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Background: Studies of the cystic fibrosis (CF) lung microbiome have consistently shown that lung function decline is associated with decreased microbial diversity due to the dominance of opportunistic pathogens. However, how this phenomenon is reflected in the metabolites and chemical environment of lung secretions remains poorly understood. Methods: Here we investigated the microbial and molecular composition of CF sputum samples using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry to determine their interrelationships and associations with clinical measures of disease severity. Results: The CF metabolome was found to exist in two states: one from patients with more severe disease that had higher molecular diversity and more Pseudomonas aeruginosa and the other from patients with better lung function having lower metabolite diversity and fewer pathogenic bacteria. The two molecular states were differentiated by the abundance and diversity of peptides and amino acids. Patients with severe disease and more pathogenic bacteria had higher levels of peptides. Analysis of the carboxyl terminal residues of these peptides indicated that neutrophil elastase and cathepsin G were responsible for their generation, and accordingly, these patients had higher levels of proteolytic activity from these enzymes in their sputum. The CF pathogen Pseudomonas aeruginosa was correlated with the abundance of amino acids and is known to primarily feed on them in the lung. Conclusions: In cases of severe CF lung disease, proteolysis by host enzymes creates an amino acid-rich environment that P. aeruginosa comes to dominate, which may contribute to the pathogen's persistence by providing its preferred carbon source.

Background: Studies of the cystic fibrosis (CF) lung microbiome have consistently shown that lung function decline is associated with decreased microbial diversity due to the dominance of opportunistic pathogens. However, how this phenomenon is reflected in the metabolites and chemical environment of lung secretions remains poorly understood. Methods: Here we investigated the microbial and molecular composition of CF sputum samples using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry to determine their interrelationships and associations with clinical measures of disease severity. Results: The CF metabolome was found to exist in two states: one from patients with more severe disease that had higher molecular diversity and more Pseudomonas aeruginosa and the other from patients with better lung function having lower metabolite diversity and fewer pathogenic bacteria. The two molecular states were differentiated by the abundance and diversity of peptides and amino acids. Patients with severe disease and more pathogenic bacteria had higher levels of peptides. Analysis of the carboxyl terminal residues of these peptides indicated that neutrophil elastase and cathepsin G were responsible for their generation, and accordingly, these patients had higher levels of proteolytic activity from these enzymes in their sputum. The CF pathogen Pseudomonas aeruginosa was correlated with the abundance of amino acids and is known to primarily feed on them in the lung. Conclusions: In cases of severe CF lung disease, proteolysis by host enzymes creates an amino acid-rich environment that P. aeruginosa comes to dominate, which may contribute to the pathogen's persistence by providing its preferred carbon source.

The main purpose of this study is to identify the effects of a good hotel design in a comprehensive manner. The systematic literature review method has been applied and the academic databases of the well-known publishers that are Science Direct, Taylor & Francis, Emerald, Sage and Wiley have been selected for advanced search. Twenty-eight research articles related to hotel design have been content analyzed. Findings of the content analysis indicate that a good hotel design can affect consumers’ emotions, self-brand connection, satisfaction, preference, behavioral intentions and loyalty, and employees’ aesthetic pleasure and well-being. Findings also demonstrate that a good design contributes to marketing and financial performances of hotels. Other contributions of a successful hotel design on the business are reduced staffing levels and maintenance costs, increased sales, greater efficiency, higher gross operating profit and the need for lower capital investment. Hotel design is closely related to sustainability, as well. Within this context, a framework identifying the effects of a good hotel design within micro and macro levels has been developed and discussed both theoretically and practically. Since the sub-purpose of the study is describing the current literature related to hotel design, some bibliometric indicators such as the journals publishing articles related to hotel design, distribution of the articles by years and number of authors studying on this topic, paper types of the articles (empirical or conceptual) and research methods (quantitative or qualitative) they applied have been examined to define more research gaps and future research directions. [ABSTRACT FROM AUTHOR]

Introduction: Cancer cells adopt a glycolytic phenotype to fulfill their energy needs in unfavorable conditions. In metabolic rewiring, cancer cells upregulate the expression of glycolytic pathway regulators including glucose transporter 1, hexokinase 2, and PKM2 (pyruvate kinase) into its M2 splice form. Among these regulators, PKM2 plays a major role in metabolic reprogramming and is overexpressed in various diseases, including cancer. Dimerization of PKM2 causes the generation of synthetic precursors from glycolytic intermediates, which are essential for cellular growth and cancer cell proliferation., Covered Areas: This article is focused on examining recent patents (2018-2023) on PKM2 activators, inhibitors and their biological and synthesis properties by using the advanced search service of the European Patent Office (EPO). Moreover, other databases including PubMed, Google Scholar and Elsevier were also examined for scientific data. On basis of their chemical structures, PKM2 activators and inhibitors are classified into pyrazole, pyrolidine-pyrazole, phenol, benzoxazine, isoselenazolo-pyridinium, phthalazine, and propiolylamide derivatives., Expert Opinion: Activating PKM2 reduces proliferation and development of cells by reducing the quantity of biomolecules needed for cell formation. PKM2 activators and inhibitors are highly effective in treating many cancer pathogens. It is important to find new, more potent and selective molecules for PKM2 activation and inhibition.

Background: The objective of this study is to investigate the antiproliferative, antioxidant, antimicrobial, and enzyme activity capacities and phytochemical compositions of Thymus pectinatus (TP), Thymus convolutus (TC), which are endemic to Türkiye. Quantitative analysis of phenolic compounds in the extracts was conducted using liquid chromatography-tandem mass spectrometry, targeting 53 phenolic compounds., Results: Rosmarinic acid, quinic acid, and cynaroside were identified as the major compounds, exhibiting quantitative variation in both extracts. The extracts had a high total phenolic content, with 113.57 ± 0.58 mg gallic acid equivalents (GAE)/g extract for TP and 130.52 ± 1.05 mg GAE/g extract for TC. Furthermore, although both extracts exhibited high total flavonoid content; the TP extract (75.12 ± 1.65 mg quercitin equivalents (QE)/g extract) displayed a higher flavonoid content than the TC extract (30.24 ± 0.74 mg QE/g extract) did. The extracts had a promising antiproliferative effect on C6, HeLa, and HT29 cancer cell lines with a less cytotoxic effect (10.5-14.2%) against normal cells. Both extracts exhibited very potent inhibitory activity against the xanthine oxidase enzyme, with half-maximal inhibitory concentration values of respectively 2.07 ± 0.03 μg mL -1 and 2.76 ± 0.06 μg mL -1 and moderate activity against tyrosinase and α-glucosidase. Docking simulations proved that rosmarinic acid and cynaroside, the major components of the extracts, were the most potent inhibitors of xanthine oxidase. According to antimicrobial activity results, the TC extract exhibited moderate activity against Staphylococcus aureus, and the TP extract had strong activity against both Enterococcus faecium and S. aureus., Conclusion: These findings emphasize the beneficial effects of the two endemic Thymus species on human health and suggest their potential use as plant-derived bioactive agents. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

A novel Schiff base namely 3,5-di-tert-butyl-6-((2-(perfluorophenyl)hydrazono)methyl)phenol was successfully synthesized and characterized using FT-IR and 1 H-NMR, 13 C-NMR, and 19 F-NMR. The crystal structure analysis of the Schiff base compound was also characterized with single crystal X-ray diffraction studies and supported the spectroscopic results. The cytotoxicity, anti-bacterial properties, and enzyme inhibition of the compound were also investigated. The molecular docking studies were performed in order to explain the interactions of the synthesized compound with target enzymes. The newly synthesized hydrazone derivative Schiff base compound showed high cellular toxicity on MCF-7 and PC-3 cells. Also, this compound caused low antibacterial effect on E. coli and S. aureus. Besides, the compound exhibited the inhibitory effect against pancreatic cholesterol esterase and carbonic anhydrase isoenzyme I, II with IC 50 values 63, 99, and 188 μM, respectively. Consequently, it has been determined that the prepared Schiff base is an active compound in terms of cytotoxicity, enzyme inhibition, and anti-bacterial properties. These results provide preliminary information for some biological features of the compound and can play a major role in drug applications of the Schiff base compound., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Introduction: Electronic personal health record (e-PHR) system enables individuals to access their health information and manage it themselves. It helps patient engagement management of health information that is accessed and shared with their healthcare providers using the platform. This improves individual healthcare through the exchange of health information between patients and healthcare providers. However, less is known about e-PHRs among healthcare professionals., Objective: Therefore, this study aimed to assess Health professionals' Knowledge and attitude and its associated factors toward e-PHR at the teaching hospital in northwest Ethiopia., Methods: An institution-based cross-sectional study design was used to determine healthcare professionals' knowledge and attitude and their associated factors toward e-PHR systems in teaching hospitals of Amhara regional state, Ethiopia, from 20 July to 20 August 2022. Pretested structured self-administered questionnaires were used to collect the data. Descriptive statistic was computed based on sociodemographic and other variables presented in the form of table graphs and texts. Bivariable and multivariable logistic analyses were performed with an adjusted odds ratio (AOR) and 95% CI to identify predictor variables., Result: Of the total study participants, 57% were males and nearly half of the respondents had a bachelor's degree. Out of 402 participants, ~65.7% [61-70%] and 55.5% [50-60%] had good knowledge and favorable attitude toward e-PHR systems, respectively. Having a social media account 4.3 [AOR = 4.3, 95% CI (2.3-7.9)], having a smartphone 4.4 [AOR = 4.4, 95% CI (2.2-8.6)], digital literacy 8.8 [(AOR = 8.8, 95% CI (4.6-15.9)], being male 2.7 [AOR = 2.7, 95% CI (1.4-5.0)], and perceived usefulness 4.5 [(AOR = 4.5, 95% CI (2.5-8.5)] were positively associated with knowledge toward e-PHR systems. Similarly, having a personal computer 1.9 [AOR = 1.9, 95% CI (1.1-3.5)], computer training 3.9 [AOR = 3.9, 95% CI (1.8-8.3)], computer skill 19.8 [AOR = 19.8, 95% CI (10.7-36.9)], and Internet access 6.0 [AOR = 6.0, 95% CI (3.0-12.0)] were predictors for attitude toward e-PHR systems., Conclusion: The findings from the study showed that healthcare professionals have good knowledge and a favorable attitude toward e-PHRs. Providing comprehensive basic computer training to improve healthcare professionals' expectation on the usefulness of e-PHR systems has a paramount contribution to the advancement of their knowledge and attitude toward successfully implementing e-PHRs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wubante, Tegegne, Melaku, Mengiste, Fentahun, Zemene, Fikadie, Musie, Keleb, Bewoketu, Adem, Esubalew, Mihretie, Ferede and Walle.)

Background: Transfusion transmissible infections (TTIs) are among the greatest threats to blood safety for recipients and the economy of the developed and developing countries. Therefore, the study of the prevalence and trends of TTIs is important to assess for its prevention and control strategies., Objectives: This study aimed to evaluate the prevalence and trend of transfusion transmissible infections among blood donors at the Bule Hora Blood Bank, West Guji, Ethiopia, from 2019 to 2021., Method: A retrospective study was conducted on all blood donors at the Bule Hora Blood Bank from 2019-2021. The data of 4193 blood donors were collected from the databank (logbook) of the blood bank using a checklist. Data were analyzed by using SPSS software, and the chi-square test was used to assess the association between independent variables and transfusion transmission infection. Different types of graphs, charts and tables were used to present the data. P values less than .05 were considered statistically significant., Result: The overall transfusion transmissible infection among blood donors was 4.6% (192). Out of the tested blood donors, 86 (2.1%) were found to be seropositive for hepatitis B virus. The trend analysis showed that the positivity rates of the screened tests were 28 (4.72%) in 2019, decreased to 77 (4.26%) in 2020 and increased to 87 (4.86%) in 2021. The sex of blood donors was significantly associated with TTIs ( P value = .021), and the positivity rates were significantly higher among male than female blood donors. The study results showed that overall seropositivity rates increased along the age groups of the donors., Conclusion: The study reported a moderate prevalence of transfusion transmissible infections among blood donors visiting the Bule hora blood bank. Health education about the transmission, prevention and create awareness of TTIs should be strengthened by the government and non-government organization., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Aldose reductase (AR) is the first enzyme of the polyol pathway that has physiological importance under hyperglycaemic conditions. The article has been focussed on AR enzyme inhibition by selected compounds. For this purpose, the in vitro inhibitory effects of various compounds on commercially available recombinant human AR (rAR) enzyme activity were investigated. The IC 50 values of compounds on rAR inhibition effect were found for 6-hydroxy flavone, syringic acid, diosmetin, 6-fluoroflavone, 7-hydroxy-4'-nitroisoflavone, myricetin as 2.05, 2.97, 15.75, 16.1, 49.5, and 63 µM, respectively. 6-Hydroxy flavone and syringic acid competitively inhibited rAR with respect to the NADPH with K i values 0.509 ± 0.036 and 0.842 ± 0.012 µM. In addition, docking studies were performed to evaluate the potential enzyme binding positions of the compounds. Our in vitro and in silico results indicated that the 6-hydroxy flavone may be a good lead compound in the development of AR inhibitors to prevent diabetic complications.

Objective: Radiation therapy is commonplace for cancer treatment but often results in fibrosis and atrophy of surrounding soft tissue. Decellularized adipose matrices (DAMs) have been reported to improve these soft tissue defects through the promotion of adipogenesis. These matrices are decellularized by a combination of physical, chemical, and enzymatic methods to minimize their immunologic effects while promoting their regenerative effects. In this study, we aimed at exploring the regenerative ability of a DAM (renuva ® ; MTF biologics, Edison, NJ) in radiation-induced soft tissue injury. Approach: Fresh human lipoaspirate or DAM was injected into the irradiated scalp of CD-1 nude mice, and volume retention was monitored radiographically over 8 weeks. Explanted grafts were histologically assessed, and overlying skin was examined histologically and biomechanically. Irradiated human skin was also evaluated from patients after fat grafting or DAM injection. However, integrating data between murine and human skin in all cohorts is limited given the genetic variability between the two species. Results: Volume retention was found to be greater with fat grafts, though DAM retention was, nonetheless, appreciated at irradiated sites. Improvement in both mouse and human irradiated skin overlying fat and DAM grafts was observed in terms of biomechanical stiffness, dermal thickness, collagen density, collagen fiber networks, and skin vascularity. Innovation: This is the first demonstration of the use of DAMs for augmenting the regenerative potential of irradiated mouse and human skin. Conclusions: These findings support the use of DAMs to address soft tissue atrophy after radiation therapy. Morphological characteristics of the irradiated skin can also be improved with DAM grafting.

Objective: Xenografts of human skin in immunodeficient mice provide a means of assessing human skin physiology and its response to wounding. Approach: We describe a novel xenograft model using full-thickness human neonatal foreskin to examine human skin wound repair. Full-thickness 8 mm human neonatal foreskin biopsies were sutured into the dorsum of NOD scid gamma (NSG; NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ) pups as subcutaneous grafts. At postnatal day 21 the subcutaneous grafts were exposed to cutaneous grafts. Following maturation of 2 months, xenografts were then wounded with 5 mm linear incisions and monitored until postwound day (PWD) 14 to study skin repair and fibrosis. To explore whether our model can be used to test the efficacy of topical therapies, wounded xenografts were injected with antifibrotic fibroblast growth factor 2 (FGF2) for the first four consecutive PWDs. Xenografts were harvested for analysis by histology and fluorescence-activated cell sorting (FACS). Results: Xenografts were successfully engrafted with evidence of mouse-human anastomoses and resembled native neonatal foreskin at the gross and microscopic level. Wounded xenografted skin scarred with human collagen and an expansion of CD26-positive human fibroblasts. Collagen scar was quantitated by neural network analysis, which revealed distinct clustering of collagen fiber networks from unwounded skin and wounded skin at PWD7 and PWD14. Collagen fiber networks within FGF2-treated wounds at PWD14 resembled those in untreated wounded xenografts at PWD7, suggesting that FGF2 treatment at time of wounding can reduce fibrosis. Innovation and Conclusion: This novel xenograft model can be used to investigate acute fibrosis, fibroblast heterogeneity, and the efficacy of antifibrotic agents during wound repair in human skin.

Anopheles species' larval habitats are diversified and season dependent. Anopheles larvae can be found at different habitats and their preference may vary seasonally. Knowledge of species diversity and distribution helps plan malaria control interventions. Anopheles larvae were sampled using the WHO standard 350 ml dipper from breeding habitats of irrigation, pond, sewage, stream, and swamp. The collected sample larvae were identified microscopically to species using morphological keys. Among Anopheles species recorded, Anopheles gambiae complex was the most abundant followed by Anopheles christyi, Anopheles cinereus, Anopheles demeilloni , and Anopheles pharoensis in descending order. Anopheles species occurred more in January than in other months of the study period and less in March and April. For any particular mosquito species, larval abundance did not significantly vary between the habitats; in other words, all habitats contributed equally. In this study, we confirmed that Anopheles mosquito larval population varied more with respect to species than to habitats and months. Interventions could be launched targeting each habitat; during the month, numbers were high., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Yelfwagash Asmare et al.)

β-Lactamases are enzymes that catalyze the hydrolysis of the β-lactam ring, resulting in loss of function in β-lactam antibiotics. In this report, the inhibition of β-lactamase enzyme by group-based selected aromatic compounds, especially containing flavone ring, was investigated in vitro and in silico . For this purpose, the inhibitory effects of 7-hydroxy-4'-nitroisoflavone, myricetin, formononetin, 3-methylflavone-8-carboxylic acid, 6-fluoroflavone and caffeic acid on β-lactamase from Bacillus cereus enzyme activity were investigated. IC 50 values of these compounds were determined to range from 53 to 346 mM. 7-hydroxy-4'-nitroisoflavone, formononetin and myricetin inhibited the enzyme with the K i values of 27.65 ± 4.22, 58.92 ± 12.83 and 67.42 ± 5.77 µM, respectively. To evaluate the potential enzyme binding positions of the active compounds, docking studies were performed. In addition to kinetic and in silico studies, the synergistic effects of the compounds with penicillin on Klebsiella pneumoniae (ATCC 700603) and Escherichia coli (ATCC 35128) were tested in vitro . Our results indicated that 7-hydroxy-4'-nitroisoflavone, 3-methylflavone-8-carboxylic acid and myricetin that combined with penicillin completely precluded the bacterial growth.Communicated by Ramaswamy H. Sarma.

Background: Striae distensae are common disfiguring cutaneous lesions but lack effective treatments because of an incomplete understanding of their pathophysiology. Dermal fibroblasts likely play an important role. The authors investigate the cellular-molecular features distinguishing fibroblasts from human striae distensae and normal skin. The authors also develop a mouse model of striae distensae., Methods: Human striae distensae and normal skin samples were compared for tensile strength and histologic structure. Fibroblasts from striae distensae and normal skin were isolated by fluorescence-activated cell sorting for gene expression analysis. Immunofluorescence staining and fluorescence-activated cell sorting were used to confirm gene expression data at the protein level. A mouse model of striae distensae formation was created by administering corticosteroids and mechanically loading the dorsal skin., Results: Human striae distensae exhibited reduced tensile strength, more disordered collagen fibers, and epidermal atrophy compared to human normal skin. There were 296 up-regulated genes in striae distensae fibroblasts, including the profibrotic lineage and surface marker CD26. Up-regulated genes were involved in profibrotic and mechanoresponsive signaling pathways (TGFβ and FAK-PI3-AKT-signaling). In contrast, 571 genes were down-regulated, including CD74 and genes of the AMPK pathway. Increased CD26 and decreased CD74 expression was confirmed by fluorescence-activated cell sorting and immunofluorescence. Similar cutaneous histologic and gene expression changes were induced in hypercortisolemic mice by mechanically loading the dorsal skin., Conclusions: Fibroblasts from human striae distensae exhibit increased profibrotic and decreased antifibrotic signaling. CD26 and CD74 are promising surface markers that may be targeted therapeutically. The authors' mouse model of striae distensae can be used as a platform to test the efficacy of potential therapeutic agents., Clinical Relevance Statement: Striae distensae are common disfiguring cutaneous lesions whose etiology remains elusive, which has hindered development of effective treatment strategies. Dermal fibroblasts likely play an important role. The authors sought to elucidate the key cellular-molecular pathways distinguishing fibroblasts in striae distensae from those in normal skin., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Introduction: In Ethiopia, more than four million children are anticipated to live under particularly difficult circumstances. Street children are subject to violence, a lack of health care, and a lack of education. Which denies them the right to live in a secure environment and exposes them to different health problems. Currently, little is known about the prevalence of Streetism, including health conditions. Therefore, this study was aimed to assess the health status of street children and determinants of Streetism., Methods: Mixed methods (sequential) were employed from February 1 to 28, 2021. Quantitative cross-sectional study design and phenomenological qualitative designs were applied. Overall, 220 street children were involved in the study. The most common reason that forced the children to resort to a street way of life is to look for a job and quarreled with parents. The data were collected using interviews methods. Chi-square test and multiple binary logistic regression were applied to examine the variations among variables with the health status of street children. Qualitative data were analyzed using the thematic analysis technique., Results: The study included a total of 220 street children. As to the quantitative study, the majority of study participants (92.73%) drank alcohol regularly. Depression (39.22%) and peer pressure (43.14%) were the most common initiation causes of drinking alcohol. According to a qualitative study report, "Street children are mostly affected by the communicable disease" and… They are addicted to substances like benzene" which had a profound effect on their health." Furthermore, the study discovered a statistically significant association between respondents' health status and sociodemographic characteristics (age and educational status), job presence, and drug use., Conclusion: This study identified the factors that drove street children to live on the streets, such as the inability to find work and disagreements with their parents. The majority of the street children were affected by preventable and treatable diseases. Unfortunately, almost all street children reported drinking alcohol, which exposed them to a variety of health problems. In general, the study discovered that street children require immediate attention. Decision-makers and academicians should collaborate to develop a plan for these children's health and social interventions., Competing Interests: The authors have declared that no competing interests exist.

Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, antibacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Radiation therapy is effective for cancer treatment but may also result in collateral soft tissue contracture, contour deformities, and non-healing wounds. Autologous fat transfer has been described to improve tissue architecture and function of radiation-induced fibrosis and these effects may be augmented by enrichment with specific adipose-derived stromal cells (ASCs) with enhanced angiogenic potential. CD34+CD146+, CD34+CD146-, or CD34+ unfractionated human ASCs were isolated by flow cytometry and used to supplement human lipoaspirate placed beneath the scalp of irradiated mice. Volume retention was followed radiographically and fat grafts as well as overlying soft tissue were harvested after eight weeks for histologic and biomechanical analyses. Radiographic evaluation revealed the highest volume retention in fat grafts supplemented with CD34+CD146+ ASCs, and these grafts were also found to have greater histologic integrity than other groups. Irradiated skin overlying CD34+CD146+ ASC-enriched grafts was significantly more vascularized than other treatment groups, had significantly less dermal thickness and collagen deposition, and the greatest improvement in fibrillin staining and return of elasticity. Radiation therapy obliterates vascularity and contributes to scarring and loss of tissue function. ASC-enrichment of fat grafts with CD34+CD146+ ASCs not only enhances fat graft vascularization and retention, but also significantly promotes improvement in overlying radiation-injured soft tissue. This regenerative effect on skin is highly promising for patients with impaired wound healing and deformities following radiotherapy., (© 2021 John Wiley & Sons Ltd.)

Objective: To assess quality of antenatal care-linked to HIV counseling and testing as an intervention for prevention of mother-to-child transmission at government health facilities in Harar Town, Eastern Ethiopia, 2020., Methods: Institutional-based cross-sectional study was done from 1 February to 30 February 2020 by applying quantitative method conducting in government health facilities in Harar town, Eastern, Ethiopia. A total of 422 participants were recruited from four governmental hospitals in Harar Town. Simple random sampling method was used to select the participants. Data were collected by three nurses selected from prospected hospitals. The collected data were cleaned, checked for quality, coded, and analyzed using "Software package Social Science, version 20" computer program., Result: From a total of 422 participants, 348 (82.5%) were satisfied with the counseling room's privacy, and having pre-test and post-test counseling by the same person provided comfort for 357 (98.9%) of clients. Three hundred eighty-nine (92.2%) felt comfortable with the counselors' client handling/respect; 386 (91.5%) were satisfied with technical competence of the counselors. About a quarter (25.4%) of clients had no discussion of prevention of mother-to-child transmission at all, and the majority (68.2%) comprehended that HIV counseling and testing could benefit prevention of mother-to-child transmission., Conclusion: Exit interview revealed that the basic topics were covered in most of the pre- and/or post-test sessions, and the majority of those counseled comprehended the information; however, nearly a quarter of the clients did not understand why they were offered HIV counseling and testing particularly during their pregnancy time., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Pathologic skin scarring presents a vast economic and medical burden. Unfortunately, the molecular mechanisms underlying scar formation remain to be elucidated. We used a hypertrophic scarring (HTS) mouse model in which Jun is overexpressed globally or specifically in α-smooth muscle or collagen type I–expressing cells to cause excessive extracellular matrix deposition by skin fibroblasts in the skin after wounding. Jun overexpression triggered dermal fibrosis by modulating distinct fibroblast subpopulations within the wound, enhancing reticular fibroblast numbers, and decreasing lipofibroblasts. Analysis of human scars further revealed that JUN is highly expressed across the wide spectrum of scars, including HTS and keloids. CRISPR-Cas9–mediated JUN deletion in human HTS fibroblasts combined with epigenomic and transcriptomic analysis of both human and mouse HTS fibroblasts revealed that JUN initiates fibrosis by regulating CD36 . Blocking CD36 with salvianolic acid B or CD36 knockout model counteracted JUN-mediated fibrosis efficacy in both human fibroblasts and mouse wounds. In summary, JUN is a critical regulator of pathological skin scarring, and targeting its downstream effector CD36 may represent a therapeutic strategy against scarring.

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Işkın" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, β-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the N α Fmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with N α Fmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the N α Fmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Decreased intake of food or fluid causes dehydration in hospitalized adult patients. This has led to a negative impact on patients and increased the morbidity and mortality rate at the Princess Noorah Oncology Center, where patients with advanced cancer who suffer from dehydration have been treated with parenteral fluids until the date of discharge from the hospital., Objective: The objective of this pilot study is to assess the effectiveness and safety of hypodermoclysis (HDC) to close the gap of treatment for home-based palliative patients with cancer., Method: During home visits, the home health care (HHC) nurse assessed these patients through history and physical examination for dehydration. Our team also incorporated the Edmonton Symptom Assessment System revised (ESAS-r) Scale in the assessment of these patients' symptoms. Informed consent has been obtained from the patient and the caregiver. The trained nurses initiated the subcutaneous infusion. The caregivers monitored it and disconnected it when completed. The study population consists of palliative patients with advanced cancer under the services of palliative care. Effectiveness and safety have been assessed using the ESAS-r scale., Results: A total of 25 (92.6%) HDC treatments were successfully completed for nine patients (seven males and two females). One female patient had only one session because her health had deteriorated for reasons other than dehydration and was transferred to the hospital. No serious side effects were observed. One (3.6%) patient developed redness at the site of cannula insertion. The mean duration of the infusions was 8.44 hours. The median age was 70 years., Conclusion: This study has concluded that HDC is effective, safe, and can enhance the patient's comfort level without the need for hospitalization. The fact that HDC can be administered at home with minimum equipment and technical support makes it an ideal option in several countries with varied income settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Adem et al.)

Fibroblast heterogeneity has been shown within the unwounded mouse dorsal dermis, with fibroblast subpopulations being identified according to anatomical location and embryonic lineage. Using lineage tracing, we demonstrate that paired related homeobox 1 (Prrx1)-expressing fibroblasts are responsible for acute and chronic fibroses in the ventral dermis. Single-cell transcriptomics further corroborated the inherent fibrotic characteristics of Prrx1 fibroblasts during wound repair. In summary, we identify and characterize a fibroblast subpopulation in the mouse ventral dermis with intrinsic scar-forming potential., Competing Interests: Declaration of Interests H.Y.C. is a co-founder of Accent Therapeutics and Boundless Bio and an advisor to 10x Genomics, Arsenal Bioscience, and Spring Discovery., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Fat grafting can reduce radiation-induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose-derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74- and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF-β3) and decreased levels of TGF-β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74- or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation-induced fibrosis., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Fat grafting is a surgical technique able to reconstruct and regenerate soft tissue. The adipose-derived stromal cells (ASCs) within the stromal vascular fraction are believed to drive these beneficial effects. ASCs are increasingly recognized to be a heterogeneous group, comprised of multiple stem and progenitor subpopulations with distinct functions. We hypothesized the existence of an ASC subpopulation with enhanced angiogenic potential. Human ASCs that were CD34+CD146+, CD34+CD146-, or CD34+ unfractionated (UF) were isolated by flow cytometry for comparison of expression of proangiogenic factors and endothelial tube-forming potential. Next, lipoaspirate was enriched with either CD34+CD146+, CD34+CD146-, CD34+ UF ASCs, or was not enriched, and grafted beneath the scalp skin of immunodeficient CD-1 Nude mice (10 000 cells/200 μL/graft). Fat retention was monitored radiographically more than 8 weeks and fat grafts were harvested for histological assessment of quality and vascularization. The CD34+CD146+ subpopulation comprised ~30% of ASCs, and exhibited increased expression of vascular endothelial growth factor and angiopoietin-1 compared to CD34+CD146- and CD34+ UF ASCs, and increased expression of fibroblast growth factor-2 compared to CD34+CD146- ASCs. The CD34+CD146+ subpopulation exhibited enhanced induction of tube-formation compared to CD34+CD146- ASCs. Upon transplantation, fat enriched CD34+CD146+ ASCs underwent less resorption and had improved histologic quality and vascularization. We have identified a subpopulation of CD34+ ASCs with enhanced angiogenic effects in vitro and in vivo, likely mediated by increased expression of potent proangiogenic factors. These findings suggest that enriching lipoaspirate with CD34+CD146+ ASCs may enhance fat graft vascularization and retention in the clinical setting., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Radiation therapy can result in pathological fibrosis of healthy soft tissue. The iron chelator deferoxamine (DFO) has been shown to improve skin vascularization when injected into radiated tissue prior to fat grafting. Here, we evaluated whether topical DFO administration using a transdermal drug delivery system prior to and immediately following irradiation (IR) can mitigate the chronic effects of radiation damage to the skin. CD-1 nude immunodeficient mice were split into four experimental groups: (1) IR alone (IR only), (2) DFO treatment for two weeks after recovery from IR (DFO post-IR), (3) DFO prophylaxis with treatment through and post-IR (DFO ppx), or (4) no irradiation or DFO (No IR). Immediately following IR, reactive oxygen species and apoptotic markers were significantly decreased and laser doppler analysis revealed significantly improved skin perfusion in mice receiving prophylactic DFO. Six weeks following IR, mice in the DFO post-IR and DFO ppx groups had improved skin perfusion and increased vascularization. DFO-treated groups also had evidence of reduced dermal thickness and collagen fiber network organization akin to non-irradiated skin. Thus, transdermal delivery of DFO improves tissue perfusion and mitigates chronic radiation-induced skin fibrosis, highlighting a potential role for DFO in the treatment of oncological patients.

Proteases are enzymes that cleave proteins and are crucial to physiological processes such as digestion, blood clotting, and wound healing. Unregulated protease activity is a biomarker of several human diseases. Synthetic peptides that are selectively hydrolyzed by a protease of interest can be used as reporter substrates of unregulated protease activity. We developed an activity-based protease sensor by immobilizing magnetic nanoparticles (MNPs) to the surface of a giant magnetoresistive spin-valve (GMR SV) sensor using peptides. Cleavage of these peptides by a protease releases the magnetic nanoparticles resulting in a time-dependent change in the local magnetic field. Using this approach, we detected a significant release of MNPs after 3.5 minutes incubation using just 4 nM of the cysteine protease, papain. In addition, we show that proteases in healthy human urine do not release the MNPs, however addition of 20 nM of papain to the urine samples resulted in a time-dependent change in magnetoresistance. This study lays the foundation for using GMR SV sensors as a platform for real-time, quantitative detection of protease activity in biological fluids.

The aim of this study was to explore the therapeutic effects of fat grafting on radiation-induced hind limb contracture. Radiation therapy (RT) is used to palliate and/or cure a range of malignancies but causes inevitable and progressive fibrosis of surrounding soft tissue. Pathological fibrosis may lead to painful contractures which limit movement and negatively impact quality of life. Fat grafting is able to reduce and/or reverse radiation-induced soft tissue fibrosis. We explored whether fat grafting could improve extensibility in irradiated and contracted hind limbs of mice. Right hind limbs of female 60-day-old CD-1 nude mice were irradiated. Chronic skin fibrosis and limb contracture developed. After 4 weeks, irradiated hind limbs were then injected with (a) fat enriched with stromal vascular cells (SVCs), (b) fat only, (c) saline, or (d) nothing (n = 10/group). Limb extension was measured at baseline and every 2 weeks for 12 weeks. Hind limb skin then underwent histological analysis and biomechanical strength testing. Irradiation significantly reduced limb extension but was progressively rescued by fat grafting. Fat grafting also reduced skin stiffness and reversed the radiation-induced histological changes in the skin. The greatest benefits were found in mice injected with fat enriched with SVCs. Hind limb radiation induces contracture in our mouse model which can be improved with fat grafting. Enriching fat with SVCs enhances these beneficial effects. These results underscore an attractive approach to address challenging soft tissue fibrosis in patients following RT., (©AlphaMed Press 2019.)

Background: In patients who are liable to the risk of pulmonary aspiration, airway control is the primary and first concern for the anesthetists both in emergency and elective surgical procedures. Rapid sequence induction is universally required in any occasion of emergent endotracheal intubation needed for unfasted patients or patients' fasting status is unknown., Methods: institutional-based prospective observational study was conducted from December 2017 to January 2018 in all elective and emergency adult or pediatric patients with a risk of pulmonary aspiration who were operated under general anesthesia with rapid sequence induction and intubation during the audit period., Result: A total of 35 patients were operated during the study period. Of these, 31 (88.57%) patients were adults and 4 (11.43%) patients were pediatrics. Most of the patients were emergency (29 (82.857%)), and the rest were elective (6 (17.142%))., Conclusion: Most anesthetists were good at preparing all available monitoring and drugs, making sure that IV line is well-functioning, preparing suction with a suction machine, preoxygenation, application of cricoid pressure, and checking the position of the ETT after intubation was performed. Preparing difficult airway equipment during planning of rapid sequence induction and intubation, giving roles and told to proceed their assigned role for the team, attempt to ventilate with a small tidal volume, and routine use of bougie or stylet to increase the chance of success of intubation needed improvement., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2019 Mamaru Mollalign et al.)

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long-term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level., (© 2018 Wiley Periodicals, Inc.)

The impact of the introduction and advancement in communication technology in recent years on exposure level of the population is largely unknown. The main aim of this study is to systematically review literature on the distribution of radiofrequency electromagnetic field (RF-EMF) exposure in the everyday environment in Europe and summarize key characteristics of various types of RF-EMF studies conducted in the European countries. We systematically searched the ISI Web of Science for relevant literature published between 1 January 2000 and 30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot measurements, personal measurement with trained researchers and personal measurement with volunteers. Twenty-one published studies met our eligibility criteria of which 10 were spot measurements studies, 5 were personal measurement studies with trained researchers (microenvironmental), 5 were personal measurement studies with volunteers and 1 was a mixed methods study combining data collected by volunteers and trained researchers. RF-EMF data included in the studies were collected between 2005 and 2013. The mean total RF-EMF exposure for spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29 and 0.54 V/m, respectively. In the personal measurements studies with trained researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m in "Outdoor". In the personal measurement studies with volunteers, the population weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in "Outdoor". Among all European microenvironments in "Transportation", the highest mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels are substantially below regulatory limits. We found considerable differences between studies according to the type of measurements procedures, which precludes cross-country comparison or evaluating temporal trends. A comparable RF-EMF monitoring concept is needed to accurately identify typical RF-EMF exposure levels in the everyday environment.

Introduction: It is well known that cancer cells have an altered metabolism both to meet the energy needs and to provide initial molecules for the synthesis of macromolecules. To cope with the new metabolic state, different forms of certain enzymes are expressed in extreme amounts. These enzymes are seen as very attractive targets to deal with cancer. Pyruvate kinases isoenzyme M2 (PKM2) is a key enzyme that determines whether glucose is used for energy or synthesis of biosynthetic molecules. The dimeric form of PKM2 main form in several cancer cells serves the formation of synthetic precursors required for the cell growth and proliferation from glycolytic intermediates., Areas Covered: This article reviews appropriate publications on PKM2 activators from the points of view of synthesis and biological activities between 2011-2017. Herein, based on the chemical structure, PKM2 activators are classified into sulfonamide, phenolic, carboxamide and pyridopyrimidinone derivatives., Expert Opinion: PKM2 activation inhibits cell growth and proliferation by decreasing a number of biomolecules required for cell building. Therefore; PKM2 activators are considered as an ideal drug for or the treatment of many cancer pathogens. It is necessary to discover new, more active and selective compounds for PKM2 activation.

G6PD, 6PGD and GR have been purified separately in the single step from rat lung using 2', 5'-ADP Sepharose 4B affinity chromatography. The purified enzymes showed a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weights of the enzymes were estimated to be 134 kDa for G6PD, 107 kDa for 6PGD and 121 kDa for GR by Sephadex G-150 gel filtration chromatography, and the subunit molecular weights was respectively found to be 66, 52 and 63 kDa by SDS-PAGE. Optimum pH, stable pH, optimum ionic strength, optimum temperature, KM and Vmax values for substrates were determined. Product inhibition studies were also performed. The enzymes were inhibited by levofloxacin, furosemide, ceftazidime, cefuroxime and gentamicin as in vitro with IC50 values in the range of 0.07-30.13 mM. In vivo studies demonstrated that lung GR was inhibited by furosemide and lung 6PGD was inhibited by levofloxacin.

The present study was aimed to investigate characterization and purification of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase from rat heart and the inhibitory effect of three drugs. The purification of the enzymes was performed using 2',5'-ADP sepharose 4B affinity material. The subunit and the natural molecular weights were analyzed by SDS-PAGE and gel filtration. Biochemical characteristics such as the optimum temperature, pH, stable pH, and salt concentration were examined for each enzyme. Types of product inhibition and Ki values with Km and Vmax values of the substrates and coenzymes were determined. According to the obtained Ki and IC50 values, furosemide, digoxin, and dopamine showed inhibitory effect on the enzyme activities at low millimolar concentrations in vitro conditions. Dopamine inhibited the activity of these enzymes as competitive, whereas furosemide and digoxin inhibited the activity of the enzyme as noncompetitive., (© 2016 Wiley Periodicals, Inc.)

Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of <60 μM. IC50 values of compounds 3-8 were calculated as 134, 415, 145, 163, 295 μM, and 3.5 mM, respectively. The molecules 9-12 showed an activation effect with values of AC50 of less than 90 μM. The IC50 values of the derivatives 13-17 were calculated as 115, 150, 200, 221, and 275 μM, respectively. The results show that catechin derivatives can be probably used as lead compounds for the design of PKM2 enzyme activators and inhibitors., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pyruvate kinase isoenzyme M2 (PKM2) is one of the most important control point enzyme in glycolysis pathway. Hence, its inhibitors and activators are currently considered as the potential anticancer agents. The effect of 28 polyphenolic compounds on the enzyme activity was investigated in vitro. Among these compounds, neoeriocitrin, (-)-catechin gallate, fisetin, (±)-taxifolin and (-)-epicatechin have the highest inhibition effect with IC50 value within 0.65-1.33 µM range. Myricetin and quercetin 3-β-D-glucoside exhibited the highest activation effect with 0.51 and 1.34 µM AC50 values, respectively. Twelve of the compounds showed inhibition effect within 7-38 µM range of IC50 value. Sinapinic acid and p-coumaric acid showed an activation effect with 26.2 and 22.2 µM AC50 values, respectively. The results propose that the polyphenolics may be the potential PKM2 inhibitors/activators, and they may be used as lead compounds for the synthesis of new inhibitors or activators of this enzyme.

Dihydrofolate reductase (DHFR) plays a fundamental role in cellular metabolism and cell growth. Inhibition of this enzyme will cause a decrease in the amount of folate that occurs in many metabolic processes, and the deficiency of which may cause various diseases. This study investigated the effects of some drugs and phenolic compounds on DHFR activity in vitro. To determine the inhibitory effect of compounds, enzyme activity was measured with a final concentration of an inhibitor ranging from 10 μM to 51 mM. DHFR was inhibited effectively by naringin, ferulic acid, and levofloxacin with IC50 values under 660 μM. Syringic acid, cefepime, ceftizoxime, cefazolin, ceftriaxone, and ceftazidime exhibited inhibitory effects on the enzyme activity with IC50 values in the range of 3.840-30.224 mM. K(i) constants were calculated using the Cheng-Prusoff equation. K(i) constants calculated in the range of 0.009-2.024 mM with respect to nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and in the range of 0.060-5.830 mM about FH2., (© 2014 Wiley Periodicals, Inc.)

PKM2 is an important target for designing anticancer drug. Inhibitors and activators of this enzyme are suitable molecules for use in treating cancer. The aim of the present study was to investigate the effect of certain flavones on PKM2. Apigenin, wogonin, flavone, 3-hydroxyflavone, 5-hydroxyflavone, 6-hydroxyflavone, and 7-hydroxyflavone effectively inhibited PKM2, with IC50 in the range of 0.99-2.120 μM. The kinetic study indicated that these compounds acted as noncompetitive with Ki values of 3.53-5.67 μM toward phosphoenolpyruvate. Scutellarin and tangeritin demonstrated strong activation effect with AC50 values < 2 μM. Diosmetin, baicalin, baicalein, and luteolin showed an intermediate-level activator effect. These results demonstrate that flavone and their analogs could serve as leading compounds to develop new potent and selective inhibitor and activator for PKM2., (© 2014 Wiley Periodicals, Inc.)

Polyphenols are the important compounds that have various bioactivities. They constitute vital active agents of not only daily diet but also natural medicines that are used traditionally. It is generally considered that they are safe because they are natural. In some conducted studies, different negative effects of these compounds were mentioned. Twelve phenolic compounds have been assayed to determine the effect of inhibition on glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro studies, the enzymes were purified from human erythrocytes using 2',5'-ADP Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid, ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin, only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect. Chlorogenic acid, p-coumaric acid, and syringic acid did not exhibit an effect on the activity of the two enzymes., (© 2014 Wiley Periodicals, Inc.)

Background: Sarcomatoid lung carcinomas are unusual, and reports from small single institution case series suggest poor survival rates. We sought to study the clinical characteristics of this form of non-small cell lung cancer using the Surveillance Epidemiology, End Results database., Methods: The Surveillance, Epidemiology, and End Results database was queried for respiratory tract malignancies of sarcomatoid histology. The demographic information and oncologic characteristics of this population were examined. A propensity score-matched analysis of patients was performed to test the hypothesis that patients with sarcomatoid cancers undergoing lobectomies perform worse that those with other non-small cell lung cancers., Results: Of 878,810 patients with lung cancer, only 3,647 patients had a diagnosis of sarcomatoid cancer (0.4%). For the additional analyses of outcomes, only patients with lifetime incidence of a single cancer, known Surveillance, Epidemiology, and End Results historic stage and inpatient reporting were selected (n = 1,921). Demographics, tumor characteristics, and outcomes of these patients were described. Non-small cell lung cancer cohorts (with and without sarcomatoid cancer propensity-matched on age, gender, race, year of diagnosis, grade, and Surveillance, Epidemiology, and End Results historic stage) that underwent lobectomies or pneumonectomies were selected (n = 758). Univariate (hazard ratio, 1.60; 95% confidence interval, 1.31-1.97) and multivariate analysis (hazard ratio, 1.67; 95% confidence interval, 1.36-2.05) revealed a significantly worse overall survival for patients with sarcomatoid cancer compared to matched nonsarcomatoid lung cancer controls., Conclusion: Sarcomatoid cancer is a rare form of lung malignancy with outcomes significantly worse than other forms of non-small cell lung cancer. Novel multimodality treatment strategies are necessary to improve outcomes of this disease., (Copyright © 2012 Mosby, Inc. All rights reserved.)

The enzymes of glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) were purified from rat kidney in one chromatographic step consisting of the use of the 2',5'-ADP Sepharose 4B by using different elution buffers. This purification procedure was accomplished with the preparation of the homogenate and affinity chromatography on 2',5'-ADP Sepharose 4B. The purity and subunit molecular weights of the enzymes were checked on SDS-PAGE and purified enzymes showed a single band on the gel. The native molecular weights of the enzymes were found with Sephadex G-150 gel filtration chromatography. Using this procedure, G6PG, having the specific activity of 32 EU/mg protein, was purified 531-fold with a yield of 88%; 6PGD, having the specific activity of 25 EU/mg protein, was purified 494-fold with a yield of 73%; and GR, having the specific activity of 33 EU/mg protein, was purified 477-fold with a yield of 76%. Their native molecular masses were estimated to be 144 kDa for G6PD, 110 kDa for 6PGD, and 121 kDa for GR and the subunit molecular weights were found to be 68, 56, and 61 kDa, respectively. A new modified method to purify G6PD, 6PGD, and GR, namely one chromatographic step using the 2',5'-ADP Sepharose 4B, is described for the first time in this study. This procedure has several advantages for purification of enzymes, such as, rapid purification, produces high yield, and uses less chemical materials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Inhibitory effects of some drugs were investigated on human erythrocyte 6-phosphogluconate dehydrogenase obtained with a 6552-fold purification in a yield of 78% using 2', 5'-ADP Separose 4B affinity gel. Which on SDS polyacrylamide gel electrophoresis showed a single band. Larnoxicam, metronidazole, imipenem, ornidazole, vancomycin, clindamycin, and amoxicillin exhibited inhibitory effects on the enzyme in vitro with IC50 values of 0.17, 0.23, 0.43, 21.79, 46.39, 117.43 and 287.35 mM, and the Ki constants 0.40 +/- 0.04, 0.57 +/- 0.06, 0.77 +/- 0.11, 42.40 +/- 2.89, 65.60 +/- 4.03, 130.22 +/- 9.21, and 287.58 +/- 10.56 mM, respectively. While vancomycin, clindamycin and amoxicillin showed competitive inhibition the other drugs displayed noncompetitive inhibition.

A large variety of animals has the ability to sense the geomagnetic field and utilize it as a source of directional (compass) information. It is not known by which biophysical mechanism this magnetoreception is achieved. We investigate the possibility that magnetoreception involves radical-pair processes that are governed by anisotropic hyperfine coupling between (unpaired) electron and nuclear spins. We will show theoretically that fields of geomagnetic field strength and weaker can produce significantly different reaction yields for different alignments of the radical pairs with the magnetic field. As a model for a magnetic sensory organ we propose a system of radical pairs being 1) orientationally ordered in a molecular substrate and 2) exhibiting changes in the reaction yields that affect the visual transduction pathway. We evaluate three-dimensional visual modulation patterns that can arise from the influence of the geomagnetic field on radical-pair systems. The variations of these patterns with orientation and field strength can furnish the magnetic compass ability of birds with the same characteristics as observed in behavioral experiments. We propose that the recently discovered photoreceptor cryptochrome is part of the magnetoreception system and suggest further studies to prove or disprove this hypothesis.