Neoteric deep eutectic solvents: history, recent developments, and catalytic applications.
Deep eutectic solvents (DESs) are modified versions of ionic liquids (ILs) and are formed by the fusion of polar components (liquids or solids) via hydrogen bonding interactions. DESs are prepared by the simple mixing of two or three cheap constituents (that are capable of self-association) with gentle heating, which leads to a drastic decrease in their melting points. The resultant clear homogeneous mixture consists of cations, anions, as well as neutral molecules; this will contribute both ionic and molecular solvent properties to the DESs. DESs have emerged as alternatives to conventional organic solvents and ILs, which meet different criteria such as availability, low cost, low toxicity, biodegradability, recyclability, ease of preparation method, tunable, and designer physiochemical properties. Many of them have attracted considerable attention and haave been applied in distinct fields of chemistry. To summarize the full-scale development of DESs, this review discusses the history, classifications, various methods of preparation, properties, and some major applications in catalysis in the last three years. This review is expected to be helpful for the further development of DESs based on a summary of the fundamental research in the field.


Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications.
In this review, the impacts of mitochondrial reactive oxygen species (ROS) on diabetes and its complications are described. In endothelial cells, high-glucose treatment increases mitochondrial ROS and normalization of the ROS production by inhibitors of mitochondrial metabolism, or by overexpression of UCP-1 or MnSOD, prevents glucose-induced activation of PKC, formation of AGE, and accumulation of sorbitol, all of which are believed to be the main molecular mechanisms of diabetic complications. Glomerular hyperfiltration, one of the characteristics of early diabetic nephropathy, may be caused by mitochondrial ROS through activation of COX-2 gene transcription, followed by PGE2 overproduction. In pancreatic beta cells, hyperglycemia also increases mitochondrial ROS, which suppresses the first phase of glucose-induced insulin secretion, at least in part, through the suppression of GAPDH activity. In liver cells, similar to that in hyperglycemia, TNF-alpha increases mitochondrial ROS, which in turn activates apoptosis signal-regulating kinase 1 (ASK1) and c-jun NH2-terminal kinases (JNK), increases serine phosphorylation of IRS-1, and decreases insulin-stimulated tyrosine phosphorylation of IRS-1, leading to insulin resistance. These results suggest the importance of mitochondrial ROS in the pathogenesis of diabetes mellitus and its complications through modification of various cellular events in many tissues, including vessels, kidney, pancreatic beta cells, and liver.


Challenging a "Cushy" Life: Potential Roles of Thermogenesis and Adipose Tissue Adaptations in Delayed Aging of Ames and Snell Dwarf Mice.
Laboratory mouse models with genetically altered growth hormone (GH) signaling and subsequent endocrine disruptions, have longer lifespans than control littermates. As such, these mice are commonly examined to determine the role of the somatotropic axis as it relates to healthspan and longevity in mammals. The two most prominent mouse mutants in this context are the genetically dwarf Ames and Snell models which have been studied extensively for over two decades. However, it has only been proposed recently that both white and brown adipose tissue depots may contribute to their delayed aging. Here we review the current state of the field and supplement it with recent data from our labs.


Sequelae of encephalitis; report of a study after the California epidemic.
In a study of almost 500 patients to determine residual effects, the sequelae of both St. Louis and Western equine encephalitis were more prominent in the younger age group. Infants under three months with Western equine encephalitis had the greatest central nervous system damage. Forty-four per cent of this entire group had sequelae. In patients between one and four years of age, the incidence of sequelae was less. The Western equine infection was associated with the more disabling residual damage. Postencephalitic convulsions were fairly common in the younger patients with Western equine disease, but not in the St. Louis group. After the age of five the sequelae rate dropped. In all age groups the Western equine residual changes were more severe than the damage of St. Louis infection. Some infants, children and adults showed remarkable improvement from sequelae even as much as two years after the abnormalities occurred. With the longer period of follow-up, some late sequelae were noted in children and adults, primarily among those who had Western equine infection.


Psychometric Properties of the Chinese Version of the Acceptance of Chronic Health Conditions (Stoma) Scale for Patients With Stoma.
Formation of a stoma is a common outcome in surgical treatment of colorectal cancer. A higher acceptance of stoma was shown to improve quality of life of patients. No instrument in Chinese is available that can be used to measure the acceptance of stoma among patients with colorectal cancer. The aims of this study were to translate and test the psychometric properties of Chinese version of Acceptance of Chronic Health Conditions (ACHC) (Stoma) scale. A sample of 100 Chinese-speaking patients with stoma was recruited from a public tertiary care hospital in Singapore. The scale was translated into Chinese and reviewed by an expert panel for semantic equivalence and content validity testing. Convergent validity was established by exploring correlations between scores of the Chinese version of the ACHC (Stoma) scale and those of the 5-level version of European Quality of Life Questionnaire-5 Dimensions. Reliability was assessed by internal consistency and test-retest reliability. The newly translated scale had high content validity (content validity index = 94%) and acceptable internal consistency (Cronbach's α = .846). The test-retest reliability was satisfactory with an intraclass coefficient of 0.997. A positive correlation was found between both scores on ACHC (Stoma) scale and EQ-5D utility score (r = 0.63, P < .01) and EQ-5D global visual analog scale (r = 0.70, P < .01). The Chinese version of the ACHC (Stoma) scale demonstrated satisfactory content validity, good convergent validity, and adequate internal consistency and stability. This scale can be used as a convenient screening tool in clinical settings to assess the level of acceptance in Chinese-speaking patients with stoma.


Platelet-rich plasma injections as a treatment for Achilles tendinopathy and plantar fasciitis in athletes.
Platelet-rich plasma (PRP) injections represent a growing interest in the use of biologic therapies for treatment of musculoskeletal injuries. One possible application of PRP is in the management of overuse injuries commonly experienced by athletes. The aim of this review is to evaluate and summarize existing evidence regarding the efficacy of PRP in the treatment of Achilles tendinopathy and plantar fasciitis in athletes. Although many lower quality single-armed studies have demonstrated clinical improvement in athletes treated for Achilles tendinopathy with PRP, higher quality randomized controlled trials (RCTs) have shown no clear benefit in athletes. Existing data suggest PRP significantly improves clinical outcomes for plantar fasciitis in the general population, but very few studies and no RCTs are available that specifically analyze outcomes in athletic populations. More research is needed to evaluate how platelet concentration, leukocyte and erythrocyte presence, and sport type may interact to affect clinical outcomes in athletes.


Resonance of a tension leg platform exited by third-harmonic force in nonlinear regular waves.
The resonance of a floating tension leg platform (TLP) excited by the third-harmonic force of a regular wave is investigated based on fully nonlinear theory with a higher order boundary element method (BEM). The total wave elevation and the total velocity potential are separated into two parts, based on the incoming wave from infinity and the disturbed potential by the body. A numerical radiation condition is then applied at the far field to absorb the disturbed potential without affecting the incident potential. The BEM mesh on the free surface is generated only once at the initial time and the element nodes are rearranged subsequently without changing their connectivity by using a spring analysis method. Through some auxiliary functions, the mutual dependence of fluid/structure motions is decoupled, which allows the body acceleration to be obtained without the knowledge of the pressure distribution. Numerical simulation is carried out for the interaction of a floating TLP with waves. The focus is on the motion principally excited by higher harmonic wave forces. In particular, the resonance of the ISSC TLP generated by the third-order force at the triple wave frequency in regular waves is investigated, together with the tensions of the tendons.


Oral immunization using live Lactococcus lactis co-expressing LACK and IL-12 protects BALB/c mice against Leishmania major infection.
Leishmaniasis is a parasitic disease affecting over 12 million individuals worldwide. Current treatments are laborious, expensive, cause severe side effects, and emerging drug resistance has been reported. While vaccination is the most cost-effective means to control infectious diseases there is no human vaccine currently available against Leishmania infections. Lactococcus lactis is a non-pathogenic, non-colonizing Gram-positive lactic acid bacterium commonly used in the dairy industry. Recently, L. lactis was used for the expression and delivery of biologically active molecules, such as antigens and cytokines, in mice and humans. In this study, we report the generation of L. lactis(alr-) strains solely expressing the protective Leishmania antigen, LACK, in the cytoplasm, secreted or anchored to the bacterial cell wall or co-expressing mouse IL-12. We show that oral immunization using live L. lactis, secreting both LACK and IL-12 was the only regimen that partially protected BALB/c mice against subsequent Leishmania major challenge. This highlights the importance of temporal and physical proximity of the delivered antigen and adjuvant for optimal immune priming by oral immunization since co-administration of L. lactis strains independently expressing secLACK and secIL-12 did not induce protective immunity. Protected animals displayed a delay in footpad swelling, which correlated with a significant reduction of parasite burden. Immunization with the L. lactis strain secreting both LACK and IL-12 induced an antigen-specific mucosal immune response and a LACK-specific T(H)1 immune response in splenocytes and mesenteric lymph node cells. Further, protection in immunized animals correlated with a strong Leishmania-specific T(H)1 immune response post-challenge, detectable in splenocytes and lymph node cells draining the site of infection. This report demonstrates the use of L. lactis as an oral live vaccine against L. major infection in susceptible BALB/c mice. The vaccine strains generated in this study provide the basis for the development of an inexpensive and safe oral live vaccine against the human parasite Leishmania.


Sensory mediation of memory blocking stressors in the pond snail Lymnaea stagnalis.
The great pond snail, Lymnaea stagnalis, is commonly used as a model species to study how stress affects the ability to form long-term memory (LTM); however, we still have little information about how the snail senses stressful stimuli. The osphradium is an external sensory organ that demonstrates electrophysiological responses to a variety of external chemical stimuli. We examined the role, if any, played by the osphradium in sensing two environmental stressors, crowding and low environmental calcium, both known to block LTM in intact animals. We severed the osphradial nerve, blocking external sensory input from this organ to the central nervous system, and then exposed the snails to low environmental calcium or crowding stress to assess whether these stressors continued to block LTM formation. When exposed to low environmental calcium, snails with their osphradial nerve severed responded as if they were maintained in our standard calcium environment. That is, they did not respond to low calcium as a stressor blocking LTM; therefore, the osphradium plays a crucial role in mediating how snails respond to this stressor. However, following crowding, LTM formation was blocked in both control groups and snails that had the osphradial nerve severed, indicating that sensory information from the osphradium is not required to sense crowded conditions. Together these data show that two stressors that result in the same behavioural phenotype, blocking LTM formation, do so via two distinct sensory pathways.


Screening for chronic kidney disease in rural Malawi: results from a diabetic clinic.
Patients with diabetes are at high risk of developing renal insufficiency and chronic kidney disease (CKD). As a result, screening for CKD is essential in diabetic patients as part of their care. This study investigated the prevalence of renal insufficiency, CKD, and correlates of CKD in diabetic patients attending Integrated Chronic Care Clinics in Neno District, Malawi. Of 203 diabetic patients, 148 (73%) were screened for CKD by measurement of serum creatinine and urinary protein between April 2016 and January 2019. 39.2% (n = 58) of the patients had abnormal estimated glomerular filtration rate (eGFR), as estimated by CKD Epidemiology Collaboration formula and/or ≥ 2+ urine protein. 13.5% (95% CI 8.4-20.0%, 20/148) of the patients had renal insufficiency based on eGFR of less than 60 ml/min/1.73 m2. 8.8% (95% CI 4.8-14.6%, 13/148) had CKD based on eGFR of less than 60 ml/min/1.73 m2 measured twice at least 3 months apart. In bivariate analysis, CKD was associated with older age, high systolic blood pressure and lower fasting blood sugar. Despite the low sample size, the study showed a moderately high prevalence of renal insufficiency and CKD in a rural cohort of diabetic patients in Malawi.


Ab initio molecular dynamics study of 45S5 bioactive silicate glass.
Bioglass 45S5, the prototype of bioactive melt-quenched silicate glasses, was modeled by means of Car-Parrinello molecular dynamics (CPMD) simulations. Although long-range structural properties cannot be modeled by using this ab initio approach, the accuracy of CPMD simulations is exploited here to provide insight into the short-range structure and to analyze vibrational and electronic properties of this biomaterial. Detailed structural analysis in the short-range scale provided insight into the local environment of modifier Na and Ca ions: a possible key role of these cations in organizing the glass network by connecting different chains and fragments into specific, rather flexible geometries was proposed. The individual contributions of different species to the vibrational density of states were separated and discussed, allowing the identification of specific features in the vibrational spectrum, such as those related to phosphate groups. The components of the electronic density of states were also analyzed, enabling us to identify correlations between the electronic structure and the structural properties, such as the different bonding character of Si-O bonds involving bridging or nonbridging oxygen atoms.


mRNA trafficking and local translation: the Yin and Yang of regulating mRNA localization in neurons.
Localized translation and the requisite trafficking of the mRNA template play significant roles in the nervous system including the establishment of dendrites and axons, axon path-finding, and synaptic plasticity. We provide a brief review on the regulation of localizing mRNA in mammalian neurons through critical post-translational modifications of the factors involved. These examples highlight the relationship between mRNA trafficking and the translational regulation of trafficked mRNAs and provide insight into how extracellular signals target these events during signal transduction.


Mononuclear cell content of human solid tumors.
The mononuclear cell content and mononuclear cell function of human solid tumors were determined. Twenty-eight primary, and 17 metastatic solid tumors, including 6 lymph node metastases, were obtained from 45 patients. Cells were released from the tumors by mincing, scraping, and sieving. Analysis of the cellular content was determined by light microscopy, and tumor lymphocyte function was determined by stimulation of blastogenesis with PHA, PWM, Con-A, MLC, and SLO. A median of 3.3 X 10(7) tumor cells with 12.5% viability was obtained per gram of tumor, and a median of 7.8 X 10(6) lymphocytes with a viability of 96% and 0.35 X 10(6) macrophages with a viability of 85% was also obtained per gram of tumor. Significant lymphocyte responses to various mitogens and antigens were obtained in 31-40% of the tumor lymphocyte preparations. From 9.4% to 23% had vigorous responses with a stimulation index greater than 10. Primary tumors contained significantly more lymphocytes than metastatic tumors; thus, the percent lymphocytes in primary tumors was 13.5% compared to 5% for metastatic tumors. In contrast, some of the lymphocyte responses were significantly greater for metastatic tumors than primary tumors. These data suggest that the direct study of lymphocytes infiltrating primary and metastatic tumors may be a useful approach to understanding tumor immunity in man.


A 'Candidatus Liberibacter solanacearum' Haplotype B-Specific Family of Candidate Bacterial Effectors.
'Candidatus Liberibacter solanacearum' (Lso) is a phloem-limited pathogen associated with devastating diseases in members of the Solanaceae and Apiaceae and vectored by several psyllid species. Different Lso haplotypes have been identified, and LsoA and LsoB are responsible for diseases in Solanaceae crops. Our efforts are aimed at identifying pathogenicity factors used by this bacterium to thrive in different hosts. Bacterial secreted proteins can play a role in host colonization or the manipulation of the host immune responses; these proteins are called effectors. In this study, we identified six LsoB-specific proteins with a conserved secretion motif as well as a conserved N-terminal domain in the mature protein. These proteins had different expression and secretion patterns but a similar subcellular localization in Nicotiana benthamiana leaves, suggesting that they play different roles regardless of their conserved secretion motif. One of these proteins, CKC_04425, was expressed at high levels in the insect vector and the host plant, indicating that it could play a role in both the plant and insect hosts, whereas the others were mainly expressed in the plant. One protein, CKC_05701, was able to efficiently suppress programmed cell death and reactive oxygen species production, suggesting that it may have a virulence role in LsoB-specific pathogenesis.


Structuration and sensemaking: frameworks for understanding the management of health information systems in the ICU.
This paper will describe two alternate conceptual frameworks (i.e. Structuration and Sensemaking) that will help to describe and provide insight into how best to implement health information systems in ICUs throughout the globe. Structuration and sensemaking are two competing ways to view the social world within hospitals. To examine the impact of information technology in health care organizations, it is important to explore the dynamic interplay between clinical decisionmaking, outcomes of HIT implementation, and individual characteristics of the organizational setting. The adaptation of information technology within health care organizations is by its very nature quite complex. The recursive pattern of social interactions that shape the implementation of technologies within that setting is key. Structuration theory provides an understanding of human work as social interaction within that organizational culture, mediated by artifacts such as tools, language, rules and procedures, and open to change. The ICU provides multiple opportunities for sensemaking. It involves caring for multiple patients simultaneously; is subject to high levels of uncertainty and is provided under significant time constraints. It is highly interdependent work, necessitating shared sensemaking as well as individual sensemaking. Sensemaking is made partially visible in this context as clinicians communicate to each other what they think is the cause of the patient's symptoms and how to treat them in the form of discussions about patient care, consultation requests, ancillary testing, and the electronic medical record. The collaborative nature of work in the ICU lends itself to the application of sensemaking and structuration theories.


Enhancement of the recollision rate in diffusion-influenced reactions in an inhomogeneous medium.
Brownian dynamics simulations were performed to determine the first collision and recollision rates of spherical reagent particles in a reaction medium made heterogeneous by the presence of randomly located inert spherical obstacles in a continuum solvent. The recollision rate vp (and hence the overall reactive collision rate when activation energy is high) was always enhanced by the presence of obstacles, the degree of enhancement increasing with the volume fraction occupied by obstacles (phi) and with decreasing reagent concentration phiR. Enhancement increased with obstacle size at high phiR, and fell with increasing obstacle size at low phiR. The vp-phiR data follow a power law, where the scaling factor betap decreased with decreasing obstacle size and increasing phi, and the prefactor kp initially increased with phi and then fell (except for large obstacles). The behavior of betap appears to be largely due to the obstacles reducing the probability that reagent particles escape from each other after collision, while the dominant factors responsible for the behavior of kp appear to be initially the effect of obstacles in enhancing effective local reagent concentration, and then (for small obstacles), their reduction of the reagent-particle coordination number. As the energy of activation falls, the reactive collision rate becomes less influenced by the reagent recollision rate and more influenced by the rate of first collision. For low-activation-energy reactions, the presence of obstacles depresses the reactive collision rate if reagent concentration is low or if the obstacles are small and their concentration high. The fall in the reactive collision rate with decreasing activation energy is steeper, the lower the reagent concentration and the smaller the obstacles.


Are all repeats created equal? Understanding DNA repeats at an individual level.
Repetitive DNA sequences, comprising up to 50 % of the genome in all eukaryotes, play important roles in a wide range of cellular functions, such as transcriptional regulation, genome stability, and cellular differentiation. However, due to technical difficulties in differentiating their sequences, DNA repeats remain one of the most mysterious parts of eukaryotic genomes. Key questions, such as how repetitive entities behave at individual level and how the internal architecture of these repeats is organized, are still poorly understood. Recent advances from our group reveal unexpected position-dependent variation within tandem DNA repeats in fission yeast. Despite sharing identical DNA sequences, the peri-centromeric repeats are organized into diverse epigenetic states and chromatin structures. We demonstrate that this position-dependent variation requires key heterochromatin factors and condensin. Our works further suggest that the peri-centromeric repeats are organized into distinct higher order structures that ensure a proper positioning of CENP-A, the centromere-specific histone H3 variant, to centromeres. These most recent developments offer insights into the mechanisms underlying the position effect within tandem DNA arrays, and have broad implications in the field of epigenetics and chromatin biology.


Identification of cordycepin biosynthesis-related genes through de novo transcriptome assembly and analysis in Cordyceps cicadae.
Cordyceps cicadae (Chanhua) is a parasitic fungus that grows on Cicada flammata larvae and is used to relieve exhaustion and treat numerous diseases, in part through its active constituent, cordycepin. We used de novo Illumina HiSeq 4000 sequencing to obtain transcriptomes of C. cicadae mycelium, fruiting body, and sclerotium, and identify differentially expressed genes. In the mycelium versus sclerotium libraries, 1576 upregulated and 2300 downregulated genes were identified. In the mycelium versus fruiting body and fruiting body versus sclerotium body libraries, 1604 and 1474 upregulated and 1365 and 1320 downregulated genes, respectively, were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified 19 genes differentially expressed in mycelium versus fruiting body as related to the purine pathway, along with 28 and 16 genes differentially expressed in the mycelium versus sclerotium and fruiting body versus sclerotium groups, respectively. Gene expression of six key enzymes was validated by quantitative polymerase chain reaction. Specifically, 5'-nucleotidase (c62060g1) and adenosine deaminase (c35629g1) in purine nucleotide metabolism, which are involved in cordycepin biosynthesis, were significantly upregulated in the sclerotium group. These findings improved our understanding of genes involved in the biosynthesis of cordycepin and other characteristic secondary metabolites in C. cicadae.


The complete genome of a baculovirus isolated from an insect of medical interest: Lonomia obliqua (Lepidoptera: Saturniidae).
Lonomia obliqua (Lepidoptera: Saturniidae) is a species of medical importance due to the severity of reactions caused by accidental contact with the caterpillar bristles. Several natural pathogens have been identified in L. obliqua, and among them the baculovirus Lonomia obliqua multiple nucleopolyhedrovirus (LoobMNPV). The complete genome of LoobMNPV was sequenced and shown to have 120,022 bp long with 134 putative open reading frames (ORFs). Phylogenetic analysis of the LoobMNPV genome showed that it belongs to Alphabaculovirus group I (lepidopteran-infective NPV). A total of 12 unique ORFs were identified with no homologs in other sequenced baculovirus genomes. One of these, the predicted protein encoded by loob035, showed significant identity to an eukaryotic transcription terminator factor (TTF2) from the Lepidoptera Danaus plexippus, suggesting an independent acquisition through horizontal gene transfer. Homologs of cathepsin and chitinase genes, which are involved in host integument liquefaction and viral spread, were not found in this genome. As L. obliqua presents a gregarious behavior during the larvae stage the impact of this deletion might be neglectable.


Biochemical and functional studies on the Burkholderia cepacia complex bceN gene, encoding a GDP-D-mannose 4,6-dehydratase.
This work reports the biochemical and functional analysis of the Burkholderia cenocepacia J2315 bceN gene, encoding a protein with GDP-D-mannose 4,6-dehydratase enzyme activity (E.C.184.108.40.206). Data presented indicate that the protein is active when in the tetrameric form, catalyzing the conversion of GDP-D-mannose into GDP-4-keto-6-deoxy-D-mannose. This sugar nucleotide is the intermediary necessary for the biosynthesis of GDP-D-rhamnose, one of the sugar residues of cepacian, the major exopolysaccharide produced by environmental and human, animal and plant pathogenic isolates of the Burkholderia cepacia complex species. Vmax and Km values of 1.5±0.2 µmol.min(-1).mg(-1) and 1024±123 µM, respectively, were obtained from the kinetic characterization of the B. cenocepacia J2315 BceN protein by NMR spectroscopy, at 25°C and in the presence of 1 mol MgCl2 per mol of protein. The enzyme activity was strongly inhibited by the substrate, with an estimated Ki of 2913±350 µM. The lack of a functional bceN gene in a mutant derived from B. cepacia IST408 slightly reduced cepacian production. However, in the B. multivorans ATCC17616 with bceN as the single gene in its genome with predicted GMD activity, a bceN mutant did not produce cepacian, indicating that this gene product is required for cepacian biosynthesis.


Does functional recovery in elderly hip fracture patients differ between patients admitted from long-term care and the community?
It is largely unknown whether functional recovery following hip fracture differs between long-term care (LTC) and community-dwelling residents. Our primary purpose was to compare recovery between these patients 6 months following hip fracture, controlling for known prognostic factors. Secondarily, we examined the contribution of residential status, in addition to patient characteristics, to functional recovery. We studied a population-based inception cohort of 451 hip fracture patients >/= 65 years old admitted to one Canadian health region hospital between July 1999 and September 2000. Participants completed the Modified Barthel Functional Index (MBI) in hospital and again via telephone interviews 6 months postoperatively. Data were also collected on surgery and rehabilitation timing, length of hospital stay (LOS). and discharge destination. Relative change from prefracture function adjusting for known prognostic factors, and the proportion of participants returning to prefracture function were compared between the LTC and community-dwelling residents. LTC residents (n = 115) were older, with lower function prefracture, more comorbidities, and increased dementia than community-dwelling residents (n = 336). Six months postfracture, 17 (22%) LTC and 180 (71%) community-dwelling residents had regained prefracture function (p <.001). LTC residents had 33% lower (-40.6, -27.2) and community-dwelling residents 11.6% lower (-14.8, -8.4) 6-month MBI scores relative to prefracture scores after risk adjustment. Residential status was significantly associated with risk-adjusted functional recovery (p <.001). Median LOS was 4 days less for LTC than for community-dwelling residents (p <.001). Twelve (10%) LTC and 266 (79%) community-dwelling residents were discharged to inpatient rehabilitation (p <.001). Following hip fracture, most LTC residents do not regain prefracture function irrespective of known prognostic factors. Further investigation is needed as to the extent to which personal and environmental characteristics contribute to outcome after hip fracture.


Sarecycline: First Global Approval.
Sarecycline (Seysara™) is an oral, once-daily, tetracycline-class drug for which a tablet formulation is approved in the USA for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients aged ≥ 9 years. The drug was developed by Paratek and Allergen and later acquired by Almirall S.A. (a Barcelona-based pharmaceutical company focused on medical dermatology). Sarceycline tablets were approved in early October 2018 and are planned to be available for patients in January 2019. Sarecycline capsules have also been studied in the USA, but no recent reports of development have been identified for this formulation. There are currently no clinical trials underway assessing sarecycline in rosacea. This article summarizes the milestones in the development of sarecycline leading to this first approval for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris.


The effective deficiency of biochemical networks.
The deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network's capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state.


Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.
We have analyzed the distribution of mitochondrial contact site and cristae organizing system (MICOS) complex proteins and mitochondrial intermembrane space bridging complex (MIB) proteins over (sub)complexes and over species. The MICOS proteins are associated with the formation and maintenance of mitochondrial cristae. Indeed, the presence of MICOS genes in genomes correlates well with the presence of cristae: all cristae containing species have at least one MICOS gene and cristae-less species have none. Mic10 is the most widespread MICOS gene, while Mic60 appears be the oldest one, as it originates in the ancestors of mitochondria, the proteobacteria. In proteobacteria the gene occurs in clusters with genes involved in heme synthesis while the protein has been observed in intracellular membranes of the alphaproteobacterium Rhodobacter sphaeroides. In contrast, Mic23 and Mic27 appear to be the youngest MICOS proteins, as they only occur in opisthokonts. The remaining MICOS proteins, Mic10, Mic19, Mic25 and Mic12, the latter we show to be orthologous to human C19orf70/QIL1, trace back to the root of the eukaryotes. Of the remaining MIB proteins, also DNAJC11 shows a high correlation with the presence of cristae. In mitochondrial protein complexome profiles, the MIB complex occurs as a defined complex and as separate subcomplexes, potentially reflecting various assembly stages. We find three main forms of the complex: A) The MICOS complex, containing all the MICOS proteins, B) a membrane bridging subcomplex, containing in addition SAMM50, MTX2 and the previously uncharacterized MTX3, and C) the complete MIB complex containing in addition DNAJC11 and MTX1.


Comorbidities in Nigerian patients with rheumatoid arthritis.
Rheumatoid arthritis has been infrequently reported among African black populations. Recent data have shown increasing reportage. Comorbidities are increasingly recognised as important in the overall morbidity, mortality and response to management. There have been few reports from Africa on the frequency and role of comorbidities associated with rheumatoid arthritis (RA) in Africans. This 20-year retrospective study looked at the frequency of various comorbidities among Nigerian patients with rheumatoid arthritis from a rheumatology facility. Data were obtained from the case record files of 283 RA patients. The chi-square test was used to assess the relationship between patient characteristics and the presence of comorbidity, while logistic regression was used to determine factors that were independently associated with the occurrence of comorbidities in these patients. The frequency of comorbidities among RA patients is high at 52.3%, mainly from common conditions such as hypertension (22.3%), dyslipidaemia (11.3%), osteoarthritis (8.1%), diabetes mellitus (7.1%), peptic ulcer disease (6.4%) and interstitial lung disease (3.5%). Increasing age (χ2 47.74, P<0.001) and prolonged duration of symptoms before diagnosis (χ2 9.0, P = 0.02) were significantly associated with the presence of comorbidity on univariate analysis, and only age was found to be independently associated with comorbidities on logistic regression. The frequencies of these comorbidities are similar in certain aspects to other such reports but differ from others. An important factor may be the delay in presentation to a rheumatologist. It is hoped that other more extensive studies will elucidate some of these findings.


Design, construction, and evaluation of "sensor lock": an electromechanical stance control knee joint.
Most currently-available stance control knee ankle foot orthoses (SCKAFOs) still need full knee extension to lock the knee joint, and they are still noisy, bulky, and heavy. Therefore, the aim of this study was to design, construct, and evaluate an original electromechanical SCKAFO knee joint that could feasibly solve these problems, and thus address the problems of current stance control knee joints with regards to their structure, function, cosmesis, and cost. Ten able-bodied (AB) participants and two (knee ankle foot orthosis) KAFO users were recruited to participate in the study. A custom SCKAFO with the same set of components was constructed for each participant. Lower limb kinematics were captured using a 6-camera, video-based motion analysis system. For AB participants, significant differences were found between normal walking and walking with the SCKAFO for temporal-spatial parameters and between orthoses with two modes of knee joints in the healthy subjects. Walking with stance control mode produced greater walking speed and step length, greater knee flexion during swing, and less pelvic obliquity than walking with a locked knee, for both AB and KAFO users. The feasibility of this new knee joint with AB people was demonstrated. Implications for rehabilitation Stance control knee ankle foot orthoses (SCKAFOs) are designed to stop knee flexion in stance phase and provide free knee movement during swing phase of walking. Due to their high cost, size, excessive weight, and poor performance, few SCKAFO were optimal clinically and commercially. The feasibility of the new knee joint with able-bodied people and poliomyelitis subjects was demonstrated.


Improved clearance of radiolabeled biotinylated monoclonal antibody following the infusion of avidin as a "chase" without decreased accumulation in the target tumor.
The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a "chase" avidin injection. A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with 125I, 131I or 99mTc. Radiolabeled biotinylated OST7 (10 micrograms) was administered intravenously into nude mice bearing human osteosarcomas and 30 micrograms of avidin was injected intravenously 6 or 24 hr later. Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of 125I-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as 99mTc and 123I.


Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation.
To investigate large tumor suppressor 1 (LATS1) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC). RNA was isolated from tumor tissue of 142 CRC patients and 40 colon mucosal biopsies of healthy controls. After reverse transcription, quantitative polymerase chain reaction (PCR) was performed, and LATS1 expression was normalized to expression of the ACTB and RPL32 housekeeping genes. To analyze hypermethylation, genomic DNA was isolated from 44 tumor CRC biopsies, and methylation-specific PCR was performed. Microsatellite instability (MSI) status was checked with PCR using BAT26, BAT25, and BAT40 markers in the genomic DNA of 84 CRC patients, followed by denaturing gel electrophoresis. Decreased LATS1 expression was found in 127/142 (89.4%) CRC cases with the average ratio of the LATS1 level 10.33 ± 32.64 in CRC patients vs 32.85 ± 33.56 in healthy controls. The lowest expression was found in Dukes' B stage tumors and G1 (well-differentiated) cells. Hypermethylation of the LATS1 promoter was present in 25/44 (57%) CRC cases analyzed. LATS1 promoter hypermethylation was strongly associated with decreased gene expression; methylated cases showed 162× lower expression of LATS1 than unmethylated cases. Although high-grade MSI (mutation in all three markers) was found in 14/84 (17%) cases and low-grade MSI (mutation in 1-2 markers) was found in 30/84 (36%) cases, we found no association with LATS1 expression. Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC.


Aproliferin: a modulator of proliferative potential.
Cellular differentiation proceeds through a series of steps in which cells undergo modifications in cellular phenotype and proliferative potential. Differentiation has been extensively studied in 3T3-T mesenchymal stem cells and growth arrest, non-terminal and terminal differentiation have been identified as three distinct stages in the adipocyte differentiation of these cells. The terminal stage of differentiation is associated with irreversible loss of proliferative potential and commitment to the expression of the adipocyte phenotype. A protein has been partially purified from human plasma that can induce the transition of 3T3-T adipocytes from the non-terminal to the terminal state of differentiation. This protein, designated aproliferin, has a mol. wt of approximately 45,000 and is trypsin, acid and heat labile. Induction of terminal differentiation by aproliferin is associated with changes in the synthesis of a limited number of cellular proteins. The ability of aproliferin to induce terminal differentiation in non-terminally differentiated cells is highly specific as a wide variety of pharmacological and biochemical agents do not mimic the effects of this agent. Apoliferin may be one of an emerging class of molecules which can affect differentiation and induce irreversible changes in cell function.


[A new method for the preparation of potassium ferrate and spectroscopic characterization].
Calcium hypochlorite was used as the raw material for preparation of the high purity potassium ferrate. The study includes the effects of reaction temperature, recrystallization temperature, reaction time, Ca(ClO)2 dosage, and the amount of calcium hypochlorite on the yield. It was determined that when the reaction temperature was 25 degrees C, recrystallization temperature 0 degree C and reaction time 40 min, the yield was more than 75%. The purity was detected by direct spectrophotometric method to be more than 92%. The product was characterized by infrated spectrum(IR), X-ray diffraction (XRD) and ultraviolet spectrum (UV) methods and proved to be potassium ferrate that was prepared by calcium hypochlorite as the raw material.


Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties.
Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic-structure-fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices.


Physical stresses related to the transport of the critically ill: optimal nursing management.
The critically ill patient's physical well being is constantly at risk. This fragile physical state means the patient is vulnerable to a host of hazards within the critical care setting, none of which are more relevant to patient outcome than the hazards awaiting them should the patient require transportation. The stresses exerted on the human body and the vulnerability of the critically ill to various means of movement, transport and subsequent environmental changes are explored through this review. The review includes a brief history of the evolution of patient transportation, which has provided a basis for the inception of formal strategies in patient management related to transportation. Within this framework current optimal nursing management minimising the detrimental effects of transport on the critically ill is reasoned to its scientific base. The basic laws of physics are an important consideration in all modes of patient movement or transport and play an integral role in the critical care nurses' practice. A clear understanding of pathophysiological and technological processes involved in caring for the critically ill and applying the principles of physics to effective contextual practice enhances the capability of the critical care nurse.


Characterization of nestin expression in astrocytes in the rat hippocampal CA1 region following transient forebrain ischemia.
Recent studies have suggested that nestin facilitates cellular structural remodeling in vasculature-associated cells in response to ischemic injury. The current study was designed to investigate the potential role of post-ischemic nestin expression in parenchymal astrocytes. With this aim, we characterized ischemia-induced nestin expression in the CA1 hippocampal region, an area that undergoes a delayed neuronal death, followed by a lack of neuronal generation after transient forebrain ischemia. Virtually all of the nestin-positive cells in the ischemic CA1 hippocampus were reactive astrocytes. However, induction of nestin expression did not correlate simply with astrogliosis, but rather showed characteristic time- and strata-dependent expression patterns. Nestin induction in astrocytes of the pyramidal cell layer was rapid and transient, while a long-lasting induction of nestin was observed in astrocytes located in the CA1 dendritic subfields, such as the stratum oriens and radiatum, until at least day 28 after ischemia. There was no detectable expression in the stratum lacunosum moleculare despite the evident astroglial reaction. Almost all of the nestin-positive cells also expressed a transcription factor for neural/glial progenitors, i.e., Sox-2 or Sox-9, and some cells were also positive for Ki-67. However, all of the nestin-positive astrocytes expressed the calcium-binding protein S100β, which is known to be expressed in a distinct, post-mitotic astrocyte population. Thus, our data indicate that in the ischemic CA1 hippocampus, nestin expression was induced in astroglia that were becoming reactive, but not in a progenitor/stem cell population, suggesting that nestin may allow for the structural remodeling of these cells in response to ischemic injury.


It Comes With the Job: Work Organizational, Job Design, and Self-Regulatory Barriers to Improving the Health Status of Train Drivers.
This study aimed to examine the impacts of key barriers to improving the occupational health status of Australian train drivers. From May to June, 2015, five semi-structured qualitative focus groups were conducted with 29 train drivers from South Australian, Victorian, and New South Wales-based rail organizations in Australia. Occupational health was impeded by multiple barriers regarding sleep (patterns/fatigue), diet (planning/context), mental health (occupational stress), rostering (low autonomy), sedentary time, low fitness motivation, and family/social life conflicts. Work organizational barriers included communication issues, low organizational support, and existing social norms. Job design barriers included rostering, fatigue, stimulant reliance, and family/social life imbalances. Self-regulatory barriers included dietary and exercise patterns habits and patterns. Occupational health interventions for Australian train drivers must address work organizational, job design, and self-regulatory barriers to healthier lifestyle behaviors.


Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience.
Programs implementing community-based directly observed therapy (DOT) have demonstrated success in the treatment of patients with tuberculosis. However, given complexities in the management and treatment of patients infected with multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT to treat MDR-TB patients has only recently been successfully attempted. We describe the first such program and highlight the crucial components and most critical challenges to creating a successful community-based MDR-TB treatment program.


Developing a Charlson Comorbidity Index for the American Indian Population Using the Epidemiologic Data from the Strong Heart Study.
The Charlson Comorbidity Index (CCI) is a frequently used mortality predictor based on a scoring system for the number and type of patient comorbidities health researchers have used since the late 1980s. The initial purpose of the CCI was to classify comorbid conditions, which could alter the risk of patient mortality within a one-year time frame. However, the CCI may not accurately reflect risk among American Indians because they are a small proportion of the U.S. population and possibly lack representation in the original patient cohort. A motivating factor in calibrating a CCI for American Indians is that this population, as a whole, experiences a greater burden of comorbidities, including diabetes mellitus, obesity, cancer, cardiovascular disease, and other chronic health conditions, than the rest of the U.S. population. This study attempted to modify the CCI to be specific to the American Indian population utilizing the data from the still ongoing The Strong Heart Study (SHS) - a multi-center population-based longitudinal study of cardiovascular disease among American Indians.A one-year survival analysis with mortality as the outcome was performed using the SHS morbidity and mortality surveillance data and assessing the impact of comorbidities in terms of hazard ratios with the training cohort. A Kaplan-Meier plot for a subset of the testing cohort was used to compare groups with selected mCCI-AI scores. A total of 3,038 Phase VI participants from the SHS comprised the study population for whom mortality and morbidity surveillance data were available through December 2019. The weights generated by the SHS participants for myocardial infarction, congestive heart failure, and high blood pressure were greater than Charlson's original weights. In addition, the weights for liver illness were equivalent to Charlson's severe form of the disease. Lung cancer had the greatest overall weight derived from a hazard ratio of 8.308. The mCCI-AI was a statistically significant predictor of one-year mortality, classifying patients into different risk strata X2 (8, N = 1,245) = 30.56 (p = .0002). The mCCI-AI exhibited superior performance over the CCI, able to discriminate between participants who died and those who survived 73% of the time.


Co-microencapsulation of BMSCs and mouse pancreatic β cells for improving the efficacy of type I diabetes therapy.
To overcome the shortcomings of pancreas transplantation and insulin injection treatment for type I diabetes, biocompatible materials were used to prepare alginate-chitosan-alginate microcapsules that co-encapsulated bone marrow mesenchymal stem cells and mouse pancreatic β cells to treat diabetic mice. Blank alginate-chitosan-alginate (ACA) microcapsules and co-microencapsulated cells were prepared using a high-voltage electrostatic method and then characterized using an inverted microscope. Cell viability was evaluated using AO/EB staining. ELISA kit was used to detect insulin secretion. Peri-orbital blood samples were obtained from the mice for blood glucose determination every week for one month. After 28 days of in vitro culture, the secretion of insulin following co-microencapsulation was higher than that observed for microencapsulated beta-TC-6 cells alone. On the 28th day after transplantation, the blood glucose level was 6.86 mmol/L in the microencapsulated beta-TC-6 group. On the 14th day, the blood glucose level was 6.80 mmol/L in the co-microencapsulated BMSC/beta-TC-6 group, which was close to the normal blood glucose level of healthy mice. These results indicated that the efficacy in reducing blood glucose was better in the co-microencapsulated BMSC/beta-TC-6 group. This primary study indicated that combining microencapsulation technology and co-culture of stem cells and somatic cells shows promise for the treatment of type I diabetes mellitus.


Structural characteristics of modified activated carbons and adsorption of explosives.
Several series of activated carbons prepared by catalytic and noncatalytic gasification and subsequent deposition of pyrocarbon by pyrolysis of methylene chloride or n-amyl alcohol were studied by FTIR, chromatography, and adsorption methods using nitrogen and probe organics (explosives). The relationships between the textural characteristics of carbon samples and the recovery rates (eta) of explosives on solid-phase extraction (SPE) using different solvents for their elution after adsorption were analyzed using experimental and quantum chemical calculation results. The eta values for nitrate esters, cyclic nitroamines, and nitroaromatics only partially correlate with different adsorbent parameters (characterizing microporosity, mesoporosity, pore size distributions, etc.), polarity of eluting solvents, or characteristics of probe molecules, since there are many factors strongly affecting the recovery rates. Some of the synthesized carbons provide higher eta values than those for such commercial adsorbents as Hypercarb and Envicarb.


Stress urinary incontinence: a review of treatment options.
Stress urinary incontinence occurs when the support structures of the pelvic floor and the urinary system are stretched, damaged, or defective. This condition is common in women of all ages, and billions of dollars are spent each year to correct the condition and improve quality of life. This article reviews three current treatments for stress urinary incontinence: the Burch colposuspension procedure, urethral slings, and radiofrequency treatments. In one study, researchers reported that patient satisfaction rates were higher for the Burch procedure than for urethral sling procedures. Other researchers found that urethral sling procedures had high rates of success but that adverse events were more common. Adverse events for both types of procedures include voiding difficulties, postoperative urge incontinence, and urinary tract infections. Radiofrequency interventions can improve the quality of life for many patients and can provide a short-term intervention for many patients who later may require a more-invasive surgical procedure.


Lactate metabolism in resting and exercising dogs.
The effect of treadmill run on the turnover rates of glucose ([2-3H]glucose) and lactate ([U-14C]lactate), on the rates of oxidation (ROX) of lactate, and its conversion to glucose (L LEADS TO G) were measured with the primed constant-infusion technique. Comparable lactate turnover rates were obtained at rest by infusing epinephrine, or Na-L(+)-lactate with or without norepinephrine. With increasing lactate levels (L) the rate of disappearance (RdL), ROX, and L leads to G increase in a linear manner. At the same lactate level, RdL, ROX, and L leads to G are significantly higher in the running dog. Exercise increased the metabolic clearance rate of lactate threefold. At rest ROX and L leads to G represented about 50% and 18-19% of RdL, respectively. The corresponding values in the running dogs were 55% and 25%, respectively. At rest about 9% of the hepatic glucose output arose from lactate while during exercise this varied from 7 to 26% depending on RdL. It is concluded that a) the working muscle produces and utilizes lactate at the same time, and b) "in vivo" the major factor which controls both ROX and gluconeogenesis is the substrate supply.


Variability of blood lead concentrations during infancy.
As part of a study of early childhood development, more than 200 children had their blood lead concentrations (PbB) determined semiannually during the first 2 yr of life. These children were selected from 11,837 consecutive births surveyed for umbilical cord PbB at Boston Lying-In Hospital. Candidate subjects were drawn from the highest, lowest, and middle deciles of PbB. The mean PbB was 7.2 +/- 5.3 (standard deviation) micrograms/dl at birth and did not change appreciably with age. However, the average change in an individual's PbB every 6 months was 4 micrograms/dl, which was several fold in excess of the analytical reproducibility. Only 25% of the children in the highest category at birth were in the highest category at 2 yr of age. Approximately 40% of the children remained in their immediately previous PbB tertile category. A stochastic description of these patterns of change fits the data. Our results should caution investigators who might wish to rely on a single determination to categorize children with PbB.


The absorption, distribution, metabolism, and excretion of 125I-labeled sfericase in rats.
125I-sfericase was given orally, intravenously, or intraduodenally to rats. In vivo behavior of radioactivity was investigated to determine absorption, distribution, metabolism, and excretion of sfericase. Moreover, the effects of TCA treatment and dialysis on the ratio of radioactivities in high molecular fractions were also studied. Following oral administration (about 10 microCi/rat), the blood radioactivity level peaked at 1-2 h and then rapidly decreased. The cumulative percentages of radioactivities in lymphatic fluid, urine, and feces within the first 24 h were 5.85%, 9.17%, and 2.56% (mean), respectively. Relatively high organ tissue levels of radioactivity were recorded for the thyroid gland, stomach, cecum, kidney, blood, and lung at 2 h, but in all except the thyroid gland a remarkable decrease in radioactivity was observed at 24 h after administration. Totals of 0.66%, 1.91%, 0.869%, and 2.36% (mean), respectively, of the radioactivity found in whole plasma and homogenates of liver, kidney, and spleen were transferred into the TCA precipitable fraction. These rates of transference were lower than those observed after iv administration (about 5 microCi/rat).


Synthesis and characterization of bimetallic metal-organic framework Cu-Ru-BTC with HKUST-1 structure.
The bimetallic metal-organic framework Cu-Ru-BTC with the stoichiometric formula Cu2.75Ru0.25(BTC)2·xH2O, which is isoreticular to HKUST-1, was successfully prepared in a direct synthesis using mild reaction conditions. The partial substitution of Cu(2+) by Ru(3+) centers in the paddlewheel structure and the absence of other Ru-containing phases was proven using X-ray absorption spectroscopy.


Phytochemistry and Pharmacological Activity of Malva sylvestris L: A Detailed Insight.
Malva sylvestris L., is commonly referred to as Mallow and is found in Europe, Asia and Africa. This has been traditionally used for inflammation, gastrointestinal disturbances, skin disorders, menstrual pains, and urological disorders. This review covers phytoconstituents and Pharmacological activities of M. sylvestris. The plant contains a large number of phytochemical constituents having diverse pharmacological activities. The plant contains many phenolic compounds responsible for its strong antioxidant activity. Coumarins from Mallow have a potential anticancer activity. Malva sylvestris also contains essential as well as non-essential elements and minerals. Many researchers have provided evidence that Malva sylvestris is a good candidate for use as a medicinal herb and has good nutritional value. The leaves, in particular, offer properties like anticancer, skin whitening, and anti-aging. Furthermore, the aqueous extract was recently shown to have an anti-ulcerogenic effect. Malva sylvestris has a high potential for use in cosmetics such as skin whitening and anti-aging treatments. Methanolic extracts of Malva sylvestris leaves, and flowers showed strong antibacterial activity against a common plant pathogen bacterium. The plant also contains Malvone A, which is responsible for antibacterial action. The plant also possesses anti-inflammatory, analgesic, wound healing properties and various other activities.


Thinking about thinking - thinking about measurement: a Rasch analysis of recursive thinking.
Two studies were conducted to examine the dimensionality and hierarchical organization of a measure of recursive thinking. In Study 1, Rasch analysis supported the claim that the recursive thinking task measures a single underlying dimension. Item difficulty, however, appeared to be influenced not only by level of embeddedness but also by syntactic features. In Study 2, this hypothesis was tested by adding new items to the recursive thinking measure. Rasch analysis of the modified recursive thinking task produced evidence for the undimensionality and segmentation. However, Study 2 did not support the idea that syntactic features influence item difficulty.


Induction of -aminolevulinic acid synthetase in chick embryo liver cells in cluture.
delta-Aminolevulinic acid synthetase is induced in chick embryo liver culture by the natural steroid, etiocholanolone, and by the foreign chemical, 3,5-dicarbethoxy-1,4-dihydrocollidine at the level of transcription. Alternatively, inducing chemicals such as allylisopropylacetamide and gamma-hexachloro-cyclohexane act primarily at the level of translation. Hemin (K(i) = 5 muM) inhibits the induction at the level of translation. In liver cell culture, the half-life of delta-aminolevulinic acid synthetase is 3 hr, that of mRNA about 5 hr.


Latency of human measles virus in hamster cells.
A latent system employing measles virus (Schwarz strain) was developed in hamster embryo fibroblasts (HEF). Measles virus-specific antigen was detected by immunofluorescence in 30 to 50% of HEF cells, and these cells released infectious virus when co-cultivated with a susceptible monkey cell line, BSC-1 cells. No infectious virus could be detected in the cells when measures were taken to exclude passage of viable latent cells onto the indicator BSC-1 cells. Infectious center assays demonstrated that about 1 in 10 of the latently infected cells in the population could release infectious virus. Infectious virus appeared within 6 hr after co-cultivation of the HEF cells with BSC-1 cells, as compared to 24 hr required for normal replication of measles virus in the BSC-1 cells. Furthermore, labeling of progeny virus ribonucleic acid (RNA) by using tritiated uridine, and inhibition of RNA or protein synthesis by 5-azacytidine or cycloheximide suggested that neither additional RNA nor protein synthesis is required after co-cultivation of the cells to effect early virus release. It can therefore be postulated that there is a block at a late step in virus replication in the latently infected hamster cells. The most obvious site would concern maturation of infectious virions at the cell membrane.


Improvement of dissolution properties of a new Helicobacter pylori eradicating agent (TG44) by inclusion complexation with beta-cyclodextrin.
The interaction of a newly developed Helicobacter pylori eradicating agent (TG44, 4-methylbenzyl-4'-[trans-4-(guanidinomethyl)cyclohexylcarbonyloxy]biphenyl-4-carboxlylate monohydrochloride) with beta-cyclodextrin (beta-CyD) in aqueous solution and in solid state was studied to gain insight into the high in-vivo H. pylori eradicating activity of TG44/beta-CyD complex. The interaction was studied by the solubility method, spectroscopic methods, powder X-ray diffractometry and differential scanning colorimetry (DSC). TG44 gave A(L)-type phase solubility diagram with beta-CyD in water, showing a linear increase in solubility of the drug up to 8 mM beta-CyD concentration. The solubility of TG44 (0.04 mM in water at 25 degrees C) increased about 70-folds at 8 mM beta-CyD. Ultraviolet, circular dichroism, fluorescence and (1)H-nuclear magnetic resonance spectroscopic studies indicated that TG44 forms the inclusion complex with beta-CyD in a 1:1 stoichiometry and the biphenyl moiety of TG44 is preferably included in the beta-CyD cavity in water. The Giordano plot made by monitoring changes in the fusion enthalpy of TG44 (about 184 degrees C) suggested that TG44 forms the 1:1 complex with beta-CyD in the solid state. The TG44/beta-CyD solid complex in a 1:1 stoichiometry was prepared by the grinding and spray-drying methods and confirmed by powder X-ray diffractometry and DSC that the complex is in an amorphous state. The initial dissolution rate of TG44/beta-CyD complex was significantly faster than those of the drug alone and the physical mixture of both components, maintaining higher supersaturated concentrations of the drug for a long time. The results suggested that the higher eradicating activity of TG44/beta-CyD complex to Helicobacter pylori, compared with that of the drug alone, is attributable at least partly to the faster dissolving property of the complex and its ability to maintain the supersaturated state of the drug in the gastric fluid.


Modified single transluminal gateway transcystic multiple drainage technique for a huge infected walled-off pancreatic necrosis: A case report.
We report a successful endoscopic ultrasonography-guided drainage of a huge infected multilocular walled-off necrosis (WON) that was treated by a modified single transluminal gateway transcystic multiple drainage (SGTMD) technique. After placing a wide-caliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward-viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases.


Chinese Herbal Medicine Dingji Fumai Decoction for Ventricular Premature Contraction: A Real-World Trial.
Chinese herbal medicine Dingji Fumai Decoction (DFD) is widely clinically used for ventricular premature contraction (VPC). This real-word trial was designed to assess the safety and effectiveness of DFD for VPC. This was a double-blinded, randomized placebo-controlled trial. Patients with VPC were randomized (1 : 1) to treatment with DFD combined with metoprolol (DFD arm) or metoprolol combined with placebo (MET arm). A primary end point was a composite of clinical symptoms and signs determined by the traditionalChinese medicine syndrome score and the number of VPC determined by the Holter examination. Second outcomes were adverse events, medication compliance, and laboratory examination. 144 patients were randomized to DFD arm (76 patients) or MET arm (68 patients), and 136 cases (71 in DFD arm and 65 in MET arm) finally completed this trial. After a 12-week follow-up, DFD arm significantly decreased traditional Chinese medicine syndrome score and the number of VPC compared with MET arm (P = 0.003 and 0.034, respectively). There was no adverse drug effect and patient medication compliance was good. Superiority with DFD arm for VPC was demonstrated over MET arm for both the safety and effectiveness end points.


Effect of intravenous recombinant alpha-2 interferon on monocyte Fc-dependent phagocytosis in patients with malignant melanoma.
Recombinant alpha interferons (IFN-alpha) have diverse effects on the immune response. Alpha IFNs have been shown to increase the number of monocyte Fc receptors and Fc dependent phagocytosis in vitro. Therefore, we prospectively evaluated Fc-dependent phagocytic activity in a group of 14 patients with Stage III melanoma receiving from 10 to 100 X 10(6) u of recombinant DNA-produced alpha-2 interferon (IFN-alpha 2) five days a week for four weeks. Monocyte Fc-dependent phagocytosis (FcDP) was assayed by measuring the ingestion of 51Cr-labeled, IgG-coated sheep erythrocytes before, and on Days 2, 5, and 19 of IFN therapy. Each patient was simultaneously compared with the same unmatched normal controls during the assay period. Monocyte FcDP was unchanged in 8/14 patients on each of the three sampling days. Increases in FcDP occurred in 4/14 patients on Day 2 and only 1/14 on Day 19. Recombinant DNA-produced IFN-alpha 2 did not persistently augment monocyte FcDP irrespective of the dose administered. Moreover, there may be untoward effects on monocyte FcDP in vivo from intravenous administration of high dose IFN-alpha 2 since a distinct, but statistically insignificant (p = 0.06) trend of inhibition of FcDP by Day 19 of therapy was observed. Monocyte FcDP activity of normal controls fluctuated from day to day. The intrinsic variability in monocyte FcDP as assessed by this technique may conceal an effect(s) of IFN preparations in vivo. Additional studies are needed to further define the effects of purified IFN preparations on monocyte and tissue-derived macrophage effector functions.


Tapentadol Prolonged Release for Severe Chronic Osteoarthritis Pain in the Elderly-A Subgroup Analysis of Routine Clinical Practice Data.
Tapentadol prolonged release (PR) has been shown effective and generally well tolerated in a broad range of chronic pain conditions. This subgroup analysis investigated its benefits for elderly patients with severe chronic osteoarthritis (OA) pain in routine clinical practice. Patients and Methods. Data of all patients with chronic OA pain were extracted from the database of a prospective, 3-month noninterventional tapentadol PR trial. The data of elderly OA patients (>65 years of age; n = 752) were compared with the data of younger OA patients (≤65 years; n = 282). Almost all patients (elderly 98.7% and younger patients 99.3%) had received long-term analgesic medication prior to the start of tapentadol PR treatment but presented with severe pain accompanied by considerable impairments in sleep quality and quality of life measures. Tapentadol PR provided effective pain relief in both patient groups, with slightly better outcomes in younger patients. However, the mean baseline pain intensity of 7.1 (SD 1.5) was reduced by 3.8 points (p ≤ 0.001), and sleep and quality of life measures had also markedly improved in the elderly: quality of sleep by 3 points, quality of life by 3.4 points, social activities by 3 points, and independence by 2.7 points (p ≤ 0.001 for all measures; 11-point scale). At the end of observation, 68% of the elderly had clinically relevant pain reductions of at least 50% (vs baseline), and 87.9% attained either their intended pain reduction target and/or an additional individual treatment target (both predefined during baseline examination). Only 8.4% of the elderly experienced adverse drug reactions, most frequently nausea (2.7% of patients) and dizziness (1.5%). Tapentadol PR provided effective and well-tolerated treatment of severe chronic OA pain for elderly patients in routine clinical practice. The favorable tolerability profile in particular suggests tapentadol PR as a treatment option before classical strong opioids are considered.


Application of Allogeneic Human Acellular Dermal Matrix Reduces the Incidence of Fistula in Hypospadias Repair.
Urethrocutaneous fistula is one of the most common complications arising from hypospadias surgery. The purpose of our study was to investigate the effectiveness and safety of allogeneic human acellular dermal matrix (HADM) application as a means of preventing the occurrence of urethrocutaneous fistula following hypospadias surgery. This is a non-randomized study of 219 cases (out of 270 patients with hypospadias) which satisfied inclusion and exclusion criteria. These patients were divided into two groups: 101 HADM patients, and 118 control patients (who did not receive HADM). In the control group, 77 boys were treated by single-stage urethroplasty (TIP) and 41 underwent staged urethroplasty (Thiersch-Duplay). In the HADM group, 59 boys underwent the TIP and 42 underwent the Thiersch-Duplay. In the postoperative period, we recorded the incidence of infection, urethrocutaneous fistula, and urethral stricture complications in these two groups of patients. The effectiveness and safety of HADM in preventing urethrocutaneous fistula following hypospadias surgery were evaluated according to these indicators. In the control group, following the operation there were 16 cases of infection, 38 cases of urethrocutaneous fistula after extubating, and 5 cases of urethral stricture. In the HADM group, there were 19 cases of postoperative infection, 12 cases of urethrocutaneous fistula after extubating, and 5 children with urethral stricture. In comparing the two groups, it was found that the postoperative infection rate (13.6 vs. 18.8%) and the incidence of urethral stricture (4.2 vs. 5.0%) were not statistically significant (P > 0.05), while the postoperative urethrocutaneous fistula rate (32.2 vs. 11.9%) was statistically significant (P < 0.001). It is found that HADM application can significantly reduce the incidence of urethrocutaneous fistula complications, without increasing the risk of infection and urethral stricture.


12-lipoxygenase products are potent inhibitors of prostacyclin-induced renin release.
In isolated human or rat glomeruli, arachidonic acid can be metabolized by the cyclooxygenase pathway to prostaglandins or by the lipoxygenase pathway to hydroxyeicosatetraenoic acids (HETES). We have recently shown that 12-lipoxygenase products are potent inhibitors of renin release. Since prostacyclin (PGI2) is a potential renin secretagogue, we studied the direct effects of 12-lipoxygenase products on prostacyclin-induced renin secretion. Treatment of rat renal cortical slices with picomolar concentrations of 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 12-HETE blocked the prostacyclin- or iloprost (an analog of PGI2)-induced renin secretion. The inhibitory effects of 12-lipoxygenase products were not exhibited by the 5-lipoxygenase-derived products, leukotriene B4 and 5-HPETE. These results suggest that HETES are not only potent modulators of prostacyclin actions on renin, but that the concerted actions of these compounds in cells may be critical determinants of the juxtaglomerular cell secretion of renin.


[Preparation, premedication and parental presence].
40% to 60% of children undergoing surgery under general anaesthesia develop anxiety in the preoperative period. Multiple factors contribute to the genesis of this disorder. Preoperative anxiety may complicate the induction of anaesthesia and can cause behavioural modifications in children even long after surgical procedures have been completed. It is important to focus on prevention of such problems. A preparation program, premedication and parental presence during induction of anaesthesia are valid tools for achieving this goal. We are herewith presenting a play preparation program carried out by play specialists and offered to all children prior to surgery. This approach proved effective in reducing preoperative anxiety in children and their mothers.


The Influence of Select Medications on Prospective Hemorrhage Risk in Patients with Spinal or Cerebral Cavernous Malformations.
Effects of select medications on hemorrhage risk in patients with cerebral or spinal cavernous malformations (CMs) are unknown. From a single-institution prospective cohort of patients with CM (2015-2021), demographics, mode of clinical presentation, and radiographic data were collected. Follow-up was performed with electronic medical record review, in-person visits, and written surveys. Select medication use was ascertained from the time of CM diagnosis to a censor date of first prospective symptomatic hemorrhage, complete surgical excision of sporadic form CM, last follow-up, or death. Using Cox proportional hazards regression model, we assessed effects of antithrombotic agents, fish oil, selective serotonin reuptake inhibitors (SSRIs), vitamin E and D supplementation, statins, and beta blockers on prospective hemorrhage risk. The study included 364 patients with spinal or cerebral CM (58.0% female; 20.0% familial form; 42.3% presentation to medical attention owing to hemorrhage; 25.8% brainstem location). During a follow-up of 2018 patient-years, 103 prospective hemorrhages occurred. No studied medications increased the prospective CM hemorrhage risk. Antithrombotics, vitamin D supplementation, fish oil, and SSRI were associated with lower hemorrhage risk even after adjusting for age at diagnosis, hemorrhage at diagnosis, and brainstem location. Use of select medications with antithrombotic properties do not increase the risk of CM hemorrhage. Vitamin D supplementation, any antithrombotic agent, fish oil, and SSRI were associated with a lower prospective hemorrhage risk. Further studies should evaluate the mechanism of action and potential benefit of these select medications.


Maternal drug use during pregnancy and asthma risk among children.
Maternal use of some drugs, notably paracetamol and drugs for gastroesophageal reflux, has been associated with an increased risk of childhood asthma in the child. We wanted to analyze these associations with consideration to the confounding of maternal asthma. Childhood asthma was identified from the Swedish National Prescription Register and maternal drug use during the latter part of pregnancy from antenatal records, computerized in the Swedish Medical Birth Register. Risks were estimated as odds ratios (OR) with 95% confidence intervals, using Mantel-Haenszel technique with adjustment for year of birth, maternal age, parity, smoking habits, and BMI. A statistical association between maternal use of many different drugs, including paracetamol, and childhood asthma existed but was mainly due to concomitant drug use, related to maternal asthma. The only associations that appeared to be true were with drugs for gastroesophageal reflux (adjusted (OR) = 1.32, 95% CI, 1.18-1.54) and with opiates (adjusted OR = 1.56 (96% CI, 1.05-2.34). Maternal use of paracetamol did not seem to increase the risk of childhood asthma, but the previously described association with drugs for gastroesophageal reflux was supported. The analysis is complicated by the confounding from maternal asthma.


Noise-bias and polarization-artifact corrected optical coherence tomography by maximum a-posteriori intensity estimation.
We propose using maximum a-posteriori (MAP) estimation to improve the image signal-to-noise ratio (SNR) in polarization diversity (PD) optical coherence tomography. PD-detection removes polarization artifacts, which are common when imaging highly birefringent tissue or when using a flexible fiber catheter. However, dividing the probe power to two polarization detection channels inevitably reduces the SNR. Applying MAP estimation to PD-OCT allows for the removal of polarization artifacts while maintaining and improving image SNR. The effectiveness of the MAP-PD method is evaluated by comparing it with MAP-non-PD, intensity averaged PD, and intensity averaged non-PD methods. Evaluation was conducted in vivo with human eyes. The MAP-PD method is found to be optimal, demonstrating high SNR and artifact suppression, especially for highly birefringent tissue, such as the peripapillary sclera. The MAP-PD based attenuation coefficient image also shows better differentiation of attenuation levels than non-MAP attenuation images.


Comparative assessment of orthogonal polynomials for wavefront reconstruction over the square aperture.
Four orthogonal polynomials for reconstructing a wavefront over a square aperture based on the modal method are currently available, namely, the 2D Chebyshev polynomials, 2D Legendre polynomials, Zernike square polynomials and Numerical polynomials. They are all orthogonal over the full unit square domain. 2D Chebyshev polynomials are defined by the product of Chebyshev polynomials in x and y variables, as are 2D Legendre polynomials. Zernike square polynomials are derived by the Gram-Schmidt orthogonalization process, where the integration region across the full unit square is circumscribed outside the unit circle. Numerical polynomials are obtained by numerical calculation. The presented study is to compare these four orthogonal polynomials by theoretical analysis and numerical experiments from the aspects of reconstruction accuracy, remaining errors, and robustness. Results show that the Numerical orthogonal polynomial is superior to the other three polynomials because of its high accuracy and robustness even in the case of a wavefront with incomplete data.


Mechanism of mevalonate pyrophosphate decarboxylase: evidence for a carbocationic transition state.
Mevalonate pyrophosphate decarboxylase catalyzes the decarboxylation of mevalonate pyrophosphate to isopentyl pyrophosphate. The mechanism of action of this enzyme was investigated to elucidate the mechanism of inhibition by 3-hydroxy-3-(fluoromethyl)-5-pyrophosphopentanoic acid (II). It was previously found that II is a competitive inhibitor (Ki = 0.01 microM) of the enzyme reaction [Reardon, J.E., & Abeles, R.H. (1987) Biochemistry 26, 4717-4722; Nave, J.F., d'Orchymont, H., Ducep, J.B., Piriou, F., & Jung, M.J. (1985) Biochem. J. 227, 247-254]. We have now observed that II is decarboxylated 2500-fold more slowly than mevalonate pyrophosphate (3-hydroxy-3-methyl-5-pyrophosphopentanoic acid, I). The enzyme was exposed to saturating concentrations of II and ATP and then passed through a Penefsky column to remove excess substrate. The enzyme was denatured immediately upon emerging from the Penefsky column. Nearly 1 equiv of both 3-phospho-3-(fluoromethyl)-5-pyrophosphopentanoic acid and ADP was bound to the enzyme. 3-Hydroxy-5-pyrophosphopentanoic acid (III) is phosphorylated at the secondary hydroxyl group and released from the enzyme without decarboxylation. This reaction is 30-fold slower than the rate of decarboxylation of I. The introduction of the 3-fluoromethyl group as well as the removal of the 3-methyl group results in low rates of decarboxylation. These substrate analogs have decreased electron density relative to the tertiary carbon of the substrate. Therefore, the transition state of the decarboxylation step has considerable carbocationic character. Further support for the carbocationic transition state is provided by the finding that N-methyl-N-carboxymethyl-2-pyrophosphoethanolamine (IV) inhibits the enzyme reaction with Ki = 0.75 microM. IV is probably a transition-state analog in which the positively charged nitrogen atom is analogous to the carbocation.


The European Union General Data Protection Regulation (EU 2016/679) and the Australian My Health Record Scheme - A Comparative Study of Consent to Data Processing Provisions.
As a general rule, lawfulness of data processing under the European Union General Data Protection Regulation (EU 2016/679) (GDPR) is based on affirmative, unambiguous, voluntary, informed, and specific or "granular" consent to processing of their data, including health data, by individuals referred to as data subjects. The GDPR grants data subjects the legal right to specifically agree to (or refuse) having their data processed in any of the ways statutorily defined as "processing". Individuals also have the legal right to be fully informed about each and every intended use of their data by data processors and controllers, and the right to refuse such use. In Australia, once registered on the My Health Record (MHR) system, "healthcare recipients" as patients-cum-data subjects are called under the MHR scheme, have the right to remove documents from their MHR files and block some health care providers from accessing their data. However, this study demonstrates that the notion of "standing" consent that the MHR scheme appears to have created does not conform to any of the principles and rules governing data subjects' consent rights under GDPR.


A Comprehensive Analysis of Cribriform Morphology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy Correlated with Radical Prostatectomy Specimens.
Recently a large body of evidence has emerged indicating that cribriform morphology is an aggressive prostate cancer morphological pattern associated with higher cancer specific mortality. In a comprehensive analysis we compared traditional and contemporary prostate biopsy techniques to detect prostate cancer with cribriform morphology with radical prostatectomy serving as the reference standard. We queried a retrospectively maintained, single institution, multiparametric magnetic resonance imaging database of 1,001 patients to identify 240 who underwent magnetic resonance imaging-ultrasound fusion targeted biopsy and concurrent systematic biopsy from December 2014 to December 2016. Of the 3,978 biopsy cores obtained 694 positive cores were rereviewed by a genitourinary pathologist for pattern 4 subtype (cribriform, fused and poorly formed glands). Using paired analysis pathological results among 3 biopsy methods (systematic biopsy, targeted biopsy and systematic plus targeted biopsy) were compared. Prostatectomy specimens were also pathologically reviewed. Systematic plus targeted biopsy was superior to systematic biopsy alone or targeted biopsy alone to detect cribriform morphology (all p <0.0001). On final histopathology cribriform tumor foci were associated with an increased percent of pattern 4 involvement and extraprostatic extension (p <0.0001 and 0.003, respectively). Only 17.4% of cribriform tumors in pure form were visible on multiparametric magnetic resonance imaging. Based on final histopathology the sensitivity of systematic biopsy, targeted biopsy and systematic plus targeted biopsy for cribriform morphology was 20.7%, 28.6% and 37.1%, respectively. Although systematic plus targeted biopsy was the most accurate biopsy method to detect cribriform morphology, biopsy sensitivity and specificity remained poor.


Control of Reversible Activation Dynamics of [Ru{η6 :κ1 -C6 H5 (C6 H4 )NH2 }(XY)]n+ and the Effect of Chelating-Ligand Variation.
The potential use of organoruthenium complexes as anticancer drugs is well known. Herein, a family of activatable tethered ruthenium(II) arene complexes of general formula [Ru{η6 :κ1 -C6 H5 (C6 H4 )NH2 }(XY)]n+ (closed tether ring) bearing different chelating XY ligands (XY=aliphatic diamine, phenylenediamine, oxalato, bis(phosphino)ethane) is reported. The activation of these complexes (closed- to open-tether conversion) occurs in methanol and DMSO at different rates and to different reaction extents at equilibrium. Most importantly, RuII -complex activation (cleavage of the Ru-Ntether bond) occurs in aqueous solution at high proton concentration (upon Ntether protonation). The activation dynamics can be modulated by rational variation of the XY chelating ligand. The electron-donating capability and steric hindrance of XY have a direct impact on the reactivity of the Ru-N bond, and XY=N,N'-dimethyl-, N,N'-diethyl-, and N,N,N',N'-tetramethylethylenediamine afford complexes that are more prone to activation. Such activation in acidic media is fully reversible, and proton concentration also governs the deactivation rate, that is, tether-ring closure slows down with decreasing pH. Interaction of a closed-tether complex and its open-tether counterpart with 5'-guanosine monophosphate revealed selectivity of the active (open) complex towards interaction with nucleobases. This work presents ruthenium tether complexes as exceptional pH-dependent switches with potential applications in cancer research.


Left Common Femoral to Right Common Iliac Venous Bypass Through a Retroperitoneal Exposure.
The endovascular recanalization of the iliocaval system has replaced venous surgical reconstructions as the primary treatment option in severe post-thrombotic syndrome (PTS). We herein present a 51-year-old female with previous deep venous thrombosis, complicated with PTS with a large and complex circumferential calf ulcer measuring 25 cm of length in the left lower extremity. Venogram revealed a complete and extensive occlusion in the left iliofemoral system. A surgical bypass from the left common femoral vein to the right common iliac vein was performed. Patient recovered well and after 12 months postoperation her large wound is healing favorably with a clean and well granulated bed. Iliofemoral venous bypass is a feasible treatment for non-healing ulcer of lower extremity.


Internalised stigma, social support, coping and care-giving burden among Chinese family caregivers of adults diagnosed with schizophrenia: A parallel mediation analysis.
Care-giving burden and internalised stigma are prevalent among family caregivers of people diagnosed with schizophrenia. Internalised stigma has been regarded as a source of care-giving burden. But it remains unclear if high levels of internalised stigma directly contribute to an increased risk of care-giving burden or if the effects could be buffered by psychological factors. This cross-sectional study was to investigate the relationship between internalised stigma and care-giving burden, and to determine the mediating effects of coping styles and social support. Data were collected from 344 Chinese family caregivers of adults diagnosed with schizophrenia in a psychiatric outpatient department of a tertiary hospital in Changsha, Hunan between April and August 2018. A self-reported questionnaire was used to collect data anonymously. Instruments included the Simplified Coping Style Questionnaire, the Multidimensional Scale of Perceived Social Support, the Internalized Stigma of Mental Illness Scale and the Caregiver Burden Inventory. Data analysis was conducted using descriptive statistics, the Spearman correlation and regression analysis to estimate direct and indirect effects using bootstrap analysis. Results showed that internalised stigma, social support and passive coping were significant correlates of care-giving burden; social support partially mediated the relationship between internalised stigma and care-giving burden; active coping did not show impacts on internalised stigma and care-giving burden. This study provided social workers and healthcare providers with a better understanding of the development of care-giving burden. Comprehensive interventions should be designed to provide supportive resources and reduce the possibilities of internalisation of stigma and passive coping, to alleviate care-giving burden.


3' end processing of mouse histone pre-mRNA: evidence for additional base-pairing between U7 snRNA and pre-mRNA.
We have analysed the extent of base-pairing interactions between spacer sequences of histone pre-mRNA and U7 snRNA present in the trans-acting U7 snRNP and their importance for histone RNA 3' end processing in vitro. For the efficiently processed mouse H4-12 gene, a computer analysis revealed that additional base pairs could be formed with U7 RNA outside of the previously recognised spacer element (stem II). One complementarity (stem III) is located more 3' and involves nucleotides from the very 5' end of U7 RNA. The other, more 5' located complementarity (stem I) involves nucleotides of the Sm binding site of U7 RNA, a part known to interact with snRNP structural proteins. These potential stem structures are separated from each other by short internal loops of unpaired nucleotides. Mutational analyses of the pre-mRNA indicate that stems II and III are equally important for interaction with the U7 snRNP and for processing, whereas mutations in stem I have moderate effects on processing efficiency, but do not impair complex formation with the U7 snRNP. Thus nucleotides near the processing site may be important for processing, but do not contribute to the assembly of an active complex by forming a stem I structure. The importance of stem III was confirmed by the ability of a complementary mutation in U7 RNA to suppress a stem III mutation in a complementation assay using Xenopus laevis oocytes. The main role of the factor(s) binding to the upstream hairpin loop is to stabilise the U7-pre-mRNA complex. This was shown by either stabilising (by mutation) or destabilising (by increased temperature) the U7-pre-mRNA base-pairing under conditions where hairpin factor binding was either allowed or prevented (by mutation or competition). The hairpin dependence of processing was found to be inversely related to the strength of the U7-pre-mRNA interaction.


Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma.
Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.


Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines.
Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies. Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1-10, acetone 11-17 and cyclopentanone 18-24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1-24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11-17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed 1H NMR, IR, UV-Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure-activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases. Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.