Achieving healthy body weight in teenagers: evidence-based practice guidelines for community nutrition interventions.
An evidence-based review of research on obesity prevention and treatment in youth was conducted to identify successful elements of community nutrition interventions. Guidelines for dietetic practice appropriate to this age group were synthesized. Following a systematic review of English-language research papers published from 1996 to 2009, 63 interventions met inclusion criteria and were graded according to methodological quality, quantity, consistency, and reproducibility. They also were analyzed for common themes and used to develop guideline statements and a practice algorithm. A national panel of experts in community nutrition, public health, adolescent health, academia, and endocrinology assessed the guidelines and the practice algorithm for validity, acceptability, and applicability. Successful prevention strategies are comprehensive, address social and environmental influences, include nutrition education and physical activity, and use schools as a health promotion delivery venue. Computer- or technology-based and peer-modelling strategies are promising, developmentally appropriate approaches. Effective obesity treatment strategies utilize diet plans and behaviour modification techniques, and involve families in intensive, multidisciplinary interventions. Given the distinct needs of this age group, healthy body weight must be promoted through a comprehensive school-based approach. In summary, obesity prevention and treatment interventions should be comprehensive, multidisciplinary, and developmentally appropriate.


Computational model for the formation of uniform silver spheres by aggregation of nanosize precursors.
We present results of computational modeling of the formation of uniform spherical silver particles prepared by rapid mixing of ascorbic acid and silver-amine complex solutions in the absence of a dispersing agent. Using an accelerated integration scheme to speed up the calculation of particle size distributions in the latter stages, we find that the recently reported experimental results-some of which are summarized here-can be modeled effectively by the two-stage formation mechanism used previously to model the preparation of uniform gold spheres. We treat both the equilibrium concentration of silver atoms and the surface tension of silver precursor nanocrystals as free parameters, and find that the experimental reaction time scale is fit by a narrow region of this two-parameter space. The kinetic parameter required to quantitatively match the final particle size is found to be very close to that used previously in modeling the formation of gold particles, suggesting that similar kinetics governs the aggregation process and providing evidence that the two-stage model of burst nucleation of nanocrystalline precursors followed by their aggregation to form the final colloids can be applied to systems both with and without dispersing agents. The model also reproduced semiquantitatively the effects of solvent viscosity and temperature on the particle preparation.


Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.
The orexigenic and adipogenic peptide hormone ghrelin is predominantly produced and secreted by the stomach and seems to transduce changes in food intake to specific neuronal circuits in the brain. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. We therefore studied human plasma ghrelin levels in the presence and absence of elevated glucocorticoid levels of either endogenous or exogenous origin. Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29-58, median 46 years) due to Cushing's syndrome before and after successful surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5 years) before and after 30 mg prednisolone (for 5 days) once a day in the morning (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured with a commercially available radioimmunoassay. In patients with Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range 161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after prednisolone treatment. We have shown for the first time that plasma ghrelin levels are decreased under endogenously or exogenously induced hypercortisolism, making ghrelin an unlikely candidate for causing the changes in energy balance or body composition characteristic of Cushing's disease. However, the reduced ghrelin secretion could reflect a compensation mechanism in reaction to the metabolic consequences of chronic hypercortisolism.


Isolation and characterization of microsatellite loci from the tick Amblyomma aureolatum (Acari: Ixodidae).
Amblyomma aureolatum (Pallas) is the main vector of the bacterium Rickettsia rickettsii, the etiological agent of Brazilian spotted fever. This disease is the most lethal human spotted fever rickettsiosis in the world. Microsatellite loci were isolated from a dinucleotide-enriched library produced from A. aureolatum sampled in Southeastern Brazil. Eight polymorphic microsatellites were further characterized among 38 individuals sampled from São Paulo metropolitan region. The number of observed alleles ranged from 2 to 9, observed heterozygosity was 0.184-0.647, and expected heterozygosity was 0.251-0.747. Cross-species amplifications suggested that these loci will be useful for other Amblyomma species.


The VLA-2 (alpha 2 beta 1) I domain functions as a ligand-specific recognition sequence for endothelial cell attachment and spreading: molecular and functional characterization.
The integrin VLA-2 (alpha 2 beta 1), generally considered to represent the specific collagen receptor on human endothelial cells, contains an alpha 2-subunit inserted I domain with structural similarity to the type A domains found within the recently described superfamily of receptor-ligand recognition proteins. This region of the cDNA has now been isolated and used for molecular and functional characterization of this heterodimeric receptor complex. Comparative sequence analysis with the porcine homologue revealed 93% amino acid sequence identity, suggestive of a developmentally conserved function. To complete structure/function studies, this region of the human cDNA was expressed as a chimeric protein in Escherichia coli, and a rabbit polyclonal antibody (anti-I domain) was used to study determinants of endothelial cell attachment and spreading in vitro. Quantifiable and visual disruption of endothelial cell attachment to gelatin, type I collagen, and laminin was evident using the specific anti-I domain antibody, with minimal inhibitory effects demonstrable using fibronectin or fibrinogen matrices. Therefore, these data would suggest that the alpha 2 beta 1 I domain confers ligand-binding specificity for both known alpha 2 beta 1 substrates (laminin and collagen), and that this region subserves a regulatory function in the molecular processes controlling endothelial cell attachment and spreading in vitro.


Confinement-induced ordering of alkanes between an elastomer and a solid surface.
We have studied the molecular structure of liquid alkanes confined between a flexible elastomeric poly(dimethyl siloxane) lens and a rigid sapphire substrate using surface-sensitive infrared-visible sum frequency generation spectroscopy. The reduction in the gauche defects suggests ordering of liquid alkanes under confinement. The cooling of confined liquid below the freezing temperature leads to crystallization with alkane molecules lying on the substrate with the symmetry axis parallel to the surface normal. This structure is very different from the bulk alkane crystals next to sapphire or air interfaces.


The narrative and rhetoric of dreams: six literary fragments by a novelist.
Four of a novelist's dreams and two contemporaneous pieces of her fiction are examined through the lens of poststructuralism; thus viewed they display narrative coherence in form and content, a reciprocal interaction between dream and written day residue, and a rhetorical function in trauma resolution. Lacan's theories about the linguistic nature of the unconscious are particularly powerful in understanding these six works especially their recourse to figurative language in deconstructing and reconstructing the traumatized self. Dream narratology suggests the close relation of unconscious processes to creativity and the unity of storymaking and personal meaning. Narrative conventions in these dreams and related fiction illustrate the functions of metaphor and metonymy in traversing Lacan's "registers of experience" and his ideas about the "itinerary of the signifier," the way dreams and art capture the elusive object of desire. Creativity serves not only a wish-fulfillment function but also a self-fulfillment function. Dreams, then, as creative acts, claim a privilege unto themselves and support Lacan's argument for a therapeutic approach of "desirelessness."


Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats.
To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.


Identification and functional analysis of flowering related microRNAs in common wild rice (Oryza rufipogon Griff.).
MicroRNAs (miRNAs) is a class of non-coding RNAs involved in post- transcriptional control of gene expression, via degradation and/or translational inhibition. Six-hundred sixty-one rice miRNAs are known that are important in plant development. However, flowering-related miRNAs have not been characterized in Oryza rufipogon Griff. It was approved by supervision department of Guangdong wild rice protection. We analyzed flowering-related miRNAs in O. rufipogon using high-throughput sequencing (deep sequencing) to understand the changes that occurred during rice domestication, and to elucidate their functions in flowering. Three O. rufipogon sRNA libraries, two vegetative stage (CWR-V1 and CWR-V2) and one flowering stage (CWR-F2) were sequenced using Illumina deep sequencing. A total of 20,156,098, 21,531,511 and 20,995,942 high quality sRNA reads were obtained from CWR-V1, CWR-V2 and CWR-F2, respectively, of which 3,448,185, 4,265,048 and 2,833,527 reads matched known miRNAs. We identified 512 known rice miRNAs in 214 miRNA families and predicted 290 new miRNAs. Targeted functional annotation, GO and KEGG pathway analyses predicted that 187 miRNAs regulate expression of flowering-related genes. Differential expression analysis of flowering-related miRNAs showed that: expression of 95 miRNAs varied significantly between the libraries, 66 are flowering-related miRNAs, such as oru-miR97, oru-miR117, oru-miR135, oru-miR137, et al. 17 are early-flowering -related miRNAs, including osa-miR160f, osa-miR164d, osa-miR167d, osa-miR169a, osa-miR172b, oru-miR4, et al., induced during the floral transition. Real-time PCR revealed the same expression patterns as deep sequencing. miRNAs targets were confirmed for cleavage by 5'-RACE in vivo, and were negatively regulated by miRNAs. This is the first investigation of flowering miRNAs in wild rice. The result indicates that variation in miRNAs occurred during rice domestication and lays a foundation for further study of phase change and flowering in O. rufipogon. Complicated regulatory networks mediated by multiple miRNAs regulate the expression of flowering genes that control the induction of flowering.


Equine rhinitis B viruses in horse fecal samples from the Middle East.
Among all known picornaviruses, only two species, equine rhinitis A virus and equine rhinitis B virus (ERBV) are known to infect horses, causing respiratory infections. No reports have described the detection of ERBV in fecal samples of horses and no complete genome sequences of ERBV3 are available. We performed a molecular epidemiology study to detect ERBVs in horses from Dubai and Hong Kong. Complete genome sequencing of the ERBVs as well as viral loads and genome, phylogenetic and evolutionary analysis were performed on the positive samples. ERBV was detected in four (13.8 %) of the 29 fecal samples in horses from Dubai, with viral loads 8.28 × 10(3) to 5.83 × 10(4) copies per ml, but none of the 47 fecal samples in horses from Hong Kong by RT-PCR. Complete genome sequencing and phylogenetic analysis showed that three of the four strains were ERBV3 and one was ERBV2. The major difference between the genomes of ERBV3 and those of ERBV1 and ERBV2 lied in the amino acid sequences of their VP1 proteins. The Ka/Ks ratios of all the coding regions in the ERBV3 genomes were all <0.1, suggesting that ERBV3 were stably evolving in horses. Using the uncorrelated lognormal distributed relaxed clock model on VP1 gene, the date of the most recent common ancestor (MRCA) of ERBV3 was estimated to be 1785 (HPDs, 1176 to 1937) and the MRCA dates of ERBV1 and ERBV2 were estimated to be 1848 (HPDs, 1466 to 1949) respectively. Both acid stable (ERBV3) and acid labile (ERBV2) ERBVs could be found in fecal samples of horses. Detection of ERBVs in fecal samples would have implications for their transmission and potential role in gastrointestinal diseases as well as fecal sampling as an alternative method of identifying infected horses.


Hyperphosphatasemia in leiomyosarcoma of the uterus: Two case reports and a literature review.
Some tumors are known to produce alkaline phosphatase (ALP). Seven cases of uterine leiomyosarcoma were identified from the clinical records of Sakai City Medical Center from January 2006 to December 2014. Patients' ages ranged from 47 to 75 years (median: 58). Clinical stages were IB, IIB, IIIA, and IVB in four, one, one, and one cases, respectively. Of these, two were found to have hyperphosphatasemia before surgery, and the elevated ALP level decreased after surgery, and increased with disease recurrence. In the cases of hyperphosphatasemia, leiomyosarcoma cells showed positive staining for ALP. There was no correlation between serum ALP and lactate dehydrogenase, or ALP and cancer antigen 125. The combination of ALP, lactate dehydrogenase, and cancer antigen 125 may be more useful for diagnosis and follow-up of leiomyosarcoma.


Donor and recipient contribution to phenotypic traits and the expression of biomineralisation genes in the pearl oyster model Pinctada margaritifera.
Grafting associates two distinct genotypes, each of which maintains its own genetic identity throughout the life of the grafted organism. Grafting technology is well documented in the plant kingdom, but much less so in animals. The pearl oyster, Pinctada margaritifera, produces valuable pearls as a result of the biomineralisation process of a mantle graft from a donor inserted together with a nucleus into the gonad of a recipient oyster. To explore the respective roles of donor and recipient in pearl formation, a uniform experimental graft was designed using donor and recipient oysters monitored for their growth traits. At the same time, phenotypic parameters corresponding to pearl size and quality traits were recorded. Phenotypic interaction analysis demonstrated: 1) a positive correlation between recipient shell biometric parameters and pearl size, 2) an individual donor effect on cultured pearl quality traits. Furthermore, the expressions of biomineralisation biomarkers encoding proteins in the aragonite or prismatic layer showed: 1) higher gene expression levels of aragonite-related genes in the large donor phenotype in the graft tissue, and 2) correlation of gene expression in the pearl sac tissue with pearl quality traits and recipient biometric parameters. These results emphasize that pearl size is mainly driven by the recipient and that pearl quality traits are mainly driven by the donor.


Pharmacist provided medicines reconciliation within 24 hours of admission and on discharge: a randomised controlled pilot study.
The UK government currently recommends that all patients receive medicines reconciliation (MR) from a member of the pharmacy team within 24 hours of admission and subsequent discharge. The cost-effectiveness of this intervention is unknown. A pilot study to inform the design of a future randomised controlled trial to determine effectiveness and cost-effectiveness of a pharmacist-delivered service was undertaken. Patients were recruited 7 days a week from 5 adult medical wards in 1 hospital over a 9 month period and randomised using an automated system to intervention (MR within 24 hours of admission and at discharge) or usual care which may include MR (control). Recruitment and retention rates were determined. Length of stay (LOS), quality of life (EQ-5D-3L), unintentional discrepancies (UDs) and emergency readmission (ER) within 3 months were tested as outcome measures. The feasibility of identifying and measuring intervention-associated resources was determined. 200 patients were randomised to either intervention or control. Groups were comparable at baseline. 95 (99%) patients in the intervention received MR within 24 hours, while 62 (60.8%) control patients received MR at some point during admission. The intervention resolved 250 of the 255 UDs identified at admission. Only 2 UDs were identified in the intervention group at discharge compared with 268 in the control. The median LOS was 94 hours in the intervention arm and 118 hours in the control, with ER rates of 17.9% and 26.7%, respectively. Assuming 5% loss to follow-up 1120 patients (560 in each arm) are required to detect a 6% reduction in 3-month ER rates. The results suggest that changes in outcome measures resulting from MR within 24 hours were in the appropriate direction and readmission within 3 months is the most appropriate primary outcome measure. A future study to determine cost-effectiveness of the intervention is feasible and warranted. ISRCTN23949491.


Successful tunneled catheter placement in a hemodialysis patient with idiopathic multiple central venous stenoses.
Central venous stenosis (CVS) in hemodialysis patients could be secondary to central venous catheterization, high flow arteriovenous fistula, as well as extrinsic compression. However, we report a senile hemodialysis patient of left internal jugular vein stenosis and right innominate vein occlusion unrelated to any known risk factors. Aided by computed tomography and digital subtraction angiography, we managed to dilate the stenosis by percutaneous balloon angioplasty, followed by successful tunneled catheter placement. Nephrologists should be aware of idiopathic CVS and its impact on the creation and preservation of vascular access. When confronted with difficulties in catheter placement, practitioners need to consider the possibilities of idiopathic CVS and refer to radiological tests.


Is there still a place for erythrocyte sedimentation rate and C-reactive protein in systemic lupus erythematosus?
The inflammatory response during systemic lupus erythematosus (SLE) flares is known to be atypical, characterized by a disproportionately lower C-reactive protein (CRP) elevation when compared with erythrocyte sedimentation rate (ESR). Thus, in these patients, the analysis of inflammatory markers might be challenging in daily clinical practice. Clinicians need frequently to distinguish lupus reactivations and infectious conditions, and the significance of ESR and CRP seems to be different. Even though a non-specific marker of inflammation, ESR utility in SLE should not be neglected and it appears to be a useful biomarker for SLE activity assessment. Describing a specific cut-off for ESR in SLE is important for patients' follow-up, and levels up to 25-30 mm/h have been proposed as an upper limit of the normal range. Regarding CRP, even though higher baseline levels are described in SLE when compared with controls, including in remission periods, its response during flares seems to be incomplete and not always correlated with disease activity; while CRP values greater than 10 mg/l could be indicative for severe flares, when there is no serositis or arthritis, higher CRP levels above 50-60 mg/l may be associated with infection.


The ordeal of Sigmund Freud. A postscript.
A number of questions about Freud's illness and treatment remain unanswered. The author ponders the duration of Freud's survival, the histologic diagnosis of the tumor, the contemporary management of this cancer, and the doctor-patient relationships involved.


The structure of self-concept in female preadolescent twins: a behavioral genetic approach.
Two hundred and forty-three female monozygotic (MZ) and 164 female dizygotic (DZ) twin pairs, aged 11 and 12 years, who participated in the ongoing Minnesota Twin Family Study, completed six specific scales of the Piers-Harris Children's Self-Concept Scale (P-H). Model-fitting analyses yielded three major conclusions. First, approximately 30% of the variance in specific self-concepts in female preadolescents was due to genetic factors, with the remaining variance being accounted for primarily by nonshared environmental factors and measurement error. Second, the underlying common genetic, shared environmental, and nonshared environmental factors influenced specific facets of self-concept directly and independently, rather than through an intervening phenotypic general self-concept. Finally, whereas genetic, shared environmental, and nonshared environmental factors were necessary to explain the commonality among the specific self-concept scales, only genetic and nonshared environmental factors were sufficient to explain the specificity of those scales.


Ribociclib Hybrid Lipid-Polymer Nanoparticle Preparation and Characterization for Cancer Treatment.
Ribociclib is a newly approved orally administered drug for breast cancer. This study aimed to prepare, characterize, and evaluate hybrid lipid-polymer nanoparticles (PLNs) of ribociclib to enhance its in vitro dissolution rate, pharmacokinetics, and anticancer efficacy. Ribociclib-loaded PLNs were prepared by solvent evaporation using the Box-Behnken design to optimize formulation variables. Particle size, entrapment efficiency, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), in vitro release cytotoxicity, molecular modeling, and pharmacokinetic studies were examined. The ribociclib-loaded PLN (formula 1, F1) was optimized in terms of particle size (266.9 ± 4.61 nm) and encapsulation efficiency (59.1 ± 2.57 mg/mL). DSC and thermogravimetric characterization showed the absence of a crystalline structure in the prepared PLNs, confirmed by FTIR, and showed no interactions between the components and the drug. AFM showed well-dispersed heterogeneously shaped nanoparticles. The in vitro release profile exhibited significant results for the optimized formula, reaching 100% at 600 and 90 min at pH 6.8 and 1.2, respectively. The low IC50 obtained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay suggests that optimized PLN might serve as an effective delivery vehicle for cancer treatment, especially breast and lung cancer. Molecular modeling revealed several hydrogen bonds. A pharmacokinetic study in rats showed that the ribociclib formula had a 6.5-fold increase in maximum concentration (Cmax) and a 5.6-fold increase in area under the curve (AUC). Regarding the everted intestinal sac absorption, formula 1 increased ribociclib penetration relative to the physical combination and pure medication. In conclusion, optimized PLNs with enhanced physicochemical and cytotoxic properties and improved pharmacokinetic parameters were successfully prepared.


Host (avian) biting preference of southern California Culex mosquitoes (Diptera: Culicidae).
The host preference of a vector mosquito species plays a significant role in determining human and animal risk of infection with mosquito-transmitted pathogens. Host preferences of common southern California Culex species for four bird species, American crow (Corvus brachyrhynchos), house sparrow (Passer domesticus), house finch (Carpodacus mexicanus), and mourning dove (Zenaida macroura), were examined by determining the proportion of each mosquito species that successfully engorged on each of the four bird species presented equally within a net trap to wild host-seeking mosquitoes. Bloodmeals in engorged mosquitoes captured within the net trap were identified to avian species by using a multiplex polymerase chain reaction assay targeting the cytochrome b gene sequence. There were significant differences in host selection by all three Culex species captured in numbers sufficient for analysis, with Culex erythrothorax Dyar preferentially biting American crows, Culex tarsalis Coquillett preferentially biting house sparrows, and Culex quinquefasciatus Say preferentially biting house finches. All three Culex species demonstrated more frequent engorgement on passerine birds (sparrows, finches, and crows) than the nonpasserine mourning dove. A greater preference for passerine birds might be expected to increase the transmission of pathogens, such as West Nile virus, to which passerine birds are particularly competent hosts.


A prospective study of fish, marine fatty acids, and bladder cancer risk among men and women (United States).
To evaluate prospectively the association between intakes of fish, marine fatty acids, and bladder cancer risk in two ongoing cohorts, the Health Professionals Follow-up Study and the Nurses' Health Study. During 16 and 18 years of follow-up, 501 and 235 incident cases of bladder cancer were diagnosed among men and women, respectively. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between fish intake and bladder cancer risk adjusting for age, total caloric intake, pack-years of cigarette smoking, and current smoking. We observed no significant overall association between total fish intake and bladder cancer risk, even when we compared >/=1 servings of fish per day to fish intake </=1-3 servings per month. Among men, a statistically significant lower risk of bladder cancer was observed among men consuming fish or high marine fatty acid, after excluding the first 4 years of follow-up (MV RR = 0.60; 95% CI, 0.38-0.94, for >/=1 total fish servings per day compared to </=1-3 servings per month). Overall, these findings suggest that fish intake is not likely to be appreciably associated with the risk of bladder cancer.


Cloning and characterization of the peptidoglycan recognition protein genes in the mosquito, Armigeres subalbatus (Diptera: Culicidae).
Peptidoglycan recognition proteins (PGRPs) are a group of proteins that are responsible for the recognition and, in some cases, binding of peptidoglycan (PGN), a unique cell wall component of bacteria, and initiation of immune responses to various types of pathogens. In the current study, full-length cDNA sequences of multiple PGRPs, identified via a database search, were cloned in the mosquito Armigeres subalbatus (Coquillett). During cloning, a novel transcript variant (isoform) of AsPGRP-LC (As: Ar. subalbatus) was also identified that shares a large 5' end fragment with AsPGRP-LC. All four AsPGRP genes (six transcripts) contain a conserved PGRP domain, an ortholog of the amidase-2 domain. Based on predicted functional domain, the six Ar. subalbatus PGRPs resemble both short (AsPGRP-S1) and long (AsPGRP-LBa, AsPGRP-LBb, AsPGRP-LCa, AsPGRP-LCb, and AsPGRP-LE) forms of PGRPs as in other insects. Sequence alignments showed that PGRPs are conserved across Dipterans. Phylogenetic analysis indicated that PGRPs represent an ancient gene family that has primarily diverged through speciation events among these Dipterans, with only a limited number of lineage specific gene duplications. Developmental profiling of the six AsPGRP transcripts using real-time polymerase chain reaction revealed that AsPGRP-LCa and AsPGRP-LCb are constitutively expressed at high levels in all developmental stages, while AsPGRP-S1, AsPGRP-LBa, AsPGRP-LBb, and AsPGRP-LE transcripts have low expression in most of the life stages and are increased only at certain times. Tissue profiling of the six AsPGRP transcripts showed that they are expressed in various patterns, even between the different isoforms of the same PGRP gene, indicating that these AsPGRPs may play different functions.


Critical periods in childhood learning.
The human body is born with 'hard wiring' that leads the baby to pay attention to certain things in the environment, especially the communications of caregivers. These inborn predispositions are gradually shaped by the environment of the family, a 'curriculum for babies' which is rich on communication and making sense of the world. Day care and nursery education can complement and enhance the child's learning, especially if they are of high quality. Research has shown again and again that early learning has lasting effects on development although they are rarely irreversible.


Altered jaw posture and occlusal disruption patterns following mandibular advancement therapy for sleep apnea: a preliminary study of cephalometric predictors.
Reports of irreversible alteration in jaw posture and destructive occlusal contact relationships in individuals using mandibular advancement devices for obstructive sleep apnea are beginning to appear. This study sought cephalometric means of identifying such individuals before commencing therapy. Cephalograms of 34 obstructive sleep apnea sufferers who had worn mandibular advancement devices for 2 years were compared retrospectively with baseline films taken at commencement of therapy and analyzed for signs of morphologic changes in jaw position and occlusal relationship. In affected patients, two distinct morphologic species of mandibular reposturing became evident: (1) bilateral posterior open bite with destructive incisal attrition; and (2) less destructive intermediate open bite over the premolar and first molar regions. From the observed morphology patterns, gonial angle and maxillary-mandibular plane angle were analyzed as possible vertical cephalometric risk predictors, with newly defined pterygoid advancement proportion (PtAP) as a horizontal predictor. Three patients displayed the posterior open bite pattern and had gonial angles < or = 119 degrees and maxillary-mandibular plane angles < or = 16 degrees, with PtAP values > or = 0.48. Prediction intervals for the five intermediate open bite cases were 118 degrees < or = gonial angle < or = 128 degrees, and 23 degrees < or = maxillary-mandibular plane angle < or = 32 degrees. PtAP values were > or = 0.52. Cephalometric analysis can help practitioners identify which apnea patients might be likely to develop irreversible mandibular postural changes from wearing a jaw-repositioning device.


Inflammatory bowel disease in 64 black patients: analysis of course, complications, and surgery.
Sixty-four black patients with inflammatory bowel disease (IBD) were seen from 1960 to 1987 at the Medical College of Georgia, representing 22% of all patients with IBD: 38 of them had Crohn's disease (CD) and 26 had ulcerative colitis (UC). In those with CD, the small intestine alone was involved in 16% and ileocolitis was found in 58%; joint disease affected 11 patients (29%) and perianal disease 13 patients (34%). Twenty black patients (53%) underwent one disease-related surgical procedure, and 10 (50%) of those required two or more reoperations. Nine UC patients (35%) underwent surgery, and, except for three cases of sclerosing cholangitis (12%), black patients with UC showed no clinical findings different from white UC patients. In our American black patients, the course of IBD was similar to that of white patients, although in Crohn's disease the reoperation rate and the rate of joint involvement were higher in our black IBD patients; primary sclerosing cholangitis was also found in a larger percentage of black patients with UC than in our white patient population.


Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs.
Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behavior, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterizes a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration ('dose') and mechanical hypersensitivity ('response'); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behavior) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). Varicella zoster virus was propagated on fibroblast cells before s.c. injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with i.p. morphine (2.5 mg/kg), amitriptyline (10 mg/kg), gabapentin (30 mg/kg), (S)-(+)-ibuprofen (20 mg/kg) and the cannabinoid WIN55,212-2 (2 mg/kg) but not the antiviral, acyclovir (50 mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain-related co-morbidity. Further, anxiety-like behavior was attenuated by acute i.p. administration of gabapentin (30 mg/kg) in nerve-injured, but not virus-infected animals. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and provide a tool for pre-clinical screening of analgesic drugs.


Evaluation of embryo quality after concurrent use of ovarian stimulating hormones and gamma irradiation.
Radiotherapy has many side effects on fertilization in young women. Radiation can lead to ovarian failure in women who underwent abdomen or pelvic radiotherapy. This study helps us to investigate ovarian response of NMRI female mice to ovarian stimulating hormones (PMSG, HCG) after whole-body gamma irradiation. 45 pregnant mice were divided into two groups of control and experimental. The experimental group was classified into three sub-groups: Irradiation group (2 or 4Gy),Superovulation group (10 or 15IU),and superovulation and gamma-radiation group (2Gy & 10IU, 2Gy & 15IU, 4Gy & 10IU,4Gy & 15IU). Female mice were killed and embryos were removed from oviduct .The number of embryos cells counted and the quality of them was evaluated in each group. Kruskal-Wallis test and Mann-Whitney test were used to analyze the data. There was a significant difference in the number of 2-4 cells grade D embryos in 2Gy & 15IU group compared with control and 2Gy groups (p=0.01), and the number of embryos in 4Gy group was more than in 10IU and 15IU (p=0.03) and 2Gy & 15IU groups (p=0.01). It was more significantly embryos in 4Gy & 15IU group compared to 2Gy & 15IU group (p=0.01).In addition There were no significant differences in the number of 2-4 cells grades A, B and C embryos and also number of 4-8 cells grades A, B and C, D embryos in groups. The concurrent use of ovulation stimulating hormones and gamma rays ameliorates this problem of drastic decrease in number of living embryos due to whole-body irradiation.


SEM qualitative evaluation of four self-etching adhesive systems.
Recently, there has been a tendency to simplify bonding procedures. Current self-etching adhesives combine conditioning, priming and bonding functions thus reducing technique-sensitivity as well as the risk of making errors. Another important advantage of this approach is that it allows the resin to etch and infiltrate the substratum simultaneously thus reducing the risk of any discrepancy between these 2 processes. The aim of this study was to evaluate the bonding quality of 4 self-etching adhesives both on dentin and enamel using SEM analysis. Twenty caries-free molars were used. The aprismatic enamel layer was removed from the internal and external slopes of the vestibular cusps using a diamond bur. Each molar was then transversally cut just above the pulp chamber using a diamond saw (composhave 4255 Intensiv) thus obtaining twenty coronal fragments and 20 radicular fragments. Radicular and coronal fragments were then randomly divided into 5 groups. Each group consisted of 8 specimens: 4 coronal and 4 radicular ones. A different adhesive system was used for each group following the manufacturer's directions. Each group underwent the same treatment: a thin layer of flowable composite was applied and then polymerized. Subsequently, a single 2 mm layer of microhybrid composite was added. The coronal and radicular portions were longitudinally cut to show the ground enamel/adhesive, unground enamel/adhesive and dentine/adhesive interfaces. Eighty specimens were obtained and prepared for SEM observation. Forty specimens with an adhesive/enamel interface and 40 with an adhesive/dentine interface. The interfacial exam frequently showed gaps between the substratum and the restoration. The final etching was generally satisfactory on ground enamel, while it was poor on unground enamel. Sometimes gaps were evident at the adhesive interface in dentin specimens. The tested adhesive systems produced a suitable hybrid layer and a lot of resin-tags were present. Self-etching adhesives showed an adequate adhesion to dentin. However, while they provided encouraging results on ground enamel they did not show to be dependable on unground enamel.


Intersplat friction force and splat sliding in a plasma-sprayed aluminum alloy coating during nanoindentation and microindentation.
This study computes the friction force during splat sliding in the plasma-sprayed Al-Si coating based on the instrumented depth-sensing nanoindentation and microindentation experiments. A small intersplat friction force (approximately 10(-4) N) contributes to the occurrence of the splat sliding. As compared with nanoindentation, more and more splat sliding occurs during microindentation because of the increase in the applied load, which accounts for the approximately 26% loss of the elastic modulus.


Oxazole-Bridged Combretastatin A-4 Derivatives with Tethered Hydroxamic Acids: Structure⁻Activity Relations of New Inhibitors of HDAC and/or Tubulin Function.
New inhibitors of tubulin polymerization and/or histone deacetylase (HDAC) activity were synthesized by attaching alkyl tethered hydroxamic acid appendages of varying length to oxazole-bridged combretastatin A-4 analogous caps. While their antiproliferative and microtubule disrupting effect was most pronounced for derivatives with short spacers, HDAC inhibition was strongest for those with longer spacers. These findings were further supported by computational methods such as structure-based docking experiments exploring the target interactions of the derivatives with varying linkers. For instance, compounds featuring short four-atom spacers between cap and hydroxamic acid inhibited the growth of various cancer cell lines and human endothelial hybrid cells with IC50 values in the low nanomolar range. In line with their ability to inhibit the microtubule assembly, four- and five-atom spacered hydroxamic acids caused an accumulation of 518A2 melanoma cells in G2/M phase, whereas a compound featuring a six-atom spacer and performing best in HDAC inhibition, induced a G1 arrest in these cells. All these beneficial anticancer activities together with their selectivity for cancer cells over non-malignant cells, point out the great potential of these novel pleiotropic HDAC and tubulin inhibitors as drug candidates for cancer therapy.


[Sonography of the diaphragmatic pleura in tumor patients].
Report on twelve patients suffering from malignant primary disease associated with pleural effusion and diaphragmatic metastasis, basically diagnosed via sonography. In no case tumour formation could be detected by x-ray film. Cytohistological evidence of diaphragmal metastasis can be found by sonographically detected pleural tumours malignant effusion must be assumed, despite negative exudate cytology. In such cases diagnostic thoracoscopy is not necessary.


[Management endourologic of pyeloureteral junction stenosis].
To report our experience with endourologic methods in the treatment of pyeloureteral stenosis in children. From July 2004, 7 patients from 9 months to 15 years old with pyeloureteral junction stenosis (PUJ) diagnosis underwent endourologic repair. An endourological dilatation was made under radioscopic control. The procedures consist of an initial cystoscopy with a retrograde placement of catheter (4 or 5 Fr) and the guide wire (0,014''-or 0,035''). The high pressure balloon (3 to 5 Fr) was then railroad over the wire and positioned across the stenosis for dilatation. A double J stent (3 to 6 Fr) was then introduced, remaining it during 6 weeks. There was no intraoperative complications. Median inhospital stay was 2 days (range, 2 to 8). The double J stent was removed without complications. All patients are asymptomatic with improvement in excretion times (MAG3 renography) and antero-posterior renal pelvis diameter (ultrasound measurement). Balloon dilatation is a viable option in the management of PUJ obstruction even in children under one year old, with minimal morbidity.


Frequency-comb-referenced tunable diode laser spectroscopy and laser stabilization applied to laser cooling.
Laser cooling of trapped atoms and ions in optical clocks demands stable light sources with precisely known absolute frequencies. Since a frequency comb is a vital part of any optical clock, the comb lines can be used for stabilizing tunable, user-friendly diode lasers. Here, a light source for laser cooling of trapped strontium ions is described. The megahertz-level stability and absolute frequency required are realized by stabilizing a distributed-feedback semiconductor laser to a frequency comb. Simple electronics is used to lock and scan the laser across the comb lines, and comb mode number ambiguities are resolved by using a separate, saturated absorption cell that exhibits easily distinguishable hyperfine absorption lines with known frequencies. Due to the simplicity, speed, and wide tuning range it offers, the employed technique could find wider use in precision spectroscopy.


On-chip simultaneous measurement of humidity and temperature using cascaded photonic crystal microring resonators with error correction.
We present the design, fabrication, and characterization of cascaded silicon-on-insulator photonic crystal microring resonators (PhCMRRs) for dual-parameter sensing based on a multiple resonances multiple modes (MRMM) technique. Benefitting from the slow-light effect, the engineered PhCMRRs exhibit unique optical field distributions with different sensitivities via the excitation of dielectric and air modes. The multiple resonances of two distinct modes offer new possibilities for enriching the sensing receptors with additional information about environmental changes while preserving all essential properties of traditional microring resonator based sensors. As a proof of concept, we demonstrate the feasibility of extracting humidity and temperature responses simultaneously with a single spectrum measurement by employing polymethyl methacrylate as the hydrophilic coating, obtaining a relative humidity (RH) sensitivity of 3.36 pm/%RH, 5.57 pm/%RH and a temperature sensitivity of 85.9 pm/°C, 67.1 pm/°C for selected dielectric mode and air mode, respectively. Moreover, the MRMM enriched data further forges the capability to perform mutual cancellation of the measurement error, which improves the sensing performance reflected by the coefficient of determination (R2-value), calculated as 0.97 and 0.99 for RH and temperature sensing results, respectively.


MxA induction may predict sustained virologic responses of chronic hepatitis B patients with IFN-alpha treatment.
The objective of this study was to find potential biomarkers for predicting sustained virologic responses to interferon-alpha (IFN-alpha) treatment in chronic hepatitis B (CHB) patients. A total of 101 CHB patients were treated with pegylated IFN-alpha2a for 48 weeks and followed up for 24 weeks, including 34 IFN responders (IFN-Rs) and 67 IFN nonresponders (IFN-NRs). After peripheral blood mononuclear cells (PBMCs) and Epstein-Barr virus-transferred B (EBV-B) cell lines were treated with different concentrations of IFN-alpha in vitro, activated IFN-stimulated gene factor3 (ISGF3) and IFN-gamma-activation factor (GAF) were measured by EMSA, and MxA, OAS1, and PKR mRNA were measured by real-time PCR. Polymorphisms in the MxA promoter were genotyped to find the possible association. IFN-alpha-activated ISGF3 and GAF levels were similar between IFN-NRs and IFN-Rs. However, MxA mRNA induction in IFN-Rs was higher than that in IFN-NRs, and such discrepancy increased when highly concentrated IFN was used to stimulate. The OAS1 and PKR mRNA induction have a similar pattern between IFN-Rs and IFN-NRs. In addition, frequency of the MxA-88G/T genotype was significantly different between IFN-Rs and IFN-NRs, and this polymorphism was also functional because MxA mRNA induction in patients with GG genotype was lower than those with GT genotype. Regression analysis showed that MxA mRNA induction after 10,000 IU/mL IFN stimulation could serve as an independent factor for predicting IFN-alpha, with an area under curve (AUC) of 0.838, a positive predictive value of 68% for IFN-Rs, and a negative predictive value of 89% for IFN-NRs. MxA mRNA induced by IFN-alpha might predict sustained virologic responses to IFN-alpha treatment in CHB patients.


[Severe anemia caused by haemorrhoids: the casae of a young man with toxic cirrhosis].
A 38-year-old alcoholic man with severe iron deficient anaemia, and bloody-mucous stool was found to have haemorrhoidal bleeding. In spite of intravenous iron supplements haemoglobin levels were falling. He was admitted because of deteriorating condition, jaundice, severe anaemia (haemoglobin, 38 g/l) and iron deficiency. Except of toxic (alcohol) agent all other causes of liver disease could be excluded. Sclero-, and medical therapy, and abstinence resulted in a rapid improvement in his condition and subsequently rectal bleeding also disappeared. Bleeding from the upper gastrointestinal tract is a well known and serious complication in liver cirrhosis, however, a voluminous blood loss resulting in a life-threatening anaemia from lower gastrointestinal tract or haemorrhoids, as it was detected in this patient, is quite rare. Sclerotherapy seems to be an effective method with only minor complications when compared with other invasive techniques. However, the patient's compliance even in liver cirrhosis with haemorrhoidal nodes is essential for long-term success.


Heat shock factor 1 promotes TERRA transcription and telomere protection upon heat stress.
In response to metabolic or environmental stress, cells activate powerful defense mechanisms to prevent the formation and accumulation of toxic protein aggregates. The main orchestrator of this cellular response is HSF1 (heat shock factor 1), a transcription factor involved in the up-regulation of protein-coding genes with protective roles. It has become very clear that HSF1 has a broader function than initially expected. Indeed, our previous work demonstrated that, upon stress, HSF1 activates the transcription of a non-coding RNA, named Satellite III, at pericentromeric heterochromatin. Here, we observe that the function of HSF1 extends to telomeres and identify subtelomeric DNA as a new genomic target of HSF1. We show that the binding of HSF1 to subtelomeric regions plays an essential role in the upregulation of non-coding TElomeric Repeat containing RNA (TERRA) transcription upon heat shock. Importantly, our data show that telomere integrity is impacted by heat shock and that telomeric DNA damages are markedly enhanced in HSF1 deficient cells. Altogether, our findings reveal a new direct and essential function of HSF1 in the transcriptional activation of TERRA and in telomere protection upon stress.


Reconstructing the gauge earlobe defect.
The use of gauge earrings causes earlobe defects and, at times, significant contour distortion. Simple closure leads to inadequate results in most cases. We describe a stratified approach to assessing the earlobe deformity as well as specific reconstructive techniques tailored to each type of deformity to restore normal size and contour, which, to our knowledge, has not been discussed in the literature thus far. This case series reviewed the last 20 patients who requested earlobe reconstruction with at least 1 year of follow-up. Earlobe deformity can be classified into 3 groups: small, which can be closed primarily; medium (with radial earlobe distortion and thinning), which requires advancement flaps or wedge excisions; and large (with inferior displacement of earlobe border and vertical axis abnormalities), which requires advancement flaps and excision of redundant tissue. Excellent final earlobe appearance is usually observed at 6 months postoperatively. Soft-tissue loss and contour abnormalities of medium and large defects require more complex repairs to prevent excessively narrowed lobes with loss of normal rounded contours. Obtaining a normal-appearing ear is of the utmost importance for patients who require a more professional appearance.


LEACH Protocol Optimization Based on Weighting Strategy and the Improved Ant Colony Algorithm.
This article aims to address problems in the current clustering process of low-energy adaptive clustering hierarchy (LEACH) in the wireless sensor networks, such as strong randomness and local optimum in the path optimization. This article proposes an optimal combined weighting (OCW) and improved ant colony optimization (IACO) algorithm for the LEACH protocol optimization. First, cluster head nodes are updated via a dynamic replacement mechanism of the whole network cluster head nodes to reduce the network energy consumption. In order to improve the quality of the selected cluster head nodes, this article proposes the OCW method to dynamically change the weight according to the importance of the cluster head node in different regions, in accordance with the three impact factors of the node residual energy, density, and distance between the node and the sink node in different regions. Second, the network is partitioned and the transmission path among the clusters can be optimized by the transfer probability in IACO with combined local and global pheromone update mechanism. The efficacy of the proposed LEACH protocol optimization method has been verified with MATLAB simulation experiments.


Family history of coronary artery disease and adverse clinical outcomes in patients suffering from acute ST-segment elevation myocardial infarction.
A positive family history (FHx+) of coronary artery disease (CAD) is a well-known risk factor for the development of coronary pathology in first-degree relatives. We sought to evaluate the association between FHx+ of CAD and clinical outcomes in patients presenting with a first ST-elevation myocardial infarction (STEMI). A historical cohort study of all patients with a first STEMI, who were admitted to cardiac ICU between 2007 and 2016, was carried out. Univariate and multivariate analyses were carried out to compare patients with or without a FHx+ of CAD. In further analysis, propensity score matching was used to reduce differences in baseline characteristics. The study included 1785 patients, 365 (20%) of whom had FHx+ of CAD. FHx+ was associated with decreased in-hospital major adverse events and long-term mortality rates (hazard ratio=0.208, 95% confidence interval: 0.051-0.857; P=0.03). After propensity score matching, patients with FHx+ had decreased long-term mortality rates (hazard ratio=0.105, 95% confidence interval: 0.033-0.33; P<0.001). In this large cohort of patients with STEMI, FHx+ was associated with better short-term and long-term outcomes. Understanding the rule of FHx in patients with STEMI is important to evaluate the prognosis and may help to construct a prediction model for patients admitted to cardiac ICU.


[Chronic polyarthritis in advanced age].
Approximately a quarter of polyarthritis in the elderly is beginning with a single- or oligo-articular attack of big joints. The first attack of the shoulder joints is noticed especially in men. Most of the patients with rheumatoid arthritis in the elderly have a gradually progressive course. There is often showed a very high blood sedimentation rate (BSR); rheumatoid factor is rare. Generally there is a strongly marked osteoporosis. The success of therapy with disease modifying agents is comparable with that of younger patients with rheumatoid arthritis, but there is a smaller tolerance to gold and D-penicillamine. In some non-steroidal anti-rheumatic drugs a lower dosage is recommended.


Severe combat eye injuries in the Lebanon War, 1982.
The findings, treatment and follow-up of 21 severe, blunt and perforating ocular injuries that occurred during combat in the Lebanon War, 1982, are presented. The diagnostic and therapeutic approaches to complex and severe ocular injuries are discussed. The patients were followed up for 1 year and the long-term effects of the injuries on their eyesight are described.


Anthropometric and endocrine features in girls with isolated premature pubarche or non-classical congenital adrenal hyperplasia.
Clinical and hormonal changes in girls with precocious pubarche, a multifactorial entity, have not been thoroughly investigated. To describe anthropometric features and bone age in Brazilian girls with precocious pubarche, and to compare clinical and hormonal findings for patients with isolated precocious pubarche (IPP) or non-classical congenital adrenal hyperplasia (NC-CAH). Twenty-eight girls with precocious pubarche were consecutively seen at the Child and Pubertal Gynecologic Clinic and the Gynecological Endocrinology Unit of Hospital de Clinicas de Porto Alegre. Patients with central precocious puberty and pseudopuberty were excluded from the study. Diagnostic criteria: NC-CAH: 17-hydroxyprogesterone (17OHP) >12 ng/ml 60 min after 0.25 mg i.m. ACTH; IPP: hormonal levels compatible with adrenarche and normal adrenal function confirmed by ACTH testing. Anthropometric and hormonal features and bone age were assessed. Six patients had NC-CAH, and 22 IPP. NC-CAH frequency was 21.42%. Weight and BMI were above 50th percentile except for patients <4 years; 46% of the girls were either overweight or obese. Clinical and hormonal features, except for response to ACTH testing, were similar in both groups; all patients were in or above the 50th percentile for height. Bone age was advanced in 43% of the patients. There was no statistical difference between the groups. Slight acceleration of height and bone age, one of the clinical manifestations of precocious pubarche, is unlikely to be progressively severe.


Postherpetic neuralgia: case study of class 4 laser therapy intervention.
Postherpetic neuralgia (PHN) is a neuropathic sequelae in 8% to 27% of individuals with prior varicella zoster virus infection and herpes zoster resulting in retrograde demyelination, neurotoxic reactive oxygen species levels, and proinflammatory cytokine activation of microglia. Pain management strategies are well documented, but not always effective. Laser therapy has shown utility in nerve injury-related pain disorders and was considered a potentially efficacious intervention. Case report. Class 4 therapeutic laser treatment was applied with a dual wavelength GaAlAs (810 nm), GaAl (980 nm) laser, 2 to 4 W, 50% duty cycle, 10 Hz pulse active phase, 2.5 cm diameter aperture, scanning technique with skin contact, 10-minute treatment, 600 to 1200 J total, energy density of 3.5 to 7.1 J/cm average per session, and power density from 0.41 to 0.82 W/cm for 8 treatments. Outcome measures included the Neuropathy Pain Scale Questionnaire as the primary outcome measure, with the Numeric Pain Scale and total area of allodynia touch sensitivity as secondary outcome measurements. The author reports a case of PHN of 15-year duration resistant to prior interventions. Weekly laser therapy treatment over 8 weeks resulted in reduced 0 to 10 Numeric Pain Scale score from 8 to 0, Neuropathy Pain Scale Questionnaire total score from 39 to 4, and allodynia over a 60 cm surface area of the upper trunk and posterior arm totally resolved, with resolution continued at 14-month follow-up. Theoretically, laser therapy induced tissue changes in this case occurring at and below the skin surface altering inflammatory and excitatory peripheral mechanisms noted to take place in the PHN patient. Peripheral nociceptor firing must be brought back to normal thresholds to resolve such chronic neuropathic pain and inhibit the possible central sensitization component. Anti-inflammatory cytokines, growth factors, nitric oxide, adenosine triphosphate (ATP), and other mechanisms stimulated by laser therapy as noted in medical literature may be central to the favorable response seen in this patient. Controlled clinical trials of class 4 laser therapy in the PHN patient population with similar doses would be beneficial to determine if this is an effective treatment option in PHN.


A computational strategy for geometry optimization of ionic and covalent excited states, applied to butadiene and hexatriene.
We propose a computational strategy that enables ionic and covalent pipi* excited states to be described in a balanced way. This strategy depends upon (1) the restricted active space self-consistent field method, in which the dynamic correlation between core sigma and valence pi electrons can be described by adding single sigma excitations to all pi configurations and (2) the use of a new conventional one-electron basis set specifically designed for the description of valence ionic states. Together, these provide excitation energies comparable with more accurate and expensive ab initio methods--e.g., multiconfigurational second-order perturbation theory and multireference configuration interaction. Moreover, our strategy also allows full optimization of excited-state geometries--including conical intersections between ionic and covalent excited states--to be routinely carried out, thanks to the availability of analytical energy gradients. The prototype systems studied are the cis and trans isomers of butadiene and hexatriene, for which the ground 1A(1/g), lower-lying dark (i.e., symmetry forbidden covalent) 2A(1/g) and spectroscopic 1B(2/u) (valence ionic) states were investigated.


Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor.
Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.


Activity and distribution of intracellular carbonic anhydrase II and their effects on the transport activity of anion exchanger AE1/SLC4A1.
We have investigated the previously published 'metabolon hypothesis' postulating that a close association of the anion exchanger 1 (AE1) and cytosolic carbonic anhydrase II (CAII) exists that greatly increases the transport activity of AE1. We study whether there is a physical association of and direct functional interaction between CAII and AE1 in the native human red cell and in tsA201 cells coexpressing heterologous fluorescent fusion proteins CAII-CyPet and YPet-AE1. In these doubly transfected tsA201 cells, YPet-AE1 is clearly associated with the cell membrane, whereas CAII-CyPet is homogeneously distributed throughout the cell in a cytoplasmic pattern. Förster resonance energy transfer measurements fail to detect close proximity of YPet-AE1 and CAII-CyPet. The absence of an association of AE1 and CAII is supported by immunoprecipitation experiments using Flag-antibody against Flag-tagged AE1 expressed in tsA201 cells, which does not co-precipitate native CAII but co-precipitates coexpressed ankyrin. Both the CAII and the AE1 fusion proteins are fully functional in tsA201 cells as judged by CA activity and by cellular HCO3(-) permeability (P(HCO3(-))) sensitive to inhibition by 4,4-Diisothiocyano-2,2-stilbenedisulfonic acid. Expression of the non-catalytic CAII mutant V143Y leads to a drastic reduction of endogenous CAII and to a corresponding reduction of total intracellular CA activity. Overexpression of an N-terminally truncated CAII lacking the proposed site of interaction with the C-terminal cytoplasmic tail of AE1 substantially increases intracellular CA activity, as does overexpression of wild-type CAII. These variously co-transfected tsA201 cells exhibit a positive correlation between cellular P(HCO3(-)) and intracellular CA activity. The relationship reflects that expected from changes in cytoplasmic CA activity improving substrate supply to or removal from AE1, without requirement for a CAII-AE1 metabolon involving physical interaction. A functional contribution of the hypothesized CAII-AE1 metabolon to erythroid AE1-mediated HCO3(-) transport was further tested in normal red cells and red cells from CAII-deficient patients that retain substantial CA activity associated with the erythroid CAI protein lacking the proposed AE1-binding sequence. Erythroid P(HCO3(-)) was indistinguishable in these two cell types, providing no support for the proposed functional importance of the physical interaction of CAII and AE1. A theoretical model predicts that homogeneous cytoplasmic distribution of CAII is more favourable for cellular transport of HCO3(-) and CO2 than is association of CAII with the cytoplasmic surface of the plasma membrane. This is due to the fact that the relatively slow intracellular transport of H(+) makes it most efficient to place the CA in the vicinity of the haemoglobin molecules, which are homogeneously distributed over the cytoplasm.


[Comparison of different cryopreservation systems for peripheral blood stem cells].
To explore proper cryopreservative systems for hematopoietic stem cells. Peripheral blood mononuclear cells from 20 persons were mixed with different cryopreservative agent, dimethyl suflfoxide (DMSO) or combination of DMSO and hydroxyethyl starch (HES), then cooled in -80 degrees C low temperature refrigerator (Refr) or autocontrolled programmed cryogenic system (PCS), preserved in Refr or in liquid nitrogen. GM-CFU, LTC-IC, CD34+ cells and typeran blue resistance (TBR) were assayed after different period of cryopreservation. The recovery rates of CFU-GM, LTC-IC, CD34+ cells and TBR in peripheral blood mononuclear cells which were cooled and preserved in Refr with 5% DMSO-6% HES were 82.2% +/- 14.7%, 83.0% +/- 12.2%, 94.2% +/- 4.3% and 97.7% +/- 3.9% respectively, significantly higher than that in Refr with 10% DMSO (P < 0.05). When cells were cryopreservated with the same cryopreservatives, there was no significantly difference of recovery rate in group of Refr and group of Refr with PCS. Meanwhile, there was not significantly difference of recovery rate among all three groups, preserved in Refr ahead of liquid nitrogen, in Refr merely, in liquid nitrogen with PCS within one year (p > 0.05). However, the recovery rate of CFU-GM, LTC- IC, CD34+ cells and TBR decreased dramatically if cells were cooled and preserved in Refr for two years. After cells were thawed, the cell activity declined gradually at room temperature if the cryopreservatives were not removed or diluted. The cell activity of 10% DMSO group was affected more than that of 5% DMSO-6% HES group. 5% DMSO-6% HES is better than 10% DMSO as cryopreservatives for hematopoietic stem cells. Refr cryopreservation is a simple and effective method if cells would be cryopreserved for less than one year. If cells would be cryopreserved for more than one year, liquid nitrogen cryopreservation should be recommended. The cryopreservatives should be diluted or removed immediately after cells were thawed.


Evaluation of auditory perception skills development in profoundly deaf children following cochlear implantation.
Cochlear implant is a medical treatment option for individuals with severe to profound sensori-neural hearing loss on account of non-functioning cochlea or part thereof. Technology is ever evolving and the candidacy criteria are widening. Appropriate selection of patient, successful implantation of an appropriate device and adequate post-implantation rehabilitation protocol are the key factors that dictate the eventual outcome. Bilateral cochlear implantation in children and combined electro-acoustic stimulation are the new developments in this field of rehabilitation for the deaf. Pakistan Cochlear Implant Programme was started in year 2000 and one hundred and fifty subjects have undergone cochlear implant surgery so far at Karachi, Lahore and Peshawar since. This prospective study was designed to evaluate the development of auditory perception skills and language in children, over a twelve months period, following cochlear implantation. Twenty-one patients were enrolled in this evaluation. These were divided into three groups as per age factor. Group 1 included eleven children of ages less than five years, Group 2 included eight children of ages between five and nine years whereas, Group 3 included two eleven years old children. Furthermore, subjects in Group 1 & 2 were pre-lingual whereas those in Group 3 were post-lingual. The three groups were evaluated using "Evaluation of Auditory Responses to Speech" (EARS). Improvement in performance on all measures was noticed in all the groups over a twelve months period following implantation. Dynamics of improvement in auditory skills suggested more and rapid development in younger age group. Children of varying ages, both pre and post lingual, did show improvement in the development of auditory perception skills, that was evident more in the younger age group.


Purification of the guinea pig sperm PH-20 antigen and detection of a site-specific endoproteolytic activity in sperm preparations that cleaves PH-20 into two disulfide-linked fragments.
Previous work has indicated that the guinea pig sperm membrane protein, PH-20, functions in sperm-egg adhesion and that its surface expression is regulated by the acrosome reaction. The PH-20 protein was purified by monoclonal antibody affinity chromatography. Sixty-seven to one hundred percent of the PH-20 antigenic activity present in an octylglucoside (OG) extract of sperm was recovered in the purified protein. From 10(10) sperm, approximately 0.4 mg of PH-20 protein was obtained, which was about 0.24% of the total protein in the OG extract. The purified protein retained the ability to bind the three anti-PH-20 monoclonal antibodies we have isolated. Silver staining of purified PH-20 on overloaded sodium dodecyl sulfate (SDS) gels allowed the estimate that silver-stainable contaminants were present at a level of one part in 2000. The purified PH-20 protein exists in three forms separable on SDS-polyacrylamide gel electrophoresis: a major form with a molecular mass of 64 kDa, a minor form of 56 kDa, and an endoproteolytically cleaved form composed of two disulfide-linked fragments of 41-48 kDa and 27 kDa. Cleveland digests of the 64 kDa and 56 kDa polypeptides indicated that they were structurally related. A proportion of the 64 kDa polypeptide in each purified preparation had undergone endoproteolysis at a specific site, so that it was cleaved into the two disulfide-linked fragments, 41-48 kDa and 27 kDa. It is speculated that the site-specific endoproteolysis of PH-20 may occur during the acrosome reaction and have biological significance.


Development and validation of risk profiles of West African rural communities facing multiple natural hazards.
West Africa has been described as a hotspot of climate change. The reliance on rain-fed agriculture by over 65% of the population means that vulnerability to climatic hazards such as droughts, rainstorms and floods will continue. Yet, the vulnerability and risk levels faced by different rural social-ecological systems (SES) affected by multiple hazards are poorly understood. To fill this gap, this study quantifies risk and vulnerability of rural communities to drought and floods. Risk is assessed using an indicator-based approach. A stepwise methodology is followed that combines participatory approaches with statistical, remote sensing and Geographic Information System techniques to develop community level vulnerability indices in three watersheds (Dano, Burkina Faso; Dassari, Benin; Vea, Ghana). The results show varying levels of risk profiles across the three watersheds. Statistically significant high levels of mean risk in the Dano area of Burkina Faso are found whilst communities in the Dassari area of Benin show low mean risk. The high risk in the Dano area results from, among other factors, underlying high exposure to droughts and rainstorms, longer dry season duration, low caloric intake per capita, and poor local institutions. The study introduces the concept of community impact score (CIS) to validate the indicator-based risk and vulnerability modelling. The CIS measures the cumulative impact of the occurrence of multiple hazards over five years. 65.3% of the variance in observed impact of hazards/CIS was explained by the risk models and communities with high simulated disaster risk generally follow areas with high observed disaster impacts. Results from this study will help disaster managers to better understand disaster risk and develop appropriate, inclusive and well integrated mitigation and adaptation plans at the local level. It fulfills the increasing need to balance global/regional assessments with community level assessments where major decisions against risk are actually taken and implemented.


Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma.
To evaluate the therapeutic efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chemoembolization (TACE) on the patients with hepatocellular carcinoma (HCC). Between 1998 and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63 patients had a Okuda stage I lesion and 31 patients had stage II. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver cirrhosis was present in all the patients. There were 43 cases of class A and 51 class B. TACE was performed using lipiodol, 5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d). The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overall survival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 mo. On univariate analysis, age (P=0.026), Child-Pugh classification for cirrhosis of liver (P=0.010), Okuda stage (P=0.026), tumor size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose (P=0.000) proved to be significant factors for survival. On multivariate analysis, age (P=0.024), radiation dose (P=0.001), and tumor size (P=0.000) were the significant factors. 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy.


9-cis Retinoic acid modulates myotrophin expression and its miR in physiological and pathophysiological cell models.
Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic β-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic β-cells line INS-1 832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375. We also studied the effect of this molecule on 3T3-L1 pre-adipocytes cells demonstrating a down-regulation of Mtpn and a dramatic increase of miR-375. Moreover, in the in vitro breast cancer model such as MDA-MB-231 and MCF-7 cells, 9cRA showed different effect on both Mtpn and miR-375 expression. In INS-1 832/13, 3T3-L1 pre-adipocytes and MCF-7 but not in MDA-MB-231, the effect of 9cRA on Mptn gene expression and its miR was under the control of RARs and RXRs receptors, as revealed by the exposure of these cell line to LE540 or HX603 receptor antagonists. In our findings 9cRA emerges has a hormone with a regulatory action on miR-375 that in most cases interfere with Mtpn expression.


Store-Operated Ca2+ Entry in Tumor Progression: From Molecular Mechanisms to Clinical Implications.
The remodeling of Ca2+ homeostasis has been implicated as a critical event in driving malignant phenotypes, such as tumor cell proliferation, motility, and metastasis. Store-operated Ca2+ entry (SOCE) that is elicited by the depletion of the endoplasmic reticulum (ER) Ca2+ stores constitutes the major Ca2+ influx pathways in most nonexcitable cells. Functional coupling between the plasma membrane Orai channels and ER Ca2+-sensing STIM proteins regulates SOCE activation. Previous studies in the human breast, cervical, and other cancer types have shown the functional significance of STIM/Orai-dependent Ca2+ signals in cancer development and progression. This article reviews the information on the regulatory mechanisms of STIM- and Orai-dependent SOCE pathways in the malignant characteristics of cancer, such as proliferation, resistance, migration, invasion, and metastasis. The recent investigations focusing on the emerging importance of SOCE in the cells of the tumor microenvironment, such as tumor angiogenesis and antitumor immunity, are also reviewed. The clinical implications as cancer therapeutics are discussed.


Stratified randomization for platform trials with differing experimental arm eligibility.
Platform trials facilitate efficient use of resources by comparing multiple experimental agents to a common standard of care arm. They can accommodate a changing scientific paradigm within a single trial protocol by adding or dropping experimental arms-critical features for trials in rapidly developing disease areas such as COVID-19 or cancer therapeutics. However, in these trials, efficacy and safety issues may render certain participant subgroups ineligible to some experimental arms, and methods for stratified randomization do not readily apply to this setting. We propose extensions for conventional methods of stratified randomization for platform trials whose experimental arms may differ in eligibility criteria. These methods balance on a prespecified set of stratification variables observable prior to arm assignment that remains the same across experimental arms. To do so, we suggest modifying block randomization by including experimental arm eligibility as a stratifying variable, and we suggest modifying the imbalance score calculation in dynamic balancing by performing pairwise comparisons between each eligible experimental arm and standard of care arm participants eligible to that experimental arm. We provide worked examples to illustrate the proposed extensions. In addition, we also provide a formula to quantify the relative efficiency loss of platform trials with varying eligibility compared with trials with non-varying eligibility as measured by the size of the common standard of care arm. This article presents important extensions to conventional methods for stratified randomization in order to facilitate the implementation of platform trials with differing experimental arm eligibility.


Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.
Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.


The effect of sibling visitation on bacterial colonization rate in neonates.
The effect of postpartum sibling visitation on the incidence of bacterial colonization in neonates was investigated in a 32-bed obstetrical unit of a midwestern university hospital. Siblings, following a temperature check, handwashing with a Hibiclens solution, and the donning of a patient covergown, were allowed unrestricted interaction with the infant. Statistical analysis of discharge cultures of nares and umbilici revealed that there was no significant difference between the control group and the experimental group. There was no difference between the two groups in the chart audit for postnatal infection at the first pediatric visit. Data analysis supported the hypothesis that sibling visitation does not increase bacterial colonization in neonates.


Predicting Functional Connectivity From Observed and Latent Structural Connectivity via Eigenvalue Mapping.
Understanding how complex dynamic activity propagates over a static structural network is an overarching question in the field of neuroscience. Previous work has demonstrated that linear graph-theoretic models perform as well as non-linear neural simulations in predicting functional connectivity with the added benefits of low dimensionality and a closed-form solution which make them far less computationally expensive. Here we show a simple model relating the eigenvalues of the structural connectivity and functional networks using the Gamma function, producing a reliable prediction of functional connectivity with a single model parameter. We also investigate the impact of local activity diffusion and long-range interhemispheric connectivity on the structure-function model and show an improvement in functional connectivity prediction when accounting for such latent variables which are often excluded from traditional diffusion tensor imaging (DTI) methods.


Hydrothermal synthesis and magnetic properties of novel Mn(II) and Zn(II) materials with thiolato-carboxylate donor ligand frameworks.
The hydrothermal reaction of thiosalicylic acid, (C(6)H(4)(CO(2)H)(SH)-1,2) with manganese(III) acetate leads to formation of the coordination solid [Mn(5)((C(6)H(4)(CO(2))(S)-1,2)(2))(4)(mu3-OH)2] (1) via a redox reaction, where resulting manganese(II) centres are coordinated by oxygen donor atoms and S-S disulfide bridge formation is simultaneously observed. Reaction of the same ligand under similar conditions with zinc(II) chloride yields the layered coordination solid [Zn(C(6)H(4)(CO(2))(S)-1,2)] (2). Hydrothermal treatment of manganese(III) acetate with 2-mercaptonicotinic acid, (NC(5)H(3)(SH)(CO(2)H)-2,3) was found to produce the 1-dimensional chain structure [Mn(2)((NC(5)H(3)(S)(CO(2))-2,3)(2))(2)(OH(2))(4)].4H(2)O (3) which also exhibits disulfide bridge formation and oxygen-only metal interactions. Compound 3 has been studied by thermogravimetric analysis and indicates sequential loss of lattice and coordinated water, prior to more comprehensive ligand fragmentation at elevated temperatures. The magnetic behaviour of 1 and 3 has been investigated and both exhibit antiferromagnetic interactions. The magnetic behaviour of 1 has been modelled as two corner-sharing isosceles triangles whilst 3 has been modelled as a 1-dimensional chain.


Refractory Oral Ulcer Responsive to Infliximab: A Case Report.
Some oral ulcers are refractory to treatment. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) agents have been shown to induce relatively long remissions of refractory oral ulcers. A 69-year man presented with a sore throat caused by a pharyngeal ulcer in the soft palate and subsequently repeatedly developed oropharyngolaryngeal ulcers and an ulcer in the ileocecal region. Intestinal Behçet disease was suspected, but he did not meet the diagnostic criteria for this condition. Seven months after the initial presentation, he developed a lingual ulcer that did not resolve despite treatment with prednisolone. Given the suspicion of intestinal Behçet disease, 300 mg of infliximab was administered intravenously. After the third dose of infliximab with prednisolone, the ulcer began to improve. He received infliximab every 8 weeks thereafter and developed no new oropharyngolaryngeal ulcers during the 17 months after the first infusion of infliximab. When a patient has refractory oral ulcers, attention must be paid to digestive symptoms and whether the patient has a systemic disease such as Behçet disease investigated. Furthermore, administration of infliximab to patients with refractory ulcers can be considered even when they do not fulfill the clinical criteria for a systemic disease.


Historical aspects of anxiety.
Although the syndromes of anxiety have only been recognized this century, the belief that the emotion of fearful apprehension could cause physical illness has a much longer history. James Vere wrote his book entitled "A physical and moral enquiry into the causes of that internal restlessness and disorder in man which has been the complaint of all ages" in 1778. The earliest accounts of phobia, as anxiety associated with specific circumstances have been ascribed to two cases from Hippocrates, whilst one of the earliest accounts in the English language may be that of William Shakespeare in The Merchant of Venice describing a supposed phobia for cats. Robert Burton (1621) described various anxiety disorders in classical detail in his 'Anatomy of Melancholy'.


Hormonal changes associated with estrogen induced luteolysis in the pregnant hamster: a reevaluation of the luteotropic complex.
Hamsters were injected sc on Day 1 of pregnancy (sperm positive) with 50 micrograms estradiol cyclopentylpropionate (ECP) or peanut oil. On Day 5, serum progesterone (P4) was 10.6 ng/ml in controls vs 3.1 ng/ml after ECP. In the ECP group, serum prolactin (PRL) and follicle stimulating hormone (FSH) did not differ from controls but serum luteinizing hormone (LH) was significantly lower than that of the controls, and usually below the sensitivity of the radioimmunoassay (RIA). After ECP, structural signs of luteolysis (weight and histology) and absence of antral follicles characterized the ovary. Injection of an anti-LH serum on Day 4 halved serum P4 levels on Day 5 in control animals but caused no further lowering of P4 in ECP-treated hamsters. Treatment on Days 1-5 with 1.0 IU hCG or 10 micrograms LH plus ECP on Day 1 restored, by the afternoon of Day 5, serum P4 to the control range (9-10 ng/ml) and antral follicles were now present. The results indicate that a large dose of ECP causes luteolysis by reducing LH levels and reinforce the concept of a luteotropic complex in the hamster with PRL and FSH constituting the minimal components and LH serving as a synergist.


Cockayne syndrome--an audiologic and temporal bone analysis.
Cockayne's syndrome is a triad of dwarfism, retinal atrophy, and deafness. Over thirty cases have been presented in the literature. We have examined and audiometrically tested three patients (ages 13 to 17) with confirmed Cockayne's syndrome and have analyzed the temporal bones of another who died at age 24. To our knowledge this is the first reported temporal bone analysis of a patient with Cockayne's syndrome. Audiograms revealed bilateral symmetric sensorineural hearing loss that was greatest in the high frequencies. Temporal bone examinations revealed inner and outer hair cell losses in the basal turn of the cochlea with corresponding neuron losses in the spiral ganglion. We have found that the clinical and histopathologic features resemble those of presbycusis and conclude that this corresponds well with the generalized, rapid, premature aging process characteristic of this disease.


Diabetes mellitus in the context of blood transfusion.
Diabetes mellitus is one of the commonest medical conditions affecting humans. However, knowledge of diabetes mellitus in the context of blood transfusion is lacking. In this article, the eligibility of people with diabetes as donors, issues faced during blood component transfusion to diabetics and impaired glucose tolerance among chronic blood recipients will be discussed, along with discussion of the present state of evidence.


Surface-modified silica colloidal crystals: nanoporous films and membranes with controlled ionic and molecular transport.
Nanoporous membranes are important for the study of the transport of small molecules and macromolecules through confined spaces and in applications ranging from separation of biomacromolecules and pharmaceuticals to sensing and controlled release of drugs. For many of these applications, chemists need to gate the ionic and molecular flux through the nanopores, which in turn depends on the ability to control the nanopore geometry and surface chemistry. Most commonly used nanoporous membrane materials are based on polymers. However, the nanostructure of polymeric membranes is not well-defined, and their surface is hard to modify. Inorganic nanoporous materials are attractive alternatives for polymers in the preparation of nanoporous membranes. In this Account, we describe the preparation and surface modification of inorganic nanoporous films and membranes self-assembled from silica colloidal spheres. These spheres form colloidal crystals with close-packed face centered cubic lattices upon vertical deposition from colloidal solutions. Silica colloidal crystals contain ordered arrays of interconnected three dimensional voids, which function as nanopores. We can prepare silica colloidal crystals as supported thin films on various flat solid surfaces or obtain free-standing silica colloidal membranes by sintering the colloidal crystals above 1000 °C. Unmodified silica colloidal membranes are capable of size-selective separation of macromolecules, and we can surface-modify them in a well-defined and controlled manner with small molecules and polymers. For the surface modification with small molecules, we use silanol chemistry. We grow polymer brushes with narrow molecular weight distribution and controlled length on the colloidal nanopore surface using atom transfer radical polymerization or ring-opening polymerization. We can control the flux in the resulting surface-modified nanoporous films and membranes by pH and ionic strength, temperature, light, and small molecule binding. When we modify the surface of the colloidal nanopores with ionizable moieties, they can generate an electric field inside the nanopores, which repels ions of the same charge and attracts ions of the opposite charge. This allows us to electrostatically gate the ionic flux through colloidal nanopores, controlled by pH and ionic strength of the solution when surface amines or sulfonic acids are present or by irradiation with light in the case of surface spiropyran moieties. When we modify the surface of the colloidal nanopores with chiral moieties capable of stereoselective binding of enantiomers, we generate colloidal films with chiral permselectivity. By filling the colloidal nanopores with polymer brushes attached to the pore surface, we can control the ionic flux through the corresponding films and membranes electrostatically using reversibly ionizable polymer brushes. By filling the colloidal nanopores with polymer brushes whose conformation reversibly changes in response to pH, ionic strength, temperature, or small molecule binding, we can control the molecular flux sterically. There are various potential applications for surface-modified silica colloidal films and membranes. Due to their ordered nanoporous structure and mechanical durability, they are beneficial in nanofluidics, nanofiltration, separations, and fuel cells and as catalyst supports. Reversible gating of flux by external stimuli may be useful in drug release, in size-, charge-, and structure-selective separations, and in microfluidic and sensing devices.


Utilising Sentinel-1's Orbital Stability for Efficient Pre-Processing of Radiometric Terrain Corrected Gamma Nought Backscatter.
Radiometric Terrain Corrected (RTC) gamma nought backscatter, which was introduced around a decade ago, has evolved into the standard for analysis-ready Synthetic Aperture Radar (SAR) data. While working with RTC backscatter data is particularly advantageous over undulated terrain, it requires substantial computing resources given that the terrain flattening is more computationally demanding than simple orthorectification. The extra computation may become problematic when working with large SAR datasets such as the one provided by the Sentinel-1 mission. In this study, we examine existing Sentinel-1 RTC pre-processing workflows and assess ways to reduce processing and storage overheads by considering the satellite's high orbital stability. By propagating Sentinel-1's orbital deviations through the complete pre-processing chain, we show that the local contributing area and the shadow mask can be assumed to be static for each relative orbit. Providing them as a combined external static layer to the pre-processing workflow, and streamlining the transformations between ground and orbit geometry, reduces the overall processing times by half. We conducted our experiments with our in-house developed toolbox named wizsard, which allowed us to analyse various aspects of RTC, specifically run time performance, oversampling, and radiometric quality. Compared to the Sentinel Application Platform (SNAP) this implementation allowed speeding up processing by factors of 10-50. The findings of this study are not just relevant for Sentinel-1 but for all SAR missions with high spatio-temporal coverage and orbital stability.


Head and spine injuries in the young athlete.
Recent studies have shown a decrease in the mortality rates from head and neck injuries, especially in American football. This has resulted because of rule changes and their enforcement, equipment modifications, improved coaching and training techniques, and educational programs for coaches, trainers, and team physicians on the early recognition of head and neck injuries. However, morbidity data is not as complete, particularly as it applies to concussion, the most frequent type of head injury in contact sports. Questions on this condition that still need to be answered before a sound medical disposition can be made are the possible cumulative damage from repeated concussions, and whether one concussion renders a player more susceptible to a second. Presently, decisions on when to allow a football player to return to a game or participate in future contests are arbitrary and based primarily on the experience of the team physician. Data on the incidence, mechanisms, and prognosis of transient spinal cord signs and symptoms, such as spinal cord concussion and the central core symptoms, is also incomplete. What is the long-term prognosis for players who suffer frequent "burners"? Certainly, further studies are essential before these questions can be answered. Thus, the pioneer work of Richard Schneider needs to be continued.


Can microfocal prostate cancer be regarded as low-risk prostate cancer?
Prostate specific antigen (PSA) screening for prostate cancer has become widespread, the prostate biopsy technique has evolved, and the occurrence of low-risk prostate cancer has been increasing. Even low-risk patients may demonstrate disease upgrading or upstaging. We aimed to evaluate the clinical importance of a single microfocal prostate cancer at biopsy in patients subsequently treated with radical prostatectomy. A total of 337 cases of patients who underwent radical prostatectomy after prostate biopsies were retrospectively reviewed. Microfocal prostate cancer was defined as Gleason score 6 and a single positive core with ≤5% cancer involvement after the standard 12-core extended biopsy. Of the 337 prostatectomy specimens, 22 (6.5%) were microfocal prostate cancer based on prostate biopsy. On final pathology, microfocal patients were found to have significant 45% Gleason score upgrading (P=0.02) and 27% positive surgical margins (P=0.04) despite low PSA, compared with the nonmicrofocal prostate cancer group. Gleason upgrading was significantly higher in the microfocal prostate cancer group (P=0.02), whereas Gleason downgrading was significantly higher in the nonmicrofocal prostate cancer group (P<0.01). Furthermore, biochemical recurrence rate was no different between microfocal and nonmicrofocal prostate cancer at mean 31 months (P=0.18). Overall, 13 of 22 cases (53.1%) in the microfocal prostate cancer group showed Gleason upgrading or stage upgrading. Based on higher rates of Gleason score upgrading or stage upgrading cases in microfocal prostate cancer group, compared with nonmicrofocal prostate cancer group, active surveillance should be cautiously applied to these patients.