cDNAs derived from primary and small cytoplasmic Alu (scAlu) transcripts.
We have isolated and sequenced twenty-six cDNAs derived from primary Alu transcripts. Most cDNAs (22/26) sequenced end in multiple T residues, known to be at the termination for RNA polymerase III-directed transcripts. We conclude that these cDNAs were derived from authentic, RNA polymerase III-directed primary Alu transcripts. Sequence alignment of the cDNAs with Alu consensus sequences show that the cDNAs belong to different, previously described Alu subfamilies. The sequence variation observed in the 3' non-Alu regions of each of the cDNAs led us to conclude that they were derived from different genomic loci, thus demonstrating that multiple Alu loci are transcriptionally active. The subfamily distribution of the cDNAs suggests that transcriptional activity is biased towards evolutionarily younger Alu subfamilies, with a strong selection for the consensus sequence in the first 42 bases and the promoter B box. Sequence data from seven cDNAs derived from small cytoplasmic Alu (scAlu) transcripts, a processed form of Alu transcripts, also have a similar bias towards younger Alu subfamilies. About half of these cDNAs are due to processing or degradation, but the other half appear to be due to the formation of a cryptic RNA polymerase III termination signal in multiple loci. Using our sequence data, we have isolated a transcriptionally active genomic Alu element belonging to the Ya5 subfamily. In vitro transcription studies of this element suggest that its flanking sequences contribute to its transcriptional activity. The role of flanking sequences and other factors involved in transcriptional activity of Alu elements are discussed.


Fabrication of Low-Molecular-Weight Hyaluronic Acid-Carboxymethyl Cellulose Hybrid to Promote Bone Growth in Guided Bone Regeneration Surgery: An Animal Study.
Guided bone regeneration surgery is an important dental operation used to regenerate enough bone to successfully heal dental implants. When this technique is performed on maxilla sinuses, hyaluronic acid (HLA) can be used as an auxiliary material to improve the graft material handling properties. Recent studies have indicated that low-molecular hyaluronic acid (L-HLA) provides a better regeneration ability than high-molecular-weight (H-HLA) analogues. The aim of this study was to fabricate an L-HLA-carboxymethyl cellulose (CMC) hybrid to promote bone regeneration while maintaining viscosity. The proliferation effect of fabricated L-HLA was tested using dental pulp stem cells (DPSCs). The mitogen-activated protein kinase (MAPK) pathway was examined using cells cultured with L-HLA combined with extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 inhibitors. The bone growth promotion of fabricated L-HLA/CMC hybrids was tested using an animal model. Micro-computer tomography (Micro-CT) and histological images were evaluated quantitatively to compare the differences in the osteogenesis between the H-HLA and L-HLA. Our results show that the fabricated L-HLA can bind to CD44 on the DPSC cell membranes and affect MAPK pathways, resulting in a prompt proliferation rate increase. Micro CT images show that new bone formation in rabbit calvaria defects treated with L-HLA/CMC was almost two times higher than in defects filled with H-HLA/CMC (p < 0.05) at 4 weeks, a trend that remained at 8 weeks and was confirmed by HE-stained images. According to these findings, it is reasonable to conclude that L-HLA provides better bone healing than H-HLA, and that the L-HLA/CMC fabricated in this study is a potential candidate for improving bone healing efficiency when a guided bone regeneration surgery was performed.


Sequential Optimization for Efficient High-Quality Object Proposal Generation.
We are motivated by the need for a generic object proposal generation algorithm which achieves good balance between object detection recall, proposal localization quality and computational efficiency. We propose a novel object proposal algorithm, BING++, which inherits the virtue of good computational efficiency of BING [1] but significantly improves its proposal localization quality. At high level we formulate the problem of object proposal generation from a novel probabilistic perspective, based on which our BING++ manages to improve the localization quality by employing edges and segments to estimate object boundaries and update the proposals sequentially. We propose learning the parameters efficiently by searching for approximate solutions in a quantized parameter space for complexity reduction. We demonstrate the generalization of BING++ with the same fixed parameters across different object classes and datasets. Empirically our BING++ can run at half speed of BING on CPU, but significantly improve the localization quality by 18.5 and 16.7 percent on both VOC2007 and Microhsoft COCO datasets, respectively. Compared with other state-of-the-art approaches, BING++ can achieve comparable performance, but run significantly faster.


Social class in childhood and general health in adulthood: questionnaire study of contribution of psychological attributes.
To determine the contribution of psychological attributes (personality characteristics and coping styles) to the association between social class in childhood and adult health among men and women. Partly retrospective, partly cross sectional study conducted in the framework of the Dutch GLOBE study. Sample of general population from south east Netherlands consisting of 2174 men and women aged 25-74 years. Baseline self reported data from 1991 provided information on childhood and adult social class, psychological attributes, and general health. Self rated poor health. Independent of adult social class, low childhood social class was related to self rated poor health (odds ratio 1.67 (95% confidence interval 1.02 to 2.75) for subjects whose fathers were unskilled manual workers versus subjects whose fathers were higher grade professionals). Subjects whose fathers were manual workers generally had more unfavourable personality profiles and more negative coping styles. External locus of control, neuroticism, and the absence of active problem focused coping explained about half of the association between childhood social class and self rated poor health. The findings were independent of adult social class and height. A higher prevalence of negative personality profiles and adverse coping styles in subjects who grew up in lower social classes explains part of the association between social class in childhood and adult health. This finding underlines the importance of psychological mechanisms in the examination of the negative effects of adverse socioeconomic conditions in childhood.


Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.
Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation. Moreover, TBI deregulates Ca(2+) -homeostasis triggering p25 production. The protein kinase Cdk5 is aberrantly activated by p25 leading to phosphorylation of substrates including tau and Rb protein. Loss of Cdk5 attenuates TBI lesion size, indicating that Cdk5 is a critical player in TBI pathogenesis and thus may be a suitable therapeutic target for TBI.


Magnetic resonance cholangiopancreatography image enhancement for automatic disease detection.
To sufficiently improve magnetic resonance cholangiopancreatography (MRCP) quality to enable reliable computer-aided diagnosis (CAD). A set of image enhancement strategies that included filters (i.e. Gaussian, median, Wiener and Perona-Malik), wavelets (i.e. contourlet, ridgelet and a non-orthogonal noise compensation implementation), graph-cut approaches using lazy-snapping and Phase Unwrapping MAxflow, and binary thresholding using a fixed threshold and dynamic thresholding via histogram analysis were implemented to overcome the adverse characteristics of MRCP images such as acquisition noise, artifacts, partial volume effect and large inter- and intra-patient image intensity variations, all of which pose problems in application development. Subjective evaluation of several popular pre-processing techniques was undertaken to improve the quality of the 2D MRCP images and enhance the detection of the significant biliary structures within them, with the purpose of biliary disease detection. The results varied as expected since each algorithm capitalized on different characteristics of the images. For denoising, the Perona-Malik and contourlet approaches were found to be the most suitable. In terms of extraction of the significant biliary structures and removal of background, the thresholding approaches performed well. The interactive scheme performed the best, especially by using the strengths of the graph-cut algorithm enhanced by user-friendly lazy-snapping for foreground and background marker selection. Tests show promising results for some techniques, but not others, as viable image enhancement modules for automatic CAD systems for biliary and liver diseases.


New concepts in phospholipase D signaling in inflammation and cancer.
Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate the lipid second messenger phosphatidic acid (PA) and choline. PLD regulation in cells falls into two major signaling categories. One is via growth factors/mitogens, such as EGF, PDGF, insulin, and serum, and implicates tyrosine kinases; the other is via the small GTPase proteins Arf and Rho. We summarize here our lab's and other groups' contributions to those pathways and introduce several novel concepts. For the mitogen-induced signaling, new data indicate that an increase in cell transformation in PLD2-overexpressing cells is due to an increase of de novo DNA synthesis induced by PLD2, with the specific tyrosine residues involved in those functions being Y179 and Y511. Recent research has also implicated Grb2 in tyrosine phosphorylation of PLD2 that also involves Sos and the ERK pathway. The targets of phosphorylation within the PLD2 molecule that are key to its regulation have recently been precisely mapped. They are Y296, Y415, and Y511 and the responsible kinases are, respectively, EGFR, JAK3, and Src. Y296 is an inhibitory site and its phosphorylation explains the low PLD2 activity that exists in low-invasive MCF-7 breast cancer cells. Advances along the small GTPase front have implicated cell migration, as PLD1 and PLD2 cause an increase in chemotaxis of leukocytes and inflammation. PA is necessary for full chemotaxis. PA enriches the localization of the atypical guanine exchange factor (GEF), DOCK2, at the leading edge of polarized neutrophils. Further, extracellular PA serves as a neutrophil chemoattractant; PA enters the cell and activates the mTOR/S6K pathway (specifically, S6K). A clear connection between PLD with the mTOR/S6K pathway has been established, in that PA binds to mTOR and also binds to S6K independently of mTOR. Lastly, there is evidence in the upstream direction of cell signaling that mTOR and S6K keep PLD2 gene expression function down-regulated in basal conditions. In summary, the involvement of PLD2 in cell signaling continues to expand geometrically. It involves gene transcription, mitogenic and cell migration effects as seen in normal growth, tumor development, and inflammation.


Vascular effects of arginine vasopressin, angiotensin II, and norepinephrine in adrenal insufficiency.
Plasma arginine vasopressin (AVP) levels were 9.6 pg/ml in the mineralocorticoid-deficient rats, a value significantly greater than 4.8 pg/ml in the glucocorticoid-deficient rats (P less than 0.05), and 1.6 pg/ml in controls (P less than 0.001). The AVP antagonist of the vascular effect of AVP, [1(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine] AVP, [d(CH2)5Tyr(Me)AVP] (5 micrograms/kg), decreased mean arterial pressure (MAP) from 76.5 to 71.6 mmHg (P less than 0.01) in mineralocorticoid-deficient rats on day 10 but not in glucocorticoid deficient rats on day 14 (113.2-111.6 mmHg, NS) or in control rats (109.7-110.2 mmHg, NS). Plasma renin activity was 40.7 ng X ml-1 X h-1 in mineralocorticoid-deficient rats and 7.2 in glucocorticoid-deficient rats (P less than 0.001). The angiotensin II antagonist, [Sar1-Gly8]angiotensin II (5 micrograms X kg-1 X min-1), decreased MAP from 69.3 to 53.2 mmHg in mineralocorticoid-deficient rats (P less than 0.001) but not in glucocorticoid-deficient rats. Plasma norepinephrine was 1,138 pg/ml in mineralocorticoid-deficient rats and 251 pg/ml in glucocorticoid-deficient rats (P less than 0.001). The alpha-adrenergic blocker, phenoxybenzamine (3 mg/kg), reduced MAP from 82 to 51 mmHg in mineralocorticoid deficient rats (P less than 0.005), a decrease in MAP greater (P less than 0.05) than that observed in glucocorticoid-deficient rats (107.7-84.8 mmHg, P less than 0.02). In addition, the AVP antagonist caused a greater and more prolonged reduction in MAP in mineralocorticoid-deficient rats after the administration of either the angiotensin II antagonist or alpha-blocker. These results indicate that AVP, norepinephrine, and angiotensin II are involved in maintaining blood pressure in the mineralocorticoid-deficient state.


Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa.
The transglutaminase activated factor XIII (FXIIIa) acts to strengthen pathological fibrin clots and to slow their dissolution, in part by crosslinking active α(2)-antiplasmin (α(2)AP) to fibrin. We previously reported that a yeast-derived recombinant fusion protein comprising α(2)AP residues 13-42 linked to human serum albumin (HSA) weakened in vitro clots but failed to become specifically incorporated into in vivo clots. In this study, our aims were to improve both the stability and clot localization of the HSA fusion protein by replacing α(2)AP residues 13-42 with shorter sequences recognized more effectively by FXIIIa. Expression plasmids were prepared encoding recombinant HSA with the following N-terminal 23 residue extensions: H(6)NQEQVSPLTLLAG(4)Y (designated XL1); H(6)DQMMLPWAVTLG(4)Y (XL2); H(6)WQHKIDLPYNGAG(4)Y (XL3); and their 17 residue non-His-tagged equivalents (XL4, XL5, and XL6). The HSA moiety of XL4- to XL6-HSA proteins was C-terminally His-tagged. All chimerae were efficiently secreted from transformed Pichia pastoris yeast except XL3-HSA, and following nickel chelate affinity purification were found to be intact by amino acid sequencing, as was an N-terminally His-tagged version of α(2)AP(13-42)-HSA. Of the proteins tested, XL5-HSA was cross-linked to biotin pentylamine (BPA) most rapidly by FXIIIa, and was the most effective competitor of α(2)AP crosslinking not only to BPA but also to plasma fibrin clots. In the mouse ferric chloride vena cava thrombosis model, radiolabeled XL5-HSA was retained in the clot to a greater extent than recombinant HSA. In the rabbit jugular vein stasis thrombosis model, XL5-HSA was also retained in the clot, in a urea-insensitive manner indicative of crosslinking to fibrin, to a greater extent than recombinant HSA. Fusion protein XL5-HSA (DQMMLPWAVTLG4Y-HSAH6) was found to be more active as a substrate for FXIIIa-mediated transamidation than seven other candidate fusion proteins in vitro. The improved stability and reactivity of this chimeric protein was further evidenced by its incorporation into in vivo clots formed in thrombosis models in both mice and rabbits.


Paediatric end-of-life care - symptoms and problems: parent assessment.
Symptoms and problems (S&P) are under-reported in children in end-of-life care.To target future interventions, the primary aim was to examine S&P in children in end-of-life care. All parents, who lost a child under the age of 18 years due to life-limiting diagnoses in the period 2012-2014 in Denmark, were invited to complete a self-administered questionnaire in 2017. In all, 152 (38%) children were represented by 136 mothers and 57 fathers. In the present study, parents' assessments of S&P during the last month of life were restricted to children aged 3-18 years. Data were analyses by means of descriptive statistics. Children ≥3 years at the time of death were represented by 71 parents (48 mothers and 23 fathers) representing 56 out of the 152 children. Physical fatigue (93%), sleepiness (90%), poor appetite (87%), pain (84%) and nausea (84%) were the five most frequent symptoms reported by the parents. In all, 65% of the parents reported that satisfactory pain relief was obtained and 64% of the parents reported that the healthcare services to a large extent reacted quickly, when the child and/or family needed help. However, 46% of the parents experienced 'mess-ups' or sloppy services in the primary ward and 27% experienced that the children suffered from fear of death. According to the parents, children with life-limiting diagnosis are highly symptomatic and have substantial problems during end-of-life care. Our findings indicate that systematic screening of S&P in children should be considered.


Metacarpal and phalangeal osteotomy with miniplate fixation.
We reviewed the results of corrective oseotomies performed with power tools for symptomatic malunions of metacarpal and phalangeal fractures in 10 patients. At an average follow-up of 30 months, all patients had a healed osteotomy with correct alignment and had an average increase of 30 degrees in the flexion arc of the involved digit. We recommend a surgical technique of miniplate fixation over K-wire fixation where possible; it allows precise, intraoperative correction and rigid stabilization. A shortened immobilization time and early motion are significant advantages of plate fixation. However, plates cannot be used across open growth plates or directly over areas of tendon insertion. A careful preoperative plan should always be prepared prior to any corrective osteotomy. Problems such as post-operative tendinous adhesions did not occur, nor did nonunions or delayed unions.


A case of congenital bilateral stapes agenesis.
Congenital absence of the stapes and the oval window is an anomaly reported in only sporadic cases. We present a 17-year-old male patient with congenital bilateral conductive hearing loss. The external auditory canal and the tympanic membrane appeared normal on both sides. An exploratory tympanotomy in the right ear revealed dehiscence of the the horizontal segment of the facial nerve, which was displaced inferiorly, occupying the area of the absent oval window. The stapes was totally absent and a malformed long process of the incus was attached by a fibrous band to the promontory. Manipulation of the facial nerve in association with stapedectomy or vestibulotomy was avoided in order not to injure the nerve. Instead, amplification with hearing aids was recommended to the patient.


Domain-formation in DOPC/SM bilayers studied by pfg-NMR: effect of sterol structure.
Pulsed field gradient (pfg)-NMR spectroscopy was utilized to determine lipid lateral diffusion coefficients in oriented bilayers composed of 25 mol % sterol and equimolar amounts of dioleoylphosphatidylcholine and sphingomyelin. The occurrence of two lipid diffusion coefficients in a bilayer was used as evidence of lateral phase separation into liquid ordered and liquid disordered domains. It was found that cholesterol, ergosterol, sitosterol, and lathosterol induced domains, whereas lanosterol, stigmasterol, and stigmastanol resided in homogeneous membranes in the temperature interval of 24-70 degrees C. Among the domain-forming sterols, differences in the upper miscibility temperature indicated that the stability of the liquid ordered phase could be modified by small changes in the sterol structure. The domain-forming capacity for the different sterols is discussed in terms of the ordering effect of the sterols on the lipids, and it is proposed that the driving force for the lateral phase separation is the reduced solubility of the unsaturated lipid in the highly ordered phase.


Living donor liver transplantation followed by total gastrectomy--a two-stage planed operative strategy for early gastric cancer concomitant with decompensated liver cirrhosis.
With the recent popularization of living donor liver transplantation (LDLT), providing treatment for comorbidities in LDLT recipients has become important. We report the first case of a patient who was successfully treated with LDLT followed by total gastrectomy for early gastric cancer concomitant with decompensated liver cirrhosis. A 64-year-old female was admitted for the treatment of severe liver cirrhosis. The patient's preoperative liver function was evaluated as Child-Pugh classification grade C. Upper gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT to improve her liver function and coagulopathy. Nineteen days after the LDLT, we performed total gastrectomy. The patient's postoperative course was uneventful and she left our hospital on the 18th day after gastrectomy. The final pathological diagnosis of gastric cancer was Stage IA. Aggressive and adequate surgical strategy including LDLT is effective as curative treatment in patients with controllable malignancy concomitant with severe liver dysfunction.


46,XY disorder of sex development in a sudanese patient caused by a novel mutation in the HSD17B3 gene.
In this study, we present a Sudanese 46,XY patient raised as a female and diagnosed at the age of 20 years with having 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency. She presented with primary amenorrhea, undeveloped breasts and a male pattern of secondary sexual characteristics. Examination of her external genitalia showed type IV genital circumcision. Steroid measurements both in urine and serum pointed to 17β-HSD3 deficiency. A novel homozygous splice-site mutation [c.524 + 2T>A] was detected in intron 7 of the HSD17B3 gene. In this patient, steroid concentration clearly supported both the clinical diagnosis of 17β-HSD3 deficiency and the functional relevance of the mutation. Interestingly, despite of the type IV genital circumcision, the patient expressed her interest in reassigning her sex from female to male.


Evidence for a low-affinity, high-capacity uniport for amino acids in Bombyx mori larval midgut.
We investigated the kinetics of leucine influx as a function of external substrate concentration between 0.03 and 16 mM in brush-border membrane vesicles (BBMV) prepared from the middle region of Bombyx mori larval midgut. A detailed kinetic analysis of leucine uptake led to the identification, in parallel with the K(+)-dependent symporter for neutral amino acids, of a K(+)-independent, low-affinity, high-capacity system. The parameter values of the Michaelis constant (7.12 mM) and maximal rate of transport (4.48 nmol.7 s-1.mg protein-1) were not influenced by an external alkaline pH nor by a transmembrane electrical potential difference. The uniporter is poorly specific, as it displayed the following rank of preference: Leu, His, Val, Ile, Phe, Ser > Lys, Arg, Gln > Pro, 2-amino-2-norbornane-carboxylic acid, Ala, Gly. The kinetic analysis performed in BBMV prepared from the posterior midgut portion indicates that the low-affinity, high-capacity uniporter is present along the entire length of the silkworm larval midgut with similar expression and functional properties.


Tea intake is inversely related to blood pressure in older women.
Tea is rich in polyphenols, which have activities consistent with blood pressure-lowering potential. The effects of long-term regular ingestion of tea on blood pressure remain uncertain. We investigated the relationships of tea intake and a biomarker of exposure to tea-derived polyphenols (4-O-methylgallic acid) with blood pressure in a cross-sectional study of 218 women > 70 y old. Clinic blood pressures were measured and tea intake was assessed using a 24-h dietary recall; 4-O-methylgallic acid was measured for the same period in a 24-h urine sample. Mean (95% CI) daily tea intake was 525 (475, 600) mL. Mean systolic and diastolic blood pressures were 138.1 (135.6, 140.6) and 73.5 (72.1, 74.9) mm Hg. Higher tea intake and higher 4-O-methylgallic acid excretion were associated with significantly lower systolic (P = 0.002 and P = 0.040, respectively) and diastolic (P = 0.027 and P < 0.001, respectively) blood pressures. A 250 mL/d (1 cup) increase in tea intake was associated with a 2.2 (0.8, 3.6) mm Hg lower systolic blood pressure and a 0.9 (0.1, 1.7) mm Hg lower diastolic blood pressure. The observed associations for both tea intake and 4-O-methylgallic acid are consistent with the hypothesis that long-term regular ingestion of tea may have a favorable effect on blood pressure in older women.


Type-3c Diabetes Mellitus, Diabetes of Exocrine Pancreas - An Update.
The incidence of diabetes is increasing steeply; the number of diabetics has doubled over the past three decades. Surprisingly, the knowledge of type 3c diabetes mellitus (T3cDM) is still unclear to the researchers, scientist and medical practitioners, leading towards erroneous diagnosis, which is sometimes misdiagnosed as type 1 diabetes mellitus (T1DM), or more frequently type 2 diabetes mellitus (T2DM). This review is aimed to outline recent information on the etiology, pathophysiology, diagnostic procedures, and therapeutic management of T3cDM patients. The literature related to T3cDM was thoroughly searched from the public domains and reviewed extensively to construct this article. Further, existing literature related to the other forms of diabetes is reviewed for projecting the differences among the different forms of diabetes. Detailed and updated information related to epidemiological evidence, risk factors, symptoms, diagnosis, pathogenesis and management is structured in this review. T3cDM is often misdiagnosed as T2DM due to the insufficient knowledge differentiating between T2DM and T3cDM. The pathogenesis of T3cDM is explained which is often linked to the history of chronic pancreatitis, pancreatic cancer. Inflammation, and fibrosis in pancreatic tissue lead to damage both endocrine and exocrine functions, thus leading to insulin/glucagon insufficiency and pancreatic enzyme deficiency. Future advancements should be accompanied by the establishment of a quick diagnostic tool through the understanding of potential biomarkers of the disease and newer treatments for better control of the diseased condition.


Use of anti-Aedes aegypti salivary extract antibody concentration to correlate risk of vector exposure and dengue transmission risk in Colombia.
Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an "Ae. aegypti-free" area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence.


Body stalk anomaly--a case report.
A case is presented of an amnionic rupture sequence which led to massive fetal ventral herniation and lordoscoliosis. Characteristic ultrasonographic findings of an omphalocele, fetal attachment to the placenta, and the absence of free-floating umbilical cord were observed.


Survival and recovery of Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes on lettuce and parsley as affected by method of inoculation, time between inoculation and analysis, and treatment with chlorinated water.
The effects of method for applying inoculum and of drying time after inoculation on survival and recovery of foodborne pathogens on iceberg lettuce and parsley were studied. Five-strain mixtures of Escherichia coli O157:H7, Salmonella, or Listeria monocytogenes were applied to lettuce and parsley by dip, spot, or spray inoculation methods. Inocula were dried for 2 h at 22 degrees C or for 2 h at 22 degrees C and then 22 h at 4 degrees C before being treated with water (control) or chlorine (200 microg/ml). Significantly higher populations (CFU per lettuce or parsley sample) of E. coli O157:H7 and Salmonella (alpha = 0.05) were recovered from dip-inoculated produce than from spot- or spray-inoculated produce. This difference was attributed to larger numbers of cells adhering to lettuce and parsley subjected to dip inoculation. Populations of E. coli O157:H7 and Salmonella recovered from lettuce inoculated by spot and spray methods were not significantly different, but populations recovered from spot-inoculated parsley were significantly higher than those recovered from spray-inoculated parsley, even though the number of cells applied was the same. Significantly different numbers of L. monocytogenes were recovered from inoculated lettuce (dip > spray > spot); populations recovered from dip-inoculated parsley were significantly higher than those recovered from spot- or spray-inoculated parsley, which were not significantly different from each other. Populations of pathogens recovered from lettuce and parsley after drying inoculum for 2 h at 22 degrees C were significantly higher than or equal to populations recovered after drying for 2 h at 22 degrees C and then for 22 h at 4 degrees C. Significant differences (water > chlorine) were observed in populations of all pathogens recovered from treated lettuce and parsley, regardless of inoculation method and drying time. It is recommended that spot inoculation with a drying time of 2 h at 22 degrees C followed by 22 h at 4 degrees C be used to determine the efficacy of chlorine and other sanitizers in killing foodborne pathogens on lettuce and parsley.


Laceration of umbilical artery and abruptio placentae secondary to amniocentesis.
A case of a lacerated umbilical artery causing an abruptio placentae and subsequent emergency cesarean section is presented, with a review of the complications of amniocentesis. A search of the literature has failed to reveal that this particular complication has been previously reported.


Association of Neuregulin 1 rs3924999 genotype with antisaccades and smooth pursuit eye movements.
Neuregulin 1 (NRG1) has been identified as one of the leading candidate genes for schizophrenia. However, its functional mechanisms and its effects on neurocognition remain unclear. In this study, we used two well-established oculomotor endophenotypes, the antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks, to investigate the functional mechanisms of a single nucleotide polymorphism (SNP) in NRG1 (rs3924999) at the neurocognitive level in a healthy volunteer sample. A total of 114 healthy Caucasian volunteers completed genotyping for NRG1 rs3924999 and infrared oculographic assessment of AS and SPEM (at target velocities of 12 degrees , 24 degrees and 36 degrees per second). Additionally, self-report questionnaires of schizotypy, neuroticism, attention deficit hyperactivity and obsessive-compulsive traits were included. A significant effect of rs3924999 genotype, with gender as a covariate, was found for AS amplitude gain (P < 0.01), with an increasing number of A alleles being associated with increasingly hypermetric performance. No statistically significant associations were found for other AS and SPEM variables or questionnaire scores. These findings indicate that NRG1 rs3924999 affects spatial accuracy on the AS task, suggesting an influence of the gene on the neural mechanisms underlying visuospatial sensorimotor transformations, a mechanism that has been previously found to be impaired in patients with schizophrenia and their relatives.


Utilizing rapid multiple-locus variable-number tandem-repeat analysis typing to aid control of hospital-acquired Clostridium difficile Infection: a multicenter study.
The early identification of outbreaks is crucial for the control of Clostridium difficile infection. This study aimed to determine if the number of hospital-acquired C. difficile infections could be reduced by rapidly typing C. difficile strains using multiple-locus variable-number tandem-repeat analysis (MLVA) compared to typing using PCR ribotyping. A total of 16 hospitals were recruited to the study, and all periods of increased incidence (PIIs) of C. difficile infection were identified. The hospitals were randomized into two study arms, the test and the control, with all isolates typed in the test using MLVA and in the control using PCR ribotyping. Following a PII, each hospital received a structured questionnaire regarding control measures implemented or stopped prior to or following the typing results. During the study period, there were a total of 1,682 hospital-apportioned C. difficile toxin-positive cases, with 868 in the control and 814 in the test, with modeling demonstrating no differences between the two arms. A total of 245 PIIs occurred, involving 785 patients. There was a significant difference in the mean turnaround time between the ribotyping and MLVA typing (13.6 and 5.3 days, respectively [P < 0.001]). The discriminatory ability of MLVA was greater than ribotyping, with 85 outbreaks being confirmed by ribotyping and 62 by MLVA. In the test arm, 40.6% of respondents strongly agreed that the typing result had aided their management of clusters, as opposed to 9.9% in the control. The study demonstrated the utility of rapidly typing C. difficile strains, demonstrating that it aided the management of clusters, enabling effective targeting of infection control resources.


Effect of phospholipid composition on characterization of liposomes containing 9-nitrocamptothecin.
9-Nitrocamptothecin (9-NC), a newly developed camptothecin derivative, had poor solubility in any pharmaceutically acceptable solvents. One way of improving the solubility is to formulate the drug into liposomes. However, 9-NC has low affinity to lipid membranes resulting in a very low drug-to-liposome entrapment. We developed a novel liposome-based 9-NC formulation which was composed of soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), and cholesterol. Compared with conventional liposomes composed of only SPC and cholesterol, 9-NC/lipid molar ratio increased from 1:72 to 1:18 while incorporation efficiency was still maintained about 80%. In addition, after 9-NC was encapsulated into novel liposomes, pharmacokinetic results revealed an increase in area under the plasma concentration-time curve (AUC) and a decrease in distribution volume of 9-NC following intravenous administration to rats. Increased stability in plasma may account for the improved pharmacokinetic behavior of the novel liposomes. Effect of HSPC/SPC molar ratio on characterization of the novel liposomes was also investigated. Except for drug/lipid molar ratio and encapsulation efficiency, HSPC/SPC molar ratio had only a little effect on other properties of novel liposomes. In conclusion, the study suggests that the novel liposomes can act as promising carriers for hydrophobic substances such as 9-NC.


Cleft Lip and Palate Surgery Crowdfunding and Access to Care.
A total of 169 ACPA approved teams treat cleft deformities in the United States. These centers are unevenly distributed, and families may disproportionally pay extra travel costs to consult a multidisciplinary cleft team. Families experiencing hardships are able to create campaigns on GoFundMe to advertise their fundraiser publicly. The authors sought to establish whether a correlation exists between patients asking for support for cleft treatment and their geographic location in the US.A total of 635 crowdfunding campaigns for cleft lip and/or palate were reviewed from GoFundMe. Google searches for cleft lip and palate were evaluated utilizing Google Trends, with values reported as Relative Search Volumes (RSV). Driving distances and travel time to the nearest approved ACPA center were calculated using Google Maps data.There was a statistically significant difference in average driving distance and travel duration between the different subregions of the US (P = 0.0059 and 0.026, respectively). The South subregion had the highest proportion of campaigns (n = 259, 40.9%), mean driving distance (105.75 km) and mean driving duration (1 hour 8 minutes). The number of approved teams per state was negatively correlated to both RSV scores (r = -0.38, P = 0.048) and the number of campaigns (r = -0.34, P = 0.014).There is an uneven distribution of ACPA centers among the US subregions. The South seems to have the highest need for care, as identified by proportionate number of campaigns, adjusted driving distances and travel time. This data suggests that underserved areas for cleft care are correlated with greater numbers of hardship campaigns and more internet searches regarding cleft lip and palate.


Ultrasound and power Doppler evaluation of the hand and wrist in patients with psoriatic arthritis.
To evaluate the ability of high-resolution and power Doppler sonography in detecting joint and tendon abnormalities in patients with psoriatic arthritis (PsA) of the hands and wrists compared with clinical and radiological findings. Thirty-six patients with psoriatic arthritis of the hands and wrists and 10 healthy controls were examined with ultrasound (US). The degree of synovial proliferation, tenosynovitis, presence of joint effusion as well as the vascularity of synovial tissue was estimated. US findings were scored using a newly devised scoring system. Thirty-two patients had articular synovial proliferation and/or tenosynovitis/ tendinitis or joint effusion in one or more joints according to US. Twenty-two patients had tendon changes; only five had joint effusion. The synovial, Doppler, and total articular-teno scores were all significantly correlated to the number of swollen joints. The scores, however, did not correlate to other clinical or laboratory measurements of disease activity. US proved effective in demonstrating PsA involvement of the hands and wrists and was more sensitive than clinical examination in detecting pathology. Long-term follow-up studies are needed to evaluate whether this can change the traditional approach for assessing involvement of joints and tendons in PsA.


Generalization of verbal abstraction strategies by EMR children and adolescents.
The effectiveness of strategy-training programs that differed in the degree of subject self-management required on the verbal abstraction performance of 37 female and 43 male EMR children and adolescents was compared. In terms of acquisition, all three training conditions, irrespective of the degree of self-management required, were superior to the control condition. At maintenance, the two self-managing conditions (self-instruction and modeling) were superior both to more traditional instructor-controlled training (relevant attributes) and the control condition. All three training conditions were more effective in promoting generalization when compared to the control condition.


[Autosomal dominant polycystic kidney disease].
Autosomal dominant polycystic kiney disease is a hereditary systemic disorder, characterized by the developement of cysts, mainly in the kidney and liver, also with gastrointestinal and cardiovascular abnormalities. It affects 4 to 6 million people wordwide and accounts for end-stage renal disease in 7-10% of dialysis patients. The genetic penetrance is 100%, all affected individuals develop renal cysts until 70 years of age, and because of a great renal function reserve only about 50% of patients develop some degree of renal failure until the age of 60. Autosomal dominant polycystic kiney disease is a heterogeneous disorder, from a clinical as well as from a genetic point of view. There are at least three genes responsible for the disease: PKD-1 gene localized on chromosome 16p in the 16p13.3 segment which encodes Polycystin 1 protein similar to membrane receptor, PKD-2 gene localized on chromosome 4q in 4q13-23 segment which encodes Polycystin 2 protein wery similar to voltage L type Ca++ channel as well as Na+ channel and PKD-3 gene of unknown localization. Specific proteins participate in regulation od cell proliferation, apoptosis, secretion, polarity, cell-matrix interactions as cell-cell interactions and lead to the developement of cystic kidney disease. Renal manifestations of disease include structural (cyst development), functional (concentration alility falls), endocrine (renin erythropoietin) abnormalities and extra- renal manifestations. A routine diagnostic methods are good case-history about cystic kidney disease in family, ultrasonographic examination of kidneys and computerized tomography. In therapy of autosomal dominant polycystic kiney disease, low protein diets may help, treatment of arterial hypertension with ACE inhibitors and angiotensin II receptor blockers, the vasopressin V2 antagonists (VSR), rapamycin and long-acting somatostatin analogue may have some benefit.


Virion structure of baboon reovirus, a fusogenic orthoreovirus that lacks an adhesion fiber.
Baboon reovirus (BRV) is a member of the fusogenic subgroup of orthoreoviruses. Unlike most other members of its genus, BRV lacks S-segment coding sequences for the outer fiber protein that binds to cell surface receptors. It shares this lack with aquareoviruses, which constitute a related genus and are also fusogenic. We used electron cryomicroscopy and three-dimensional image reconstruction to determine the BRV virion structure at 9.0-Å resolution. The results show that BRV lacks a protruding fiber at its icosahedral 5-fold axes or elsewhere. The results also show that BRV is like nonfusogenic mammalian and fusogenic avian orthoreoviruses in having 150 copies of the core clamp protein, not 120 as in aquareoviruses. On the other hand, there are no hub-and-spoke complexes attributable to the outer shell protein in the P2 and P3 solvent channels of BRV, which makes BRV like fusogenic avian orthoreoviruses and aquareoviruses but unlike nonfusogenic mammalian orthoreoviruses. The outermost "flap" domains of the BRV core turret protein appear capable of conformational variability within the virion, a trait previously unseen among other ortho- and aquareoviruses. New cDNA sequence determinations for the BRV L1 and M2 genome segments, encoding the core turret and outer shell proteins, were helpful for interpreting the structural features of those proteins. Based on these findings, we conclude that the evolution of ortho- and aquareoviruses has included a series of discrete gains or losses of particular components, several of which cross taxonomic boundaries. Gain or loss of adhesion fibers is one of several common themes in double-stranded RNA virus evolution.


The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance.
The transmissible spongiform encephalopathies or prion diseases represent a new group of diseases with unique clinical and neuropathological features, the transmission of which is both genetic and infectious. The responsible agent is unconventional and appears to be largely composed of a glycoprotein, the prion protein PrP. This is normally present on different cells. In prion diseases, it becomes converted to the pathogenic form PrPres which is resistant to proteinase and accumulates within the brain and this process is accompanied by the development of spongiform change, gliosis and neuronal loss. The human prion diseases include Kuru a progressive cerebellar degeneration with late dementia affecting Fore tribes in New-Guinea, now almost extinct, regarded as being related to cannibalism. Creutzfeldt-Jakob disease is the more frequent human prion disease. Its incidence is approximately one case per million per year. Four variants are now recognized: sporadic, familial, iatrogenic and the new variant. The latter represents a distinct clinico-pathological entity. It is now widely accepted that it is due to the same agent responsible for Bovine Spongiform Encephalopathy in cattle. Gerstmann-Sträussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter. Fatal familial insomnia is another inherited disorder due to a mutation at codon 178 of the PRP gene associated with methionine on codon 129 of the mutant allele. The main neuropathological change is neuronal loss in the thalamus with little or no spongiosis and usually no PrPres deposition. Following the emergence of new variant CJD in 1996, surveillance of all forms of prion diseases has been now been actively introduced in many European nations in order to determine the true incidence and geographic distribution of these rare disorders in humans.


Postactivation potentiation following different modes of exercise.
The performance characteristics of skeletal muscle are transient in nature and have been shown to be significantly affected by its contractile history, where the phenomenon of acute enhancement is termed postactivation potentiation (PAP). Acute enhancement of dynamic activity has been observed when preceded by resistance exercises; however little information exists for plyometric activity as a conditioning stimulus. In addition, no study has examined PAP effects on more than one subsequent performance trial. The purpose of the present study was to determine whether countermovement jump (CMJ) performance could be enhanced if preceded by heavy-resistance exercise or by dynamic plyometric activity over 3 trials. Thirteen anaerobically trained male subjects (mean +/- SD: age, 22 +/- 3 years; height, 182.4 +/- 4.3 cm; body mass, 82.7 +/- 9.2 kg) performed in a counterbalanced order 3 half squats using a 3 repetition maximum loading (SQUAT), a set of 24 contacts of lower body plyometric exercises (PLYO), or a control of no activity (REST) 5 minutes before each CMJ. Three sets of each treatment and CMJ were performed in total and maximal displacement (dmax), peak power (Ppeak), and peak vertical force (Fpeak) were recorded, whereas rate of force development and relative force (F/body mass) were calculated for every trial. No significant differences were revealed for any of the other variables, but greater displacement was found for SQUAT compared to REST or PLYO, whereas no differences were revealed for any of the conditions for the repeated trials. Although heavy resistance-induced PAP seems to enhance jump height compared to REST or PLYO in repeated CMJ performance, it has no additional benefit on repeated trials.


Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial.
The use of wheat grass (Triticum aestivum) juice for treatment of various gastrointestinal and other conditions had been suggested by its proponents for more than 30 years, but was never clinically assessed in a controlled trial. A preliminary unpublished pilot study suggested efficacy of wheat grass juice in the treatment of ulcerative colitis (UC). A randomized, double-blind, placebo-controlled study. One gastroenterology unit in a tertiary hospital and three study coordinating centers in three major cities in Israel. Twenty-three patients diagnosed clinically and sigmoidoscopically with active distal UC were randomly allocated to receive either 100 cc of wheat grass juice, or a matching placebo, daily for 1 month. Efficacy of treatment was assessed by a 4-fold disease activity index that included rectal bleeding and number of bowel movements as determined from patient diary records, a sigmoidoscopic evaluation, and global assessment by a physician. Twenty-one patients completed the study, and full information was available on 19 of them. Treatment with wheat grass juice was associated with significant reductions in the overall disease activity index (P=0.031) and in the severity of rectal bleeding (P = 0.025). No serious side effects were found. Fresh extract of wheat grass demonstrated a prominent tracing in cyclic voltammetry methodology, presumably corresponding to four groups of compounds that exhibit anti-oxidative properties. Wheat grass juice appeared effective and safe as a single or adjuvant treatment of active distal UC.


Bronchiolitis fibrosa obliterans in adults.
Clinical, roentgenologic, and physiologic manifestations of three adult patients with biopsy-proved bronchiolitis fibrosa obliterans illustrate the varied clinical features of the different stages of this disease and emphasize the rapidly progressive nature of the disorder in some patients. Although the chronic stage of bronchiolitis fibrosa obliterans has not been shown previously to respond to corticosteroid therapy, both of our patients with this stage of the disease had a dramatic response to high-dose prednisone. Furthermore, our one patient with the acute stage of the disease had complete resolution of his disease with treatment. Our experience suggests that early diagnosis and treatment are important in determining the clinical course of the disease.


Past human expansions shaped the spatial pattern of Neanderthal ancestry.
The worldwide expansion of modern humans (Homo sapiens) started before the extinction of Neanderthals (Homo neanderthalensis). Both species coexisted and interbred, leading to slightly higher introgression in East Asians than in Europeans. This distinct ancestry level has been argued to result from selection, but range expansions of modern humans could provide an alternative explanation. This hypothesis would lead to spatial introgression gradients, increasing with distance from the expansion source. We investigate the presence of Neanderthal introgression gradients after past human expansions by analyzing Eurasian paleogenomes. We show that the out-of-Africa expansion resulted in spatial gradients of Neanderthal ancestry that persisted through time. While keeping the same gradient orientation, the expansion of early Neolithic farmers contributed decisively to reducing the Neanderthal introgression in European populations compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Paleolithic hunter-gatherers. This study shows that inferences about past human population dynamics can be made from the spatiotemporal variation in archaic introgression.


Hexuronic acid stereochemistry determination in chondroitin sulfate glycosaminoglycan oligosaccharides by electron detachment dissociation.
Electron detachment dissociation (EDD) has previously provided stereo-specific product ions that allow for the assignment of the acidic C-5stereochemistry in heparan sulfate glycosaminoglycans (GAGs), but application of the same methodology to an epimer pair in the chondroitin sulfate glycoform class does not provide the same result. A series of experiments have been conducted in which glycosaminoglycan precursor ions are independently activated by electron detachment dissociation (EDD), electron induced dissociation (EID), and negative electron transfer dissociation (NETD) to assign the stereochemistry in chondroitin sulfate (CS) epimers and investigate the mechanisms for product ion formation during EDD in CS glycoforms. This approach allows for the assignment of electronic excitation products formed by EID and detachment products to radical pathways in NETD, both of which occur simultaneously during EDD. The uronic acid stereochemistry in electron detachment spectra produces intensity differences when assigned glycosidic and cross-ring cleavages are compared. The variations in the intensities of the doubly deprotonated (0,2)X(3) and Y(3) ions have been shown to be indicative of CS-A/DS composition during the CID of binary mixtures. These ions can provide insight into the uronic acid composition of binary mixtures in EDD, but the relative abundances, although reproducible, are low compared with those in a CID spectrum acquired on an ion trap. The application of principal component analysis (PCA) presents a multivariate approach to determining the uronic acid stereochemistry spectra of these GAGs by taking advantage of the reproducible peak distributions produced by electron detachment.


Murine neonatal lymphocytes show rapid early cell cycle entry and cell division.
Neonatal animals are highly susceptible to infectious agents. At least part of this susceptibility is due to the virtual absence of immunological memory in newborns. One of the hallmarks of memory is the rapidity of the response. We show in this study that neonates may make up for their lack of memory, at least in part, by the rapid entry of large proportions of naive lymphocytes into the cell cycle. Following activation, greater percentages of both CD4(+) and CD8(+) neonatal, as compared with adult, lymph node cells showed early cell cycle entry; this was assessed by propidium iodide staining, CFSE labeling profiles, [(3)H]thymidine uptake, and up-regulation of early activation markers. This rapid cycle entry was observed following polyclonal activation with anti-CD3 or with PMA and ionomycin and in both C57BL/6 and BALB/c mice. Stimulation with specific peptide also elicited more rapid proliferative responses from neonatal vs adult TCR transgenic CD4(+) cells. In addition, more rapid cycle entry was observed in vivo, in lymphopenic RAG2(-/-) hosts. For both CD4(+) and CD8(+) cells, this phenomenon was observed out to 3 wk of life, although the differences between neonatal and adult cells became smaller with increasing time postbirth. These properties of peripheral neonatal T cells appeared to be inherited from their thymic precursors, because CD4(+)8(-) single-positive cells in the neonatal thymus also showed more rapid cycle entry, compared with their counterparts in the adult thymus. Interestingly, rapid early cycling was also observed among activated neonatal B cells, compared with adult B cells. Thus, early cell cycle entry by large proportions of cells may allow the naive lymphocyte population to efficiently mobilize responses against the broad range of pathogens first encountered in neonatal life.


A 16-month analysis of urinary tract infection in children.
Results of the examination of urine specimens with evidence of acute urinary tract infections from children aged 16 years and under in general practice were analysed during a period of 16 months. Infections were much commoner in girls than in boys, with Escherichia coli most frequently involved in both groups. Urinary tract infections caused by Proteus strains were predominantly associated with boys. Infections in girls showed a higher incidence at 3, 6 and 16 years of age. Possible reasons for these sex- and age-associated patterns of infection are discussed. It is suggested than an important factor in the prevention of urinary tract infections in young girls is proper supervision of school lavatories. The report illustrates how much useful information can be obtained from the analysis of diagnostic results based on a simple but thorough laboratory approach.


Papuan mitochondrial genomes and the settlement of Sahul.
New Guineans represent one of the oldest locally continuous populations outside Africa, harboring among the greatest linguistic and genetic diversity on the planet. Archeological and genetic evidence suggest that their ancestors reached Sahul (present day New Guinea and Australia) by at least 55,000 years ago (kya). However, little is known about this early settlement phase or subsequent dispersal and population structuring over the subsequent period of time. Here we report 379 complete Papuan mitochondrial genomes from across Papua New Guinea, which allow us to reconstruct the phylogenetic and phylogeographic history of northern Sahul. Our results support the arrival of two groups of settlers in Sahul within the same broad time window (50-65 kya), each carrying a different set of maternal lineages and settling Northern and Southern Sahul separately. Strong geographic structure in northern Sahul remains visible today, indicating limited dispersal over time despite major climatic, cultural, and historical changes. However, following a period of isolation lasting nearly 20 ky after initial settlement, environmental changes postdating the Last Glacial Maximum stimulated diversification of mtDNA lineages and greater interactions within and beyond Northern Sahul, to Southern Sahul, Wallacea and beyond. Later, in the Holocene, populations from New Guinea, in contrast to those of Australia, participated in early interactions with incoming Asian populations from Island Southeast Asia and continuing into Oceania.


A new perspective on economic analysis in health care? A critical review of 'The Economics of Health Reconsidered' by Tom Rice.
A recently published book, 'The Economics of Health Reconsidered' by Tom Rice, provides a strong critique of the role of markets in health care. Many of the issues of 'market failure' raised by Rice, however, have been, to varying extents, recognised previously in the health economics literature (at least outside the U.S.). What perhaps sets Rice's book apart from previous attempts to document such issues is its elegance and the methodical manner in which this critique is delivered. Significantly the critique is based solely on conventional economic arguments. There has, however, been an emerging strand of the health economics literature not acknowledged in Rice's book which has approached some of these issues of market failure from a different perspective. Notably this research has involved, in part, borrowing from the ideas and methodological traditions of other disciplines. The emphasis in this work has been to expand the scope and the concerns of economic analysis in health care.


Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.
To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.


Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis.
Under pathologic conditions, renal tubular epithelial cells can undergo epithelial to mesenchymal transition (EMT), a phenotypic conversion that is believed to play a critical role in renal interstitial fibrogenesis. However, the underlying mechanism that governs this process remains largely unknown. Here we demonstrate that integrin-linked kinase (ILK) plays an important role in mediating tubular EMT induced by TGF-beta1. TGF-beta1 induced ILK expression in renal tubular epithelial cells in a time- and dose-dependent manner, which was dependent on intracellular Smad signaling. Forced expression of ILK in human kidney proximal tubular epithelial cells suppressed E-cadherin expression and induced fibronectin expression and its extracellular assembly. ILK also induced MMP-2 expression and promoted cell migration and invasion in Matrigel. Conversely, ectopic expression of a dominant-negative, kinase-dead form of ILK largely abrogated TGF-beta1-initiated tubular cell phenotypic conversion. In vivo, ILK was markedly induced in renal tubular epithelia in mouse models of chronic renal diseases, and such induction was spatially and temporally correlated with tubular EMT. Moreover, inhibition of ILK expression by HGF was associated with blockade of tubular EMT and attenuation of renal fibrosis. These findings suggest that ILK is a critical mediator for tubular EMT and likely plays a crucial role in the pathogenesis of chronic renal fibrosis.


Risk of tuberculosis in correctional healthcare workers.
The objective of this study was to determine the prevalence, incidence, and risk factors for occupational infection with tuberculosis among healthcare workers employed in correctional facilities. The authors conducted a self-administered survey, clinical interview, and tuberculin skin testing. The overall tuberculin skin test point prevalence rate was 17.7%, the reactivity rate was 2.2%, and the annual incidence was 1.3%. At the multivariate level, after controlling for bacille Calmette-Guérin vaccination, only origin of birth remained significantly associated with prevalence of tuberculosis infection. Although the prevalence of tuberculin reactivity was high in this population, the risk factors were predominantly demographic rather than occupational. Nevertheless, continued vigilance to control occupational exposure to this and other respiratory pathogens is warranted, given the potential for future outbreaks of tuberculosis, as well as other known and emerging airborne pathogens.


[Ortega and the theory of relativity].
Ortega y Gasset's thinking on Einstein and relativity, set out in the course of his extensive works, is constructed in the light of three of his fundamental ideas: 1) science, a special form of belief; 2) physics, a science par excellence; and 3) relativity, the intellectual fact of the highest order of its time; dedicating special attention to the essay: "The historical meaning of Einstein's theory". And it is completed with his critical attitude to the so-called "fundamental crisis" and his diagnosis of the grave problems suffered by physics in the wake of the relativistic and quantum revolutions.


Developmental changes in inhibin-alpha gene expression in the mouse testis.
Inhibin is a gonadal hormone which is composed of an alpha-subunit and one of two related beta-subunits (betaA, betaB). Inhibin is important for pituitary FSH regulation, normal follicle development and maintenance of the estrous cycle in the female, whereas the role of inhibin in the male is less clear. Thus, we examined the expression of the inhibin-alpha gene in testis during sexual maturation in male mice, to try to gain insight into its functions in the male. Male mice of the ICR strain attained fertility at 6 weeks of age, and histological analysis revealed that a functional testis was formed, with seminiferous tubules which contain mature sperm and with an abundant population of Leydig cells. Parallel with this sexual maturation, inhibin-alpha subunit protein synthesis increased, whereas synthesis of the activin betaA and activin betaB followed with a delayed time course. Inhibin-alpha mRNA also increased during this critical period, and this corresponded to a change in the methylation status of the inhibin-alpha gene. Taken together, our data reveal that activation of inhibin-alpha gene during testis development correlated with the histological maturation of the testis and the acquisition of fertility in male mice.


Dominant marker (inter-simple sequence repeat-polymerase chain reaction) versus codominant marker (RLEP-polymerase chain reaction) for laboratory diagnosis of leprosy: A comparative evaluation.
Leprosy is a contagious disease and was eliminated globally in 2002. Since then, new cases were continuously detected from different parts of the world. Untreated leprosy cases shed millions of bacteria and are the main cause of dissemination of the disease. Currently, leprosy is detected by acid-fast bacilli (AFB) microscopy and has a low sensitivity ranging from 10% to 50%. The correlation between clinical findings and microscopy is unable to provide a conclusive case detection. Thus, in the present study, we compared to molecular methods, namely RLEP-polymerase chain reaction (RLEP-PCR) and inter-simple sequence repeat-PCR (ISSR-PCR) taking AFB microscopy as a gold standard for the detection of leprosy. A total of 168 clinically diagnosed leprosy patients were recruited in this study including 58 multibacillary and 110 paucibacillary patients. Slit-skin smear samples were taken for both microscopy and molecular study. Primers for RLEP-PCR were taken from the previous reports. The primers for ISSR-PCR were designed by screening the whole genome of Mycobacterium leprae TN strain (GenBank accession AL450380) for the presence of simple sequence repeats. One primer (TA)8CA3was synthesized and used for molecular amplification of ISSR-PCR. We found that the efficacy of the AFB microscopy was 24.40%, whereas the efficacy of RLEP-PCR and ISSR-PCR was 63.09% and 73.21% (P = 0.000, 0.000, and 0.469), respectively. The area under the curve of receiver operating characteristic curve for the comparison of three diagnostic methods was 0.845. An enhancement of 48.81% in the case detection rate by ISSR-PCR over AFB microscopy and 10.12% over RLEP-PCR was also found. Our study clearly reveals that ISSR-PCR is a better tool for diagnosis of leprosy than AFB microscopy and RLEP-PCR. Interestingly, both the PCR techniques RLEP-PCR and ISSR-PCR are able to detect samples which were negative for AFB microscopy. Thus, the demonstration of ISSR-PCR in SSS samples can provide a better sensitive and confirmative tool for early diagnosis of leprosy.


Bitter Orange (Citrus aurantium Linné) Improves Obesity by Regulating Adipogenesis and Thermogenesis through AMPK Activation.
Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.


Integrated device for the measurement of systemic and local oxygen transport during physical exercise.
Current methods for monitoring exercise exertion rely upon heart rate monitors, which represent a crude and lagging indicator of conditioning. The rationale for the present study is that both systemic and local metabolic mechanisms are responsible for physical performance, and therefore they should be simultaneously quantified to achieve an objective assessment of human conditioning. We propose a compact, wearable near-infrared spectroscopy (NIRS) device integrated with electrocardiography (ECG) and photoplethysmography (PPG) to simultaneously assess the cardiovascular and local response to exercise. The system was tested on subjects performing a graded maximal exercise by comparing our readings with metabolic variables measured with respiratory gas analysis. We found strong correlations between local deoxyhemoglobin concentration [HHb], heart rate and oxygen uptake, as well as between oxyhemoglobin concentration [HbO(2)] and stroke volume. This study shows that combined NIRS, ECG and PPG measurements yield useful information to understand the interplay between systemic and local muscular responses to exercise.


The cost-effectiveness of vaccination against Lyme disease.
Vaccination against Lyme disease appears to be safe and effective; however, the cost per quality-adjusted life-year (QALY) gained with vaccination is unknown. We developed a decision-analytic model to evaluate the cost-effectiveness of vaccination compared with no vaccination in individuals living in endemic areas of Lyme disease. Our analysis encompassed a 10-year time horizon including a 2-year vaccination schedule with an additional year of vaccine effectiveness. The costs and probabilities of vaccination risk, compliance and efficacy, and Lyme disease clinical sequelae and treatment were estimated from the literature. Health-related quality-of-life weights of the various clinical sequelae of Lyme disease infection were obtained from a sample of 105 residents from Nantucket Island, Massachusetts. Vaccinating 10 000 residents living in endemic areas with a probability of Lyme disease per season of 0.01 averted 202 cases of Lyme disease during a 10-year period. The additional cost per QALY gained compared with no vaccination was $62 300. Vaccination cost $12 600/QALY gained for endemic areas with an attack rate of 2.5% per season, and $145 200/QALY gained for an attack rate of 0.5%. Vaccinating individuals over an accelerated 2-month vaccination schedule improved the cost-effectiveness to $53 700/QALY gained. If a yearly booster shot is required for persisting efficacy, the marginal cost-effectiveness ratio increases to $72 700/QALY. The cost-effectiveness of vaccination was most sensitive to the Lyme disease treatment efficacy and assumptions about the persistence of vaccination effect. Vaccination against Lyme disease appears only to be economically attractive for individuals who have a seasonal probability of Borrelia burgdorferi infection of greater than 1%.


Identification, expression, localization and serological characterization of a tryptophan-rich antigen from the human malaria parasite Plasmodium vivax.
Plasmodium vivax is most common but non-cultivable human malaria parasite which is poorly characterized at the molecular level. Here, we describe the identification and characterization of a P. vivax Tryptophan-Rich Antigen (PvTRAg) which contains unusually high (8.28%) tryptophan residues and is expressed by all blood stages of the parasite. The pvtrag gene comprises a 978bp open reading frame interrupted by two introns. The first intron is located in the 5'-untranslated region while the second one is positioned 174bp downstream to the ATG codon. The encoded approximately 40kDa protein contains a transmembrane domain near the N-terminus followed by a tryptophan-rich domain with significantly high surface probability and antigenic index. It is localized in the parasite cytoplasm as well as in the cytoplasm of the parasitized erythrocyte. The purified E. coli expressed recombinant PvTRAg protein showed a very high seropositivity rate for the presence of antibodies amongst the P. vivax patients, indicating that the antigen generates significant humoral immune response during the natural course of P. vivax infection. Analysis of various field isolates revealed that the tryptophan-rich domain is highly conserved except for three-point mutations. The PvTRAg could be a potential vaccine candidate since similar tryptophan-rich antigens of P. yoelii have shown protection against malaria in murine model.


Protein tyrosine phosphatase alpha (PTPalpha) and contactin form a novel neuronal receptor complex linked to the intracellular tyrosine kinase fyn.
Glycosyl phosphatidylinositol (GPI)-linked receptors and receptor protein tyrosine phosphatases (RPTPs), both play key roles in nervous system development, although the molecular mechanisms are largely unknown. Despite lacking a transmembrane domain, GPI receptors can recruit intracellular src family tyrosine kinases to receptor complexes. Few ligands for the extracellular regions of RPTPs are known, relegating most to the status of orphan receptors. We demonstrate that PTPalpha, an RPTP that dephosphorylates and activates src family kinases, forms a novel membrane-spanning complex with the neuronal GPI-anchored receptor contactin. PTPalpha and contactin associate in a lateral (cis) complex mediated through the extracellular region of PTPalpha. This complex is stable to isolation from brain lysates or transfected cells through immunoprecipitation and to antibody-induced coclustering of PTPalpha and contactin within cells. This is the first demonstration of a receptor PTP in a cis configuration with another cell surface receptor, suggesting an additional mode for regulation of a PTP. The transmembrane and catalytic nature of PTPalpha indicate that it likely forms the transducing element of the complex, and we postulate that the role of contactin is to assemble a phosphorylation-competent system at the cell surface, conferring a dynamic signal transduction capability to the recognition element.


Stroke Patients' Experiences in an Adaptive Healing Room in a Stroke Rehabilitation Unit.
This study evaluated the user experiences (UX) of stroke patients residing in the adaptive healing room (AHR) and compared them to the UX of patients residing in standard private rooms (SPRs). Healing environments in healthcare settings can promote patients' healing processes, outcomes, and psychological well-being. The AHR was designed as a healing environment for stroke patients and has been previously evaluated in laboratory settings. This study was the first to evaluate it in its intended context-a stroke rehabilitation unit. The UX of 10 patients residing in the AHR and 15 patients residing in SPRs were collected via structured interviews with a set of open-ended questions and analyzed using quantitative and qualitative methods. The AHR design features (orientation screen, skylight, and nature view) were rated positively by most patients. The skylight emerged as the least favorable. Responses to open-ended questions revealed that UX may be further improved if patients have more control over some of the settings (e.g., light intensity and nature views), and if the system allowed for more stimulation for patients at later stages of their recovery. Additionally, the results suggest that patients in the AHR have better UX than patients in the SPRs. The AHR has the potential to improve UX in the stroke rehabilitation unit. Patient feedback can be used to refine the AHR before carrying out clinical trials to assess the effect of the AHR on patient outcomes (e.g., sleep, mood, and length of stay) and stroke recovery.


Differential rates of apoptosis and recruitment limit eosinophil accumulation in the lungs of asthma-resistant CBA/Ca mice.
The accumulation of eosinophils is a common feature of allergic airway inflammation and correlates with disease severity. In an ovalbumin (OVA)-induced murine model of allergic lung disease, CBA/Ca mice develop much lower levels of lung eosinophilia, lung oedema, mucus hypersecretion and airways obstruction than BALB/c and C57BL/6 strains. In this study these strains have been examined to identify mechanisms that control the recruitment and survival of eosinophils in the allergic lung. Following immunization with OVA, CBA/Ca mice developed a robust systemic allergic response, with high levels of total and OVA-specific IgE and increases in peripheral blood eosinophils. Lung eotaxin-1 levels and expression of CD18 on eosinophils recovered by bronchoalveolar lavage (BAL) were least pronounced in CBA/Ca mice, whereas mRNA for L-selectin was highest in eosinophils from C57BL/6 mice. Apoptosis of BAL eosinophils ex vivo was most pronounced in the CBA/Ca strain. BALB/c mice expressed the highest levels of the eosinophil growth and survival factor interleukin (IL)-5 in the lungs and BAL eosinophils from these animals expressed more of the anti-apoptotic proteins Bcl-xL and Bcl-2 than cells from the other strains. A combination of lower levels of recruitment and rapid apoptosis may therefore limit the accumulation of eosinophils and pathology in the lungs of CBA/Ca mice. In addition, although the level of pathology that developed in C57BL/6 and BALB/c mice was similar, some of the underlying mechanisms are likely to differ.


Locomotion control of hybrid cockroach robots.
Natural systems retain significant advantages over engineered systems in many aspects, including size and versatility. In this research, we develop a hybrid robotic system using American (Periplaneta americana) and discoid (Blaberus discoidalis) cockroaches that uses the natural locomotion and robustness of the insect. A tethered control system was firstly characterized using American cockroaches, wherein implanted electrodes were used to apply an electrical stimulus to the prothoracic ganglia. Using this approach, larger discoid cockroaches were engineered into a remotely controlled hybrid robotic system. Locomotion control was achieved through electrical stimulation of the prothoracic ganglia, via a remotely operated backpack system and implanted electrodes. The backpack consisted of a microcontroller with integrated transceiver protocol, and a rechargeable battery. The hybrid discoid roach was able to walk, and turn in response to an electrical stimulus to its nervous system with high repeatability of 60%.


The 510(k) Third Party Review Program: Promise and Potential.
Every year, the Food and Drug Administration (FDA) clears approximately 3,000 medical devices for marketing via the 510(k) pathway. These constitute 99% of all devices approved for human use and includes the premarket review of many devices incorporating newer technology such as artificial intelligence (AI), machine learning (ML), and other software. As the complexity of these novel technologies and the number of applications is expected to increase in the coming years, statutory changes such as the 2016 21st Century Cures Act, regulations, and guidance documents have increased both the volume and complexity of device review. Thus, the ability to streamline the review of less complex, low-to-moderate risk devices through the 510(k) pathway will maximize the FDA's capability to address other important, future-oriented regulatory questions. For over twenty five years, third party review organizations have served a defined function to assist with the review of 510(k) applications for a set of enumerated device classes. This paper reviews the history of FDA device regulation, the evolution of the 510(k) review pathway, and the recent history of the 510(k) third party review program. Finally, the paper addresses policy concerns from all stakeholders - including the FDA - along with policy suggestions to improve the third party review program and FDA device regulation writ large.


Oosorption in the endoparasitoid, Pteromalus puparum.
Oosorption is the resorption of oocytes in the ovaries, and is usually induced by environmental stress. It has been demonstrated in some insect species, but overall the mechanisms of oosorption are poorly understood. In this study, the oosorption in the endoparasitic wasp, Pteromalus puparum L. (Hymenoptera: Pteromalidae), was observed in response to starvation. To explore the details of oosorption in P. puparum, both levels of hemolymph vitellogenin and ovarian vitellin were determined using sandwich ELISA. The results indicated that both levels of vitellin and total protein in the ovaries were significantly decreased 48 h after eclosion in starved P. puparum, while those of vitellogenin and total protein in the hemolymph were increased. In addition, observation of the ultrastructure of mature oocytes in the ovarioles revealed changes in yolk protein content. Those protein yolk spheres and lipid yolk spheres that had accumulated in the oocytes, were transferred out of the oocytes of starved females. It was assumed that once oosorption was induced in P. puparum, vitellin in the oocytes was transported outside and released into the hemolymph. This information helps to elucidate a mechanism of oosorption in insects.


Human Papillomavirus-Driven Squamous Lesions: High-Risk Genotype Found in Conjunctival Papillomas, Dysplasia, and Carcinoma.
Human papillomavirus (HPV) is a causative agent for intraepithelial squamous neoplasms, particularly on mucosal surfaces. HPV has a well-established association with squamous cell carcinoma (SCC) of the oropharynx and genital tract, and recent studies suggest a potential role in ocular and periocular squamous neoplasms. Multiple high-risk HPV genotypes are associated with histologically similar squamous neoplasms, and some HPV genotypes have been differentially associated with high- or low-grade lesions. Squamous lesions were screened with immunohistochemical markers p16 and Ki-67 to compare expression in conjunctival papillomas (n = 21) to papillomas with high-grade dysplasia, SCC in situ, and invasive SCC (n = 40). Polymerase chain reaction was performed using the Roche COBAS HPV assay to identify the 14 most common high-risk HPV genotypes. Compared with squamous papillomas, the lesions showing high-grade dysplasia or worse expressed p16 with greater intensity and in a greater percentage of the lesion. A trend toward mild Ki-67 expression in papillomas versus marked Ki-67 expression in high-grade squamous lesions was also observed. HPV-16 was present in 7 of the SCC in situ and invasive SCC lesions but none of the papillomas. HPV may have an important role in squamous lesions of the conjunctiva. In addition to positive polymerase chain reaction results, strong and diffuse p16 expression with marked Ki-67 is strongly suggestive of an HPV-driven lesion.


Sex differences in yohimbine-induced increases in the reinforcing efficacy of nicotine in adolescent rats.
Stress is an important factor in the initiation and maintenance of smoking in adolescents. Women are more vulnerable to the development of addiction to smoking and have more difficulty quitting than men. Women also showe enhanced responses to stress. Despite these differences, no work has been done examining the effects of stress on the reinforcing efficacy of self-administered nicotine in adolescent rats, or if there are sex differences. Male and female adolescent Long Evans rats were trained to self-administer one of three different intravenous doses of nicotine (7.5, 15, 30 μg/kg/infusion) first on fixed ratio, and then on a progressive ratio (PR) schedule beginning on postnatal day 33. The effect of the pharmacological stressor yohimbine (0.3, 0.6 mg/kg, i.p.) on the reinforcing efficacy of nicotine was then determined using the PR schedule. Yohimbine stimulated nicotine intake and increased PR breakpoints and numbers of infusions received in both male and female adolescent rats. The infusion dose of nicotine was positively associated with yohimbine-induced increases in responding. Female rats showed significantly increased breakpoints at yohimbine doses and nicotine infusion doses at which males did not. The effects of the pharmacological stressor, yohimbine on the reinforcing efficacy of nicotine are therefore linked to sex and nicotine infusion dose. Female rats are more sensitive to stress-induced potentiation of nicotine self-administration.


[Mental health in evacuees from the 3.11 complex disaster in Japan].
Two years after the "3.11" complex disaster--the Great East Japan Earthquake, the resulting tsunami, and the Fukushima nuclear power plant accident--that occurred on March 11, 2011, approximately 150,000 people were still living as evacuees, with approximately 50,000 evacuees living outside Fukushima Prefecture. In a survey conducted by the Asahi Shimbun newspaper in February 2012, the top three sources of anxiety among evacuees were radiation contamination (mentioned by 56% of respondents), income (48%), and school attendance of children (21%). In June 2012, results from the Mental Health Survey, which was conducted as part of the Fukushima Health Management Survey, indicated that 14.8% of adult evacuees had K6 scores equal to or greater than the standard cut-off of 13, a much higher proportion than the 3% found in previous studies. In the same survey, 21.5% of child evacuees had SDQ scores equal to or greater than the standard cut-off of 16, whereas previous studies suggest a typical ratio of around 9.5%. It is natural for people to experience anxiety when facing radiation exposure, even at low levels. Here the important thing is to be "accurately" afraid: people should pay attention to scientific facts, and avoid danger appropriately, but not be unduly frightened. However, some people remain anxious even when objective radiation levels are low enough to not result in harm. A number of parents with young children decided to relocate outside of Fukushima Prefecture. In consideration of the desires of these parents to have areas where their children could play without being concerned about radiation, some municipalities constructed spacious indoor play facilities where parents have increased opportunities to communicate with each other, which actually leads to effective risk communication. Compared to the trajectory of mental health recovery after the 1995 Hanshin-Awaji Earthquake, recovery after the present disaster is delayed, particularly in Fukushima. In Fukushima, many disturbing events, such as the issue of water contaminated by radiation, have distressed evacuees, resulting in their delayed recovery in terms of mental health.


Health care for some: a Nigerian study of who gets what, where and why?
The persistent underdevelopment of health in the Third World belies the optimism of the "Health care for all by the year 2000" campaign. In order to understand the underdevelopment of health, it is essential to examine the historical evolution of specific health systems. These ideas are developed in a case study of health care in Kano State, Nigeria. The nature and contemporary development of the health care system, which includes state voluntary agency and private sector outlets for Western scientific medicine and a large and varied traditional medicine sector, are examined. Although the deepening health care crisis may potentially spur a reconsideration of priorities and strategies, past experience suggests that a stubborn retention of a pared-down and increasingly unjust version of the present system is more likely.


[Nanotechnology: a big revolution from the small world].
Nanotechnology is a multidisciplinary field originating from the interaction of several different disciplines, such as engineering, physics, biology and chemistry. New materials and devices effectively interact with the body at molecular level, yielding a brand new range of highly selective and targeted applications designed to maximize the therapeutic efficiency while reducing the side effects. Liposomes, quantum dots, carbon nanotubes and superparamagnetic nanoparticles are among the most assessed nanotechnologies. Meanwhile, other futuristic platforms are paving the way toward a new scientific paradigm, able to deeply change the research path in the medical science. The growth of nanotechnology, driven by the dramatic advances in science and technology, clearly creates new opportunities for the development of the medical science and disease treatment in human health care. Despite the concerns and the on-going studies about their safety, nanotechnology clearly emerges as holding the promise of delivering one of the greatest breakthroughs in the history of medical science.


Differential expression of the c-fos protein and synaptophysin in zebrin II positive and zebrin II negative cerebellar cortical areas in 4-aminopyridine seizures.
The present study examined temporal activation patterns of rat cerebellar cortical neurons in 4-aminopyridine induced seizures, using c-fos protein as a marker of neuronal activity. C-fos-containing cells were counted in each cerebellar cortical layer, and cell count was compared between zebrin II positive and zebrin II negative bands of the lobules of the vermis and cerebellar hemispheres. We found significant activation of granule cells and interneurons of the molecular layer in zebrin II positive bands. The Purkinje cells, in contrast, exhibited non-significant, scattered c-fos immunoreactivity across all bands. Fluctuation of synaptophysin expression in the mossy fibre rosettes of the granular layer was determined via light microscopic immunohistochemistry. We detected a transient, significant decrease in synaptophysin staining density following 4-aminopyridine seizures, which may indicate short-term synaptic depression. We also identified different timing of increased c-fos expression in the neurons of the cerebellar cortex in different cortical zones. In particular, the activation pattern of the interneurons of the molecular layer reflected the climbing fibre distribution, reflecting the zonal olivo-cortico-nuclear organization. Seizure-induced activation of the granule cells corresponded with the zebrin II positive zones. This observation raises the possibility that zebrin II positive compartments may be more susceptible to cerebellar convulsions.


Psychoactive drugs in seven nursing homes.
We wanted to pinpoint any differences in treatment between participating nursing homes, investigate which drugs are currently prescribed most frequently for long-term patients in nursing homes, estimate prevalence of administration for the following drug groups: neuroleptics, antidepressants, antidementia agents, opioids and the neuroleptics/anti-Parkinson's drug combination, and study comorbidity correlations. We also wanted to study differences in the administration of medications to patients with reduced cognitive functions in relation to those with normal cognition. Information about 513 patients was collected from seven nursing homes in the city of Bergen, Norway, during the period March-April 2008. This consisted of copying personal medication records, weighing, recording the previous weight from records, electrocardiography, anamnestic particulars of any stroke suffered, recording if there is cognitive impairment or not and analyzing a standardized set of blood samples. Considerable treatment differences existed between nursing homes, both percentage patients and Defined Daily Dosages. Patients with reduced cognitive functions were prescribed less drugs in general, except neuroleptics. Of all patients, 41.5% were given antidepressants, 24.4% neuroleptics, 22.0% benzodiazepines, 8.0% anticholinesterases and 5.0% memantine. The ratio of traditional to atypical neuroleptics was 122:23. In all, 30.0% of the patients taking neuroleptics were on more than one drug and 35.0% of the patients had opioids by way of regular or as-needed drugs, ratio 14.6%:28.7%. Of 146 patients on neuroleptics, five patients had anti-Parkinson's drugs too. The average use of regular drugs for patient with intact cognition was 7.1 drugs, and for patients with reduced cognitive functions 5.7 drugs. There are differences in treatment with psychoactive drugs between nursing homes. Patients with reduced cognitive functions receive less cardiovascular drugs than patients with normal cognition. The reason for this still remains unclear. Improvement strategies are needed. The proportion of patients per institution on selected drugs can serve as a feedback parameter in quality systems.


Localization and interconversion of tetrahydropteroylglutamates in isolated pea mitochondria.
1. Mitochondria were extracted from 4-day-old pea cotyledons and purified on a sucrose density gradient. 2. Microbiological assay of the purified mitochondrial fraction with Lactobacillus casei (A.T.C.C. 7469), Streptococcus faecalis (A.T.C.C. 8043) and Pediococcus cerevisiae (A.T.C.C. 8081) revealed a discrete pool of conjugated and unconjugated derivatives of tetrahydropteroylglutamic acid. 3. Solubilization and chromatographic studies of the mitochondrial fraction demonstrated the presence of formylated and methylated derivatives, 10-formyltetrahydropteroylmonoglutamic acid, 5-formyltetrahydropteroylmonoglutamic acid and 5-formyltetrahydropteroyldiglutamic acid being the major derivatives present. 4. The principal mitochondrial pteroylglutamates were labelled when dry seeds were allowed to imbibe [2-(14)C]pteroylglutamic acid and 5-[methyl-(14)C]-methyltetrahydropteroylmonoglutamic acid. 5. The ability of isolated mitochondria to catalyse oxidation and reduction of tetrahydropteroylglutamic acid derivatives was demonstrated in feeding experiments in which [(14)C]formaldehyde, [3-(14)C]serine, sodium [(14)C]formate, 5-[methyl-(14)C]methyltetrahydropteroylmonoglutamic acid or [2-(14)C]-glycine served as C(1) donor. In addition, (14)C was incorporated into free amino acids related to C(1) metabolism.


All-printed flexible organic transistors enabled by surface tension-guided blade coating.
A combination of surface energy-guided blade coating and inkjet printing is used to fabricate an all-printed high performance, high yield, and low variability organic thin film transistor (OTFT) array on a plastic substrate. Functional inks and printing processes were optimized to yield self-assembled homogenous thin films in every layer of the OTFT stack. Specifically, we investigated the effect of capillary number, semiconductor ink composition (small molecule-polymer ratio), and additive high boiling point solvent concentrations on film fidelity, pattern design, device performance and yields.


Do you really get what you are looking for? Exploring the medical call writing trend in tertiary care hospitals.
To explore the trend of medical call writing by doctors working in tertiary care hospitals. A quantitative descriptive cross-sectional study was carried out to evaluate the quality of medical calls written by the doctors at three tertiary care hospitals of Peshawar, Khyber Pakhtunkhwa between June 2016 to June 2017. An instrument was developed following AMEE Guide 87. Its content validity and reliability were established by 33 consultants from twenty specialties. A total of 198 medical calls (66 each) were collected from medicine, surgery and allied specialties and evaluated on the basis of validated instrument. During instrument development, six items with content Validity Ratio of 0.78 & Kappa value of 0.70 were deemed most significant in every medical call written. Among all the calls, the great majority (96% and 84.34%) mentioned the reason for referral (item 1) and history of presenting problem (item 2), respectively, while item 6 (explicit mention of the doctor who will receive the call) was addressed the least (17.6%). Item 3 (Result of physical examination) and 4 (what tests have been done/arranged by the referring doctor and a summary of the main findings) were stated in < 30% of the calls whereas item 5 (diagnosis/provisional diagnosis) was specified in less than half of the calls. In this study, the written medical calls of different specialties were evaluated using specifically designed six items instrument. Unfortunately, the content of medical calls assessed was found to be inadequate probably because medical call writing is not explicitly taught at under and postgraduate levels.