Force of knee extensor and flexor muscles and cross-sectional area determined by nuclear magnetic resonance imaging.
The maximal strengths of knee extensor (E) and flexor (F) muscles were compared in a group of 6 male subjects aged 24-31 years. Cross-sectional area (CSA) of E and F was evaluated from planimetric measurements of Nuclear Magnetic Resonance (NMR) imaging axial scans, carried out at five levels along the thigh. Maximal CSA for E was found at 2/3 upper femur height and at 1/3 lower femur height for F. Maximum isometric force (MIF) of E was found to be 135% greater than that of F. The maximum CSA of E was found to be 93% larger than CSA of F. The calculated mechanical advantage of the flexors was estimated to be 13.8% higher than that of the knee extensors (0.116 +/- 0.012 and 0.132 +/- 0.005, respectively). However, when MIF of E and F were standardised for their respective CSA, no significant difference was found between their stress: 80.1 +/- 15.5 N.cm-2 for E and 70.5 +/- 7.0 N.cm-2 for F. From the present study, it is concluded that no significant difference exists between the maximum stress of knee extensor and flexor muscles despite large differences in their absolute values of force and CSA and that the NMR imaging technique enables accurate in-vivo determination of the CSA of individual muscles.


Recent advances in targeted strategies for triple-negative breast cancer.
Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, negatively expresses estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is the main form of treatment for patients with TNBC, the effectiveness of chemotherapy for TNBC is still limited. The search for more effective therapies is urgent. Multiple targeted therapeutic strategies have emerged according to the specific molecules and signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, epidermal growth factor receptor inhibitors, Notch inhibitors, poly ADP-ribose polymerase inhibitors, and antibody-drug conjugates. Moreover, immune checkpoint inhibitors, for example, pembrolizumab, atezolizumab, and durvalumab, are widely explored in the clinic. We summarize recent advances in targeted therapy and immunotherapy in TNBC, with the aim of serving as a reference for the development of individualized treatment of patients with TNBC in the future.


Is Illinois heeding the call to regionalize pancreatic surgery?
Recommendations to refer pancreatic procedures to high-volume centers have been in place for a decade. We sought to determine whether regionalization of pancreatic procedures to high-volume centers is occurring in Illinois. We compared pancreatic procedures performed in Illinois hospitals from 2000 to 2004 [time period (TP) 1] versus 2005-2009 (TP2) for changes in inpatient mortality and hospital volume. Hospitals were categorized into low- (LVH), intermediate- (IVH), or high-volume (HVH). From TP1 to TP2, there was a 23% increase in absolute case volume (2,232-2,737), despite fewer hospitals performing pancreatic procedures (114-95). In hospital mortality decreased (5.5-3.3%, P < 0.01) and was lowest at HVHs. LVHs and IVHs were associated with a 4.7 and 3.0 higher odds of mortality, respectively (both P < 0.001). Overall, HVHs performed 659 (+73%) more procedures, whereas cumulative procedure volume dropped by 154 cases at LVHs (+1%) and IVHs (-18%). We observed limited evidence of regionalization of pancreatic procedures in Illinois. The increase in HVH case volume cannot be solely attributed to regionalization, given the corresponding modest decrease seen at non-HVHs. There is opportunity for Illinois hospitals to implement strategies such as selective referral to improve mortality after pancreatic resection.


Genes and pseudogenes for human U2 RNA. Implications for the mechanism of pseudogene formation.
Three loci, designated U2/4, U2/6 and U2/7, which contain sequences related to human U2 RNA, have been studied. The U2/6 locus contains a tandem array of bona fide U2 genes. U2/4 and U2/7, in contrast, contain pseudogenes of whose sequences deviate significantly from that of mammalian U2 RNA. The two pseudogenes appear to have been created by different mechanisms. The sequences that flank the pseudogene in the U2/4 locus lack homology to the corresponding sequences in functional human U2 genes, except for 10 base-pairs immediately following the 3' end. The conserved 3'-flanking segment is homologous to those nucleotides that are present in a U2 RNA precursor. No direct repeats flank the pseudogene in the U2/4 locus. The observations thus suggest that a complementary DNA copy of the U2 RNA precursor was inserted into a blunt-ended chromosomal break to generate the U2/4 locus. The U2/7 locus, in contrast, revealed flanking sequence homology when compared to functional U2 genes, both on the 5' and 3' sides of the pseudogene. The homology was interrupted on both sides by repetitive sequences belonging to the Alu family. On the 5' side the homology continues beyond the Alu repeats whereas on the 3' side it ends precisely at the Alu repeat. This Alu repeat is inserted in a region where a homocopolymeric region of alternating C and T residues is located in functional U2 loci. The observed organization of the U2/7 locus suggests that a previously functional U2 locus was invaded by Alu repeats and subsequently accumulated base substitutions to become a pseudogene.


Chromatography of a Triton extracted beef cardiac cytochrome C1 preparation on diethylaminoethyl cellulose.
During the chromatography of a Triton X-100 extracted preparation of the mitochondrial membrane proteins on diethylaminoethyl cellulose, we have observed two chromatographic fractions containing cytochrome c1. One elutes from diethylaminoethyl cellulose with aqueous buffers alone, and the other elutes with those buffers after the addition of the nonionic detergent Triton X-100. The two forms occur in equimolar ratios and each retains its original chromatographic character on rechromatography, with no conversion of one form into the other.


Rationale behind the optimum efficiency of columns packed with new 1.9μm fully porous particles of narrow particle size distribution.
Columns packed with new commercially available 1.9 fully porous particles of narrow particle size distribution (nPSD) are characterized by extremely high efficiency. Under typical reversed phase conditions, these columns are able to generate very high number of theoretical plates (in the order of 300,000plates/m and more). In this paper, we investigate the origin of the high performance of these nPSD columns by performing a series of measurements that include, in addition to the traditional determination of the van Deemter curve, peak parking, pore blocking and inverse size exclusion experiments. Two nPSD columns (both 100×3.0mm) have been considered in this study: the first one, packed with particles of 80Å pore size, is commercially available. The second one is a prototype column packed with 1.9 fully porous particles of 120Å pore size. The main conclusion of our study is that these nPSD columns are characterized by extremely low eddy dispersion, while longitudinal diffusion and mass transfer kinetics are substantially equivalent to those of other fully porous particles of similar chemistry.


Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis rats: long-term evaluation of effects on ovarian structure and function.
To assess the long-term efficacy of intraperitoneal (IP) and subcutaneous (SC) ovarian autotransplantation in rats. Experimental animal study. Unit of Experimental Research, Barcelona University School of Medicine. Female syngeneic Lewis rats aged 14 weeks. Group A, control group undergoing ovariectomy (n = 15); group B, undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In groups B and C, five animals were killed and their ovaries removed for morphometric analysis at 30 days after transplantation; five additional animals were killed at 180 days, and the remaining five animals were killed at 360 days. Ovarian morphometric analysis and serial measurement of E(2) and FSH serum levels. RESULT(S); The mean number of antral follicles in the control group A was significantly higher than that observed in the ovarian grafts collected and examined 30 days after grafting in rats from groups B and C, but the mean granulosa cell area was significantly higher in both transplantation groups than in controls because of ovarian follicular hyperplasia. Histological examination of ovaries removed at 6 and 12 months after grafting in groups B and C showed increasing degrees of fibrosis, loss of primordial follicles, and the presence of epithelial cysts. In groups B and C, from day 30 after surgery onward, serum E(2) was significantly higher and FSH significantly lower, respectively, than in group A. E(2) and FSH patterns in groups B and C were similar throughout the study period. Heterotopic ovarian transplantation without vascular pedicle in rats is characterized by follicular hyperplasia endocrinologically functional, followed by progressive loss of follicles in heterotopic ovarian autografts.


Enhancement in Bacterial Cellulolytic Enzyme Production Using Acid-Pretreated Banana Peel Waste: A Comparative Evaluation.
Banana peel waste is one of the major contributors in the issue raised from solid waste, however, it can be valorized effectively due to high content of cellulose and hemicellulose. Significant conversion of banana waste includes cellulolytic enzymes and bioenergy production. In the present study, bacterial cellulase was produced using raw banana peel and ripe banana peel under SSF. Additionally, impact of acid pretreatment was investigated as one of strategy to improve cellulolytic enzyme production. A comparative evaluation of raw and ripe banana peels showed that ripe banana peels showed better enzyme production after pretreatment with 0.5% dilute HCl acid. In the series of enhancement of the enzyme production, temperature and pH of the SSF medium were also investigated, and found temperature 35 °C and pH 6.0 were optimum to produce maximum 3.5-U/ml FPA, 39-U/ml BGL, and 54-U/ml EG in 18-h SSF incubation. The study presented eco-friendly waste management to produce industrial enzyme for its promising application in waste valorization and biorefinery area.


Assignment Of Hexuronic Acid Stereochemistry In Synthetic Heparan Sulfate Tetrasaccharides With 2-O-Sulfo Uronic Acids Using Electron Detachment Dissociation.
The present work focuses on the assignment of uronic acid stereochemistry in heparan sulfate (HS) oligomers. The structural elucidation of HS glycosaminoglycans is the subject of considerable importance due to the biological and biomedical significance of this class of carbohydrates. They are highly heterogeneous due to their non-template biosynthesis. Advances in tandem mass spectrometry activation methods, particularly electron detachment dissociation (EDD), has led to the development of methods to assign sites of sulfo modification in glycosaminoglycan oligomers, but there are few reports of the assignment of uronic acid stereochemistry, necessary to distinguish glucuronic acid (GlcA) from iduronic acid (IdoA). Whereas preceding studies focused on uronic acid epimers with no sulfo modification, the current work extends the assignment of the hexuronic acid stereochemistry to 2-O-sulfo uronic acid epimeric tetrasaccharides. The presence of a 2-O-sulfo group on the central uronic acid was found to greatly influence the formation of B3, C2, Z2, and Y1 ions in glucuronic acid and Y2 and 1,5X2 for iduronic acid. The intensity of these peaks can be combined to yield a diagnostic ratios (DR), which can be used to confidently assign the uronic acid stereochemistry.


The universal stress protein paralogues of Escherichia coli are co-ordinately regulated and co-operate in the defence against DNA damage.
We have cloned, characterized and inactivated genes encoding putative UspA paralogues in Escherichia coli. The yecG (uspC), yiiT (uspD) and ydaA (uspE) genes were demonstrated to encode protein pro-ducts and these were mapped to spots in the E. coli proteomic database. Expression analysis using chromosomal transcriptional lacZ fusions and two-dimensional gels revealed that all usp genes analysed are regulated in a similar fashion. Thus, uspC, D and E are all induced in stationary phase and by a variety of stresses causing growth arrest of cells. Induction is independent of rpoS but is abolished in a deltarelA deltaspoT (ppGpp0) background and rescued by suppressor mutations rendering the beta-subunit of RNA polymerase to behave like a stringent polymerase. Ectopic elevation of ppGpp levels in growing cells, by overproducing the RelA protein, triggered the induction of all usp genes. The expression of all usp genes was also elevated by a mutation in the ftsK cell division gene, and this super-induction could be suppressed by inactivating recA indicating that the usp paralogues are involved in the management of DNA. Indeed, uspC, uspD and uspE deletion mutants were all found to be sensitive to UV exposure. Overexpression of UspD could compensate for the lack of a chromosomal uspD gene but not a uspA gene. Similarly, UspA overproduction could only compensate for the lack of chromosomal uspA. Moreover, combination of usp mutations had no additive effect on UV sensitivity indicating that they are all co-operating and required in the same pathway, which could explain the co-ordinated regulation of the genes.


Empowerment of patients and communication with health care professionals through an electronic health record.
The aim of this project was to design and develop a personal electronic health record (EHR) in order to support patient empowerment and additionally to enhance their communication and information exchange with health professionals through this EHR. The functionality of a personal Electronic Healthcare Record (EHR) may vary from a simple web-based interface for interactive data entry and data review up to a much more powerful system additionally supporting electronic data/document communication between clinical information systems of primary care practitioners or hospitals and even reminder based support for the empowered citizen, to actively take care of his health, based on relevant disease management programs. It is one means to support patient empowerment, additionally supported by tools for building a patient community. Since storage and communication of data in an EHR comprises sensible personal health data, each of those functions needs specific security and access management requirements to be considered and implemented. Clinical pilot projects are already done or under development.


Optimal spore germination in Clostridium botulinum ATCC 3502 requires the presence of functional copies of SleB and YpeB, but not CwlJ.
Germination, the process by which dormant endospores return to vegetative growth, is a critical process in the life cycle of the notorious pathogen Clostridium botulinum. Crucial is the degradation by hydrolytic enzymes of an inner peptidoglycan spore layer termed the cortex. Two mechanistically different systems of cortex lysis exist in spores of Clostridium species. C. botulinum ATCC 3502 harbours the Bacillus-like system of SleB, CwlJ and YpeB cortex lytic enzymes (CLEs). Through the construction of insertional gene knockout mutants in the sleB, cwlJ and ypeB genes of C. botulinum ATCC 3502 and the production of spores of each mutant strain, the effect on germination was assessed. This study demonstrates a reduced germination efficiency in spores carrying mutations in either sleB or ypeB with an approximate 2-fold reduction in heat resistant colony forming units (CFU/OD600) when plated on rich media. This reduction could be restored to wild-type levels by removing the spore coat and plating on media supplemented with lysozyme. It was observed that cwlJ spores displayed a similar germination efficiency as wild-type spores (P > 0.05). An optimal germinant commixture was identified to include a combination of l-alanine with sodium bicarbonate as it resulted in a 32% drop in OD600, while the additional incorporation of l-lactate resulted in a 57% decrease. Studies of the germination efficiency of spores prepared from all three CLE mutants was performed by monitoring the associated decrease in optical density but a germination defect was not observed in any of the CLE mutant strains. This was likely due to the lack of specificity of this particular assay. Taken together, these data indicate that functional copies of SleB and YpeB, but not CwlJ are required for the optimal germination of the spores of C. botulinum ATCC 3502.


Changes in the kinetics of muscle contraction in vitamin D-depleted rats.
Using an in situ rat soleus neuromuscular preparation, changes in the muscle contraction kinetics in response to vitamine D depletion were studied. For a single isometric contraction, the time-to-peak tension (Tp) and the time-for-recovery-half-way-to-resting tension (T1/2r) were recorded. For a 150 Hz, 300 msec tetanus, the T1/2r was determined. Animals raised on high-calcium, high-phosphate, vitamin D-depleted diets showed prolongation of all parameters. Repletion of vitamin D returned Tp and T1/2r values to normal. Neither dietary calcium deficiency nor thyroparathyroidectomy produced an prolongation of Tp or T1/2r values. Therefore, based upon the experimental data, it appears that vitamin D or one of its metabolites, independent of any effect on the serum calcium or serum phosphate concentration, is necessary for normal muscle relaxation.


Exercise training restores ischemic preconditioning in the aging heart.
To investigate the effects of ischemic preconditioning in hearts from adult and both sedentary and trained senescent rats. Ischemic preconditioning does not prevent postischemic dysfunction in the aging heart, probably because of reduction of cardiac norepinephrine release. Exercise training can reverse the age-related decrease of norepinephrine production. We investigated the effects on mechanical parameters of ischemic preconditioning against 20 min of global ischemia followed by 40 min of reperfusion in isolated perfused hearts from adult (six months) and sedentary or trained (six weeks of graduated swim training) senescent (24 months) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent-developed pressure was significantly improved after preconditioning in adult hearts (91.6+/-9.6%) versus unconditioned controls (54.2+/-5.1%, p<0.01). The effect of preconditioning on developed pressure recovery was absent in sedentary but present in trained senescent hearts (39.6+/-4.1% vs. 64.3+/-7.1%, p<0.05). Norepinephrine release significantly increased after preconditioning in adult and in trained but not in sedentary senescent hearts. The depletion of myocardial norepinephrine stores by reserpine abolished preconditioning effects in adult and trained senescent hearts. In adult and trained but not in sedentary senescent hearts, preconditioning reduces postischemic dysfunction and is associated with an increase in norepinephrine release. Preconditioning was blocked by reserpine in both adult and trained senescent hearts. Thus, exercise training may restore preconditioning in the senescent heart through an increase of norepinephrine release.


Temporal and social contexts of heroin-using populations. An illustration of the snowball sampling technique.
Snowball sampling is a method that has been used in the social sciences to study sensitive topics, rare traits, personal networks, and social relationships. The method involves the selection of samples utilizing "insider" knowledge and referral chains among subjects who possess common traits that are of research interest. It is especially useful in generating samples for which clinical sampling frames may be difficult to obtain or are biased in some way. In this paper, snowball samples of heroin users in two Dutch cities have been analyzed for the purpose of providing descriptions and limited inferences about the temporal and social contexts of their lifestyles. Two distinct heroin-using populations have been discovered who are distinguished by their life cycle stage. Significant contextual explanations have been found involving the passage from adolescent peer group to criminal occupation, the functioning of network "knots" and "outcroppings," and the frequency of social contact. It is suggested that the snowball sampling method may have utility in studying the temporal and social contexts of other populations of clinical interest.


Adipose tissue triglyceride fatty acids and atherosclerosis in Alaska Natives and non-Natives.
Essential polyunsaturated fatty acids (PUFA) of the omega-3 family are believed to protect against cardiovascular disease. A rich source of omega-3 PUFA is found in fish and marine mammals (seal, walrus, whale), which are a large part of the traditional diet of Alaska Natives (Eskimo, American Indians, Aleuts), a group that has been reported to have a lower mortality rate from cardiovascular disease than non-Natives. An autopsy study using standardized methods to evaluate the extent of atherosclerosis and its risk factors, and analyses of stored triglyceride fatty acids was conducted in a sample of Alaska Native subjects and non-Native subjects living in Alaska. Findings indicate that Alaska Natives had less advanced atherosclerosis in coronary arteries, along with higher proportions of omega-3 and lower proportions of omega-6 PUFA in adipose tissue, than did non-Natives. We conclude that high dietary intake of omega-3 PUFA may account for the lower extent of coronary artery atherosclerosis, contributing to the reported lower heart disease mortality among Alaska Natives.


Otopharmacology.
Therapy for diseases of the ear canal is, in most respects, similar to therapy for other diseases of dogs and cats. As a target for drug therapy, however, the unique anatomy of the external ear canal presents differences that are both advantageous and disadvantageous. This article will describe principles of therapy and pharmacologic properties from the perspective of topical therapy directed at the surface of the ear canal, the epidermis, and the dermis.


Mental health problems and resilience in adolescents during the COVID-19 pandemic in a post-armed conflict area in Colombia.
The impact of COVID-19 pandemic on mental health of adolescents are emerging and require particular attention in settings where challenges like armed conflict, poverty and internal displacement have previously affected their mental wellbeing. This study aimed to determine the prevalence of anxiety symptoms, depressive symptomatology, probable post-traumatic stress disorder and resilience in school-attending adolescents in a post-conflict area of Tolima, Colombia during the COVID-19. A cross-sectional study was carried out with 657 adolescents from 12 to 18 years old, recruited by convenience sampling in 8 public schools in the south of Tolima, Colombia, who completed a self-administered questionnaire. Mental health information was obtained through screening scales for anxiety symptoms (GAD-7), depressive symptomatology (PHQ-8), probable post-traumatic stress disorder (PCL-5) and resilience (CD-RISC-25). The prevalence observed for moderate to severe anxiety symptoms was 18.9% (95% CI 16.0-22.1) and for moderate to severe depressive symptomatology was 30.0% (95% CI 26.5-33.7). A prevalence of probable post-traumatic stress disorder (PTSD) of 22.3% (95% CI 18.1-27.2) was found. The CD-RISC-25 results for resilience had a median score of 54 [IQR 30]. These results suggest that approximately two-thirds of school-attending adolescents in this post-conflict area experienced at least one mental health problem such as anxiety symptoms, depressive symptomatology or probable PTSD during the COVID-19 pandemic. Future studies are of interest to establish the causal relationship between these findings and the impact of the pandemic. These findings highlight the challenge that schools have after pandemic to address the mental health of their students in order to promoting adequate coping strategies and implement prompt multidisciplinary interventions to reduce the burden of mental health problems in adolescents.


Effects of CuCl2 on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart.
CuCl2 non-competitively inhibited the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent phosphodiesterase from bovine heart in the presence of 5 mM Mg2+, 10 muM Ca2+ and phosphodiesterase activator with Ki values of approximately 2 muM for both substrates. CuCl2 inhibition was also non-competitive with Mg2+, Ca2+ and phosphodiesterase activator. Dialysis demonstrated that CuCl2 inhibition is reversible. Treatment of the enzyme with p-hydroxymercuribenzoate resulted in the loss of enzyme activity, suggesting the presence of sulfhydryl groups essential for enzyme activity. The inhibitory activity of CuCl2 was not additive with that of p-hydroxymercuribenzoate, therefore CuCl2 may inhibit enzyme activity by binding to one or more essential sulfhydryl groups. CuCl2 also inhibited the hydrolysis of cyclic AMP by the cyclic AMP-specific phosphodiesterase from bovine heart with an I50 value of 18 muM. Several effects of Cu2+ are discussed which have been noted in other studies and might be due, in part, to changes in cyclic nucleotide levels following alterations in phosphodiesterase activity.


Detecting Posttranslational Modifications of Hsp90 Isoforms.
The molecular chaperone heat shock protein 90 (Hsp90) is essential in eukaryotes. Hsp90 chaperones proteins that are important determinants of multistep carcinogenesis. There are multiple Hsp90 isoforms including the cytosolic Hsp90α and Hsp90β as well as GRP94 located in the endoplasmic reticulum and TRAP1 in the mitochondria. The chaperone function of Hsp90 is linked to its ability to bind and hydrolyze ATP. Co-chaperones and posttranslational modifications (such as phosphorylation, SUMOylation, and ubiquitination) are important for Hsp90 stability and regulation of its ATPase activity. Both mammalian and yeast cells can be used to express and purify Hsp90 and TRAP1 and also detect post-translational modifications by immunoblotting.


Trends in Hospitalization and Mortality Rates Due to Acute Cardiovascular Disease in Castile and León, 2001 to 2015.
To analyze hospitalization and mortality rates due to acute cardiovascular disease (ACVD). We conducted a cross-sectional study of the hospital discharge database of Castile and León from 2001 to 2015, selecting patients with a principal discharge diagnosis of acute myocardial infarction (AMI), unstable angina, heart failure, or acute ischemic stroke (AIS). Trends in the rates of hospitalization/100 000 inhabitants/y and hospital mortality/1000 hospitalizations/y, overall and by sex, were studied by joinpoint regression analysis. A total of 239 586 ACVD cases (AMI 55 004; unstable angina 15 406; heart failure 111 647; AIS 57 529) were studied. The following statistically significant trends were observed: hospitalization: ACVD, upward from 2001 to 2007 (5.14; 95%CI, 3.5-6.8; P < .005), downward from 2011 to 2015 (3.7; 95%CI, 1.0-6.4; P < .05); unstable angina, downward from 2001 to 2010 (-12.73; 95%CI, -14.8 to -10.6; P < .05); AMI, upward from 2001 to 2003 (15.6; 95%CI, 3.8-28.9; P < .05), downward from 2003 to 2015 (-1.20; 95%CI, -1.8 to -0.6; P < .05); heart failure, upward from 2001 to 2007 (10.70; 95%CI, 8.7-12.8; P < .05), upward from 2007 to 2015 (1.10; 95%CI, 0.1-2.1; P < .05); AIS, upward from 2001 to 2007 (4.44; 95%CI, 2.9-6.0; P < .05). Mortality rates: downward from 2001 to 2015 in ACVD (-1.16; 95%CI, -2.1 to -0.2; P < .05), AMI (-3.37, 95%CI, -4.4 to -2, 3, P < .05), heart failure (-1.25; 95%CI, -2.3 to -0.1; P < .05) and AIS (-1.78; 95%CI, -2.9 to -0.6; P < .05); unstable angina, upward from 2001 to 2007 (24.73; 95%CI, 14.2-36.2; P < .05). The ACVD analyzed showed a rising trend in hospitalization rates from 2001 to 2015, which was especially marked for heart failure, and a decreasing trend in hospital mortality rates, which were similar in men and women. These data point to a stabilization and a decline in hospital mortality, attributable to established prevention measures.


The Timed Manual Performance test as a predictor of hospitalization and death in a community-based elderly population.
To determine the usefulness of timed manual performance measurements (TMP) as predictors of health outcomes, hospitalization, and mortality in a large, heterogeneous sample of elderly people living in the community. Prospective cohort study. Central North Carolina. 1,286 community-dwelling older people. Demographic background, health problems, number of prescribed medications, perceived health, quality of life, and the TMP, a 27-item test that has been shown to predict functional dependency and need of health-care services in older people. During the 2-year follow-up period, 127 people died and 200 were hospitalized. Scores for those who were able to complete the original TMP, as well as scores for two shorter versions of the TMP, predicted mortality and, to a lesser extent, hospitalization within 2 years. For both original and shorter versions of the TMP, relative risk of death was approximately 2.5 times greater for those in the poorest performance quartile, as compared with the best performing quartile, when adjusted for age, gender, race, and number of prescribed medications. TMP tests and an index of IADL were independent predictors of death. TMP scores may be useful in the clinical setting as a vital sign of functioning, providing a means of targeting those individuals at increased risk of mortality.


Apolipoprotein E and its mimetic peptide suppress Th1 and Th17 responses in experimental autoimmune encephalomyelitis.
Apolipoprotein E (apoE) has been detected to possess anti-inflammatory properties that can contribute to protection against experimental autoimmune encephalomyelitis (EAE). However, its impact on Th1 and Th17 responses in EAE is unclear. In this study, we induced EAE in apoE-/- mice and wild-type mice. We observed that the absence of apoE resulted in the increased proportion of Th1 and Th17 cells in the spleens and brains, as well as up-regulated expressions of proinflammatory cytokines (IL-17, IFN-γ, TNF-α, IL-12, IL-1β and IL-6) and transcription factors (RORγt and T-bet) in the CNS. ApoE-/- mice also showed the increased release of proinflammatory cytokines by macrophages in vitro. In addition, we used a mimetic peptide of apoE, which mimic the functions of apoE except for lipid transport. ApoE mimetic peptide could reverse the above negative effect in EAE. Thus, apoE can modulate Th1 and Th17 responses, likely through its inhibitory effect on the secretion of cytokines by macrophages. Our result also suggests that apoE mimetic peptide might be developed into a therapeutic agent for multiple sclerosis.


Pre-existing chiasma syndromes do not entirely remit following transsphenoidal surgery for pituitary adenomas.
It is not known whether following transsphenoidal surgery for pituitary adenomas the vision of patients with preoperative chiasma syndromes (CS) does improve to the degree of vision of patients without preoperative CS. The purpose of this study is to answer the question above. Pertinent data of a successive series of patients operated transsphenoidally for the first time for pituitary adenoma were retrospectively analysed. Of the 304 patients, 35.1% presented preoperatively with CS. The median visual acuity (VA) of these patients improved significantly from preoperative (right eye, 0.63 (0; 1.25); left eye, 0.56 (0; 1.4)) to postoperative (right eye, 0.8 (0; 1.25); left eye, 0.74 (0; 1.25)). The median number of impaired quadrants of the binocular visual fields (VF) improved significantly from preoperative (2 (0; 8)) to postoperative CS (0 (0; 4)). In patients without preoperative CS, postoperative vision (VA as well as VF) remained unchanged. Postoperatively, VA of patients with preoperative CS remained significantly lower than that of patients without preoperative CS (right eye, 0.96 (0.2; 1.4); left eye, 0.94 (0.05; 1.4)). Postoperatively, the number of impaired quadrants of the binocular VF of patients with preoperative CS remained significantly higher than in patients without preoperative CS (0 (0; 1)). In this unselected patient series, the vision (VA as well as VF) of patients with preoperative CS did not improved postoperatively to the degree of the vision of patients without preoperative CS. Thus, in patients with adenomatous chiasma compression transsphenoidal surgery may be indicated before CS develops.


Hospital pharmacy practice in Saudi Arabia: Prescribing and transcribing in the Riyadh region.
The purpose of this survey is to outline pharmacy services in hospitals on a regional level in the Kingdom of Saudi Arabia. A modified-American Society of Health-System Pharmacists (ASHP) survey questionnaire as pertinent to Saudi Arabia was used to conduct a national survey. After discussing with the pharmacy directors of 48 hospitals in the Riyadh region over the phone on the survey's purpose, the questionnaires were personally delivered and collected upon completion. The hospital lists were drawn from the Ministry of Health hospital database. Twenty-nine hospitals participated in the survey giving a response rate of 60.4%. Approximately 60% of the hospitals which participated in the survey required prior approval for the use of non-formulary medications. About 83.3% of hospitals reviewed compliance with clinical practice guidelines and 72.7% hospitals reported that pharmacists are also actively involved in these activities. Pharmacists in more than 95% of hospitals provided consultations on drug information. A staff pharmacist routinely answering questions was the most frequently cited (74.1%) method by which objective drug information was provided to prescribers. Electronic drug information resources were available in 77.7% of hospitals, although internet use is not widely available to hospital pharmacists, with only 58.6% of hospitals providing pharmacist access to the internet. About, 34.5% of hospitals had computerized prescriber order entry (CPOE) systems with clinical decision-support systems (CDSSs) and 51.9% of the hospitals had electronic medical record (EMR) system. Hospital pharmacists are increasingly using electronic technologies to improve prescribing and transcribing of medications in Saudi Arabia.


William L. McGuire Memorial Symposium. Control of breast cancer cell growth by steroids and growth factors: interactions and mechanisms.
Over the past two decades, the simple model for control of breast cancer growth involving one or two factors acting directly or indirectly via endocrine pathways has turned into a complex model implicating numerous interacting factors and the diverse cell populations constituting breast tumors. Current approaches to breast cancer therapy now require integration of these multiple parameters and enhanced understanding of the different levels of their intricate interactions.


A vibrational spectroscopic study of the phosphate mineral cyrilovite Na(Fe3+)3(PO4)2(OH)4·2(H2O) and in comparison with wardite.
Vibrational spectroscopy enables subtle details of the molecular structure of cyrilovite to be determined. Single crystals of a pure phase from a Brazilian pegmatite were used. Cyrilovite is the Fe(3+) member of the wardite group. The infrared and Raman spectroscopy were applied to compare the structure of cyrilovite with that of wardite. The Raman spectrum of cyrilovite in the 800-1400 cm(-1) spectral range shows two intense bands at 992 and 1055 cm(-1) assigned to the ν1PO4(3-) symmetric stretching vibrations. A series of low intensity bands at 1105, 1136, 1177 and 1184 cm(-1) are assigned to the ν3PO4(3-) antisymmetric stretching modes. The infrared spectrum of cyrilovite in the 500-1300 cm(-1) shows much greater complexity than the Raman spectrum. Strong infrared bands are found at 970 and 1007 cm(-1) and are attributed to the ν1PO4(3-) symmetric stretching mode. Raman bands are observed at 612 and 631 cm(-1) and are assigned to the ν4 out of plane bending modes of the PO4(3-) unit. In the 2600-3800 cm(-1) spectral range, intense Raman bands for cyrilovite are found at 3328 and 3452 cm(-1) with a broad shoulder at 3194 cm(-1) and are assigned to OH stretching vibrations. Sharp infrared bands are observed at 3485 and 3538 cm(-1). Raman spectroscopy complimented with infrared spectroscopy has enabled the structure of cyrilovite to be ascertained and compared with that of wardite.


Construction of dual active sites on the CuAg plasmonic aerogel for simultaneously efficient photocatalytic CO2 reduction and H2 production.
Photocatalytic CO2 reduction and H2 production are a competitive reaction, and existing active sites cannot take into account the simultaneous gas-solid and liquid-solid reaction processes. Hence, a metallic aerogel (CuAg2.5) with dual active sites was constructed via straightforward in-situ reduction process. CuAg2.5 aerosol has larger porosity and CO2 adsorption capacity, which enables H2O and CO2 to fully contact it. The CuAg2.5 can also construct the cooperative dual active sites, which can conduct CO2 reduction reaction on Ag surface and proton reduction reaction on Cu surface, respectively, thereby efficiently guiding the rapid migration of photogenerated carriers. The yields of CO (18533 µmol g-1) and H2 (20340 µmol g-1) for CuAg2.5 are much higher than those of single metals. The ratio of CO and H2 can also regulated via changing the ratio of Ag and Cu. This work gives new insights into the fabrication of unique high-efficiency plasmonic photocatalysts.


Transcriptional inhibition of the Catalase gene in phosphine-induced oxidative stress in Drosophila melanogaster.
Phosphine (PH3) is a toxic substance to pest insects and is therefore commonly used in pest control. The oxidative damage induced by PH3 is considered to be one of the primary mechanisms of its toxicity in pest insects; however, the precise mode of PH3 action in this process is still unclear. In this study, we evaluated the responses of several oxidative biomarkers and two of the main antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), after fumigation treatment with PH3 in Drosophila melanogaster as a model system. The results showed that larvae exposed to sub-lethal levels of PH3 (0.028 mg/L) exhibited lower aerobic respiration rates and higher levels of hydrogen peroxide (H2O2) and lipid peroxidation (LPO). Furthermore, unlike SOD, the activity and expression of CAT and its encoding gene were downregulated by PH3 in a time- and dose-dependent manner. Finally, the responses of six potential transcription factors of PH3 were determined by real-time polymerase chain reaction to explore the regulation mechanism of DmCAT by PH3. There were no significant effects of PH3 on three nuclear factor-kappa B homologs (DORSAL, DIF, and RELISH) or two activator protein-1 genes (JUN and FOS), while dramatic inhibition of DNA replication-related element factor (DREF) expression was observed after fumigation with PH3, suggesting that PH3 could inhibit the expression of DmCAT via the DRE/DREF system. These results confirmed that PH3 induces oxidative stress and targets CAT by downregulating its encoding gene in Drosophila. Our results provide new insight into the signal transduction mechanism between PH3 and its target genes.


Abortive infection of influenza virus in Ehrlich ascites tumor cells. Unusual fragility of virus particles.
Noninfectious virus particles were produced in Ehrlich ascites tumor cells infected intraperitoneally with fowl plague virus. The PFU yield of virus per cell was less than 0.1 and the ratio PFU/HA units in the progeny virus was less than 10(3). The virus particles had the same morphology and size as egg-grown virus but were more fragile. They were disrupted by centrifugation through sucrose and caesium chloride gradients, but this disruption was avoided by fixing the particles with formaldehyde before centrifugation. Analysis of polypeptides by SDS-PAGE showed that ascites-grown virus particles contained reduced amounts of matrix protein compared with egg-grown virus.


Genetic variation in chromatin state across multiple tissues in Drosophila melanogaster.
We use ATAC-seq to examine chromatin accessibility for four different tissues in Drosophila melanogaster: adult female brain, ovaries, and both wing and eye-antennal imaginal discs from males. Each tissue is assayed in eight different inbred strain genetic backgrounds, seven associated with a reference quality genome assembly. We develop a method for the quantile normalization of ATAC-seq fragments and test for differences in coverage among genotypes, tissues, and their interaction at 44099 peaks throughout the euchromatic genome. For the strains with reference quality genome assemblies, we correct ATAC-seq profiles for read mis-mapping due to nearby polymorphic structural variants (SVs). Comparing coverage among genotypes without accounting for SVs results in a highly elevated rate (55%) of identifying false positive differences in chromatin state between genotypes. After SV correction, we identify 1050, 30383, and 4508 regions whose peak heights are polymorphic among genotypes, among tissues, or exhibit genotype-by-tissue interactions, respectively. Finally, we identify 3988 candidate causative variants that explain at least 80% of the variance in chromatin state at nearby ATAC-seq peaks.


A feasibility study for recording of dispensing errors and near misses' in four UK primary care pharmacies.
Medication errors can occur at the prescribing, transcription, dispensing and administration stage of drug therapy. However, publication of the Organisation with a Memory (OWAM) by the Department of Health in the UK has raised awareness of the need for pharmacies to collect information about dispensing errors and near misses, which occur within an organisation. Such information provides valuable insights into the vulnerabilities of dispensing procedures and identifies areas for improvement in dispensing systems The main aim of this study was to investigate the feasibility of a self-reporting system for dispensing errors and near misses in primary care (community) pharmacies. It was also to identify the types of errors or near misses commonly encountered in community pharmacies. A data collection form was designed and modified for use after a pilot study. Four community pharmacies volunteered to participate in this feasibility study. The data collection was conducted in two phases each of 4 weeks' duration. Any dispensing errors and near misses that occurred during the study periods were recorded by the pharmacy staff in a standard data collection form. A focus group discussion was held with the dispensing staff of participating pharmacies to identify and evaluate the feasibility of the reporting system. Out of a total of 51 357 items dispensed during the two phases of the study, 39 dispensing errors (0.08%) and 247 near misses (0.48%) were detected. The results show that near misses occurred six times more often than dispensing errors, indicating the importance of final checking in pharmacies. The most common types of dispensing errors or near misses appeared to be incorrect strength of medication, followed by incorrect drug, incorrect quantity, incorrect dosage form and incorrect label. Feedback during the focus group discussion indicated that the outcome of the self-reporting scheme was more important than the incidence of errors or near misses. Participating pharmacies also agreed that the self-reporting scheme used was feasible and they would continue using the scheme although some incentives would be helpful. The quantitative results of this study and the qualitative feedback from the participating pharmacies indicate that the self-reporting scheme used is practical and feasible.


Cerebral hemodynamics during cardiopulmonary bypass in children using near-infrared spectroscopy.
We describe a new noninvasive method using near-infrared spectroscopy for monitoring cerebral hemodynamics during cardiopulmonary bypass in children. All patients were undergoing open heart operations for repair of congenital heart defects. Standardized anesthesia, an alpha-stat method of blood gas management, and nonpulsatile flow were used in all cases. All measurements during bypass were made after steady-state conditions had been reached. Cerebral blood flow was measured on 13 occasions in 4 children, aged between 4 and 10 months (median, 5 months). Values of 15.9 to 53.5 mL x 100 g-1 x min-1 were obtained. Cerebral blood volume was measured in 1 patient, aged 4 months. Volumes of 4.3 to 8.0 mL x 100 g-1 were obtained on bypass at full pump flow (2.4 L.min-1 x m-2). On bypass at half flow, the volume increased to 14.7 mL x 100 g-1. Change in cerebral blood volume with changing carbon dioxide tension (CBVR) was measured in 13 patients aged from 1 to 90 months (median, 13.5 months). Preoperatively, CBVR was 0.12 +/- 0.07 mL x 100 g-1 x kPa-1 and was independent of mean arterial pressure, which remained between 40 and 80 mm Hg in all cases. During hypothermic bypass (25 degrees C), CBVR was significantly reduced to 0.05 +/- 0.02 mL x 100 g-1 x kPa-1. In addition, there were three values at mean arterial pressure of lower than 40 mm Hg in which CBVR was negative (-0.04 +/- 0.01 mL x 100 g-1 x kPa-1). We conclude that near-infrared spectroscopy is useful for the noninvasive investigation of cerebral hemodynamics during cardiopulmonary bypass.


Mu-opiate receptor binding and function in HOT and COLD selected lines of mice.
mu-Opiate receptor binding and function were examined in mice selectively bred for sensitivity (COLD) and resistance (HOT) to ethanol-induced hypothermia. These mice also have differential hypothermic sensitivity to mu-opiates. mu-Opiate receptor density was higher in the frontal cortex of HOT mice compared with COLD mice, but was the same in other brain areas. In addition, there were no line differences in Kd values. Basal adenylate cyclase (AC) activity was similar in both lines, as was the response to forskolin (FS) stimulation. Morphine was more effective at inhibiting FS-AC activity in the hypothalamus of HOT mice compared with COLD mice but was equally effective in the frontal and parietal cortex. There were no differences between lines in basal Ca2+, Mg2+, or Ca2+/Mg(2+)-ATPase activity. Further, 30 min after treatment ATPase activities were not altered in ethanol- or levorphanol-treated mice. These results suggests that mu-opiate biochemical pathways, but not ATPase enzyme systems, may be involved in mediating differential hypothermic sensitivity observed in HOT and COLD mice.


FABP7 promotes cell proliferation and survival in colon cancer through MEK/ERK signaling pathway.
Colon cancer (CC), one of the most frequently diagnosed malignancies deriving from the digestive system, has greatly threatened human health and life. Fatty acid binding protein 7 (FABP7), an intracellular protein with the tissue-specific expression pattern, has been reported to be implicated in diverse types of human tumors. However, the biological role of FABP7 in CC is still poorly understood. The current study aimed to investigate the role of FABP7 in CC and illuminate the potential molecular mechanisms. In this present study, we found that FABP7 was highly expressed in CC tissues and cell lines, suggesting the possible involvement of FABP7 in CC tumorigenesis. Moreover, functional investigations showed that FABP7-overexpression promoted CC cell proliferation, colony formation, cell cycle progression and inhibited cell apoptosis; on the contrary, FABP7 knockdown produced an inhibitory effects on CC cell proliferation and survival. Notably, FABP7 knockdown inhibited colon tumor growth in vivo. In addition, mechanistic investigations demonstrated that FABP7 exerted its promoting effects on CC cell proliferation and survival through activation of the MEK/ERK signaling pathway. Collectively, our data indicate that FABP7 may be used as a novel diagnostic bio-marker and a potential therapeutic target for CC.


The effects of methylprednisolone and mitoxantrone on CCL5-induced migration of lymphocytes in multiple sclerosis.
Chemokines are involved in migration of inflammatory cells to the central nervous system (CNS) in multiple sclerosis (MS). The aim of this study was the analysis of the impact of MS treatment on CCL5-induced migration of leukocyte subpopulations. Migration of lymphocytes and monocytes from blood of MS patients treated with methylprednisolone (MP) or mitoxantrone (MTX) was analysed in a chemotaxis chamber. CCL5-induced migration of lymphocytes from untreated MS patients was significantly increased over controls. The treatment of MS with MP and MTX reduced this chemotaxis. The plasma level of CCL5 was increased in MS patients before treatment and was also significantly decreased in the treatment of MS with MP and MTX. This observation supports the hypothesis that in MS, chemokine CCL5 may induce migration of leukocytes to the CNS and suggests that treatment of the disease with MP and MTX may reduce this migration.


Comparison of deforestation and forest land use factors for malaria elimination in Myanmar.
Within the remote region of Ann Township in Myanmar's Rakhine State, malaria prevalence has remained steady at ∼10% of the population from 2016-2019. Previous studies have linked areas of higher malaria prevalence in the region to heavily forested areas, however, little is known about how people live, work, and move through these areas. This work aims to disentangle landscape from land use in regard to malaria exposure. We investigated the roles of forest cover, forest loss, and land use activities with malaria prevalence through the combined use of land use surveys, malaria surveillance, and satellite earth observations. Our results confirm previous research that linked areas of high forest cover with high malaria prevalence. However, areas experiencing high levels of deforestation were not associated with malaria prevalence. The land use factors that contribute most significantly to increased malaria risk remained those which put people in direct contact with forests, including conducting forest chores, having an outdoor job, and having a primary occupation in the logging and/or plantation industry. Malaria prevention methods in Myanmar should focus on anyone who lives near forests or engages in land use activities that bring them within proximity of forested landscapes, whether through occupation or chores.


Pathological study on amyloidosis--scanning electron microscopic observation of amyloid-laden mouse liver.
Amyloidosis of liver in mice induced by casein injection was studied by scanning electron microscopy (SEM). In the fractured-surfaces of the central portion of amyloid nodules, they appeared as chestnut-bur-like structures and were composed of numerous thread-like structures of fasciculated amyloid fibrils and of stick-like structures of amyloid bundles in three dimensional figure. In the cytoplasm of the Kupffer cell, amyloid bundles were revealed as band-like bulges. These bulges were projected from the Kupffer cell into the Disse's space and continued with thread-like structures outside the cytoplasm of Kupffer cells.


Case report: Congenital mesoblastic nephroma.
Congenital mesoblastic nephroma is a common benign renal tumor that mainly affects infants below the age of six months (Daskas et al., 2002). Identifying the pathology type is crucial for determining the appropriate plan of action and predicting the patient's prognosis. A one-day-old Hispanic neonate was referred for surgical evaluation after detecting a LUQ mass. Ultrasound imaging revealed a heterogenous solid mass that infiltrated the hilum of the left kidney. The patient underwent a left radical nephrectomy, and the pathology results indicated that the mass was consistent with the classic type of congenital mesoblastic nephroma. The patient will be closely monitored by nephrology with frequent abdominal ultrasounds. The case describes a one-day-old female baby with an asymptomatic LUQ abdominal mass, which was diagnosed as mesoblastic nephroma. The baby was born full-term with no significant medical history, and after experiencing hypertensive episodes, she underwent a left radical nephrectomy to remove the tumor. Pathology confirmed mesoblastic nephroma, classic type, and the patient was diagnosed with stage I disease since the tumor was entirely resected with no renal vessel involvement. Follow-up ultrasounds were recommended to monitor for recurrence, and chemotherapy may be considered if recurrence occurs (Pachl et al., 2020). Calcium and renin levels should also be monitored (Bendre et al., 2014). Although congenital mesoblastic nephroma is typically benign, patients require ongoing monitoring for potential paraneoplastic syndromes. Furthermore, certain types of mesoblastic nephroma can progress to malignancy, necessitating close follow-up during the first few years of life.


Backbone charge transport in double-stranded DNA.
Understanding charge transport in DNA molecules is a long-standing problem of fundamental importance across disciplines1,2. It is also of great technological interest due to DNA's ability to form versatile and complex programmable structures. Charge transport in DNA-based junctions has been reported using a wide variety of set-ups2-4, but experiments so far have yielded seemingly contradictory results that range from insulating5-8 or semiconducting9,10 to metallic-like behaviour11. As a result, the intrinsic charge transport mechanism in molecular junction set-ups is not well understood, which is mainly due to the lack of techniques to form reproducible and stable contacts with individual long DNA molecules. Here we report charge-transport measurements through single 30-nm-long double-stranded DNA (dsDNA) molecules with an experimental set-up that enables us to address individual molecules repeatedly and to measure the current-voltage characteristics from 5 K up to room temperature. Strikingly, we observed very high currents of tens of nanoamperes, which flowed through both homogeneous and non-homogeneous base-pair sequences. The currents are fairly temperature independent in the range 5-60 K and show a power-law decrease with temperature above 60 K, which is reminiscent of charge transport in organic crystals. Moreover, we show that the presence of even a single discontinuity ('nick') in both strands that compose the dsDNA leads to complete suppression of the current, which suggests that the backbones mediate the long-distance conduction in dsDNA, contrary to the common wisdom in DNA electronics2-4.


Corrigendum to "The Treatment of Giant Periurethral Condyloma in Pregnancy Using an Ultrasonic Thermal Scalpel: A Case Report and New Single Session Treatment Option".
[This corrects the article DOI: 10.1155/2015/792412.].


Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.
To evaluate the safety profile and efficacy of salvage regimens containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice daily. Prospective, single-center study. The patient database of the department of infectious diseases was screened for patients who had failed at least two successive three-drug combinations. These patients were proposed to take APV and RTV in association with two to four other drugs. They were followed monthly for 6 months. Seventeen patients were included. They had been previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/- 0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to-treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The most common adverse events were grade 1 or 2 diarrhea and an increase of cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/- 1749 ng/mL on week 24. These data show that the combination of low-dose RTV and reduced doses of APV is safe. This combination can be added to nonnucleoside analogs.


Linear, non-mitochondrial plasmids of Alternaria alternata.
Three plasmids, with sizes of 7.0 kbp, 6.8 kbp, and 5.0 kbp and designated pAal-1, pAal-2 and pAal-3 respectively, have been found in a tentoxin-producing isolate of Alternaria alternata. Exonuclease digestions show these plasmids to be linear with blocked 5' ends. Plasmid pAal-1 does not hybridize to nuclear DNA, mitochondrial DNA, or double-stranded RNA from a mycovirus found in the isolate, but does hybridize weakly to a series of linear DNAs which are not visible on gels and may include pAal-2 and pAal-3. Cellular fractionation shows that, unlike other linear fungal plasmids, these plasmids are not localized in the mitochondria. Plasmids have not been found in other tentoxin-producing isolates and there is no evidence that these plasmids have any effect on the production of tentoxin.


Electron density mapping of triblock copolymers associated with model biomembranes: insights into conformational states and effect on bilayer structure.
One-dimensional electron-density profiles derived from synchrotron small-angle X-ray scattering (SAXS) have been constructed and used to determine the conformational state of selected poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers and the region of their association with a lipid bilayer. The number of molecular repeat units in the hydrophobic PPO block has been found to determine both the nature of triblock polymer-membrane association and the conformational state of the symmetric, flanking hydrophilic PEO units. For DMPC-based biomembranes, polymers whose PPO chain length is less than that of the bilayer thickness insert weakly into the membrane with the PEO blocks on the same side of the bilayer, leading to delocalization of the PEO at the membrane-water interface. This polymer architecture has been found not to alter the membrane fluidity and roughness. Conversely, polymers whose chain length is sufficient to span the lipid bilayer are tightly integrated, projecting their PEO chains into the water channels on opposing sides of the bilayer. The coiled conformational state of the PEO chains produces steric pressure on the bilayer, causing a thinning of the membrane and leading to a rigid, less-mobile bilayer than systems where the polymer is introduced as the lipid conjugate.


Whole-Genome Sequence of Paenibacillus marchantiae Isolated from the Liverwort Marchantia polymorpha subsp. ruderalis Ecotype BoGa.
The bacterium Paenibacillus marchantiae was isolated from male plants of the liverwort Marchantia polymorpha subsp. ruderalis ecotype BoGa. Here, we report on the complete genome sequence generated from long Nanopore reads. The genome sequence comprises 6,983,959 bp with a GC content of 46.02% and 6,195 predicted protein-coding genes.


Surface Wear and Retention Force of Zirconia and PEKK Implant-retained Crowns.
The aim of this study was to evaluate the surface wear and retention force of telescopic attachments made of zirconia primary crowns and poly-ether- ketone -ketone (PEKK) secondary crowns for 2-implant retained mandibular complete overdentures. Ten healthy completely edentulous patients aged 55-60 years were selected for this study. Each patient received two implants in the mandibular canine regions. Maxillary conventional complete dentures were constructed against implant-retained mandibular overdentures for all patients. Zirconia- PEKK telescopic attachments were fabricated to retain the overdentures where primary copings were constructed of zirconia and secondary ones were constructed of PEKK. Retention force and surface wear were evaluated at the time of overdenture insertion (T0), and after 6 months of overdenture use (T6). The results revealed less wear of zirconia copings compared to PEKK ones at T0 and T6. However, both materials showed insignificant wear after 6 months of overdenture use. A significant increase in retention force was observed after 6 months of overdenture use. Within limitations of this study, PEKK may be considered a promising alternative material for telescopic secondary crowns construction combined to zirconia primary ones, regarding the wear resistance and the satisfactory retention forces.


Magnetic resonance imaging in leukodystrophies of childhood.
Magnetic resonance imaging (MRI) is particularly valuable in the diagnosis of childhood brain disorders with abnormal myelination because MRI may identify lesions not always seen with x-ray CT scans. We report the clinical and magnetic resonance findings of six children with leukodystrophy. T2 weighted (spin-echo) images disclosed striking asymmetric involvement of cerebral white matter, particularly in periventricular white matter and visual radiations. Calculated T1 values were significantly elevated in the children with leukodystrophy.


AP2 transcription factor CBX1 with a specific function in symbiotic exchange of nutrients in mycorrhizal Lotus japonicus.
The arbuscular mycorrhizal (AM) symbiosis, a widespread mutualistic association between land plants and fungi, depends on reciprocal exchange of phosphorus driven by proton-coupled phosphate uptake into host plants and carbon supplied to AM fungi by host-dependent sugar and lipid biosynthesis. The molecular mechanisms and cis-regulatory modules underlying the control of phosphate uptake and de novo fatty acid synthesis in AM symbiosis are poorly understood. Here, we show that the AP2 family transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1 (CBX1), a WRINKLED1 (WRI1) homolog, directly binds the evolutionary conserved CTTC motif that is enriched in mycorrhiza-regulated genes and activates Lotus japonicus phosphate transporter 4 (LjPT4) in vivo and in vitro. Moreover, the mycorrhiza-inducible gene encoding H+-ATPase (LjHA1), implicated in energizing nutrient uptake at the symbiotic interface across the periarbuscular membrane, is coregulated with LjPT4 by CBX1. Accordingly, CBX1-defective mutants show reduced mycorrhizal colonization. Furthermore, genome-wide-binding profiles, DNA-binding studies, and heterologous expression reveal additional binding of CBX1 to AW box, the consensus DNA-binding motif for WRI1, that is enriched in promoters of glycolysis and fatty acid biosynthesis genes. We show that CBX1 activates expression of lipid metabolic genes including glycerol-3-phosphate acyltransferase RAM2 implicated in acylglycerol biosynthesis. Our finding defines the role of CBX1 as a regulator of host genes involved in phosphate uptake and lipid synthesis through binding to the CTTC/AW molecular module, and supports a model underlying bidirectional exchange of phosphorus and carbon, a fundamental trait in the mutualistic AM symbiosis.


A volumetric MRI and magnetization transfer imaging follow-up study of patients with first-episode schizophrenia.
Conventional MRI studies have not provided definitive evidence of progressive loss of brain volume in the early stages of schizophrenia, although more subtle changes may have gone undetected. We have looked for such subtle changes using volumetric MRI and magnetization transfer imaging (MTI), an advanced MRI technique sensitive to subtle neuropathological abnormalities. Magnetization transfer images and high-resolution volumetric T1-weighted images were acquired from 16 patients with first-episode schizophrenia at the start of the study and 3.7 years later. A group of 12 healthy controls were also scanned on two occasions. Images were processed using a voxel-based approach that allows whole-brain analysis. There was a group difference with a significant volume loss in the patients' white matter adjacent to the lateral ventricles in the right and left temporal lobes, in medial temporal gyrus, and in the white matter in and around the right middle frontal gyrus. No cortical differences were detected between the groups using MTI or volumetric MRI. The absence of any time-by-group interaction suggests that these abnormalities do not progress in the early stages of the disease. The results of the study need to be interpreted in the light of the small sample size and of the limitations of current image analysis methods.


The IRF6 rs2013162 and MTHFR A1298C rs1801131 Gene Polymorphisms Related to non-Syndromic Cleft lip and Palate among Deutero-Malay in Indonesia.
This study aimed to identify risk factors for NSCLP by analyzing polymorphisms in IRF6 rs2013162 and MTHFR A1298C rs1801131 in the Deutero Malay Population in Indonesia. DNA isolation from venous blood samples was done followed by PCR and PCR-RFLPs method. 115 NSCLP subjects and 120 healthy control subjects. The odds ratio (OR) determined to evaluate the risk factors is the main outcome measure. The study is a case-control design using samples from the venous blood of 115 NSCLP subjects and 120 healthy control subjects. After DNA was extracted, the PCR-RFLPs method was performed using the DdeI restriction enzyme on 100 blood samples of the IRF6 rs2013162 group and Mboll restriction enzyme on 135 blood samples of the MTHFR A1298C rs1801131 group. The Chi-Square test was used with the Exact Fisher alternatives, depending on the expected count value. The results showed that the T mutant allele (OR = 4.125, P < .05) and GT genotype (OR = 21.00, P < .05) of IRF6 rs2013162 and the C mutant allele (OR = 3.781, P < .05), AC genotype (OR = 5, P < .05) and CC genotype (OR = 9,681, P < .05) of the MTHFR A1298C is associated to a greater risk of NSCLP. IRF6 rs2013162 and MTHFR A1298C rs1801131 gene polymorphisms are strongly associated with NSCLP among the Deutero Malay population in the Indonesian population.


[A case of suspected tuberculous retroperitoneal abscess effectively cured using sclerotherapy with minocycline].
A twenty-five-year-old female was admitted with lower right abdominal pain, right coxalgia and an inability to extend her right inferior limb. She had a history of tuberculosis pleurisy two years before. Abdominal ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a right retroperitoneal mass which was suspected to be an abscess or tumor. Percutaneous aspiration of the mass was followed by the administration (p.o.) of antituberculosis drugs (pyrazinamide, ethanbutol, isoniazide, refampicin). One month after initial drainage, the tube was removed but intra-cystic fluid collection was still visible a month later using CT and MRI. Therefore, a second percutaneous aspiration was followed by the instillation of streptomycin and minocycline hydrochloride. Six months after employing this therapy, no fluid collection was found.


Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin.
The development of in vitro dissolution tests using the paddle and basket apparatus is described with respect to the qualification/validation of the testing procedure. Three examples of immediate release products containing phenoxymethylpenicillin potassium, glimepiride, and levofloxacin providing different solubility characteristics are evaluated. The solubility was high in the case of phenoxymethylpenicillin potassium and levofloxacin and low for glimepiride according to the biopharmaceutics classification system. The permeability is studied using the human colorectal carcinoma cell line CaCo-2. The permeability (10(-6) cm/s) of phenoxymethylpenicillin potassium, glimepiride, and levofloxacin was high. The determined permeability data are confirmed by absorption data obtained by means of numerical deconvolution of plasma concentrations. Recommendations are given for the biopharmaceutical characterization of the three immediate release drug products, taking into account in vitro and in vivo comparison as well as the biopharmaceutics drug classification system. The evaluated acceptance criteria are the following: phenoxymethylpenicillin potassium (80% in 30 min), glimepiride (80% in 15 min) and levofloxacin (80% in 30 min). Typically, for immediate release formulations, one limit is specified for the dissolution to ensure the release of the active ingredient within the present time period. Since phenoxymethylpenicillin potassium and levofloxacin belong to Case 1, no in vitro/in vivo correlation is expected, absorption may be gastric emptying dependent. Glimepiride is categorized to Case 2. Nevertheless, a correlation with the in vivo dissolution profile does not exist, because of the pH-dependent low solubility of the drug. Finally, recommendations are made for the batch control of drug products in accordance with the four Cases.


Ca2+ dynamics in interstitial cells: foundational mechanisms for the motor patterns in the gastrointestinal tract.
The gastrointestinal (GI) tract displays multiple motor patterns that move nutrients and wastes through the body. Smooth muscle cells (SMCs) provide the forces necessary for GI motility, but interstitial cells, electrically coupled to SMCs, tune SMC excitability, transduce inputs from enteric motor neurons, and generate pacemaker activity that underlies major motor patterns, such as peristalsis and segmentation. The interstitial cells regulating SMCs are interstitial cells of Cajal (ICC) and PDGF receptor (PDGFR)α+ cells. Together these cells form the SIP syncytium. ICC and PDGFRα+ cells express signature Ca2+-dependent conductances: ICC express Ca2+-activated Cl- channels, encoded by Ano1, that generate inward current, and PDGFRα+ cells express Ca2+-activated K+ channels, encoded by Kcnn3, that generate outward current. The open probabilities of interstitial cell conductances are controlled by Ca2+ release from the endoplasmic reticulum. The resulting Ca2+ transients occur spontaneously in a stochastic manner. Ca2+ transients in ICC induce spontaneous transient inward currents and spontaneous transient depolarizations (STDs). Neurotransmission increases or decreases Ca2+ transients, and the resulting depolarizing or hyperpolarizing responses conduct to other cells in the SIP syncytium. In pacemaker ICC, STDs activate voltage-dependent Ca2+ influx, which initiates a cluster of Ca2+ transients and sustains activation of ANO1 channels and depolarization during slow waves. Regulation of GI motility has traditionally been described as neurogenic and myogenic. Recent advances in understanding Ca2+ handling mechanisms in interstitial cells and how these mechanisms influence motor patterns of the GI tract suggest that the term "myogenic" should be replaced by the term "SIPgenic," as this review discusses.


Podocyte-associated proteins FAT, alpha-actinin-4 and filtrin are expressed in Langerhans islets of the pancreas.
Nephrin is a crucial podocyte molecule in the kidney glomerular filtration barrier and it is also expressed in Langerhans islet beta cells of the pancreas. Recently, genetic mapping of proteinuric kidney disease genes and animal models have revealed further important molecules for the kidney filtration function including alpha-actinin-4, podocin, FAT, and NEPH1. This study was addressed to explore the pancreatic expression of the podocyte molecules podocin, FAT, alpha-actinin-4, NEPH1, NEPH2, filtrin/NEPH3, synaptopodin and CD2 associated protein (CD2AP). The mRNA and protein expressions were studied by RT-PCR and immunoblotting, and localization in the pancreas was investigated by immunofluorescence. Of the nephrin-associated podocyte proteins, filtrin/NEPH3, FAT, and alpha-actinin-4 were found to be expressed in the pancreas at the gene and protein level and localized to Langerhans islets. Immunoreactivity with the podocin antibody was detected mostly in the exocrine pancreas. NEPH1 and synaptopodin expression was detected only at the mRNA level. Further studies are needed to unravel the functional role of these podocyte-associated molecules in the pancreatic Langerhans islets.


CD8(+) T cells in human autoimmune arthritis: the unusual suspects.
CD8(+) T cells are key players in the body's defence against viral infections and cancer. To date, data on the role of CD8(+) T cells in autoimmune diseases have been scarce, especially when compared with the wealth of research on CD4(+) T cells. However, growing evidence suggests that CD8(+) T-cell homeostasis is impaired in human autoimmune diseases. The contribution of CD8(+) T cells to autoimmune arthritis is indicated by the close association of MHC class I polymorphisms with disease risk, as well as the correlation between CD8(+) T-cell phenotype and disease outcome. The heterogeneous phenotype, resistance to regulation and impaired regulatory function of CD8(+) T cells - especially at the target organ - might contribute to the persistence of autoimmune inflammation. Moreover, newly identified populations of tissue-resident CD8(+) T cells and their interaction with antigen-presenting cells might have a key role in disease pathology. In this Review, we assess the link between CD8(+) T cells, autoimmune arthritis and the basis of their homeostatic changes under inflammatory conditions. Improved insight into CD8(+) T cell-specific pathogenicity will be essential for a better understanding of autoimmune arthritis and the identification of new therapeutic targets.


[Alzheimer's disease].
The primary degenerative dementia of Alzheimer type, present denomination, represents a medical, social and economical problem. The early diagnosis, based on medical criteria, might improve some aspects of the expected evolution of these, up to date, hopeless patients.


The Fontan circulation and the liver: A magnetic resonance diffusion-weighted imaging study.
Patients with a Fontan circulation tend to develop liver fibrosis, liver cirrhosis and even hepatocellular carcinoma. The aim of this study is to use the magnetic resonance technique diffusing-weighted imaging (DWI) for detecting liver fibrosis/cirrhosis in Fontan patients and to establish whether DWI results are associated with functional aspects of the Fontan circulation. In a cross-sectional study, 59 Fontan patients were evaluated by liver DWI. The association between apparent diffusion coefficients (ADC) and patient characteristics, laboratory measurements and functional aspects of the Fontan circulation (NYHA class, maximum oxygen uptake during exercise and cardiac index) was assessed. Liver ADC values were low (0.82×10(-3)±0.11×10(-3) mm2/s) compared with literature values for healthy volunteers and correlated negatively with calculated liver fibrosis/cirrhosis scores (Fib-4 score, p=0.019; AST/ALT ratio, p=0.009) and gamma-glutamyl transferase (p=0.001). Furthermore, ADC values correlated negatively with follow-up duration (p<0.001) and positively with cardiac index (p=0.019). No correlation between ADC values and exercise tests was found. In multivariable analysis, the ADC values were independently correlated with follow-up duration after Fontan completion. The results of the current study suggest that progressive liver damage due to chronic congestion and potential hypoperfusion is reflected in the liver ADC values in Fontan patients. This study highlights that liver damage in the context of the Fontan circulation might be far more common than previously thought, and that the implementation of liver assessment in the routine follow-up of Fontan patients is recommendable.


Methicillin-Resistant Staphylococcus aureus Grown on Vancomycin-Supplemented Screening Agar Displays Enhanced Biofilm Formation.
Brain heart infusion agar containing 3 mg/liter vancomycin (BHI-V3) was used to screen for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). There was markedly greater biofilm formation by isolates that grew on BHI-V3 than by strains that did not grow on BHI-V3. Increased biofilm formation by hVISA may be mediated by FnbA- and polysaccharide intercellular adhesin-dependent pathways, and upregulation of atlA and sarA may also contribute to enhanced biofilm formation by hVISA upon prolonged exposure to vancomycin.


Use of endoscopic retrograde cholangiopancreatography to dislodge clip impingement on the common hepatic duct.
Despite advances in technical skill, bile duct injury during laparoscopic cholecystectomy is not an uncommon complication. We describe a technique of using ERCP, sphincterotomy, and balloon dilatation to dislodge clip impingement on the common hepatic duct after laparoscopic cholecystectomy.


Low plasma activated protein C-protein C inhibitor complex concentration is associated with vascular access failure in hemodialysis patients.
Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI). The plasma concentration of the complex between APC and PCI (P-APC-PCI complex) is increased in hypercoagulable states and is therefore a sensitive indicator of the degree of activation of blood coagulation. Thirty-five HD patients dialyzed through a functioning AVFG were studied. The period of patency of AVFGs was recorded. Blood was drawn before and after the HD session for the analysis of the APC-PCI complex, soluble TM concentration and activity, von Willebrand factor antigen and homocysteine. Patients with frequent AVFG failures (n = 8) had a significantly lower level of P-APC-PCI complex (median 0.09 microg/l) than those with less frequent AVFG failures (median 0.18 microg/l; n = 27; p = 0.04). No other significant differences were found between the groups. Thus, a low level of P-APC-PCI complex may be associated with an increased risk of AVFG failure in HD patients. Further prospective studies are needed to confirm these results and to evaluate the possibility of prophylactic measures.


A Pilot With Electrical Pain in the Face.
An intracranial epidermoid cyst is an unusual but treatable cause of trigeminal neuralgia.


Gay Midlife Men's Intergenerational and Interpersonal (Non)Accommodation in the Negotiation of HIV Infection Risk: Implications for Sexual Vitality, Generational Distinctiveness, and Self-Preservation.
This study utilizes interview data and a communication accommodation framework to explore how early midlife gay men negotiate HIV infection risk vis-à-vis a younger gay male sexual culture that has evolved in terms of its regard for dangers associated with HIV infection. Analysis of face-to-face interviews with 33 gay men (aged 40-53) in four U.S. cities revealed a model of gay intergenerational sexual (non)accommodation. The model includes forms of communicative convergence and nonaccommodating behavior that serve some men's achievement or continuation of sexual vitality and/or positive generational distinctiveness. Similarities and extensions to communication accommodation theory are discussed, as are the model's implications for understanding some gay men's management of sexual health at midlife.


[Modulation of the rhythmic activity of neuron PPa2 of Helix pomatia in response to noradrenaline].
In isolated nervous system of the grape snail Helix pomatia, results of norepinephrine effects upon activity of the PPa2 neurons involved rhythmic activity with maximum of interval distribution within the 2-3-sec range. Norepinephrine induced trains of EPs with maximum of interval distribution within the 10-13-sec range. Endogenous mechanisms of generation of the periodic oscillations of membrane potentials under the effect of norepinephrine, is discussed.


Studies into radiolytic decomposition of fluorine-18 labeled radiopharmaceuticals for positron emission tomography.
Radiolytic decomposition of high specific concentration radiopharmaceuticals is an undesired side-effect that can hamper development of novel PET tracers. This was particularly evident in a series of carbon-11 and fluorine-18 labeled mono- and dimethyl-substituted aryl amines, where rapid decomposition was observed in isolation and formulation steps. We tested a number of additives that inhibit radiolysis and can be safely added to the synthesis procedures (purification and isolation) and reformulation steps to provide suitable clinical formulations. Ethanol and sodium ascorbate are established anti-oxidant stabilizers that completely inhibit radiolytic decomposition and are amenable to human use. Herein, we also demonstrate for the first time that nitrones are non-toxic radical scavengers that are capable of inhibiting radiolysis.


Role of initial bacterial community in the aerobic sludge granulation and performance.
The structure of bacterial community was greatly varied from different seed sludge sources, which affected the sludge characteristics. To explore the role of different functional bacteria in AGS granulation and pollutant degradation, three different resources of seed sludge obtained from pharmaceutical wastewater (R1), livestock (R2), and municipal sludge (R3) were employed in this study. Results showed that the initial bacterial community had important significance for AGS formation and pollutants removal. Seed sludge taken from R3 granulated faster than those from R1 and R2. A large number of mature granules were formed after 20 days of operation in R3. In addition, the final mixed liquor suspended solids (MLSS) reached 6853 mg L-1, with 48 mL g-1 sludge volume index (SVI) in R3, indicating that it had better settling performance and granulation. In the stable stage of R3, the removal rates of COD, NH4+-N, and TN reached 99.2%, 98.5%, and 97.6%, respectively. The α-diversity analysis showed that the bacterial community of seed sludge greatly determined the microbial composition of AGS. Firmicutes, Gracilibacteria, and Spirochaetes were abundant in R3, which maintained the structures and functions of aerobic granules. This study might provide approaches and insights for AGS culture from different sludge sources.


In vitro Scolicidal effects of Androctonus crassicauda (Olivier, 1807) venom against the protoscolices of Echinococcus granulosus.
Hydatidosis is a zoonotic disease that commonly occurs in several places around the world, especially in the Middle East, due to infection by the larval stage of Echinococcus granulosus. This disease impacts an immense effect on the economic and public health of both humans and animals. Despite their effectiveness, the unacceptable side effects and progressive resistance to scolicidal agents may limit their use. According to their biopharmaceutical activity and benefits, numerous studies have reported that scorpion venom and its derivatives represent important resources for therapeutic applications. Therefore, this study was designed to investigate the in vitro scolicidal consequences of the crude venom of Androctonus crassicauda on E. granulosus. For this purpose, protoscolices from infected organs of camel containing hydatid cysts were collected, separated, and washed. The scolicidal impacts of three different concentrations of the crude venom (20, 50, and 100 µg/mL) were tested at different times of exposure (30, 60, 120, and 240 min). Particularly, eosin exclusion test was used to examine the viability of the protoscolices. The study results showed that the crude venom at 100 μg/mL destroys all protoscolices after 240 min incubation. Also, the scolicidal activity of venom increased significantly according to the time of exposure. In conclusion, the crude venom of A. crassicauda demonstrated high scolicidal activity in vitro against protoscolices of hydatid cysts in low concentration and short exposure time. However, the efficacy of scorpion venom remains to be evaluated in vivo for the treatment of hydatidosis in both humans and domesticated animals.


Deep pectoral myopathy: an experimental simulation in the fowl.
Surgical occlusion of the subclavian artery of domestic fowls has been found to induce a condition closely resembling, in location and histopathology, the deep pectoral myopathy of turkeys. The operative procedure is described and the significance of the collateral blood supply in the pathogenesis of the lesion is briefly discussed.


Limb fractures and nonaccidental injury in children less than 24 months of age.
The pattern of limb fractures in children aged 24 months or younger is poorly understood. This age group is particularly vulnerable to nonaccidental injury, which can be difficult for inexperienced clinicians to detect. The aim of this study is to identify fracture patterns in children below the age of 24 months. Data was collected prospectively. For all fractures, the mechanism of injury including height of fall (cm), severity of injury, outcome and deprivation scores were collected. Information on children referred for child-protection review was also noted. During the 12 months of the year 2003, 122 new patients aged less than 24 months presented with limb fractures directly to the Emergency Department of the Royal Hospital for Sick Children, giving an incidence of 4.55 per 1000 in the 0-12-month group and 17 per 1000 in the 13-24-month group. Sixty-three (52%) children sustained the injury during a fall and only 7% of children were admitted, the rest being followed up as outpatients. Thirty-eight (31%) had simple distal radius/ulna fractures. Five children with unclear histories or mechanisms of injury underwent formal child-protection procedures. All were less than 14 months of age. Fractures are relatively rare in the first 2 years of life. Child protection needs to be considered in all children, but specifically in those patients with atypical fractures presenting with an unclear mechanism of injury.


Healthcare provider counselling for weight management behaviours among adults with overweight or obesity: a cross-sectional analysis of National Health and Nutrition Examination Survey, 2011-2018.
To determine if adults with overweight or obesity received counselling from their healthcare providers (HCPs) to lose weight and/or adopt healthful behaviours associated with weight loss, and whether they took action on their HCPs' recommendations. Cross-sectional analysis of 2011-2018 National Health and Nutrition Examination Survey (NHANES) data. NHANES respondents aged 18+ who were overweight/obese and had seen an HCP in the previous 12 months (n=13 158). Respondents reported if their HCPs recommended they control/lose weight, increase exercise/physical activity (PA) and/or reduce fat/calorie intake, and if they adopted the offered recommendation(s). Weighted logistic regression models examined receipt of HCP counselling by sex, age, race/ethnicity, and weight status accounting for demographic characteristics and complex sampling. Similar analyses examined reported adoption of HCPs' recommendations. The sample was 53.1% women, 45.0% were overweight and 55.0% had obesity. In total, 40.4% received counselling to control/lose weight, 49.5% to increase exercise/PA and 38.9% to reduce fat/calorie intake. The following groups were less likely (p<0.001) to receive counselling: men; younger adults (aged 18-39) versus middle-aged (aged 40-64) and older adults (aged 65+); White versus Black and Hispanic respondents; overweight respondents versus respondents with obesity. Approximately half of those advised to make changes reported doing so (53.6% controlled/lost weight, 57.3% increased exercise/PA, 51.8% reduced fat/calorie intake). Differences in the adoption of recommendations were identified by sex, age group, race/ethnicity and weight status (all p<0.05); women, middle-aged and older adults, Black and Hispanic respondents and individuals with obesity were more likely to adopt one or more recommendations. Most respondents did not receive HCP counselling, and approximately half of those who received counselling reported taking action. HCPs may need training to provide counselling and to offer recommendations tailored to the social contexts of populations less likely to adopt weight control related recommendations.


Impaired systolic dysfunction of left ventricular longitudinal fibers: a sign of early hypertensive cardiomyopathy.
Atrioventricular plane displacement (AVPD) study by M-mode echocardiography can supply useful clinical information about left ventricular (LV) long-axis function. We assessed the hypothesis that AVPD estimation could be used to detect early hypertensive cardiomyopathy. The study population included 81 hypertensive patients with normal LV ejection fraction and fractional shortening, and 50 age- and gender-matched healthy controls. By utilizing M-mode and apical views, the following parameters were estimated: early mitral flow peak velocity (E) and deceleration time (DT), peak velocity of late mitral flow (A), A/E ratio, isovolumic relaxation time (IVRT), total AVPD, AVPD motion during atrial systole (At), systolic AVPD (total AVPD-At), and At/total AVPD ratio. Of 81 hypertensive patients, 16 (19.7%) had a normal (Group 1) and 65 (80.3%) an impaired LV relaxation filling pattern (Group 2). Mean total AVPD-At was significantly lower in Group 2 than in Group 1 (7.1 +/- 2 vs. 10.3 +/- 3 mm, p<0.001) and in Group 1 compared with healthy subjects (10.3 +/- 3 vs. 13.1 +/- 1 mm, p<0.001). Mean At and At/total AVPD were significantly higher in Group 2 than in Group 1 (46.9 +/- 8.6 vs. 37.7 +/- 8.7%, p<0.001), but not in Group 1 compared with healthy subjects (37.7 +/- 8.7 vs. 36 +/- 6%, p>0.05). Hypertensive patients without overt systolic dysfunction demonstrate LV long-axis systolic dysfunction, while long-axis diastolic dysfunction always coexists with abnormal diastolic filling patterns. This suggests that long-axis systolic dysfunction precedes diastolic dysfunction at the same axis in hypertensive patients.


Asymmetric dimethyl arginine levels correlate with cardiovascular risk factors in patients with erectile dysfunction.
Erectile dysfunction is related to penile arterial endothelial nitric oxide production. Asymmetric dimethylarginine (ADMA) and E-selectin are often considered plasma markers of endothelial function. This study investigated the relationship between these plasma markers and cardiovascular risk factors in patients with erectile dysfunction. Cardiovascular risk factors, ADMA and E-selectin were assessed in 45 patients with erectile dysfunction. Plasma markers showed associations with baseline risk factors. E-selectin levels showed an inverse relationship with age (p = 0.005) and statin therapy (p = 0.03) and a weak association with concomitant beta-blocker therapy (p = 0.05). Compared to these relatively weak associations with cardiovascular risk factors, ADMA levels showed strong associations with pulse pressure (p < 0.001), lack of smoking (p = 0.002) and lipoprotein (a) (p = 0.004) concentrations and weak associations with LDL-cholesterol (p = 0.02), and C-reactive protein levels (p = 0.04). ADMA levels correlated with E-selectin (partial r = 0.76; p < 0.001) after adjustment for lipoprotein (a), pulse pressure and smoking. No change in E-selectin or ADMA levels was seen after 70 days therapy with sildenafil and no relationship was found between either plasma marker and the acute pulse wave response to a single challenge dose of sildenafil. ADMA levels correlate at baseline with some cardiovascular risk factors including inflammatory markers and lipoprotein (a) in patients with erectile dysfunction.


Characterization of a facultatively psychrophilic bacterium, vibrio rumoiensis sp. nov., that exhibits high catalase activity
A novel facultatively psychrophilic bacterium, strain S-1, which exhibits extraordinarily high catalase activity was isolated from the drain pool of a fish product processing plant that uses H2O2 as a bleaching and microbicidal agent. The catalase activity of the isolate was 1 or 2 orders of magnitude higher than those of Corynebacterium glutamicum, Staphylococcus aureus, Pseudomonas fluorescens, and five other species tested in this study. The strain seemed to possess only one kind of catalase, according to the results of polyacrylamide gel electrophoresis of the cell extract. The optimum temperature for catalase activity was about 30 degreesC, which was about 20 degreesC lower than that for bovine catalase activity. Electron microscopic observation revealed that the surface of the microorganism was covered by blebs. Although the isolate was nonflagellated, its taxonomic position on the basis of physiological and biochemical characteristics and analysis of 16S rRNA sequence and DNA-DNA relatedness data indicated that strain S-1 is a new species belonging to the genus Vibrio. Accordingly, we propose the name Vibrio rumoiensis. The type strain is S-1 (FERM P-14531).


UV damage and photoreactivation potentials of larval shrimp, Pandalus platyceros, and adult euphausiids, Thysanoessa raschii.
Previously reported thresholds for UV-B dose and dose-rate were determined under artificial light regimes using more than an order of magnitude less visible light than found naturally. Near-UV and/or visible light is needed for photoreactivation, and the accuracy of earlier findings may have been influenced by less than maximum photorepair in the laboratory. Experiments with shrimp larvae and adult euphausiids, comparing survival at various UV-B doses and dose-rates combined with different levels of near-UV and visible irradiance, suggest that photorepair occurs in these organisms. Further, this apparent photorepair reaches maximum levels at relatively low visible light intensities.Previously reported tolerance limits for shrimp larvae and adult euphausiids were confirmed (in particular, the relationship between dose/dose-rate safe and lethal limits in shrimp). Also, the earlier experimental design did not appear to have affected these limits since additional near-UV and visible light did not substantially alter the results.In experiments using a 44-1 plastic cylinder (140-cm water depth), adult euphausiids successfully avoided moderate UV-B combined with visible light, but were attracted to and ultimately killed by higher levels of UV-B combined with low visible light. The apparent inability of euphausiids to directly detect harmful levels of UV-B irradiance would become an important factor in a new solar spectral distribution caused by ozone depletion.


The anticonvulsive activity and toxicity of diazepam in three different formulations. An experimental study in mice.
The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid.


Totally endoscopic quadruple coronary artery bypass grafting is feasible using robotic technology.
Multivessel robotic totally endoscopic coronary artery bypass grafting is currently under development. Quadruple totally endoscopic coronary artery bypass has so far not been reported. A 75-year-old patient with multivessel coronary artery disease underwent daVinci Si-assisted completely endoscopic placement of a left internal mammary artery bypass to the left anterior descending artery and construction of a right internal mammary artery Y-graft off the left internal mammary artery to the posterior descending artery. The left internal mammary artery was also connected to a diagonal branch as a sequential graft. The obtuse marginal branch was revascularized using an endoscopically harvested vein graft originating from the left axillary artery.