (SOD), thiol/catalase (CAT) as well as Vascular endothelial growth factor (VEGF) and Transforming growth factor beta (TGF-β). Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory components include fibronectin, Interleukin) IL-1β (, Tumor necrosis factor alpha) TNF-α (, Interferon gamma) INF-γ (, and Monocyte Chemotactic Protein 1 (MCP-1). Our findings demonstrated that targeting the AT1R receptor may inhibit tumor-growth and ameliorate fibrosis and inflammation associated with CRC via modulation of AT1 and TGF-β pathways.

We fabricate large-area atomically thin MoS₂ layers through the direct transformation of crystalline molybdenum trioxide (MoO₃) by sulfurization at relatively low temperatures. The obtained MoS₂ sheets are polycrystalline (~10-20 nm single-crystal domain size) with areas of up to 300×300 µm² with 2-4 layers in thickness and show a marked p-type behaviour. The synthesized films are characterized by a combination of complementary techniques: Raman spectroscopy, X-ray diffraction, transmission electron microscopy and electronic transport measurements.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 functionalized gold nanoparticles (AuNPs) for tumor specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities, but not on corresponding normal tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

This study aimed to assess the ecotoxicological effects of the interaction of fullerene (C₆₀) and benzo[a]pyrene (B[a]P) on the marine mussel, Mytilus galloprovincialis. The uptake of nC₆₀, B[a]P and mixtures of nC₆₀ and B[a]P into tissues was confirmed by GC-MS, LC-HRMS and ICP-MS. Biomarkers of DNA damage as well as proteomics analysis were applied to unravel the toxic effect of B[a]P and C₆₀. Antagonistic responses were observed at the genotoxic and proteomic level. Differentially expressed proteins (DEPs) were only identified in the B[a]P single exposure and the B[a]P mixture exposure groups containing 1 mg/L of C₆₀, the majority of which were down-regulated (~52%). No DEPs were identified at any of the concentrations of nC₆₀ (p < 0.05, 1% FDR). Using DEPs identified at a threshold of (p < 0.05; B[a]P and B[a]P mixture with nC₆₀), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that these proteins were enriched with a broad spectrum of biological processes and pathways, including those broadly associated with protein processing, cellular processes and environmental information processing. Among those significantly enriched pathways, the ribosome was consistently the top enriched term irrespective of treatment or concentration and plays an important role as the site of biological protein synthesis and translation. Our results demonstrate the complex multi-modal response to environmental stressors in M. galloprovincialis.

We describe the draft genome of a Bovine enterovirus (EV) recovered from sewage in Nigeria. The virus replicates on both RD and L20B cell lines, but is negative for all EV screens in use by the GPEI. It contains 7,368nt, with 50.2% G+C content and an ORF with 6,525nt (2,174aa).

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Accelerating, exact, explicit and simple solutions of relativistic hydrodynamics allow for a simple and natural description of highly relativistic p+p collisions. These solutions yield a finite rapidity distribution, thus they lead to an advanced estimate of the initial energy density of high energy collisions. We show that such an advanced estimate yields an initial energy density in $\sqrt{s}=7$ and 8 TeV p+p collisions at LHC around or above the critical energy density from lattice QCD, and a corresponding initial temperature above the critical temperature from QCD and the Hagedorn temperature. This suggests that the collision energy of the LHC corresponds to a large enough initial energy density to create a non-hadronic perfect fluid even in pp collisions. %We also show, that several times the %critical energy density may have been reached in high multiplicity events, hinting at a non-hadronic medium created in %high multiplicity $\sqrt{s}=7$ and 8 TeV p+p collisions.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Arsenic trioxide (ATO) has been shown to inhibit pancreatic cell growth in vitro and to promote the inhibitory effects of gemcitabine on pancreatic cancer in vivo. However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against pancreatic cancer cells. The effects of this peptide-linked arsenic compound and ATO on pancreatic cancer growth were tested in vitro and in a mouse model. The data demonstrated that the peptide-linked arsenic compound inhibited pancreatic cancer cell growth more potently with IC50 values 10 times lower than ATO. Like ATO, the peptide-linked compound induced cell death and cell cycle arrest. More importantly, the peptide-linked arsenic compound inhibited pancreatic cancer growth in mice and enhanced the inhibitory effect of gemcitabine on pancreatic cancer growth at 2 times lower molar concentration than ATO. These results indicate that the peptide-linked arsenic compound inhibited pancreatic cancer more potently than ATO and suggest a potential clinical use for the combination of gemcitabine with the peptide-linked arsenic compound for the treatment of pancreatic cancer.

Breast cancer (BC) is the most common invasive neoplasm and affects many women of working age. The return to work (RTW) of female survivors (BCSs) is associated with a better quality of life and longer survival. A tailored intervention to promote RTW was launched in 2022. A year later, the women were contacted to find out if RTW had occurred regularly and what their health conditions were compared to baseline. BCSs reported excessive fatigue, poor sleep quality, anxiety, depression and reduced work ability; these parameters had not improved significantly compared to baseline. Thematic analysis of the interviews confirmed the presence of personal, company and societal factors that could hinder or favor RTW. The interviews demonstrated that, even in an economically developed country that has provided numerous benefits for BCSs, protection is not always effective. Personalized intervention seems necessary to complete the process of reintegrating BCSs into their future working careers.

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥ 80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-). Methods: In 12/2021, a REDCap survey was circulated electronically to 6,918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: 2,437 participants responded (35 % response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- (p

Eruption of rash along with spiking fever in travelers returning from tropics may be suspicious of arboviral diseases, and isolation can mitigate to prevent further transmission in non-endemic countries. The case presented was seen at the Fever Clinic at Hospital for Tropical Diseases in Bangkok, Thailand. The presenting complaints were fever, headache, myalgia, and a distinctive erythematous blanching rash. Despite a negative dengue NS1 test on the initial day, anti-dengue IgM and IgG were detectable on day five of illness. Dengue, a major cause of traveler’s fever with rash is of particular concern due to outbreak such as Thailand’s, exceeding to over one hundred thousand cases over nine months. The influx of 28 million travelers in 2023, many with naive immunity to many arboviruses, raises fear of transmission to temperature regions. We casually observe this impact in France, where Aedes albopictus presence led to 1099 imported dengue cases from Thailand, resulting in six autochthonous clusters. Heightened vigilance is crucial, urging consideration of dengue as a potential diagnosis in travelers with febrile rash, even prior to lab confirmation. Immediate isolation of patients is essential to prevent autochthonous transmission, reducing outbreak risk and averting public health crises.

In the last decade, three-dimensional (3D) printing has allowed the field of complex microfluidic channels to expand rapidly towards channels with variable cross-sections (i.e., beyond simple rounded media with a constant diameter) and channels. Whose trajectory can be outside a single plane and has gained numerous macro- and nanoscale manufacturing advances. Three-dimensional printing is being explored for various biomedical applications and the fabrication of nanomedicines using additive manufacturing techniques. Employing 3D-printed templates for macro-to-micro interfacing, a passively operated microfluidic device was designed. The research seeks to fabricate a biodevice that enables insulin microdosing, creating a subsystem like a microvalve and a microchannel matrix using additive manufacturing techniques. Our systems feature designs that enhance fluid dynamics without affecting the stability of the insulin. We propose using Humalog insulin in tropical climates (up to 30°C) without refrigeration for 28 days. The microvalve has a spiral trajectory with four outlet channels distributed along it. These channels align with the microchannels organized in a 10 mm x 15 mm matrix with 25 microchannels, each with a 770 µm internal diameter. The system delivers a dose of 2,3 mL in 6 minutes. We designed these systems for insulin micro-dosing, but they can also serve similar devices for other drugs.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing, the current stem cell interventions that disrupt or augment the bone healing process, and finally, consider the future direction/therapeutic options related to stem cells and bone healing.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

Sorghum (Sorghum bicolor L.) ranks fifth as the most crucial cereal crop globally, yet its seed morphology remains relatively unexplored. This study investigated seed morphology in sorghum based on 115 mini core and 130 Senegalese germplasms. Eight seed morphology traits encompassing size, shape, and color parameters were assessed. Statistical analyses explored potential associations between these traits and resistance to three major sorghum diseases: anthracnose, head smut, and downy mildew. Furthermore, genome-wide association studies (GWAS) were conducted using phenotypic data from over 24,000 seeds and over 290,000 publicly available single nucleotide polymorphisms (SNPs) through the Genome Association and Prediction Integrated Tool (GAPIT) R package. Significant SNPs associated with various seed morphology traits were identified and mapped onto the reference sorghum genome to identify novel candidate defense genes.

The product of ozonolysis, Glycero-(9,10-trioxolane)-trioleate (ozonide of oleic acid triglyceride, [OTOA]), was incorporated into polylactic acid/polycaprolactone (PLA/PCL) blend films in the amount of 1, 5, 10, 20, 30, and 40% w/w. The morphological, mechanical, thermal and antibacterial properties of the biodegradable blend after the OTOA addition were studied. According to DSC and XRD data, the crystallinity degree of PLA/PCL+OTOA films tended to decrease with increase in OTOA content that could be explained by its plasticizing effect. Morphological analysis showed that the structure of the films with the OTOA concentration above 20% drastically changed. Specifically, the interface between the PLA/PCL matrix and OTOA was formed, thereby forming a capsule with the embedded antibacterial agent. The moisture permeability of the resulting PLA/PCL+OTOA films decreased due to the formation of uniformly distributed hydrophobic amorphous zones that prevents water penetration. This architecture affects the tensile characteristics of the films: strength decreases to 5.6 MPa, elastic modulus E by 40%. The behavior of film elasticity is associated with the redistribution of amorphous regions in the matrix. Additionally, PLA/PCL+OTOA films with 20, 30 and 40% of OTOA showed good antibacterial properties on Pseudomonas aeruginosa, Raoultella terrigena (Klebsiella terrigena) and Agrobacterium tumefaciens. Developed PLA/PCL+OTOA films could be used as packaging materials and wound dressings. By variation of the OTOA content, it is possible to tailor the physical-chemical and antibacterial properties of the developed films for various applications.

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p&lt;0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

Intrauterine growth restriction (IUGR) and being born small for gestational age (SGA) are two distinct conditions with different implications for child development. IUGR is associated with greater perinatal morbidity and mortality and can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnios, lack of growth in the interval, estimated weight <3rd percentile). IUGR may also be present in neonates with birth weights above the 10th percentile. Recognizing fetuses being “at risk” of a higher perinatal mortality and morbidity rate in order to monitor them accordingly and deliver them in good time is still challenging. This review article summarizes approaches to increase the diagnostic accuracy of IUGR and presents current concepts of pathophysiology with a focus on oxidative stress and consecutive inflammatory and metabolic changes. Since prenatal influences affect the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood and look at future scientific challenges. It should be emphasized that prenatal and postnatal care of IUGR neonates should be regarded as a continuum.

Renal cell carcinoma (RCC), alternative term for kidney cancer, is becoming more common worldwide each year, and there are many different contributing factors. Among all cancers, RCC is the 14th most prevalent; and it ranks as the 14th and 9th most prevalent cancer overall for women and men respectively. RCC cases increased by more than 430,000 in 2020. While disease burdens are highest in Eastern Europe (Belarus and Russia) and North America (Canada and the United States), Africa, Asia, and Latin America are predicted to report increase in prevalence as these regions embrace change in lifestyle. The majority of RCC cases are accidentally found on imaging, and survival is greatly impacted by the disease stage at diagnosis, with a metastatic cancer having a 5-year survival rate of 12%. As a consequence of early discovery and more improved treatments, RCC mortality has declined. The key epidemiologic variables of RCC include vast regional and geographical heterogeneity in prevalence rates, and the cause is largely unclear. Recognized risk factors include smoking, being overweight, having previous episodes of hypertension, and suffering chronic renal illness. Unexpectedly swift, RCC diagnosis and therapy have advanced. RCC prevalence continues to rise although survival rates have sharply improved. Cancer survival and treatment have improved, and more gains are projected as a result of clinical and translational research. In this review, kidney cancer statistics and recent literatures are examined on a global scale. It covered aspects of kidney cancer, including its epidemiology, causes, risk factors, current immunotherapy, chances for prevention, and future planning.

Biomass and biowaste valorisation is of major interest nowadays because of the spirit of circular economy and of the neutral environmental fingerprint global target. In the current project chondroitin sulphate (ChS) was incorporated with the crustaceous’ and shrimp’s byproduct chitosan (Chi) and the fish industry byproduct gelatine (FG) to obtain dense hydrogel membranes. Glycerol (Gly) was utilized to avoid brittleness. The formation of the hydrogel membranes is attributed to secondary interactions between the natural polymers and the plasticizer. The prepared hydrogel membranes were characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The surface morphology of the membranes was examined using scanning electron microscopy (SEM). Dynamic mechanical analysis (DMA) and tensile tests were also performed to evaluate the mechanical response of the membranes. The samples were also evaluated for membrane wettability, degradation rate and water vapor transmission rate (WVTR). Finally, in vitro endothelial cell attachment on the membrane were addressed. The overall results of the study indicate that the hydrogel membranes could be appropriate for external application in wound healing applications as dressings.

Aging is a complex process associated with tissue degeneration and an increased risk of age-related diseases. This study aimed to evaluate the impact of Terasen®, a nutraceutical containing standardized extracts of Euterpe oleracea, Myrciaria dubia, and purified oil of Bixa orellana and Astrocaryum aculeatum on the lifespan of Caenorhabditis elegans, a widely used model organism for aging research. The findings demonstrated that Terasen® exhibited significant antioxidant activity and influenced the feeding behavior of C. elegans, leading to a reduced pharyngeal pumping rate and a decreased number of offspring produced by treated individuals. Notably, Terasen® also displayed a remarkable ability to extend the lifespan of C. elegans. These findings suggest that Terasen® may possess promising anti-aging effects in vivo, warranting further investigation.

The creation of mitochondria-targeted vector systems is a new tool for the treatment of socially significant diseases. Phosphonium groups provide targeted delivery of drugs through biological barriers to organelles. For this purpose, a new class of alkyl(diethylamino)(phenyl) phosphonium iodides (bromides) 1 containing one, two, or three diethylamino groups were obtained by the reaction of alkyl iodides (bromides) with (diethylamino)(phenyl)phosphines under mild conditions and high yields. The structure of compounds 1 was established by NMR and XRD. In vitro a high cytotoxicity against the lines M-Hela, HuTu 80, PC3, DU-145, PANC-1 and MCF-7 was found. Selectivity index are in the range of 0.06-4.0 M (SI 17-277) for the most active compounds. ROS production, mitochondrial localization and the process of cellular apoptosis were investigated. Decorated by 1 of lipid systems (liposomes and solid lipid nanoparticles) improve the cytotoxicity and a decrease in toxicity against normal cell lines. Compounds 1 induce apoptosis proceeding along the mitochondrial pathway. Aminophosphonium salts 1 also exhibit a high selective activity against the Gram-positive bacteria strains S. aureus 209P, B. segeus 8035, including methicillin-resistant strains of S. aureus (MRSA-1, MRSA-2), comparable to the activity of the fluoroquinolone antibiotic norfloxacin. A moderate in vivo toxicity in CD-1 mice was established for the lead compounds.

Background: Accurate estimation of dietary intake is challenging. But whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK for onward deployment to LMICs. Methods: Wearable camera devices were used to capture food intake of eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images of the eating occasions. Food images were assessed for portion size, energy, and nutrient intake, and relative validity of the method compared to the weighed food records. Results: Pearson and Intra-class correlation coefficient of estimates of intakes of food, energy and 19 nutrients ranged from 0.60 to 0.95 and 0.67 to 0.90, respectively. Bland-Altman analysis showed good agreement between the image-based method and weighed food record. Under-estimation of dietary intake by the image-based method ranged from 4 to 23%. Conclusions: Passive food image capture and analysis provides an objective assessment of dietary intake comparable to weighed food records.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

Background and Objectives: Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess the anticoagulation status and LAAC indications in patients with AF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA2DS2-VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA2DS2-VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA2DS2-VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA2DS2-VASc &gt; 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 64 patients with NVAF (60 had only one risk factor and 2 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had eGFR&lt; 15 ml/min/1.73m2. Moreover, 33 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. One out of four AF patients should be screened for LAAC.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

Plant N concentration (PNC) has been commonly used to guide farmers in assessing maize (Zea mays L.) N status and making in-season N fertilization decisions. However, PNC varies based on the development stage and therefore a relationship between biomass and N concentration is needed (i.e., critical N dilution curves; CNDC) to better understand when plants are N deficient. A few CNDC have been developed and used for plant N status diagnoses, but have not been tested in the US Midwest. The objective of this study was to evaluate under highly diverse soil and weather conditions in the US Midwest the performance of CNDCs developed in France and China for assessing maize N status. Maize N rate response trials were conducted across eight US Midwest states over three years. This analysis utilized plant and soil measurements at V9 and VT development stages and final grain yield. Results showed that the French CNDC (y=34.0x-0.37, where y is critical PNC, x is aboveground biomass) was better with a 91% N status classification accuracy compared to only 62% with the Chinese CNDC (y=36.5x-0.48). The N nutrition index (NNI), which is the quotient of the measured PNC and the calculated critical N concentration (Nc), based on the French CNDC was significantly related to soil nitrate-N content (R2=0.38-0.56). Relative grain yield on average reached a plateau at NNI values of 1.36 at V9 and 1.21 at VT, but for individual sites ranged from 0.80 to 1.41 at V9 and from 0.62 to 1.75 at VT. The NNI threshold values or ranges optimal for crop biomass production may not be optimal for grain yield production. It is concluded that the CNDC developed in France is suitable as a general diagnostic tool for assessing maize N status in US Midwest. However, the threshold values of NNI for diagnosing maize N status and guiding N applications vary significantly across the region, making it challenging for guiding specific on-farm N management. More studies are needed to determine how to effectively use CNDC to make in-season N recommendations in the US Midwest.

Background and Objectives: The Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) is designed to assess affective temperaments. The short version of TEMPS-A (TEMPS-A-SV) was translated into diverse languages for its broad application in research and clinical settings. However, no study was conducted to validate the Korean version of TEMPS-A-SV among patients with mood disorders. The purpose of this study is to examine the reliability and validity of the TEMPS-A-SV in mood disorder patients of the Korean population. Materials and Methods: In this cross-sectional retrospective study, a total of 715 patients (267 patients with major depressive disorder, 94 patients with bipolar disorder I, and 354 patients with bipolar disorder II) completed the Korean TEMPS-A-SV. Cronbach's alpha and McDonald’s omega was used to assess reliability. Exploratory factor analysis (EFA) was also performed. Spearman's correlation coefficient was used to examine associations between five temperaments. The difference in five temperament scores between gender or diagnosis groups were analyzed, and the correlation between five temperament scores and age were tested. Results: The Korean TEMPS-A-SV displayed good internal consistency (α = 0.65–0.88, ω = 0.66–0.9) and significant correlations between the subscales except one (correlation between hyperthymic and anxious). Using EFA, a two-factor structure was produced: Factor I (cyclothymic, depressive, irritable, and anxious) and Factor II (hyperthymic). The cyclothymic temperament score differed by gender and the anxious temperament score was significantly correlated with age. All the temperaments, except for irritable temperament, showed significant differences between diagnosis groups. Conclusions: Overall, our findings indicate that TEMPS-A-SV is a valid and reliable measure of estimating affective temperaments among Koreans. Our results confirm validity of TEMPS-A-SV among Korean patients with mood disorders. However, more study is required on affective temperaments and associated characteristics in people with mood disorders.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

Tick-borne encephalitis virus (TBEV) is a RNA-containing enveloped virus, a member of the Flaviviridae family. Here we describe a detailed analysis of the size and structure of inactivated TBEV (the Sofyin-Chumakov TBEV strain, used in vaccines). Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, AFM, and NTA. All methods confirmed that the particles were monodisperse, and their mean size was ~50 nm. Cryo-EM data were used to obtain a 3D electron density model of the virus with clearly distinguishable E-proteins. STEM-EELS analysis detected phosphorous in the particles, which was interpreted as the RNA signal. Altogether, the described analytical procedures can be valuable for the further analysis of vaccine inactivated virus samples.

Dengue Fever (DF) is an important arthropod-borne viral infection, which has repeatedly oc-curred as outbreaks in eastern and northeastern Ethiopia since 2013. A cross-sectional epidemio-logical outbreak investigation was carried out from September - November 2019 on febrile pa-tients (confirmed malaria negative) who presented with suspected and confirmed DF at both public and private health facilities in Gewane District, Afar Region, northeastern Ethiopia. Ento-mological investigation of containers found in randomly selected houses belonging to DF positive patients was undertaken, to survey for the presence of Aedes larvae or pupae. A total of 1185 DF cases was recorded from six heath facilities during the 3-month study period. The mean age of DF cases was 27.2 years and 42.7% of the cases were female. The most affected age group was 15-49 years (78.98%). However, the attack rate (AR) was highest in the 49+ age group (134.2). A total of 162 artificial containers were inspected from 62 houses, with 49.4% found positive for Aedes larva/pupae. Aedes mosquitoes were mostly found breeding in buckets/bowls, clay jars, plastic tanks, and tires. World Health Organization entomological indices classified the study site as high risk for dengue outbreaks (House Index=45.2%, Container Index=49.4% and Breteau In-dex=129). Study findings highlight the importance of vector control to prevent future dengue out-breaks in the region. The scarcity of drinking water and changing climactic conditions may have also contributed to the occurrence of this outbreak.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Mixture of abramis brama (freshwater bream), carassius carassius (crucian carp), and sander lucioperca (pike perch) scales was used for the preparation of fish scale powder containing about 26.5 wt. % of removed when heating components preferably of organic nature, and 63.5 wt. % of mineral components. Fish scale powder enriched with inorganic components was prepared from washed, dried, and ground fish scale mixture using vibration sieving. Inorganic powders consisting of hydroxyapatite and magnesium whitlockite were obtained via heat treatment of this fish scale powder at 800-1000 oC. Particles of these inorganic powders consisted of sintered grains with dimensions less than 100 nm after heat treatment at 800 oC, less than 200 nm after heat treatment at 900 oC, and 100-500 nm after heat treatment at 1000 oC. Fish scale powder enriched with inorganic components as well as heat-treated inorganic powders consisting of hydroxyapatite and magnesium whitlockite can be recommended for the production of different materials such as ceramics or composites.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); N=5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; N=15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (N=5/group) or fludrocortisone (N=15/group) into male ApoE -/- mice fed a normal laboratory diet or LDL receptor -/- mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE -/- mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor -/- mice fed normal diet, 5 had ascending/arch pathologies, 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor -/- mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Given the low incidence, only ascending aortic diameter in LDLR -/- mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. The findings in mouse studies have the potential to provide caution to people who are taking or have taken fludrocortisone that could have an increased risk of aortic pathologies.

Brachytherapy is often applied to oral cancers, with good outcomes and minimal loss of oral function. Especially, mold brachytherapy is best suited for superficial oral cancers with little or no bone invasion, such as gingival cancer, palatal mucosal cancer, or buccal mucosal cancer because of the thin tissue thickness that needs to be irradiated. A few cases have been reported on mold brachytherapy for gingival cancers, especially with high-dose-rates (HDR), these treatments were performed during hospitalization. We report a case of lower gingival squamous cell carcinoma (SCC) treated with HDR mold brachytherapy in an outpatient setting. A 71-year-old male with lower gingival SCC had received HDR mold brachytherapy (54 Gy, 9 fractions, 5 days) as an outpatient. Eighteen months after the mold therapy, the patient had no recurrence and no metastasis. A search of the literature revealed no previous report of a case of gingival cancer treated with HDR mold brachytherapy in an outpatient.

Abstract: High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

(1) Background: Loneliness, little studied in Nursing Homes (NHs), can affect physical and mental health. We aimed to verify the prevalence of loneliness in 5 NHs and its associated factors. (2) Methods: Cross-sectional study. Older adults aged 65 or over with preserved cognitive status were included. The De Jong Gierveld Loneliness Scale was used to assess overall, social, and emotional loneliness; sociodemographic and health-related variables were collected. The chi-square (or Fisher’s) test and logistic regression were used for bivariate and multivariate analysis respectively. (3) Results: The final sample consisted of 65 participants (81.5% female) with a mean age of 84±7.13. Prevalence of overall loneliness was 70.7% (95%CI:58.2-81.4), social loneliness 44.6% (95% CI: 33.1-56.6) and emotional loneliness 46.2% (95% CI: 34.5–58.1). Overall loneliness was associated with lower perceived quality of life (Odds Ratio-OR= 5.52, 95% CI:1.25-24.38) and NH with state subsidized places (OR=0.19, 95% CI: 0.05-0.74); social loneliness with having 0-1 children (OR=0.25, 95% CI: 0.08-0.77), and emotional loneliness with depression (OR=4.54, 95% CI: 1.28-16.08) and urinary incontinence (UI) (OR=4.65, 95% CI: 1.23-17.52). (4) Conclusions: Loneliness was present in almost 71% of residents and was associated with the type of NH and poorer quality of life, emotional loneliness with depression and UI and social loneliness with having less than 2 children.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low and high density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p=0.003), and non-significantly with HDL-C (p=0.06) and TL (p=0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p=0.04), LDL-C (p=0.04), and TL (p=0.02). Our data indicate that in-utero exposures to POPs may be associated with long-lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

The integration of 3D city models with Building Information Models (BIM), abbreviated as GeoBIM, facilitates improved data support to several applications, e.g. 3D map updates, building permits issuing, detailed city analysis, infrastructure design, context-based building design, to name a few. To solve the integration, several issues need to be tackled and solved, i.e. harmonization of features, interoperability, format conversions, integration of procedures. The GeoBIM benchmark 2019, funded by ISPRS and EuroSDR, evaluated the state of implementation of tools addressing some of those issues. In particular, in the part of the benchmark described in this paper, the application of georeferencing to Industry Foundation Classes (IFC) models and making consistent conversions between 3D city models and BIM are investigated, considering the OGC CityGML and buildingSMART IFC as reference standards. In the benchmark, sample datasets in the two reference standards were provided. External volunteers were asked to describe and test georeferencing procedures for IFC models and conversion tools between CityGML and IFC. From the analysis of the delivered answers and processed datasets, it was possible to notice that while there are tools and procedures available to support georeferencing and data conversion, comprehensive definition of the requirements, clear rules to perform such two tasks, as well as solid technological solutions implementing them, are still lacking in functionalities. Those specific issues can be a sensible starting point for planning the next GeoBIM integration agendas.

Laminopathies are causally associated with mutations on Lamin A gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we have generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models include different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy (LMNA-associated congenital muscular dystrophy). We have characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and p-ERK and p-AKT levels. Our results indicate that Lmna exon 4 mutants show abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC complex are altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

The tumor organoid (tumoroid) model in three-dimensional (3D) culture systems has been developed to reflect more closely the in vivo tumors than 2D-cultured tumor cells. Notably, extracellular vesicles (EVs) are efficiently collectible from the culture supernatant of gel-free tumoroids. Matrix metalloproteinase (MMP) 3 is a multi-functional factor playing crucial roles in tumor progression. However, roles of MMP3 within tumor growth and EVs have not unveiled. Here, we investigated the protumorigenic roles of MMP3 on integrities of tumoroids and EVs. We generated MMP3-knockout (KO) cells using the CRISPR/Cas9 system from rapidly metastatic LuM1 tumor cells. Moreover, we established fluorescent cell lines with palmitoylation signal-fused fluorescent proteins (tdTomato and enhanced GFP). Then we confirmed the exchange of EVs between cellular populations and tumoroids. LuM1-tumoroids released large EVs (300-1000 nm) and small EVs (50-200 nm) while the knockout of MMP3 resulted in the additional release of broken EVs from tumoroids. The loss of MMP3 leads to a significant reduction in tumoroid size and to the development of the necrotic area within tumoroids. MMP3 and CD9 (a category-1 EV marker tetraspanin protein) were significantly down-regulated in MMP3-KO cells and their EV fraction. These weakened phenotypes by MMP3 KO were markedly rescued by the addition of MMP3-rich EVs or conditioned medium (CM) collected from LuM1-tumoroids, which caused a dramatic rise in the expression of MMP3, CD9, and Ki-67 (a marker of proliferating cells) in the MMP3-null/CD9-low tumoroids. Notably, MMP3 enriched in tumoroids-derived EVs and CM deeply penetrated into recipient MMP3-KO tumoroids, resulting in a remarkable enlargement of solid tumoroids, while MMP3-null EVs did not. These data demonstrate that EVs can mediate molecular transfer of MMP3 resulting in increasing the proliferation and CD9+ tumorigenesis, indicating crucial roles of MMP3 in tumor progression.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

Li-ion cell designs, component integrity and manufacturing processes all have critical influence on the safety of Li-ion batteries. Any internal defective features that induce a short circuit, can trigger a thermal runaway: a cascade of reactions, leading to a device fire. As consumer device manufacturers push aggressively for increased battery energy, instances of field failure are increasingly reported. Notably Samsung made a press release in 2017 following a total product recall of their Galaxy Note 7 mobile phone, confirming speculation that the events were attributable to the battery and its mode of manufacture. Recent incidences of battery swelling on the new iPhone 8 have been reported in the media, and the techniques and lessons reported herein may have future relevance. Here we look deeper into the key components of one of these cells and confirm evidence of cracking of electrode material in tightly folded areas, combined with a delamination of surface coating on the separator, which itself is an unusually thin monolayer. We report microstructural information about the electrodes, battery welding attributes and thermal mapping of the battery whilst operational. The findings point to the most likely combination of events and highlights the impact of design features, whilst providing structural considerations most likely to have led to the reported incidences relating to this phone.

Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

This research integrates systemic and participatory techniques to model the Russian Federation construction innovation system. Understanding this complex construction innovation system, and determining the best levers for enhancing it, requires the dynamic modelling of a number of factors such as flows of resources and activities, policies, uncertainty and time. To build the foundations for such a dynamic model, the employed study method utilised an integrated stakeholder-based participatory approach coupled with structural analysis (MICMAC - Matrice d'Impacts Croisés Multiplication Appliquée à un Classement Cross-Impact Matrix). This method identified the key factors of the Russian Federation construction innovation system, their causal relationship (i.e. influence/dependence map) and ultimately a causal loop diagram. The generated model reveals pathways to improving construction innovation in the Russian Federation, and underpins the future development of an operationalised systems dynamic model.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Glucocorticoids (GCs) are widely used in blood cancer treatment despite their multiple adverse effects. Biological response to GCs is mediated by glucocorticoid receptor (GR) by transactivation (TA), associated with side effects, and transrepression (TR), mediating anticancer effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could be better option for cancer treatment. One of well-characterized SEGRAs is 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), demonstrated anticancer activity in vitro and in vivo, however its translational potential is limited due to chemical instability. CpdA derivatives CpdA-01-08 were designed by two synthetic strategies. Derivative CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. Analysis of CpdA-03 ligand properties in lymphoma Granta and leukemia CEM cell lines revealed its SEGRA profile: it induced GR TR without triggering GR TA, as evidenced by changes in expression of GR target genes. Effects of CpdA-03 on cell viability, growth, and apoptosis were similar to reference GR ligand, dexamethasone (Dex), and the proto-type compound CpdA. In vivo testing of CpdA-03 anti-lymphoma activity in transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, this work introduces CpdA-03 as promising new SEGRA with potential for further development as anti-lymphoma drug with fewer side effects.

The production of Moringa oleifera capsules has emerged as a promising agricultural activity in Mexico, driven by the plant’s well-documented health and nutritional benefits. In response, farmers have begun producing Moringa oleifera as a dietary supplement, using artisanal methods with minimal production controls. This study aimed to estimate the processing times of the Moringa oleifera production system using simulation modeling with Arena® software, and to evaluate the economic feasibility of capsule production. Methodologically, it was approached as a case study in the state of Veracruz, processing times were estimated through systematic sampling and modeled with Arena simulation software. Three simulation scenarios were considered to select a technically and economically viable alternative for agricultural producers: one with a 200-capsule encapsulator (1E200C), another with two 200-capsule encapsulators (2E200C) and a third with an 800-capsule encapsulator (1E800C). For the initial diagnosis a research stay was conducted for 180 days, and the production capacity was set at 24,000 capsules due to raw material limitations. Results indicated that the 1E800C scenario reduced processing time by 60% compared to the1E200C scenario, and by 35% compared to the 2E200C scenario. Additionally, the 1E800C model required only 2 days (16 hours) of work, while the 2E200C required 4 days (32 hours), and the 1E200C required 7 days (56 hours). In terms of production costs per unit of 90 capsules, the 1E200C was 3.93 USD the 2E200C 3.64 USD and the 1E800C 3.45 USD The study concluded that due to raw material limitations, the company can produce 12,800 units per year of 90 capsules. It is recommended to adopt the 1E800C encapsulator, which would lower overall production costs by 12.23%, representing 0.48 USD per unit produced, resulting in an additional profit of 6,150.50 USD Over a five-year evaluation period, the benefit-cost ratio was 5.03, the NPV was 922,370.11 and the IRR was 42.09%, indicating that this type of agribusiness in Mexico is both technically and economically feasible.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

The age-related mortality and morbidity risk of COVID-19 has been considered speculative without enough scientific evidence. This study aimed to collect more evidence on the association between patient age and risk of severe disease state and/or mortality from SARS-CoV-2 infection. Genomic dataset along with metadata (3608 samples) retrieved from GISAID from different geographical regions were grouped into 10 age groups (0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100 years) as well as high-risk or low-risk according to patient clinical status. Genomic sequences were aligned and analyzed using MAFFT and FASTTREE to build a phylogenetic tree in order to identify age-risk associations based on phylogenetic clustering. Case fatality rates (CFR), as well as the Odds ratio (OR) for high-risk outcomes, were calculated for different age groups. Results revealed that individuals aged between 25-50 years have the best immune response to the infection. On the other hand, disease fatality was higher in patients aging above 50 years. We created an application to calculate the OR of being at high risk given a certain age threshold from GISAID datasets. OR values increased between ages 1-10 years (1.271) and 11-20 years (1.313) but reduced at age range 21-30 years (1.290) and increased again for 61-70 years (2.465). CFR calculated for each of the age groups had peak values at 90-100 years (26.8%) and the lowest at 0-10 years (0%). The CFR for ages above 50 years was about twice greater (11.6%-26.8%) than that for ages below (0-6.6%). The phylogenetic analysis revealed that the majority of samples obtained from India showed low-risk among different age groups and were defined as clade GH. Another cluster from Singapore visualization showed unfavorable patient outcome across several age groups and were classified under clade O. To conclude, this study analyses showed a variety of age-risk associations. As scientists from different countries upload more genomes to globally shared databases, more evidence will reinforce mortality risk associations in COVID-19 patients.

Ectopic expression of the MYB transcription factor of AmROSEA1 from Antirrhinum majus has been reported to change anthocyanin and other metabolites in several species. In this study, we found that overexpression of AmRosea1 significantly improved the tolerance of transgenic rice to drought and salinity stress. Transcriptome analysis revealed that a considerable amount of stress-related genes were affected by exogenous AmRosea1 during both drought and salinity stress treatments. These affected genes are involved in stress signal transduction, the hormone signal pathway, ion homeostasis and the enzymes that remove peroxides. This work suggests that the AmRosea1 gene is a potential candidate for genetic engineering of crops.

While adeno-associated viral (AAV) vectors are successfully used in a variety of in vivo gene therapy applications, they continue to be hampered by the immune system. Here, we sought to identify innate and cytokine signaling pathways that promote CD8+ T cell responses against the transgene product upon vector administration to murine skeletal muscle. Eliminating just one of several pathways (including DNA sensing via TLR9, IL-1 receptor signaling, and possibly endosomal sensing of double-stranded RNA) substantially reduced the CD8+ T cell response at lower vector doses but was surprisingly ineffective at higher doses. Using genetic, antibody-mediated, and vector engineering approaches, we show that blockade of at least two innate pathways is required to achieve an effect at higher vector doses. Concurrent blockade of IL-1R1>MyD88 and TLR9>MyD88>IFN I>IFNaR pathways was often but not always synergistic and had limited utility in preventing antibody formation against the transgene product. We further provide evidence that CpG depletion of vector genomes and inclusion of TLR9 inhibitory sequences can have a synergistic effect. However, even low-frequency CD8+ T cell responses could eliminate transgene expression. Thus, innate immune avoidance/blockade strategies, albeit helpful, may not be sufficient to prevent destructive cellular responses in muscle gene transfer because of redundancy of immune activating pathways.

Background: Corticosteroids (CS) are crucial for managing various medical conditions, but long-term use is associated with significant risks. Balancing the therapeutic benefits and potential hazards requires careful prescription and monitoring. This study explores Jordanian physicians' knowledge, experiences, and concerns regarding CS prescriptions. Methods: This was a cross-sectional study conducted between March and August 2023, using an online link distributed using social media platforms. Results: A total of 171 physicians enrolled in the study were predominantly male, with a median age of 31 years. Two-thirds worked in central Jordan, and one-third were general practitioners. The majority (86.5%) had experience both in topical (83.1%) and injectable (81.1%) dosage forms. Physicians demonstrated high knowledge (median score 11/11) and major concerns (median fear score 3.5/5) about CS. Major worries included the risk of osteoporosis (73.7%) and hyperglycemia (66.7%). Sociodemographic factors did not significantly impact their knowledge or fears. Conclusion: Our study showed that physicians have a high knowledge level about CSs but have major concerns about CS side effects, particularly osteoporosis and hyperglycemia. These findings highlight the need for targeted interventions to address these fears, enhancing physician confidence and improving patient management outcomes.

The proliferation of fake news on social media platforms poses significant challenges to information authenticity and public trust. In this study, the impact of various word embedding techniques on the performance of both machine learning and deep learning models for fake news detection is systematically evaluated. The comprehensive TruthSeeker dataset, which spans over a decade of labeled news articles and social media posts, is utilized. Three popular word embedding techniques are analyzed: TF-IDF, Word2Vec, and FastText. These embeddings were tested with multiple machine learning classifiers, including logistic regression, naive Bayes, K-nearest neighbors, support vector machines, multilayer perceptrons, decision trees, and random forests, as well as deep learning models, specifically convolutional neural networks (CNNs). Among machine learning models, the Support Vector Machine (SVM) with TF-IDF achieved the highest accuracy of 99.03%, precision of 98.92%, recall of 99.15%, and F1 score of 99.03%. The Multilayer Perceptron (MLP) also demonstrated strong performance with Word2Vec, reaching an accuracy of 95.24%, precision of 94.95%, recall of 95.50%, and F1 score of 95.07%. For deep learning models, CNNs combined with TF-IDF embeddings showed outstanding results, achieving an accuracy of 98.99%, precision of 98.56%, recall of 99.48%, and F1 score of 99.02%. These results highlight the critical role of word embeddings in enhancing model accuracy and reliability in misinformation detection.

Fluoride (iF) is important inorganic pollutant in groundwater in central México. The aim of this study was estimated environmental risk exposure of iF in residents of Jerez Zacatecas México. Fifty-five tap water samples were collected from households to determine iF concentrations using the ion-selective electrode method. Based on these environmental values, the Hazard Quotient (HQ) was estimated following the methodology of the Pan American Health Organization (PAHO). Subsequently, risk maps were generated from these values to visualize the spatial distribution of high-risk areas within the city. iF in tap water ranger in concentration from 1.3 – 7.3 mg/L (ppm). We estimated HQ in a range of 0.63 to 3.73. iF ex-posure in tap water is a health problem that must be addressed, carrying out risk communication actions that allow the population to take care of their health through simple actions, avoiding future health costs.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

The Automatic Dependent Surveillance-Broadcast (ADS-B) protocol stands as a cornerstone in modern aviation surveillance and Aircraft Traffic Control systems, integral to the NextGen project initiated by the US Department of Federal Aviation Administration (FAA) in 2005. ADS-B utilizes data links to autonomously broadcast Aircraft navigational and identification information to augment air transportation system capacity and safety. However, concerns regarding the protocol's security persist, particularly as its adoption expands. The unencrypted nature of transmitted aircraft data and the absence of robust authentication mechanisms render the protocol susceptible to exploitation by malicious actors. In this study, we comprehensively reviewed existing research in the field, identifying a crucial gap necessitating a holistic survey. Prior surveys have predominantly focused on specific aspects, such as vulnerabilities, attacks, or critiques of existing solutions. Our survey addresses this gap by thoroughly exploring the aviation system, providing readers with a nuanced understanding of ADS-B security. Utilizing a detailed SWOT analysis diagram, our paper delves into the vulnerabilities inherent in the ADS-B protocol outlines potential threats and scrutinizes various attack scenarios. We systematically categorize and analyze existing security solutions, considering cost-effectiveness, scalability, implementation complexity, and coverage against diverse attack vectors. Furthermore, we critically evaluate these solutions, elucidate ADS-B security requirements, discuss current challenges, and propose future research directions. This survey serves as a comprehensive resource for researchers and practitioners alike, shedding light on the multifaceted landscape of ADS-B security and paving the way for enhanced aviation system resilience in the face of evolving cybersecurity threats.

Invasive species are one of the five main causes of biodiversity loss, along with habitat destruction, overexploitation, pollution, and climate change. Represent one of the first barriers to overcome in ecological conservation programs, since are difficult to control and eradicate. Due to the lack of records of invasive exotic species in Panama, this research is necessary to identify and register the documented groups of invasive species of the Chordates and Arthropod groups in Panama. This exhaustive search of invasive species was carried out in different bibliographic databases, electronic portals and scientific journals which addressed the topic at a global level. The results indicate that approximately 133 invasive exotic species of the Arthropoda and Chordata Phylum have been reported in Panama. Of the 133 species, 49 species belong to the Arthropoda Phylum and 84 species belong to the Chordate Phylum. The Panamanian economic activity could promote the introduction of alien species in this country. The study provides the first list of invasive exotic chordate and arthropod species reported for the Republic of Panama.

Infantile Neuroaxonal Dystrophy (INAD) is a rare neurodegenerative disorder, affecting 1:1,000,000 population. It results from pathogenic variants in the PLA2G6 gene located on chromosome (22q13.1). The onset of symptoms usually occurs between 6 to 18 months, causing developmental regression leading to debilitating symptoms such as muscle weakness, dementia, and loss of basic skills. Eventually, it progresses to life-threatening symptoms including breathing difficulties, which limits the life expectancy to 5-10 years. While potential genetic therapy for treatment is are being developed, they are yet to be approved for use, and management remains essentially supportive. This case report is of a 9-year-old Pakistani girl with INAD. She presented with recurrent chest infections, developmental regression, loss of speech, paralysis, hypertension, and eventually breathing difficulties. Brain magnetic resonance imaging and genetic testing con-firmed the diagnosis. This case posed diagnostic challenges in view of its overlapping clinical presentation. Through this report, we aim to raise awareness about the condition among practitioners, outline the importance of genetic counseling in susceptible couples and suggest potential areas of further research.

The solar energy can mitigate the power supply shortage in remote regions for portable irrigation systems. The accurate prediction of solar irradiance is crucial for determining the quantity of solar panels and the power capacity of photovoltaic power generation (PVPG) systems for mobile sprinkler machines. In this study, a prediction method is proposed to forecast the solar irradiance of typical irrigation areas. The impact of the meteorological parameters on the solar irradiance is studied, and four different parameter combinations are formed and considered as input to the prediction model. Based on meteorological data provided by ten typical radiation stations uniformly distributed nationwide, an Extreme Gradient Boosting (XGBoost) model optimized using the Whale Optimization Algorithm (WOA) is developed to predict the solar radiation. The prediction accuracy and stability of the proposed method are then evaluated for different input parameters through training and testing. The differences between the prediction performances of models trained based on single-station data and mixed data from multiple stations are also compared. The obtained results show that the proposed model achieves the highest prediction accuracy when the maximum temperature, minimum temperature, sunshine hours ratio, relative humidity, wind speed, and extraterrestrial radiation are used as the input parameters. The prediction effectiveness is also verified based on measured data. The WOA-XGBoost model has higher prediction accuracy than the XGBoost model, with predicted values falling within acceptable ranges. The model developed using mixed data of multiple stations can be applied for forecasting solar irradiance in different regions. This study provides a foundation for the optimization of the configuration of PVPG systems for mobile sprinkler machines.

Surgical simulators are crucial in early craniofacial and plastic surgical training, necessitating synthetic materials that accurately replicate tissue properties. Recent critiques of our lab’s currently deployed silicone surrogate have highlighted numerous areas for improvement. To further refine our models, our group's objective is to find a composition of materials that is closest in fidelity to native oral mucosa during surgical rehearsal by expert craniofacial surgeons. Fifteen platinum silicone-based surrogate samples were constructed with variable hardness and slacker percentages. These samples underwent evaluation of tactile sensation, hardness, needle puncture, cut resistance, suture retention, defect repair, and tensile elasticity. Expert craniofacial surgeon evaluators provided focused qualitative feedback on selected top-performing samples for further assessment and statistical comparisons. Evaluation revealed surrogate characteristics with satisfactory to good performance. Sample 977 exhibited the highest performance, and comparison with the original surrogate (sample 810) demonstrated significant improvements in critical areas, emphasizing the efficacy of the refined composition. The study identified a silicone composition that directly addresses the feedback received by our team’s original silicone surrogate. The study underscores the delicate balance between biofidelity and practicality in surgical simulation. The need for ongoing refinement in surrogate materials is evident to optimize training experiences for early surgical learners.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

Mississippi youth are demographically unique compared to that of the nation. The purpose of this study was to determine the trend of drug use among adolescents of the United States and Mississippi, and to estimate the differences of drug use prevalence as a whole, and by gender and by race. National and Mississippi YRBSS data from 2001 to 2021 were obtained for analysis. Summary statistics, prevalence ratio, and survey Chi-squared tests of independence statistics were generated for the comparison for all students, and by gender and race separately. Trend analysis was conducted using logistic regression combined with joinpoint regression. Six survey questions being studied were: have you ever used marijuana, inhalant, heroin, methamphetamines, injected drugs, and were you offered, sold, or given an illegal drug on school property during the last 12 months. Survey packages in R were used to account for the complex sampling design of YRBSS data. On the national level, all six drug related risk behaviors being studied showed significant decrease from 2001 to 2021. In Mississippi however, only “ever used marijuana” showed a trend of decrease, while three remain unchanged, and two increased. 2021 YRBSS data shows that Mississippi adolescents exhibited significantly higher prevalence of drug use, and are more likely to be offered, sold or given an illegal drug on school property. Our study suggests an urgent need for drug use intervention among Mississippi adolescents. More concerted actions at the community, school and government level are needed for reducing youth drug use and controlling the drug traffic on school property.

Efficient utilization of biomass requires conversion into forms that can be optimally applied in energy generation. Briquetting involves compaction of biomass into solid blocks that are more efficient than raw biomass and provides for ease of transport and handling. These are improved when the briquettes possess high shatter index and compressive strength. Due to difference in nature and composition, it is imperative to define optimum conditions for the production of quality and durable briquettes for individual biomass compacted into briquettes. This study studied the effects of process variables on the strength and durability of biomass briquettes produced using Abura sawdust. The lateral compressive strength and drop shatter index were investigated whilst varying the temperature (100-150 °C), pressure (9-15 MPa) and hold time (15-30 min). The compressive strength ranged between 2.06 and 5.15 MPa whilst the shatter index was between 50 and 600. The pressure was significant to the determination of the compressive strength (p &lt; 0.1) and the shatter index (p &lt; 0.05). Mechanical characteristics of the binderless Abura sawdust briquettes can be improved by optimizing the densification variables during the briquetting process when moderate pressures are used for compaction.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

Zinc (Zn) is the second most abundant metal in the human body, and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself, and then the quantity of other food constituents such as phytate, protein and calcium (Ca). In cells, Zn is involved in regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. Cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, the Solute-Linked Carrier 30A and 39A (SLC30A and SLC39A), known as the ZnT and the Zrt-/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases, including those induced by COVID-19 infections, among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to the potential protective effects of Zn against bone, lung and heart diseases associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Neonatal electronic cardiac monitoring in labor and delivery room (DR-ECG) is shown to be sustained at a tertiary care regional perinatal center despite COVID-19 and other complex organizational challenges. In this contemporary cohort, initial increase in chest compressions at birth associated with the introduction of DR-ECG monitoring was mitigated by focused educational interventions on effective ventilation with no difference in neonatal mortality. DR-ECG may help our understanding of human and system factors, identify potential better practices for optimal resuscitation team performance and assess impact of targeted training initiatives on clinical outcomes.

Despite their relatively low incidence globally, CNS tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes..

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Conobea scoparioides (Plantaginaceae) is an herbaceous plant known as "pataqueira" that grows wild in seasonally wet areas of the Amazon region. It is used for aromatic baths and anti-protozoan remedies by the Brazilian Amazon native people. The main volatile compounds identified in the essential oil of "Pataqueira" were the phenolic monoterpenes thymol and thymol methyl ether and their precursors, the monoterpene hydrocarbons α-phellandrene and p-cymene. A hydrotalcite synthesized from blast-furnace slag exhibited a 3:2 (Mg/Al) molar ratio, and this layered double hydroxide (LDH) was evaluated as a catalyst in converting the main monoterpenes of the "Pataqueira" oil. This action significantly increased thymol content, from 41% to 95%, associated with the percentual reduction of other main components, such as thymol methyl ether, α-phellandrene, and p-cymene. The LDH reaction showed a strong tendency towards producing hydroxylated derivatives, and its behavior was similar to the hypothetical plant biosynthetic pathway, which leads to the production of the monoterpenes of "Pataqueira" oil. Thymol and its derivatives are potent antiseptics applied in pharmaceutical and hygienic products as antibacterial, antifungal, and antioxidant properties, among others. The present work reports a natural source with a high thymol content in aromatic plants from the Amazon, with evident economic value.

Modular steel buildings (MSBs) interlocking inter-module connections (IMCs) have piqued researchers’ interest. However, the existing literature has not yet studied the optimisation of its plate thicknesses. This paper, therefore, focuses on optimising interlocking (IMCs) plate thickness in (MSBs), leveraging previous experimental and numerical simulation methodologies. Various numerical models for four MSBs interlocking (IMCs) with plate thicknesses (4 mm, 6 mm, 10 mm, and 12 mm) were developed under compression loading conditions. The study’s novelty lay in its comprehensive parametric analysis, which evaluated the slip phenomenon in (MSBs) connections and introduced a slip prediction model validated against empirical data. Further innovative machine learning approach was utilised to predict slip values based on applied force through a random forest regression model trained using the 'Treebagger' function. Sensitivity analysis and comparisons with alternative methods were utilised to underscore the reliability and applicability of the findings. The results showed that 11.03 mm was the optimal plate thickness for interlocking (IMCs) in modular steel buildings, with up to 8.08% reduced material costs. Increasing plate thickness boosts its deformation resistance by up to 50.75%. ‘TreeBagger’ random forest for anomaly detection and machine learning improves slip prediction up to 7% at higher force levels.

Zirconia-reinforced lithium silicate (ZLS) is utilized as a material for prosthetic tooth crowns, offering enhanced strength compared to other dental glass-ceramics. In this study, we investigate a commercial ZLS material, provided in a fully crystallized form. We examine the effects of an optional post-processing heat treatment on micro-contact damage using controlled indentation tests simulating the primary modes of contact during chewing: axial and sliding. Our findings indicate that the heat treatment does not affect mechanical properties such as the elastic modulus, hardness and indentation fracture toughness. However, it does enhance the resistance to contact damage by fracture and chipping in both axial and sliding modes, as well as the resistance to crack initiation measured from sliding tests. This improvement is attributed to the refinement of the flaw population achieved through the heat treatment. The results are analysed within the framework of contact and fracture mechanics, and the implications for prosthetic dentistry are briefly discussed.

This study examines the capacity of a Site-Specific Fodder Management Decision Support System (SSFM-DSS) model to assist in successful cultivation of sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G. Don.], with a specific focus on small-scale agricultural systems in the southeastern United States (U.S.). The study emphasizes incorporating advanced geospatial technologies, such as Geographic Information Systems (GIS), remote sensing, and Global Navigation Satellite Systems (GNSS), to improve fodder production. The research showcases the versatility of SL under varying environmental conditions, underscoring its significance in promoting sustainable livestock production. The methodology integrates empirical field data, geospatial analysis, and predictive modeling to formulate an SSFM strategy customized to address the distinct difficulties climate change presents, such as sudden and severe drought conditions. The study introduces an automated geospatial model for assessing the appropriateness of SL production throughout Alabama, Georgia, and South Carolina. The model uses many environmental criteria, including soil properties, climate fluctuations, and terrain. Furthermore, the research was instrumental in development of a WebGIS Dashboard, which offers farmers a decision assistance system to enhance the sustainable production of SL. The results highlight the significant impact that a SSFM-DSS can have on promoting sustainable agricultural practices, providing a solution to address the issues of food security and environmental concerns in agriculture.

Metabarcoding of prokaryotic and fungal ribosomal DNA was used to describe the microbial communities in soils of remnant equatorial rainforest, maize-bean intercrop, and sugarcane in western Kenya. Cropping systems influenced the microbial community composition and functional traits (energy source and nutrient cycling) of bulk soil in each crop. Microbial richness and diversity tended to increase with cultivation intensity. Soil of maize-bean intercrop had lower percentages and sugarcane had higher percentages of unique amplicon sequence variants of both bacteria and fungi compared to the remnant forest. Functional traits were altered by cultivation intensity. Compared to remnant forest soils, maize-bean intercrop soil had lower percentages of aerobic chemoheterotrophic bacteria and higher percentages of N-cycling bacteria, while sugarcane had higher percentages of aerobic chemoheterotrophic bacteria and lower percentages of N-cycling bacteria. In the face of increasing forest loss and pressures for agricultural productivity, this landscape provides a rich site for studying the impacts of cropping systems on soil health.

Background: The adoption of self-care behaviors among patients with congestive heart failure (CHF) is essential for the management of their health condition. However, there is a lack of tools for estimating self-care in CHF patients. We aim to develop and validate the Hippocratic heart failure self-care scale (HHFSCS). Methods: the scale includes 22 items which are reviewed by a committee of experts. Individuals indicate the frequency at which they follow each self-behavior on a five-point Likert scale. Adult patients with CHF (n=250) from a General Hospital, in Athens, were participated in the study from June 2020 to March 2021. Reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and the Principal Components Method were used to assess the psychometric measurements. Results: The Cronbach’s alpha coefficient of the HHFSCS was 0.807. The exploratory factor analysis identified two domains that accounted for 88.44% of the variance of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test-retest showed a significant strong correlation (r=0.973, p&lt;0.001). Conclusions: The HHFSCS is a reliable and valid tool for assessing self-behaviors in CHF patients. Health professionals can use it in their clinical practice to improve the management of patient’s health conditions.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Livestock management is challenging for resource-poor (R-P) farmers due to unavailability of quality feed, limited professional advice and rumor-spreading about animal health condition in a herd. This research seeks to improve animal health in southern Africa by promoting sericea lespedeza (Lespedeza cuneata), a nutraceutical fodder legume. An automated geospatial model for precision agriculture (PA) can identify suitable locations for its cultivation. Additionally, a novel approach of radio frequency identifier (RFID) supported telemetry technology can track animal movement, and the analyses of data using artificial intelligence can determine sickness of small ruminants. This RFID-based system is being connected to a smartphone app (under construction) to alert farmers of potential livestock health issues in real-time so they can take immediate corrective measures. An accompanying Decision Support System (DSS) site is being developed for R-P farmers to obtain all possible support on livestock production, including the designed PA and RFID-based DSS.

MFGE8 is a major exosome (EV) protein known to mediate inflammation and atherosclerosis in type 2 diabetes mellitus (T2DM) in animal studies. However, its role in the pathophysiology of human T2DM, obesity, and cardiovascular disease has been controversial and less explored. Earlier, we reported a rare Asian Indian population-specific missense variant (rs371227978; Arg148His) in the MFGE8 associated with increased circulating Mfge8 and T2DM. Here, we have further investigated the role of Mfge8 with T2DM risk in additional Asian Indians (n=4917) and Europeans and other multiethnic cohorts from UK Biobank (UKBB) (n= 455,808) and the US (n=1150). We also evaluated the exposure of Mfge8-enriched human EVs (with and without mutation) in zebrafish (ZF) for their impact on the cardiometabolic organ system. Most individual carriers of Arg148His variant not only had high circulating Mfge8 but also showed a positive significant correlation with glucose (r= 0.42; p = 4.9x10-04), while the non-carriers showed a negative correlation of Mfge8 with glucose (r = -0.38; p = 0.001) in Asian Indians. However, the same variant was monomorphic in Europeans and other ethnic groups of UKBB and US cohorts. Even in the absence of Arg148His variant, serum Mfge8 correlated significantly with blood glucose both in Caucasians (r = 0.56; p = 8.4x10-10) and individuals from other ethnicities (African Americans, Hispanics, and others) (r = 0.31; p = 5.8x10-4). Since Mfge8 is an EV marker, the exposure of Mfge8-enriched human EVs to ZF larvae rapidly developed fatty liver disease and heart hypertrophy and exhibited redundant growth with poor muscular architecture with and without the high-fat diet (HFD), while the control group fishes developed fatty liver disease and heart hypertrophy only after the HFD feeding. With strong evidence from animal studies supporting the role of Mfge8 in obesity, insulin resistance, and the development of atherosclerosis in T2DM, the current research suggests that circulating Mfge8 may be a potential marker for preventing or reducing the risk of T2DM and cardiovascular disease.

The increasing global concern over plastic waste and its environmental impact has led to a growing interest in the development of sustainable packaging alternatives. This study focuses on the innovative use of expired dairy products as a potential resource for producing edible packaging materials. Expired dairy products, which are typically discarded, contribute to food waste and environmental pollution. By modifying these products to packaging materials, a dual-purpose solution addressing both waste reduction and sustainable packaging is evaluated. Expired milk and yogurt were selected as the primary raw materials due to their protein and carbohydrate content. The extracted casein was combined with various concentrations of chitosan while in some cases glycerol was used. The materials were characterized with attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray analysis (XRD) to examine the interactions between the components of the formed binary blend. Scanning electron microscopy (SEM) was used to evaluate the surface morphology of the blends, while dynamic mechanical analysis (DMA) and tensile experiments were conducted to study the thermomechanical properties of the materials. Barrier properties, including water vapor transmission (WVTR) and oxygen permeability (OTR), were measured to assess the materials' potential to preserve food freshness. The findings reveal that expired dairy-based edible packaging materials exhibit promising mechanical properties, comparable to conventional plastic packaging. The barrier properties and especially the zero oxygen permeability of the membranes, indicate that these materials have the potential to effectively protect food products from external factors that could compromise quality and shelf life. The materials show encouraging signs of eco-friendliness, with a notable reduction in environmental persistence compared to conventional plastic packaging.

This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) among non-carbapenemase producing (NCP) and carbapenemase producing (CP) Escherichia coli and Klebsiella pneumoniae. As mutations for ertapenem resistance establish the genetic background for non-carbapenemase meropenem resistance, there is a great need for antibiotic stewards and researchers to understand the determinants of a strain’s propensity to become resistant. Whole genome sequencing was conducted on clinical carbapenem-resistant E. coli (CREC) and K. pneumoniae (CRKP) across 5 hospitals in San Antonio, U.S. from 2012-2018. The majority of carbapenem resistant Enterobacterales (CRE) were NCP (54%; 41/76). The blaCTX-M was found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Antimicrobial susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p &lt; 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p &lt; 0.001). ErMs strains carrying blaCTX-M, had approximately 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem and meropenem susceptible (EsMs) isolates (3.7 v. 0.9, p &lt; 0.001). ErMs also carried more mobile genetic elements (MGEs), particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p &lt; 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. To thwart potential mismanagement of CRE infected patients, future efforts should focus on understanding the mechanism(s) underlying OmpC loss, developing rapid methods to detect blaCTX-M copy number variants, and targeted antimicrobials for NCPE and ErMs strains.

Background: COVID-19 was initially identified as a respiratory system disorder, but it has been discovered to interact with and influence the cardiovascular system. COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes. Nevertheless, clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. Objective: This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, assessing the long-term CV consequences of COVID-19, and aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequlea in COVID-19 patients. Methods: For this purpose, a through review of literature and published data was carried out from first report of COVID-19 till October 2023 to find out a comprehensive account of clinical, cellular and molecular genetic factors underlying COVID-19-associated cardiovascular diseases. Results: We found that the relationship between COVID-19 and CV risk is complex and multifaceted. In addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects. We provide a detailed account of the involvement of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications. Conclusions: The relationship between COVID-19 and CV risk is complex and multifaceted. While COVID-19 primarily affects the respiratory system, it can also significantly affect CV health. as compared to classical cardiovascular diseases, there are new clinical, cellular and molecular biological factors in CVDs related to COVID-19, that need specific diagnostic assays, prognostic stratification and treatment modules. Therefore, specail care is must taken to treat cardiovascular diseases associated with COVID-19.

Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13-82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the Global quality of life scale and 18% of the TESS so psychometrically it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

Jatropha multifida L. is a plant belong to Euphorbiaceae family used in Benin pharmacopoeia because of its medicinal properties. The objective of this work is to appreciate the therapeutic power of this plant through the evaluation of some of its biological activities. After the preliminary phytochemistry, the polyphenols and flavonoids were quantified and identified by the LC-MS-ESI. The antimicrobial power of the extracts was investigated by agar medium diffusion. The antioxidant power of the extracts was evaluated by the reduction of the DPPH radical, the ABTS radical cation, the feric ion (FRAP) and the lipid peroxidation (LPO). Anti-inflammatory activity was assessed by inhibition of protein (albumin) denaturation. Indeed, different phenolic and flavonoid compounds namely, 2-Hydroxybenzoic acid, o-Coumaroylquinic acid, Apigenin-apiosyl-glucoside, Luteolin-galactoside, Luteolin-glucoside, Luteolin-rhamnoside, Quercetin-glucoside, Quercetin-arabinoside, Dicaffeoyquinic acid, Kaempferol-rhamnoside were identify. The J. mutifida extracts has a bactericidal effect with reference strains of wich CMBs vary from 22.67 mg/ml (S. aureus, S. enteridis, L. monocytogenes and C. albicans) to 47.61 mg/ml (E. coli) and with the meat isolated strains (S. equorum, S. saprophiticus, S. haemoliticus, S. cohnii and S. lentus). Ethanolic extract show the highest DPPH radical scavenging activity (IC₅₀ = 0.72±0.03 mg/ml) while methanolic extract showed the highest ferric ion reduction (46.23±1.10 µgEAA/g). Contrary to the FRAP method, the reducing power with ABTS method of water-ethanolic extract was greater (0.49±0.11 mol ET/g). The same extract show the highest albumin denaturation inhibition power (97.31±0.35%) at 1000µg/ml. J. multifida extracts are rich in bioactive compound with good biological activity

Introduction: Child stunting remains a public health concern. It is characterized as poor cognitive and physical development in children due to inadequate nutrition during the first 1,000 days of life. Across South Asia, Pakistan has the second-highest prevalence of stunting. This study has assessed the most recent nationally representative data, the National Nutrition Survey (NNS) 2018, to identify the stunting prevalence and determinants among Pakistani children under five. Methods: The NNS 2018, a cross-sectional household-level survey, was used to conduct a secondary analysis. Data on malnutrition, dietary practices, and food insecurity was used to identify the prevalence of stunting among children under five years by demographic, socioeconomic, and geographic characteristics. The prevalence of stunting was calculated using the World Health Organization (WHO) height for age z-score references. Univariate and multivariable logistic regressions were conducted to identify factors associated with child stunting. Results: Analysis showed that out % of 52,602 children under five, 40.0% were found stunted. Male children living in rural areas were more susceptible to stunting. Furthermore, stunting was more prevalent among children whose mothers had no education, were between 20 and 34, and were employed. In the multivariable logistic regression, male children (AOR=1.08, 95% CI[1.04-1.14], P<0.001) from rural areas (AOR=1.07, 95% CI [1.01-1.14], P=0.014), with the presence of diarrhea in the last two weeks (AOR=1.15, 95% CI [1.06-1.25], P<0.001), with mothers who have no education (AOR=1.57, 95% CI [1.42-1.73], P<0.001) or lower levels of education (Primary: AOR=1.35, 95% CI [1.21-1.51], P<0.001; Middle: AOR=1.29, 95% CI [1.15-1.45], P<0.001) had higher odds of stunting. Younger children aged <6 months (AOR=0.53, 95% CI [0.48-0.58], P<0.001) and 6-23 months (AOR=0.89, 95% CI [0.84-0.94], P<0.001), with mothers aged 35-49 years (AOR=0.78, 95% CI [0.66-0.92], P=0.003) had lower odds of stunting. At the household level, the odds of child stunting were higher in the poorest households (AOR=1.64, 95% CI [1.46-1.83], P<0.001), with ≥7 members (AOR=1.09, 95% CI [1.04-1.15], P<0.001), with no access to improved sanitation facilities (AOR=1.14, 95% CI [1.06-1.22], P<0.001) and experiencing severe food insecurity (AOR=1.07, 95% CI [1.01-1.14], P=0.02). Conclusion: Child stunting in Pakistan is strongly associated with various factors, including gender, age, diarrhea, residence, maternal age and education, household size, food and wealth status, and access to sanitation. To address this, interventions must be introduced to make locally available food and nutritious supplements more affordable, improve access to safe water and sanitation, and promote female education for long-term reduction in stunting rates.

Historically, viral hepatitis is a considerable public health problem in Central Asian countries, which may have worsened after dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n=1075). Participants, children and adults, were recruited from an outpatient clinic. Data were collected during face-to-face interviews. A blood sample (6 ml) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D and E). Poststratification weighting was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval: 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg positive participants, five (15%) were anti-HDV positive. Our study confirms that Kyrgyzstan remains a high endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

The unprecedented COVID-19 pandemic posed major challenges to local, regional, and global economies and health systems, and fast clinical diagnostic workflows were urgently needed to contain the spread of SARS-CoV-2. Here, we describe the platform and workflow established at the Cornell COVID-19 Testing Laboratory (CCTL) for high-throughput testing of clinical samples from the university and the surrounding community. This workflow enabled efficient and rapid detection, and successful control of SARS-CoV-2 infection on campus and its surrounding communities. Our cost-effective and fully automated workflow enabled testing of over 8,000 pooled samples per day and provided results for over 2 million samples. Automation of time- and effort-intensive sample processing steps such as accessioning and pooling increased laboratory efficiency. Customized software applications were developed to track and store samples, deconvolute positive pools, track and report results and for workflow integration from sample receipt to result reporting. Additionally, quality control dashboards and turn-around time tracking applications were built to monitor assay and laboratory performance. As infectious disease outbreaks pose a constant threat to both human and animal health, the highly effective workflow implemented at CCTL could be modeled to establish regional high-capacity testing hubs for infectious disease preparedness and emergency response.

Background: Although metastatic GCT is highly curable with initial cisplatin-based chemotherapy (CT), 20-30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remains lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. Methods: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. Results: Respondents included 30 staff; from 18 cancer centers across provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available for (70%) in 13 centers. HDCT regimen used included carboplatin and etoposide for 2 cycles (76% in 7 centers), 3 cycles (6% in two centers), and the TICE protocol (11%, in 2 centers). “Bridging” CDCT was used by 65% respondents. Post HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%) and sur-veillance only (6.3%). Conclusions: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.