Comparative In Vitro and In Vivo Studies on Feline, Canine, and Human Merkel Cell Carcinoma.
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, and most human MCC cases are infected by Merkel cell polyomavirus (MCPyV). However, the underlying pathogeneses of MCC in animals remain unclear. In the present study, newly established cell lines from feline and canine MCC, a MCPyV-positive human MCC cell line, and MCC tissues from 25 cats and 1 dog were examined and compared pathologically. Feline and canine MCCs were composed of tumor cells arranged in trabeculae and solid packets. Twenty out of 25 feline MCC cases (80%) had other proliferative cutaneous lesions, such as carcinoma in situ and squamous cell carcinoma. Among the 25 feline MCC cases, tumor cells were immunopositive for cytokeratins (CKs), including CK5/6 (4/25 cases, 16%), CK7 (5, 20%), CK18 (25, 100%), CK19 (20, 80%), and CK20 (20, 80%). The tumor cells of feline MCC were also immunopositive for synaptophysin (24/25, 96%) and CD56 (22/25, 88%). The tumor cells of canine MCC were immunopositive for CK18, CK19, CK20, and synaptophysin. Cultured feline and canine MCC cells grew in adherent monolayers and exhibited diffuse cytoplasmic immunoreactivity for CKs, whereas human MCC cells grew in suspension and exhibited dot-like cytoplasmic immunoreactivity for CKs. Differences in the distribution of CKs between human and animal MCC may be attributed to cell adhesion propensities. MCPyV genes and antigen were not detected in feline or canine MCC, suggesting a different etiology from human MCC.


Nitrification Inhibitor 3,4-Dimethylpyrazole Phosphate Application During the Later Stage of Apple Fruit Expansion Regulates Soil Mineral Nitrogen and Tree Carbon-Nitrogen Nutrition, and Improves Fruit Quality.
In order to solve the problems of nitrogen (N) losses and fruit quality degradation caused by excessive N fertilizer application, different dosages of the nitrification inhibitor, 3,4-dimethylpyrazole phosphate (DMPP) (0, 0.5, 1, 2, and 4 mg kg-1 soil), were applied during the later stage of 'Red Fuji' apple (Malus domestica Borkh.) fruit expansion in 2017 and 2018. The effects of DMPP on soil N transformation, carbon (C)-N nutrition of tree, and fruit quality were investigated. Results revealed that DMPP decreased the abundance of ammonia-oxidizing bacteria (AOB) amoA gene, increased the retention of NH4 +-N, and decreased NO3 --N concentration and its vertical migration in soil. DMPP reduced 15N loss rates and increased 15N residual and recovery rates compared to the control. 13C and 15N double isotope labeling results revealed that DMPP reduced the capacity of 15N absorption and regulation in fruits, decreased 15N accumulation in fruits and whole plant, and increased the distribution of 13C from vegetative organs to fruits. DMPP increased fruit anthocyanin and soluble sugar contents, and had no significant effect on fruit yield. The comprehensive analysis revealed that the application of 1 mg DMPP kg-1 soil during the later stage of fruit expansion effectively reduced losses due to N and alleviated quality degradation caused by excessive N fertilizer application.


The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated with hip bone mineral density (BMD) in Chinese nuclear families.
Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis. In this study, we simultaneously tested linkage and/or association of the -1997 G/T polymorphism in the COLIA1 upstream regulatory region with the variation of bone mineral density (BMD) in 1263 subjects from 402 Chinese nuclear families, consisted of both parents and at least one healthy female offspring from 20 to 45 years of age. All the subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD of the lumbar spine (L1-L4) and hip (respective and combined phenotype of the femoral neck, trochanter, and intertrochanter) was measured by dual-energy X-ray absorptiometry (DXA). By using the tests implemented in program QTDT (quantitative transmission disequilibrium test), we found significant within-family association (via TDT) between the -1997 G/T polymorphism with BMD variation at all the hip sites (respective and combined phenotypes, P < 0.05). The amount of BMD variation explained by the -1997G/T polymorphism was 1.6%, 2.0%, 1.2%, and 1.3% at the total hip, femoral neck, trochanter, and intertrochanter, respectively. Because of the limited number of sib pairs in this sample, we did not find evidence of linkage. In summary, the -1997 G/T polymorphism in the COLIA1 gene is likely to be in linkage disequilibrium with a nearby functional polymorphism affecting hip BMD, or the -1997 G/T polymorphism itself may have an important effect on the variation of hip BMD in our Chinese sample.


Feedback seeking in children and adolescents: associations with self-perceptions, attachment representations, and depression.
Because the feedback children and adolescents receive is important to their development, 2 experimental studies were designed to examine children's (M = 12 years) and adolescents' (M = 17 years) active selection of the quality of feedback they wish to receive. In both studies evidence emerged that participants' self-perceptions influence their feedback seeking. Participants with positive self-perceptions sought more positive feedback than participants with negative self-perceptions and sought more positive feedback than expected by chance. Participants with negative self-perceptions lacked this tendency to seek positive feedback and sometimes sought less positive feedback than expected by chance. As expected, depression and attachment-related measures were also associated with participants' feedback seeking. Contributions of feedback-seeking patterns to stability and change in children's and adolescents' development are discussed.


Hsa_circ_0006872 promotes cigarette smoke-induced apoptosis, inflammation and oxidative stress in HPMECs and BEAS-2B cells through the miR-145-5p/NF-κB axis.
Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD). Circular RNAs (circRNAs) are involved in regulating various biological processes. This study aimed to explore the role and molecular basis of hsa_circ_0006872 in cigarette smoke extract (CSE)-induced cell injury. HPMECs and BEAS-2B cells were treated with CSE to mimic COPD in vitro. The levels of hsa_circ_0006872 and miR-145-5p were measured by quantitative real-time polymerase chain reaction. Cell proliferation was assessed via Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to evaluate apoptosis and cell cycle. The levels of inflammatory factors were assayed via enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress markers were determined via commercial kits. The interaction between hsa_circ_0006872 and miR-145-5p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Protein expression was measured using Western blot assay. Hsa_circ_0006872 level was elevated in COPD patients and was negatively correlated with miR-145-5p level. CSE exposure promoted apoptosis, inflammation and oxidative stress of HPMECs and BEAS-2B cells, while hsa_circ_0006872 down-regulation undermined the effects. In addition, hsa_circ_0006872 silencing inhibited CSE-induced cell injury via regulating miR-145-5p. Moreover, CSE contributed to the activation of NF-κB pathway through hsa_circ_0006872/miR-145-5p axis. Hsa_circ_0006872 facilitated CSE-triggered apoptosis, inflammation and oxidative stress in HPMECs and BEAS-2B cells by regulating miR-145-5p/NF-κB pathway.


[Fatal complication of intravenous administration of synthetic adrenocorticotrophin].
Synthetic 1-24adrenocorticotrophin (tetracosactid, Synacthen) is used in clinical medicine for diagnostic and therapeutic purposes. Side effects may occur due to unphysiological stimulation of endogenous adrenocortical hormone production. Allergic reactions to tetracosactid are rare. Anaphylactic shock leading to death was observed after intravenous injection of tetracosactid in a 14-year-old girl with bronchial asthma. Adrenocorticotrophin antibodies could be demonstrated after death in serum and ascitic fluid using the double antibody method.


Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter.
The human UDP glucuronosyltransferase UGT2B17, glucuronidates androgens and is expressed in the liver and the prostate. Although evidence suggests that variations in UGT2B17 expression between tissues may be a critical determinant of androgen response, the factors that regulate UGT2B17 expression in the liver and prostate are unknown. In this study, we have isolated a 596 bp promoter of the UGT2B17 gene and studied its regulation in the liver cell line, HepG2 and the prostate cell line, LNCaP. The transcription start site of UGT2B17 was mapped and proteins that bound to the proximal promoter were detected by DNase1 footprint analysis. A region (-40 to -52 bp) which resembled a hepatocyte nuclear factor 1 (HNF1) binding site bound proteins in nuclear extracts from HepG2 cells, but did not bind proteins from LNCaP nuclear extracts. In HepG2 cells, HNF1alpha bound to this region and activated the UGT2B17 promoter, as assessed by functional and gel shift assays. HNF1alpha activation of the promoter was prevented by mutation or deletion of the putative HNF1 site. The related transcription factor HNF1beta, which is present in HepG2 cells, did not activate the promoter. The UGT2B17 promoter could also be activated by exogenous HNF1alpha in LNCaP cells. However, because these cells do not contain HNF1alpha, other transcription factors must regulate the UGT2B17 promoter. Cotransfection experiments showed that HNF1beta, elevates promoter activity in LNCaP cells. This activation did not involve the putative HNF1 region (-40 to -52 bp) since mutation of this region did not affect promoter activation by HNF1beta. These results suggest that the UGT2B17 promoter is regulated by different factors in liver-derived HepG2 and prostate-derived LNCaP cells.


Plasma and cerebrospinal fluid human immunodeficiency virus type-1 (HIV-1) RNA levels in HIV-related cognitive impairment.
Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.


Polyploid measles virus with hexameric genome length.
Particles of most virus species accurately package a single genome, but there are indications that the pleomorphic particles of parainfluenza viruses incorporate multiple genomes. We characterized a stable measles virus mutant that efficiently packages at least two genomes. The first genome is recombinant and codes for a defective attachment protein with an appended domain interfering with fusion-support function. The second has one adenosine insertion in a purine run that interrupts translation of the appended domain and restores function. In that genome, a one base deletion in a different purine run abolishes polymerase synthesis, but restores hexameric genome length, thus ensuring accurate RNA encapsidation, which is necessary for efficient replication. Thus, the two genomes are complementary. The infection kinetics of this mutant indicate that packaging of multiple genomes does not negatively affect growth. We also show that polyploid particles are produced in standard infections at no expense to infectivity. Our results illustrate how the particles of parainfluenza viruses efficiently accommodate cargoes of different volume, and suggest a mechanism by which segmented genomes may have evolved.


Sagittal alignment of the cervical spine: do we know enough for successful surgery?
Over the past decade, there has been growing interest in the sagittal alignment of the cervical spine and its correlation to clinical outcomes. It is now known that cervical lordosis is not universally physiological and should not be pursued in all patients undergoing surgery. Rather, it is increasingly understood that it is how these angular parameters (lordosis or kyphosis) interact with translational parameters that is reflective of overall cervical spine and whole spine balance, which in turn impacts patient outcomes. This review synthesises currently available evidence relating to the sagittal alignment of the cervical spine. Radiographic assessment of the cervical spine including horizontal gaze is discussed and alignment in physiological and pathological states analysed. The interdependence of spinal segments is reviewed, with cervical alignment correction influencing the adjacent thoracic spine, and similarly lumbar lordosis (LL) and global balance correction changing cervical spine alignment. Cervical kyphosis with associated cervical sagittal imbalance is known to lead to poorer post-operative outcomes, and this dichotomy in outcomes has not been shown to improve even with alignment correction. Further work is required to uncover the extent to which cervical spine alignment correction should be attempted toward improved patient outcomes, in order to plan and deliver patient-specific surgical realignment targets.


Breast reconstruction with SGAP and IGAP flaps.
Perforator flaps represent the latest in the evolution of soft-tissue flaps. They allow the transfer of the patient's own skin and fat in a reliable manner with minimal donor-site morbidity. The powerful perforator flap concept allows transfer of tissue from numerous, well-described donor sites to almost any distant site with suitable recipient vessels. Large-volume flaps can be reliably supported with perforators from areas such as the buttock and transferred microsurgically for breast reconstruction. The ideal tissue for breast reconstruction is fat with or without skin, not implants or muscle. Absolute contraindications specific to perforator flaps in our practice include history of previous liposuction of the donor site, some previous donor-site surgery, or active smoking (within 1 month before surgery). Perforator flaps are supplied by blood vessels that arise from named, axial vessels and perforate through or around overlying muscles and septa to vascularize the overlying skin and fat. During flap harvest, these perforators are meticulously dissected free from the surrounding muscle, which is spread in the direction of the muscle fibers and preserved intact. The pedicle is anastomosed to recipient vessels in the chest, and the donor site is closed without the use of synthetic mesh. Perforator flaps allow for safe, reliable tissue transfer from a variety of sites and provide ideal tissue for breast reconstruction, with minimal donor-site morbidity.


[The relationship between concentrations of pepsinogens in blood serum and pathohystologic parameters of stomach adenomas and adenocarcinomas].
The article demonstrates that in patients with adenomas of stomach the concentration of pepsinogen I in blood serum and the rate between pepsinogen I and pepsinogen II is decreased. In case of adenomas and adenocarcinomas of stomach the concentration of pepsinogen I and the rate between pepsinogen I and pepsinogen II are in inverse correlation relationship with indicators of proliferative activity of epithelial cells and tumor cells correspondingly. The threshold level was the rate between pepsinogen I and pepsinogen II can be used as criteria of intensity ofproliferative activity of epithelial cells of adenomas and cells of adenocarcinomas of stomach.


Prognostic impact of underlying liver fibrosis and cirrhosis after curative resection of hepatocellular carcinoma.
In the case of hepatocellular carcinoma (HCC), underlying liver pathology may not only determine the feasibility of surgery but may also affect the postsurgical outcome. We report our experience after curative liver resection for HCC in patients with normal liver, liver fibrosis, and liver cirrhosis. A total of 72 patients after liver resection with curative intention were analyzed. Histopathologic findings of tumor-unaffected liver tissue were used for retrospective classification: group A (normal liver); group B (liver fibrosis); group C (liver cirrhosis). The groups were compared for differences in short-term surgical results, total survival, and recurrence-free survival. The rate of major complications was 34.7% and did not significantly differ among groups. The overall perioperative mortality rate was 9.7%, with one patient dying in group A and three patients dying in each of the other two groups. Including perioperative mortality, the median overall survival for the whole group was 37.3 months (95% confidence interval 29.3-45.2 months). The respective 1-, 2-, and 5-year survival rates for group A (n = 21) were 86%, 71%, and 50% and for group C (n = 24) 62%, 50%, and 17%. The overall survival of group B (n = 27) was intermediate (log-rank, P = 0.032). The respective recurrence-free survival rates were 76%, 42%, and 20% for group A and 39%, 13%, and 4% for group C, with group B being intermediate (log-rank, P = 0.016). Our data demonstrate that liver resection in the presence of compensated liver cirrhosis is feasible but associated with a significantly impaired prognosis for overall and recurrence-free survival. The management of cirrhotic patients with compensated liver function and HCC therefore also requires the opportunity for transplantation.


The pressure within a collapsed tube, with special reference to urethral pressure.
A definition is proposed for tube pressure (the pressure within a collapsible tube in the collapsed state, e.g. the urethral pressure or the pressure in the anal or oesophageal sphincter) which conforms to the common sense view that it is a measure of the ability of the tube to prevent leakage. It is not dependent on the orientation of a measuring probe in the tube. The orientation effects which have previously been reported are due to attempted bending of a stiff measuring catheter by internally and externally applied forces. A satisfactory way of measuring the tube pressure, by slow perfusion through a thin, flexible catheter with an end hole, and of testing whether it is a meaningful concept in a given case, is proposed. It is illustrated by measurements of urethral pressure in 42 continent and incontinent females. No cases of urinary incontinence due to poor urethral sealing ability are observed, indicating that tube pressure is a meaningful concept. The theory of viscosity-limited flow through a compressive zone in a collapsible tube, on which the perfusion method of measuring tube pressure is based, is developed.


Native top-down electrospray ionization-mass spectrometry of 158 kDa protein complex by high-resolution Fourier transform ion cyclotron resonance mass spectrometry.
Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) delivers high resolving power, mass measurement accuracy, and the capabilities for unambiguously sequencing by a top-down MS approach. Here, we report isotopic resolution of a 158 kDa protein complex, tetrameric aldolase with an average absolute deviation of 0.36 ppm and an average resolving power of ~520 000 at m/z 6033 for the 26+ charge state in magnitude mode. Phase correction further improves the resolving power and average absolute deviation by 1.3-fold. Furthermore, native top-down electron capture dissociation (ECD) enables the sequencing of 168 C-terminal amino acid (AA) residues out of 463 total AAs. Combining the data from top-down MS of native and denatured aldolase complexes, a total of 56% of the total backbone bonds were cleaved. The observation of complementary product ion pairs confirms the correctness of the sequence and also the accuracy of the mass fitting of the isotopic distribution of the aldolase tetramer. Top-down MS of the native protein provides complementary sequence information to top-down ECD and collisonally activated dissociation (CAD) MS of the denatured protein. Moreover, native top-down ECD of aldolase tetramer reveals that ECD fragmentation is not limited only to the flexible regions of protein complexes and that regions located on the surface topology are prone to ECD cleavage.


REVISED TRAUMA SCORE AS A PREDICTOR OF OUTCOME IN TRAUMA CASES: EXPERIENCES AT A TERTIARY CARE HOSPITAL IN KARACHI, PAKISTAN.
Trauma scores help classify trauma patients, and assist in clinical decision-making. The Revised Trauma Score (RTS) is widely used internationally but its effectiveness as a tool for predicting outcome in paediatric trauma patients in our setting, has yet to be established, mainly owing to lack of use. The aim of this study was to determine the effectiveness of RTS as a predictor of outcome in paediatric trauma patients in Pakistan. We conducted a retrospective review of patient medical records at Aga Khan University Hospital, Karachi, from October 2006 to October 2009 and all patients aged less than 14 years, presenting with trauma were selected. Information was collected regarding demographics, vital signs at the time of presentation, length of stay (LOS) in the ward, ICU and the hospital, complications during hospital stay and mortality. Data was analysed in SPSS-17.0. The sample was 501 patients with a mean age of 5.3 years. Two third (66%) were males and 34% were females. Using available data, RTS was calculated for 394 patients, who were then divided into two groups based on the RTS. For 32 patients with a RTS less than 10, the length of stay in the ward, ICU and the hospital were all shorter than the 363 patients with a RTS greater than 10 (p-value <0.001). In our setting, RTS is a good predictor of outcome in paediatric trauma patients. It can aid in the assessment of severity of injury in, and objective assessment and triaging of paediatric trauma patients.


The effects of psychological inoculation on cognitive barriers against condom use in women with HIV: A controlled pilot study.
Past studies have shown that in attempts to prevent HIV, health education yields little change in condom use. The reason may be that education fails to target barriers for changing behaviour. The present controlled pilot study tested whether psychological inoculation (PI) reduces such barriers for using male condoms. Twenty-two Nigerian women with HIV were randomly assigned to receive PI or health education (control). In the PI condition, women learned to refute sentences reflecting barriers against condom use, while controls learned how to use condoms and the consequences of their non-use. Barriers for condom use, self-efficacy to negotiate condom use with partners and actual condom use were self-reported before and one week after interventions. Results revealed that only in the PI group were there statistically significant increases in condom use negotiating self-efficacy and reductions in barriers concerning motivation, sexual satisfaction and partners. Controls reported no statistically significant changes. However, actual reported condom use was unchanged in both groups. Thus, it is feasible to conduct PI interventions in an African sample of HIV patients. Furthermore, PI can reduce cognitive barriers for condom use, while health education yields little changes in such outcomes over time. If replicated in larger samples with longer follow-ups, these findings could eventually have implications for HIV prevention in several world regions.


Enthalpy-Entropy Compensation in the Promiscuous Interaction of an Intrinsically Disordered Protein with Homologous Protein Partners.
Intrinsically disordered proteins (IDPs) can engage in promiscuous interactions with their protein targets; however, it is not clear how this feature is encoded in the primary sequence of the IDPs and to what extent the surface properties and the shape of the binding cavity dictate the binding mode and the final bound conformation. Here we show, using a combination of nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), that the promiscuous interaction of the intrinsically disordered regulatory domain of the mitogen-activated protein kinase kinase MKK4 with p38α and JNK1 is facilitated by folding-upon-binding into two different conformations, despite the high sequence conservation and structural homology between p38α and JNK1. Our results support a model whereby the specific surface properties of JNK1 and p38α dictate the bound conformation of MKK4 and that enthalpy-entropy compensation plays a major role in maintaining comparable binding affinities for MKK4 towards the two kinases.


Immunoglobulin phagocytosis by granulocytes from sera and synovial fluids in various rheumatoid and nonrheumatoid diseases.
(1) The phagocytosis of human IgG, IgM, and C3 by granulocytes from various rheumatoid and nonrheumatoid sera and synovial fluids (SF) was investigated by direct examination of the patient's leucocytes and indirect testing by incubation of normal donor leucocytes with various sera and SF. (2) In rheumatoid arthritis (RA) phagocytosis of IgM, IgG, and C3 was common from sera and SF. There was a strong correlation of IgM and C3 phagocytosis with the occurence of rheumatoid factor. The phagocytosed IgM is probably rheumatoid factor. In SF both the direct and indirect test method yielded equally positive results; in serum the direct test was negative throughout. (3) In systemic lupus erythematosus there was phagocytosis of IgG, IgM and C3 from serum (indirect test), IgM not being correlated with the latex-fixation test and probably of antinuclear antibody nature. Phagocytosis decreased after treatment of the disease. Sera from many other rheumatic disease frequently gave weak IgG phagocytosis, but rarely did IgM or C3. (4) IgG, and sometimes C3, was frequently taken up from IgG myeloma sera (indirect test). IgM and IgG were taken up from Waldenström's macroglobulinaemia sera, independent of IgM concentration. It is possible that an aggregation tendancy of particular paraproteins determines Ig uptake from these sera. (5) IgG was taken up from half of the studied sera of infectious diseases in the indirect test, including two cases with Hodgkin's disease as well. Three sera from patients with untreated trypanosomiasis were positive for IgG as well as for IgM. (6) Normal healthy control sera remained negative, even after prolonged preservation or frequent freezing and thawing: only among very old sera were a few positive observations recorded. Immunoglobulin phagocytosis appears to be a common phenomenon in a number of conditions. It seems probable that soluble immune complexes, or in other cases nonimmune aggregates, may cause phagocytosis.


Growth Hormone Stimulation Tests in Children with Kabuki Syndrome.
Kabuki syndrome is a multiple congenital malformation syndrome with a variety of clinical features including short stature. The cause of this postnatal short stature remains unknown. Eighteen children with genetically proven Kabuki syndrome (8 boys and 10 girls; ages 3.3-9.9 years, with a mean of 6.7 years) who underwent growth hormone (GH) stimulation tests were evaluated in a prospective study. Two GH stimulation tests were conducted, including insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) serum levels. GH stimulation peaks in relation to age, sex, height, body mass index (BMI), IGF-I, and IGFBP-3 SD scores (SDS) were analyzed. Five of the 18 children (27.8%) were biochemically GH deficient. This was not correlated with BMI SDS. Of all patients, only 1 had an IGF-I below -2 SD and did not fulfill the GH deficiency criteria. The mean IGF-I level was below normal (-0.8 SD). All subjects had normal IGFBP-3 levels. The utility of performing GH stimulation tests on Kabuki syndrome children as an indication of GH status in short stature is questionable. IGF-I levels did correlate neither with the GH stimulation peak nor consequently with the diagnosis of GH deficiency.


Inhibition of nitric oxide synthase ameliorates cellular injury in sickle cell mouse kidneys.
In previous studies of transgenic sickle cell mice, increased renal expression of inducible nitric oxide synthase (iNOS) and endothelial cell isoform of NOS (EcNOS) was found by Western blot and immunohistochemistry. In addition, putative evidence of peroxynitrite (ONOO-) formation was found in the form of positive immunostaining and immunoblot for nitrotyrosine. Apoptosis was also detected by DNA strand breakage and TUNEL assay. The present study was carried out to examine the role of NO/ONOO- in mediating renal tubular cell apoptosis in sickle cell mouse kidneys. Mercaptoethylguanidine (MEG), a compound that selectively inhibits iNOS and also is a scavenger of ONOO-, was administered intraperitoneally over a five-day period to control and betas mice. Immunohistochemistry of iNOS and nitrotyrosine, DNA electrophoresis, ApoTACS assay for apoptosis, and Western blot of poly(ADP-ribose) polymerase (PARP) were carried out. MEG administration virtually eliminated renal immunostaining of iNOS and nitrotyrosine and prevented DNA strand breakage. In addition, Western blot analysis of PARP, a nuclear DNA-reparative enzyme activated in response to DNA strand breakage, was found to be cleavaged in hypoxic betas mice, but was partially protected in MEG-treated betas hypoxic mice. Finally, apoptosis was markedly reduced by MEG in betas hypoxic mice. These observations provide evidence that NO and/or ONOO- are responsible for initiating cell damage, which leads to apoptosis in sickle cell mouse kidneys.


A preliminary report on psychiatric impairments and quality of life among Kaohsiung gas explosion victims 6 months after the event.
To investigate the prevalence and related risk factors for probable disaster-related psychiatric disorders, such as major depressive episodes (MDEs) and posttraumatic stress disorder (PTSD), among the victims of a petrochemical gas explosion in Kaohsiung, Taiwan, 6 months after the event. Additionally, the quality of life (QOL) of victims with related risk factors was simultaneously investigated. A community-based screening survey with cross-sectional assessments was conducted. The victims of a petrochemical gas explosion were surveyed 6 months after the event. We used two scales, the Disaster-Related Psychological Screening Test and Short Form 12v2, to survey a representative sample of 502 participants (average age: 42.90 ± 16.61 years; M: 270, average age: 40.89 ± 16.40 years; F: 232; average age: 45.25 ± 16.58 years). The Chinese version of SPSS 17.0 software was used to perform the analysis. Non-PTSD or non-MDE (non-P or M), probable PTSD, probable MDE and probable PTSD, and MDE were present in 341 (67.9%), 54 (10.8%), 37 (7.4%) and 70 (13.9%) participants, respectively. QOL worsened (negative trend) among the groups in the following order: non-P or M, probable PTSD or MDE alone, and probable PTSD and MDE. The risk factors for probable PTSD or MDE were female gender, older age, physical injury, significant financial loss, and lack of religious belief. The risk factors for poorer QOL subscales were older age, financial problems, physical injury, higher educational level, religious beliefs, and probable PTSD and/or MDE. This study shows that probable PTSD/MDE is associated with lower QOL, supporting the need for early mental health rehabilitation after a disaster. Therefore, rapid screening and early mental rehabilitation are very important.


Fyn is not essential for Bcr-Abl-induced leukemogenesis in mouse bone marrow transplantation models.
The Bcr-Abl oncogene causes human Philadelphia chromosome-positive (Ph(+)) leukemias, including B-cell acute lymphoblastic leukemia (B-ALL) and chronic myeloid leukemia (CML) with chronic phase (CML-CP) to blast crisis (CML-BC). Previous studies have demonstrated that Src family kinases are required for the induction of B-ALL, but not for CML, which is induced by Bcr-Abl in mice. In contrast, it has been reported that Fyn is up-regulated in human CML-BC compared with CML-CP, implicating Fyn in the blast crisis transition. Here, we aimed to delineate the exact role of Fyn in the induction/progression of Ph(+) leukemias. We found that Fyn is expressed in mouse hematopoietic cells at varying stages of development, including c-kit(+)Sca-1(+)Lin(-) cells. Notably, Fyn is highly expressed in some of human lymphomas, but not in human Ph(+) leukemias including CML-BC. In mouse bone marrow transplantation models, mice transplanted with wild-type or Fyn-deficient bone marrow cells transduced with Bcr-Abl showed no differences in the development of B-ALL or CML-like diseases. Similarly, Fyn deficiency failed to impact the development of myeloid CML-BC induced by Bcr-Abl and Hes1. Elevated expression of Fyn was not found in mouse samples of Bcr-Abl-mediated CML- and CML-BC-like diseases. Thus, Fyn is not required for the pathogenesis of Bcr-Abl-mediated leukemias.


Chronic expression of p16INK4a in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation.
p16INK4a (CDKN2A) is a central tumor suppressor, which induces cell-cycle arrest and senescence. Cells expressing p16INK4a accumulate in aging tissues and appear in premalignant lesions, yet their physiologic effects are poorly understood. We found that prolonged expression of transgenic p16INK4a in the mouse epidermis induces hyperplasia and dysplasia, involving high proliferation rates of keratinocytes not expressing the transgene. Continuous p16INK4a expression increases the number of epidermal papillomas formed after carcinogen treatment. Wnt-pathway ligands and targets are activated upon prolonged p16INK4a expression, and Wnt inhibition suppresses p16INK4a-induced hyperplasia. Senolytic treatment reduces p16INK4a-expressing cell numbers, and inhibits Wnt activation and hyperplasia. In human actinic keratosis, a precursor of squamous cell carcinoma, p16INK4a-expressing cells are found adjacent to dividing cells, consistent with paracrine interaction. These findings reveal that chronic p16INK4a expression is sufficient to induce hyperplasia through Wnt-mediated paracrine stimulation, and suggest that this tumor suppressor can promote early premalignant epidermal lesion formation.


Is a pacemaker indicated for vasovagal patients with severe cardioinhibitory reflex as identified by the ATP test? A preliminary randomized trial.
A previous observational study suggested that, in syncopal elderly patients with vasovagal syndrome, a test using adenosine-5'-triphosphate (intravenous ATP 20 mg. 2 ml-1) could identify a subgroup of patients at high risk of severe cardioinhibitory response and guide the therapeutic strategy. To test one aspect of these results prospectively, we designed a small study focusing only on vasovagal patients with abnormal response to ATP testing. Twenty patients hospitalized for syncope, which was considered to be vasovagal, and exhibiting an abnormal ATP test--defined by a longer than 10 s cardiac pause--were randomized to two groups: half to implantation with a dual-chamber pacemaker and half to usual medical care. All patients who were not hospitalized for recurrences were assessed every 6 months in the clinic or by telephone. At baseline, the randomized patient groups were similar in their demographic and health characteristics and in the results of their ATP tests, for example the mean cardiac pause (21.4 +/- 9.3 vs 15.9 +/- 3.7 s) and the mean interval between escape beats during the pause (7.29 +/- 4.2 vs 7.48 +/- 3.3 s). During a mean follow-up of 52 months, recurrences appeared in six of the 10 usual-care patients (range 0.2-29 months) but in none of the implanted patients (P < 0.02). This limited trial (1) supports the conclusion that patients with an abnormal ATP test who receive a dual-chamber pacemaker suffer fewer recurrences than those who are monitored only; and (2) consequently further supports the hypothesis that, among vasovagal patients, a cardiac pause of longer than 10 s in patients administered ATP identifies those at high risk of symptomatic vagal cardiac inhibition.


Irritable bowel syndrome and health seeking behaviour in different communities of Pakistan.
To investigate the frequency of irritable bowel syndrome (IBS) and health seeking behaviour in patients belonging to different ethnic groups and their squatter settlements in two cities of Pakistan. Questionnaire based on Rome II criteria for the diagnosis of IBS was sent to 1167 persons living in, Karachi and Bahawalpur and their squatter settlements in Baloch Colony and Tibba Badar Sher respectively. About 90% (1048) completed the questionnaire. The overall frequency of IBS was 14% with a mean age of 30 +/- 12.5 years and range of 16-85 years. Of the IBS positive patients, 56% (82/146) were males. IBS was significantly more common (p = 0.05) in males belonging to age group 16-30 years. The most common presenting symptoms were abdominal pain (100%), altered bowel habits (51%), and diarrhoea (54%). There was no difference in the prevalence of IBS in Karachi and Baloch Colony as compared to Bahawalpur and Tibba Badar Sher. IBS patients seeking health care advice were 17.6% as compared to 12.6 % non healthcare seekers. Of the healthcare seekers there were 29 (35.4%) males (p = 0.002). The overall mean age of health care seeking IBS patients was 32.8 +/-13.8 years (p < 0.001). All IBS patients seeking healthcare advice had abdominal pain (p < 0.001), while 61% had altered stool consistency (p < 0.001) and 46% had stool frequency (p < 0.001) as compared to IBS non healthcare seekers. IBS is seen in both urban and suburban communities. Health seeking behaviour is common in males and with abdominal pain.


The value of MUTYH testing in patients with early onset microsatellite stable colorectal cancer referred for hereditary nonpolyposis colon cancer syndrome testing.
MUTYH adenomatous polyposis (MAP) can mimic both the familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) phenotypes. As a result of MAP's phenotypic overlap with FAP, some DNA diagnostic laboratories perform MUTYH testing in conjunction with APC testing in patients with suspected FAP or attenuated FAP (AFAP). In addition to testing FAP/AFAP samples for MUTYH mutations, we were interested whether there would also be value in testing samples referred for HNPCC testing. To determine this, we tested a consecutive series of 229 samples referred for HNPCC testing for the two most common MUTYH mutations in the Caucasian population. To enrich our study population with MAP cases, we only included samples from patients with early onset colorectal cancer (CRC diagnosed <50 years old) in whom HNPCC had been excluded by microsatellite instability testing (microsatellite stable or low microsatellite instability). Four biallelic (2%) and six monoallelic (3%) MUTYH mutation carriers were identified. No clinical factors predicted MUTYH mutation status. Specifically, a family history of vertical transmission of CRC or having few polyps (<15) did not rule out the possibility of biallelic MUTYH mutations. Thus, MUTYH mutation testing may be a reasonable cascade test in early onset CRC found to have proficient DNA mismatch repair, regardless of pattern of family history or number of polyps.


Primary vitamin D deficiency in children.
In recent years, the prevalence of vitamin D (calciferol) deficiency has increased and rickets has re-emerged in the UK and other developed countries as a public health problem. Infants, toddlers and adolescents in 'at risk' ethnic minorities (e.g. Asian, African Caribbean and Middle Eastern) are particularly likely to be vitamin D-deficient or to have rickets. Also at particular risk are babies and toddlers who have been exclusively breast-fed during infancy without receiving vitamin supplements, or whose mothers did not have vitamin D supplements during pregnancy. Here we discuss the management of children with primary vitamin D deficiency (i.e. that due to nutrient deficiency).


Perceptions of athletic training services by collegiate student-athletes: a measurement of athlete satisfaction.
I evaluated the perceptions student-athletes had of their athletic trainers and of the medical coverage provided them by the athletic departments at their institutions. My intent was to assess differences between male and female athletes, between athletes of high-profile and low-profile sports, and between athletes who competed at the NCAA Division I and Division II levels. The research design was also directed at identifying any subgroup of student-athletes who demonstrated a significantly different perception toward their athletic trainer(s). Questionnaires were sent to 32 athletic training programs at 28 NCAA Division I and II institutions. Eighteen of the 32 programs participated, yielding a 56% response. A total of 343 student-athletes from 18 selected athletic programs at both the NCAA Division I and II levels participated. One questionnaire contained response errors and was not included in the analysis. A questionnaire was developed and pilot tested at 3 collegiate settings apart from those participating in the study. Validity and reliability analyses were conducted and confirmed by additional professionals in the field of athletic training. Cumulative mean perception scores between groups were measured using independent t tests. Differences in scores between subgroups were measured using a 1-way analysis of variance. I observed significant differences in mean cumulative perception scores between sex and sport-profile groups. Male athletes and athletes in high-profile sports demonstrated a higher mean perception score than did females and athletes in low-profile sports. There was no difference in scores when compared across athletic divisions. Subgroups of all the athletes participating were identified. Several subgroups demonstrated significant differences in mean cumulative perception scores. Males and females in low-profile sports at Division II schools and females in high-profile sports at Division II schools had significantly lower mean perception scores than did other subgroups of athletes.


Specific in vitro cleavage of a Leishmania virus capsid-RNA-dependent RNA polymerase polyprotein by a host cysteine-like protease.
Antibodies raised against baculovirus-expressed RNA-dependent RNA polymerase (RDRP) recognized a 95-kDa antigen and two smaller proteins in sucrose-purified Leishmania virus particles isolated from infected parasites. The 95-kDa antigen is similar in size to one predicted by translation of the RDRP open reading frame (ORF) alone. In an effort to reconcile in vitro observations of translational frameshifting on Leishmania RNA virus 1-4 transcripts, we have developed an in vitro cleavage assay system to explore the possibility that the fusion polyprotein is proteolytically processed. We show that coincubation a synthetic Cap-Pol fusion protein with lysates from Leishmania parasites yields major cleavage products similar in size to those encoded by the individual capsid and RDRP genes as well as the antigens detected in vivo. The major 82- and 95-kDa major cleavage products are specifically immunoprecipitated by capsid- or polymerase-specific antibodies, respectively, showing that cleavage occurs at or near the junction of the two functional domains. Protease inhibitor studies suggest that a cysteine-like protease is responsible for cleavage in the in vitro assay system developed here. From these results, we suggest that failure to detect a capsid-polymerase fusion protein produced by translational frameshifting in vivo may be due to specific proteolytic processing.


Smoking and mortality in stroke survivors: can we eliminate the paradox?
Many studies have suggested that smoking does not increase mortality in stroke survivors. Index event bias, a sample selection bias, potentially explains this paradoxical finding. Therefore, we compared all-cause, cardiovascular disease (CVD), and cancer mortality by cigarette smoking status among stroke survivors using methods to account for index event bias. Among 5797 stroke survivors of 45 years or older who responded to the National Health Interview Survey years 1997-2004, an annual, population-based survey of community-dwelling US adults, linked to the National Death Index, we estimated all-cause, CVD, and cancer mortality by smoking status using Cox proportional regression and propensity score analysis to account for demographic, socioeconomic, and clinical factors. Mean follow-up was 4.5 years. From 1997 to 2004, 18.7% of stroke survivors smoked. There were 1988 deaths in this stroke survivor cohort, with 50% of deaths because of CVD and 15% because of cancer. Current smokers had an increased risk of all-cause mortality (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.14-1.63) and cancer mortality (HR, 3.83; 95% CI, 2.48-5.91) compared with never smokers, after controlling for demographic, socioeconomic, and clinical factors. Current smokers had an increased risk of CVD mortality controlling for age and sex (HR, 1.29; 95% CI, 1.01-1.64), but this risk did not persist after controlling for socioeconomic and clinical factors (HR, 1.15; 95% CI, .88-1.50). Stroke survivors who smoke have an increased risk of all-cause mortality, which is largely because of cancer mortality. Socioeconomic and clinical factors explain stroke survivors' higher risk of CVD mortality associated with smoking.


Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer.
Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.


Leaving Homelessness Behind: Housing Decisions among Families Exiting Shelter1.
Because homelessness assistance programs are designed to help families, it is important for policymakers and practitioners to understand how families experiencing homelessness make housing decisions, particularly when they decide not to use available services. This study explores those decisions using in-depth qualitative interviews with 80 families recruited in shelters across four sites approximately six months after they were assigned to one of four conditions (permanent housing subsidies, project-based transitional housing, community-based rapid re-housing, and usual care). Familiar neighborhoods near children's schools, transportation, family and friends, and stability were important to families across conditions. Program restrictions on eligibility constrained family choices. Subsidized housing was the most desired intervention and families leased up at higher rates than in other studies of poor families. Respondents were least comfortable in and most likely to leave transitional housing. Uncertainty associated with community-based rapid re-housing generated considerable anxiety. Across interventions, many families had to make unhappy compromises, often leading to further moves. Policy recommendations are offered.


Vaccination of children and adolescents with rheumatic diseases.
Children with rheumatic diseases (RDs) are at greater risk of infection because of their aberrant immunity and frequent use of immunosuppressive drugs. However, the use of vaccinations in such children is debated by many experts who think that the patients' immune response is insufficient to assure protection; some of them are also afraid that vaccines could trigger a persistent autoimmune response and lead to severe clinical problems including a relapse of the RD. This review describes the available data regarding the risks of vaccine administration, and the immunogenicity, efficacy and tolerability of the vaccines usually recommended for children with RDs. The data not only show that the schedule suggested for otherwise healthy children should be followed, but also that pneumococcal and influenza vaccinations should be strongly recommended because of the known risk of severe infections in patients with RD. However, there are areas in which further research is urgently required.


Lactobacillus kitasatonis sp. nov., from chicken intestine.
Four strains isolated from chicken small intestine and strains JCM 1038 and JCM 1039 (designated as Lactobacillus acidophilus) were characterized by phenotypic and molecular taxonomic methods. They were Gram-positive, catalase-negative, facultatively anaerobic rods that did not produce gas from glucose. These strains had similar phenotypic characteristics and exhibited intergroup DNA relatedness values of >77 %, indicating that they comprised a single species. The 16S rRNA gene sequence of a representative strain, JCM 1039(T) (designated as type strain in this study), was determined and aligned with those of other Lactobacillus species. JCM 1039(T) was placed in the Lactobacillus delbrueckii cluster of the genus Lactobacillus on the basis of phylogenetic analysis and formed an independent cluster that was distinct from its closest neighbours, Lactobacillus amylovorus, Lactobacillus crispatus, Lactobacillus gallinarum, L. acidophilus and Lactobacillus helveticus. Results of DNA-DNA hybridization experiments and whole-cell protein profiles clearly indicated that these strains represent a novel Lactobacillus species, for which the name Lactobacillus kitasatonis sp. nov. is proposed; the type strain of this species is JCM 1039(T).


Descriptor-Driven de Novo Design Algorithms for DOCK6 Using RDKit.
Structure-based methods that employ principles of de novo design can be used to construct small organic molecules from scratch using pre-existing fragment libraries to sample chemical space and are an important class of computational algorithms for drug-lead discovery. Here, we present a powerful new design method for DOCK6 that employs a Descriptor-Driven De Novo strategy (termed D3N) in which user-defined cheminformatics descriptors (and their target ranges) are calculated at each layer of growth using the open-source toolkit RDKit. The objective is to tailor ligand growth toward desirable regions of chemical space. The approach was extensively validated through: (1) comparison of cheminformatics descriptors computed using the new DOCK6/RDKit interface versus the standard Python/RDKit installation, (2) examination of descriptor distributions generated using D3N growth under different conditions (target ranges and environments), and (3) construction of ligands with very tight (pinpoint) descriptor ranges using clinically relevant compounds as a reference. Our testing confirms that the new DOCK6/RDKit integration is robust, showcases how the new D3N routines can be used to direct sampling around user-defined chemical spaces, and highlights the utility of on-the-fly descriptor calculations for ligand design to important drug targets.


Role of EBAG9 protein in coat protein complex I-dependent glycoprotein maturation and secretion processes in tumor cells.
Many proteins mature within the secretory pathway by the acquisition of glycans. Failure to maintain the proper distribution of the glycosylation machinery might lead to disease. High expression levels of the ubiquitous Golgi protein estrogen receptor-binding fragment-associated gene 9 (EBAG9) in human tumors correlate with poor clinical prognosis, and EBAG9 overexpression in epithelial cell lines induces truncated glycans, typical of many carcinomas. Here, we addressed the pathogenetic link between EBAG9 expression and the alteration of the cellular glycome. We applied confocal microscopy, live imaging, pulse-chase labeling in conjunction with immunoprecipitation, and enzymatic activity assays in a variety of EBAG9-overexpressing or depleted epithelial tumor cell lines. EBAG9 shuttles between the ER-Golgi intermediate compartment and the cis-Golgi, and we demonstrate association of EBAG9 with coat protein complex I (COPI)-coated transport vesicles. EBAG9 overexpression imposes delay of endoplasmic reticulum-to-Golgi transport and mislocalizes components of the ER quality control and glycosylation machinery. Conversely, EBAG9 down-regulation accelerates glycoprotein transport through the Golgi and enhances mannosidase activity. Thus, EBAG9 acts as a negative regulator of a COPI-dependent ER-to-Golgi transport pathway in epithelial cells and represents a novel pathogenetic principle in which interference with intracellular membrane trafficking results in the emergence of a tumor-associated glycome.


Social anxiety disorder in adolescents who stutter: A risk for school refusal.
Stuttering is a childhood-onset fluency disorder. Part of the counseling for middle and high school students with persistent stuttering is related to school refusal. Anxiety disorders are known to contribute to school refusal. However, it is not known whether social anxiety disorder (SAD) is a factor in school refusal among adolescents who stutter. In our first study, we examined the relationship between school refusal and SAD in 84 middle and high school students who stutter; 26% of the 84 students were in the school refusal group and the remaining 74% were in the school attendance group. The second study examined whether SAD was associated with 10 factors related to speech and stuttering frequency using the Japanese version of the Liebowitz Social Anxiety Scale for Children and Adolescents to determine the presence of SAD. Of the 84 students in the first study, 40 participated in the second study. The school refusal group of adolescents who stutter had significantly higher rates of SAD than the school attendance group. Fifty percent of adolescents who stutter met the criteria for SAD. Moreover, adolescents who stutter with SAD had significantly higher scores on the items "When speaking in public, do you experience tremors in your limbs?" and "After you stutter, do you have negative thoughts about yourself?" than the adolescents who stutter without SAD. When examining adolescents who stutter, checking for comorbid SAD may lead to better support. Moreover, noticing their repetitive negative thinking, nervousness, and trembling during speech may help to resolve SAD.


Thyroid malignancy among goitrous thyroid lesions: a review of hospital-based studies in Malaysia and Myanmar.
Endemic goitre is a major concern in many parts of the world, including Southeast Asia. Goitrous thyroid lesion is postulated as a precursor lesion to thyroid cancer (TC). This paper reviews the prevalence rates and characteristics of TC among cases of goitrous thyroid-swelling in different parts of Malaysia and Myanmar. Recorded data from hospital-based retrospective studies of thyroid cases, whose study periods ranged from three to 11 years, were analysed. These included research findings from the author's publications as well as other published review articles of retrospective analyses. The incidence of TC varies among gender, age, race/ethnicity and histological type. There appears to be a higher rate of occurrence among females aged 21-60 years. Papillary thyroid carcinoma is the more common histological type compared to follicular cancer. This review also presents a descriptive analysis and discussion on studies conducted in other countries. Further exploration is warranted in order to uncover the possible risk factors for the rising incidence of TC.


Construction and validation of sham insoles used in clinical trials: A systematic review.
Insoles are commonly prescribed to treat pathologies in a variety of patient groups; however, there is limited evidence to guide clinical decision-making. A well-validated sham insole is critical to conducting a double-blind placebo-controlled trial. The aims were to establish: (1) How are sham insoles constructed? (2) What measures are undertaken to ensure adequate blinding? (3) What methods are used to validate the biomechanical effects? A systematic search of the methodology of level I-II therapeutic evidence. Searches were conducted in MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials. Inclusion criteria were placebo-controlled clinical trials, sham insoles used, treatment insoles alter biomechanics, treatment insoles meet the ISO definition of foot orthotics, sham and treatment insoles tested in normal walking, and article available in English. The search generated 270 results. Twenty-four trials were included. 19% of sham insoles were described sufficiently to be replicated. The most common sham construction characteristics were full length, ethylene-vinyl acetate material, and flat insoles. 58% of studies were double-blinded; however, many did not describe any blinding methods. There is evidence that blinding the intervention details and a similar insole appearance is effective to blind participants. 13% of studies included a shoe-only condition to allow assessment of the biomechanical effects of sham insoles. There is inconsistent construction, blinding, and biomechanical validation of sham insoles. This casts a substantial doubt on the quality and reliability of the evidence base to support the prescription of insoles.


Effects of oxidized cellulose and microfibrillar collagen on infection.
Topical hemostatic agents may be used to control bleeding from a variety of surgical sites. Oxidized cellulose (Surgicel), gelatin sponge (Gelfoam), and microfibrillar collagen (Avitene) are the hemostatic agents in widest use. Oxidized cellulose has previously been shown to be superior to gelatin sponge with respect to infection. Microfibrillar collagen has not been studied in this regard. Contamination of experimental wounds with an inoculum of 3.2 to 3.6 X 10(4) colony-forming units of Staphylococcus aureus did not produce any infection. The addition of 20 mg of oxidized cellulose to wounds that received the same level of bacterial contamination resulted in nine infected wounds of 20 (45%). When the wounds were treated with 20 mg of microfibrillar collagen prior to contamination, 18 of 20 (90%) developed infection. The observed difference between the two hemostatic agents was significant (P less than 0.008). When 5 and 10 mg of oxidized cellulose was added to experimentally contaminated wounds, infection did not ensue. The incidence of infection increased strikingly when the amount of oxidized cellulose employed was increased to 20 and 30 mg. No such dose effect was observed for microfibrillar collagen. Infection developed even when very small quantities of the agent were used. Both oxidized cellulose and microfibrillar collagen may promote infection. The present study, in which a subcutaneous wound model was used, suggests an advantage of oxidized cellulose as compared with microfibrillar collagen from the standpoint of infection. Further studies with these agents in other body sites seem warranted.


Active orthostatic stress and respiratory sinus arrhythmia in patients with Chagas' disease with preserved left ventricular global systolic function.
To assess the use of the active orthostatic stress test for detecting vagal dysfunction in patients with Chagas' disease with preserved overall systolic function, and to compare it with the respiratory sinus arrhythmia test. Sixty-one chagasic patients (Ch) and 38 nonchagasic (NCh) patients with no significant evidence of heart disease or systemic diseases underwent Doppler echocardiography and autonomic function tests. The respiratory sinus arrhythmia test was performed through electrocardiographic recording during deep breathing, at 6 ripm, calculating the E:I ratio (mean ratio between the longest expiratory RR interval and the shortest inspiratory RR interval at each cycle). The electrocardiogram was recorded during the act of standing and during the following 30 seconds (active orthostatic stress test), and the max RR/min RR ratio (the longest and shortest RR intervals right after change in posture) was calculated. The indices were adjusted for significant covariables. The max RR/min RR ratio (NCh: 1.52 [1.44-1.74] x Ch: 1.43 [1.33-1.51], P < 0.001) and the E:I ratio (NCh: 1.38 +/- 0.02 x Ch: 1.25 +/- 0.02, P<0.001) were lower among chagasic patients. A high correlation was observed between the adjusted max RR/min RR ratio and E:I ratio (r = 0.628, P < 0.001), but neither significantly correlated with left ventricular ejection fraction. Chagasic patients with preserved left ventricular overall systolic function showed a significant reduction in the vagal indices obtained on short-lasting tests, as compared with normal controls. The active orthostatic stress test that, showed a good correlation with the respiratory sinus arrhythmia maneuver, constituted a valid option for the outpatient care assessment of vagal control.


A review of pharmacist recommendations in an aged care facility.
The aim of this study was to analyse the types of and rationale for the clinical recommendations made by the pharmacist in a rural aged care facility to improve patient safety. The classes of drugs associated with the pharmacist's recommendations were also identified. A related aim was to determine their degree of acceptance by medical practitioners. A retrospective, cross-sectional study design was used to review 56 aged care residents' case notes over a 12-month period. The main outcome measures included: the types of and reasons for recommendations made by the pharmacist; classes of drugs associated with the pharmacist's recommendations; and the implementation rate of the pharmacist's recommendations by the medical practitioner. A total of 196 recommendations were made by the pharmacist to the residents' existing medications. The main types of recommendations were alteration to residents' monitoring (49%), discontinuation of drug treatment (19%) followed by initiation of drug treatment (17%). The main reasons for the recommendations were to reduce potential side-effects (45%), symptom control (32%) and to increase drug efficacy (19%). Analysis of medical practitioners' case notes estimated that 70% of the pharmacist's recommendations were being implemented by the residents' medical practitioner. This case notes analysis reinforces the importance of doctor-pharmacist collaboration in the management of residents' medications in aged care facilities.


Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.
Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.


Effects of testosterone and photoperiodic condition on song production and vocal control region volumes in adult male dark-eyed juncos (Junco hyemalis).
In seasonally breeding male oscines, song learning and expression are controlled by brain regions (vocal control regions, VCRs) that exhibit seasonal neural plasticity in adulthood. Several VCRs contain androgen receptors, and gonadal androgens play important roles in the control of seasonal structural and functional changes of VCRs. Recent studies also found that adult VCRs are influenced by factors other than gonadal hormones, including photoperiod, but the relative importance of these factors and their mechanisms of action are poorly understood. To address this issue, we investigated the contributions of photoperiod and testicular androgens to the regulation of VCR volumes and to the control of song expression in adult dark-eyed juncos, Junco hyemalis. Exposing castrated (CX) photosensitive males to long days (LD) enhanced their high vocal center (HVc) volumes compared to those of males held on short days (SD). These volumes were not further increased by concurrent testosterone (T) treatment, revealing a marked and gonadal androgen-independent stimulatory influence of photoperiod on the size of this brain region. HVc sizes were smaller in LD-exposed photorefractory than photosensitive males irrespective of whether birds were intact or had been castrated before photoperiodic manipulations, but HVc sizes increased in response to T treatment in intact photorefractory males. Thus, LD exposure can increase HVc volumes in the absence of gonadal T, but large volume induction in photorefractory males requires elevated plasma T levels. Testosterone treatment of SD-exposed photosensitive males increased HVc, but not Area X, MAN, or RA volumes. Only T-treated males sang and this treatment given to castrates was equally effective behaviorally when administered to photosensitive, photostimulated, or photorefractory juncos. This result indicates that the stimulating influence of LD exposure on HVc volumes is insufficient to induce song in the absence of elevated plasma T levels.


Does the LENT score risk-stratify patients with malignant pleural mesothelioma? An observational study.
Malignant pleural mesothelioma (MPM) is a rare, highly aggressive and deadly disease with a poor patient life expectancy. A few years ago, the main challenge was the histological diagnosis of this disease; at present, the search for the best therapeutic strategy is now a priority. However, an optimal therapeutic strategy is not yet clear, despite growing efforts in the treatment armamentarium and research, and at the era of tailored and individualized treatment, tools to predict patient survival are needed for therapeutic decision-making. Among them, the LENT scoring system was developed to predict prognosis in patients with malignant pleural effusion. The aim of this study was to assess the performance of the LENT score in predicting prognosis in patients with MPM. A retrospective observational study was conducted by analyzing the prospective collected databases of patients undergoing medical thoracoscopy in a single center with a final diagnosis of MPM confirmed by the MESOPATH National Reference Center. A total of 41 patients with MPM were studied. All patients underwent platinum-based chemotherapy combined with pemetrexed ± bevacizumab. No high-risk category patients were found using the LENT scoring system in this cohort. The median (range) LENT score at the time of medical thoracoscopy was 0 (0-3) and the median survival was 15.5 (2-54) months for the entire cohort. The median survival of low-risk and moderate-risk category patients was 21.4 months (2-54, 32 patients) and 6.7 months (2-19, nine patients), respectively. A total of 27 patients with MPM of epithelial subgroup had a median LENT score of 1 (0-2) with a 26 (2-54) months median survival. The median LENT score and median survival of nonepithelial mesothelioma patients (biphasic MPM subgroup, eight patients; sarcomatoid MPM subgroup, six patients) were 0 (0-3) and 11 (2-52) months, respectively. Applied to a homogenous cohort of MPM patients, the LENT score underestimated prognosis and was not useful per se for the management of this disease, as evidenced in the epithelial mesothelioma subgroup of patients in our study.


Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common.
In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated.


Paleopathology and osteobiography of the people of Peñuelas, Chile's semiarid north.
The Museo de La Serena, IV Region, Chile has collections of skeletal remains representing the agricultural Diaguita people of 500 years ago excavated in the 1980s from the sites Peñuelas 21 and 24, Chile's semiarid north. Their excellent preservation has permitted an osteobiographical and radiographic analysis to better understand the patterns of the disease. This research continues the osteological analyses begun in 1989 by Rosado that seek to understand the impact the transition to and adoption of farming had on the health of prehistoric populations. Because of the significance of paleopathology in the understanding of cultural and biological adaptations, it has also become necessary to assess the preservation status and design a conservation protocol to protect and document the remains. The objectives of this communication are to: establish demographic patterns of the skeletal samples and identify and diagnose skeletal paleopathologies via photography and radiographs. Intentional cranial alteration, limb and cranial fractures, dental wear, and dental abscesses and caries are among the interesting paleopathologies so far documented. Intentional cranial alteration is very common and is manifested as tabular erect in both males and females. The high frequency of carious lesions indicates a diet that emphasized carbohydrates. Skeletal radiographs are available for several of the individuals in the sample and this has afforded a more detailed description of the paleopathologies originally documented via photography.


Multifocal septic osteomyelitis mimicking skeletal metastatic disease in a patient with prostate cancer.
We present an unusual case of a 59 years old patient with prostate cancer, who was referred to our hospital with pleurodenia, low back and other sites of bone ostalgia, for bone scintiscan. The patient underwent a whole body bone scanning after the intravenous administration of 740MBq (99m)Tc-methylene diphosphonate (MDP). The main findings of the study were: increased radiotracer uptake at the T5, T9-T10 vertebrae, the head of the 11th rib and the area of the left sternoclavicular joint (SCJ), which were initially attributed to skeletal metastatic lesions. Another "hot" area in the left knee, was consistent with severe arthritis. Physical examination revealed fever up to 38.7°C, tenderness and swelling of his left knee and various painful sites. Due to persistent fever and markedly raised inflammatory markers (ESR 102mm/h, CRP 73.8mg/L, WBC 16.800 cells/μ L - neutrophils 78%, lymphocytes 15%, monocytes 5%, eosinophils 1%), the patient was further referred for a magnetic resonance (MR) scan with specific interest on the thoracic spine and the SCJ. In the sagittal short-tau inversion recovery (STIR) MR image, abnormally high signal involving both T9 and T10 vertebral bodies due to bone marrow oedema and irregularity of the endplates with focal destruction areas, were observed. The T9-T10 intervertebral disc had an abnormally high signal suggestive of "hot disc" sign and also a prevertebral soft tissue mass abutting the anterior aspect of the involved vertebral bodies. The axial T1-weighted image with fat saturation post gadolinium (Gd), revealed diffuse strong enhancement in the vertebral body, the paraspinal soft tissue mass and the adjacent right rib. Circumferential epidural enhancement indicative of intra-canal spread of the infection, was also noticed. Additional MR sequences covered the level of the SCJ. Extensive subarticular and soft tissue changes with fluid collection and bone oedema of the left SCJ were shown with the typical pattern of diffuse enhancement suggestive of septic arthritis. The MR imaging findings combined with the scintigraphic findings were consistent with subacute multifocal septic arthritis involving the axial skeleton, as a pyogenic spondylodiscitis at the T9-T10 level, the left SCJ joint and the left knee joint. Subsequently, aspiration of the SCJ and the left knee joint was performed. A purulent fluid was drained and sent to microbiology. The sample revealed 96.000 cells/μL (95% neutrophils) and methicillin-resistant Staphylococcus aureus (MRSA). The patient received intravenous vancomucin (2gr. twice a day for 14 days) and subsequently the dose was adjusted to maintain the vancomucin serum levels between 17 and 20mcg/mL. The total treatment duration was 12 weeks. Four months later the patient had fully recovered and his blood tests were normal. The patient had not been referred to an oncology department yet, as the onset of the arthritis occurred about two weeks after the diagnosis of prostate cancer. In conclusion, we present a patient with known malignancy, fever, skeletal pain and multiple bone lesions in the (99m)Tc-MDP and the MRI examination, not due to metastatic disease but to septic arthritis.


Pressure ulcer patient and wound assessment: an AHCPR clinical practice guideline update.
The Agency for Health Care Policy and Research (AHCPR) clinical practice guidelines on the treatment of pressure ulcers are based on the literature published before 1994. For the patient and wound assessment recommendations, a review of the literature from 1993 to 1998 was conducted in an effort to update this section of the guideline. In addition, the strength-of-evidence rating system used was critiqued for its narrow definitions, particularly as it pertains to recommendations related to assessment practices. Studies to determine the prospective validity of the entire guideline, as well as further research to assess the validity of individual recommendations, is needed.


Prevention of intracerebral haemorrhage.
Nontraumatic intracerebral haemorrhages arise from a wide range of causes falling into two broad groups: discreet vascular "ictohaemorrhagic" lesions such as aneurysms, arteriovenous malformations, cavernomas, tumours, and dural fistulae; and more generalised amyloid or hypertension related conditions. It is now possible using family history, associated risk factors and gradient echo MRI to predict cases at high risk of hypertensive or amyloid related haemorrhage. There is considerable potential for prevention of hypertensive haemorrhages by treatment of high risk cases with antihypertensive medication. As yet no effective preventative treatment for amyloid angiopathy related ICH has emerged although a variety of drugs are under investigation. Prevention of haemorrhage from ictohaemorrhagic lesions revolves around removal or obliteration of the lesion. Although there is a wide range of such lesions available treatments come down to three modalities. These are surgical excision, stereotactic radiosurgery and endovascular embolisation.


Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition.
In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex--the W and Y chromosomes. By contrast, the sex chromosomes found in both sexes--the Z and X chromosomes--are assumed to have diverged little from their autosomal progenitors. Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.


Outer membrane permeability barrier disruption by polymyxin in polymyxin-susceptible and -resistant Salmonella typhimurium.
In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant Salmonella typhimurium mutants (pmrA strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of pmrA strains to deoxycholate-induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the pmrA mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the pmrA mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the pmrA effect in the outer membrane.


Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta).
Primaquine (PQ) remains the sole available drug to prevent relapse of Plasmodium vivax malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to Plasmodium cynomolgi-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (-)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (-)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (-)-PQ at 4.5 mg/kg. (-)-PQ in combination with chloroquine was successful in preventing P. cynomolgi disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (-)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers.


Myoclonus-dystonia and Silver-Russell syndrome resulting from maternal uniparental disomy of chromosome 7.
Myoclonus-dystonia (M-D) is a movement disorder that is often associated with mutations in epsilon-sarcoglycan (SGCE), a maternally imprinted gene at 7q21.3. We report a 24-year-old male with short stature (<5th percentile) and a movement disorder clinically consistent with M-D. Single nucleotide polymorphism (SNP) array did not identify significant copy number changes, but revealed three long continuous stretches of homozygosity on chromosome 7 suggestive of uniparental disomy. Parental SNP arrays confirmed that the proband had maternal uniparental disomy of chromosome 7 (mUPD7) with regions of heterodisomy and isodisomy. mUPD7 is the cause of approximately 5-10% of Silver-Russell syndrome (SRS), a disorder characterized by prenatal and postnatal growth retardation. Although SRS was not suspected in our patient, these findings explain his short stature. SGCE methylation testing showed loss of the unmethylated paternal allele. Our findings provide a unifying diagnosis for his short stature and M-D and help to optimize his medication regimen. In conclusion, we show that M-D is a clinical feature that may be associated with SRS due to mUPD7. Individuals with mUPD7 should be monitored for the development of movement disorders. Conversely, individuals with M-D and short stature should be evaluated for SRS.


Neuroactive steroids and Parkinson's disease: Review of human and animal studies.
The greater prevalence and incidence of Parkinson's disease (PD) in men suggest a beneficial effect of sex hormones. Neuroactive steroids have neuroprotective activities thus offering interesting option for disease-modifying therapy for PD. Neuroactive steroids are also neuromodulators of neurotransmitter systems and may thus help to control PD symptoms and side effect of dopamine medication. Here, we review the effect on sex hormones (estrogen, androgen, progesterone and its metabolites) as well as androstenediol, pregnenolone and dehydroepiandrosterone) in human studies and in animal models of PD. The effect of neuroactive steroids is reviewed by considering sex and hormonal status to help identify specifically for women and men with PD what might be a preventive approach or a symptomatic treatment. PD is a complex disease and the pathogenesis likely involves multiple cellular processes. Thus it might be useful to target different cellular mechanisms that contribute to neuronal loss and neuroactive steroids provide therapeutics options as they have multiple mechanisms of action.


Multiple Sexual Partners as Major Predictor of Human Immunodeficiency Virus Seropositivity Among Pregnant Women, Osun State, Nigeria.
Concerning human immunodeficiency virus (HIV) epidemiology, pregnant women (PW) are particularly vulnerable and severely affected. Nigeria has over 40 years of HIV epidemiology and enlightenments; to suggest control hub, we sought to know extant variables predicting HIV positivity among PW in selected towns in Osun State. Our hypothesis: none of the study PW's variables predicts HIV seropositivity. With ethics approval from UNIOSUN Health Research Ethics Committee, 900 consecutively selected consenting PW attending antenatal care (ANC) facilities in four towns (capital city inclusive) provided relevant sociodemographic/behavioral data with questionnaire forms; each participant was aseptically bled and plasma screened with the Alere Determine® Rapid HIV-1/2 Kit. The presumptive reactive plasma samples (and some randomly selected nonreactive samples) were confirmed with Genscreen® ULTRA HIV-1/2 P24 antigen/antibody ELISA. Microsoft Excel and SPSS 16.0 were used for result analysis using t-test, CHI2 test, and binary logistic regression. The PW were 15-50 years of age (n = 900; mean: 26.6 years [95% CI: 26.1-26.9 years]); they were predominantly 15-29 years (71.1%), married (90.8%), with one lifetime sexual partner (86.4%). Seropositive PW by screening and confirmatory tests were, respectively, 14 (1.6% [95% CI: 0.9-2.6%]) and 15 (1.7% [95% CI: 0.9-2.7%]). The latter were predominantly 20-30 years (80.0%), married (93.3%), with ≤ secondary school education (86.7%), reportedly never screened for HIV (60.0%), with 86.7% aware HIV is sexually transmitted. Analysis showed only ≥ three lifetime sexual partners was independently associated with HIV seropositivity (p = 0.03; odds ratio (OR) = 17.0). Although educational status was not associated with seropositivity, PW having primary school education had about 6 times higher likelihood of seropositivity (p = 0.06; OR = 5.7 [95% CI: 0.94-35.1]). Also, primigravida had about twice higher likelihood of seropositivity (p = 0.44; OR = 1.5 [95% CI: 0.54-4.17]). HIV seropositivity was relatively low and majorly predicted by ≥ three lifetime sexual partners; suggesting this as prime focus of HIV counseling among PW attending ANC in Osun State, Nigeria.


Accuracy of papilledema and pseudopapilledema detection: a multispecialty study.
Present trends in medical care suggest that primary care physicians will exert increasing control over patient access to medical specialty consultation and diagnostic testing. Therefore, it is important to determine whether primary care physicians can reliably identify papilledema. A prospective study involving 429 physicians was undertaken to assess the accuracy of papilledema and pseudopapilledema detection by five groups of physicians, family practice physicians, neurologists, neuro-ophthalmologists, neurosurgeons, and ophthalmologists. Neuro-ophthalmologists and ophthalmologists did better than family physicians, neurologists, and neurosurgeons in identifying both papilledema and pseudopapilledema (P less than .05). Neuro-ophthalmologists more accurately identified pseudopapilledema than all other groups in the study (P less than .05). Family physicians did as well as, or better than, neurologists and neurosurgeons in identifying all classifications of acute and chronic papilledema defined in the study. Family physicians did not perform as well as the other four groups in differentiating pseudopapilledema from papilledema (P less than .05). Although the sensitivity of detecting papilledema was high (84.5%) for family physicians, the specificity was low (59.3%). Preliminary data indicate that family physicians with prior exposure to clinical ophthalmology in medical school did better than those who had not had training. It is possible that additional exposure to clinical ophthalmology during residency training might yield improved performance.


Dysregulation of mechanosensory circuits coordinating the actions of antagonist motor pools following peripheral nerve injury and muscle reinnervation.
Movement disorders observed following peripheral nerve injury and muscle reinnervation suggest discoordination in the activation of antagonist muscles. Although underlying mechanisms remain undecided, dysfunction in spinal reflex circuits is a reasonable candidate. Based on the well known role of reflex inhibition between agonist and antagonist muscles in normal animals, we hypothesized its reduction following muscle reinnervation, similar to that associated with other disorders exhibiting antagonist discoordination, e.g. spinal cord injury and dystonia. Experiments performed on acutely-decerebrated rats examined interactions of mechanosensory reflexes between ipsilateral muscles acting as mechanical antagonists at the ankle joint: ankle extensor, gastrocnemii (G) muscles (agonists) and ankle flexor, tibialis anterior (TA) muscle (antagonist). The force of agonist stretch reflex contraction was measured for its suppression or facilitation by concurrent conditioning stretch of the antagonist muscle. Data were compared between two groups of adult rats, an antagonist reinnervation group with TA muscle reinnervated and a control group with TA normally innervated. Results revealed a three-fold increase in reflex suppression in the antagonist reinnervation group, contrary to our predicted decrease. Reflex facilitation also increased, not only in strength, seven-fold, but also in its frequency of stochastic occurrence across stimulus trials. These observations suggest dysregulation in specific spinal reflex circuits as novel candidate origins of modified antagonist muscle coordination following peripheral nerve injury and muscle reinnervation.


Predicting shunt failure on the basis of clinical symptoms and signs in children.
In evaluating pediatric patients for shunt malfunction, predictive values for symptoms and signs are important in deciding which patients should undergo an imaging study, whereas determining clinical findings that correlate with a low probability of shunt failure could simplify management. Data obtained during the recently completed Pediatric Shunt Design Trial (PSDT) were analyzed. Predictive values were calculated for symptoms and signs of shunt failure. To refine predictive capability, a shunt score based on a cluster of signs and symptoms was derived and validated using multivariate methods. Four hundred thirty-one patient encounters after recent shunt insertions were analyzed. For encounters that took place within 5 months after shunt insertion (early encounters), predictive values for symptoms and signs included the following: nausea and vomiting (positive predictive value [PPV] 79%, likelihood ratio [LR] 10.4), irritability (PPV 78%, LR 9.8), decreased level of consciousness (LOC) (PPV 100%), erythema (PPV 100%), and bulging fontanelle (PPV 92%, LR 33.1). Between 9 months and 2 years after shunt insertion (late encounters), only loss of developmental milestones (PPV 83%, LR 36.7) and decreased LOC (PPV 100%) were strongly associated with shunt failure. However, the absence of a symptom or sign still left a 15 to 29% (early encounter group) or 9 to 13% (late encounter group) chance of shunt failure. Using the shunt score developed for early encounters, which sums from 1 to 3 points according to the specific symptoms or signs present, patients with scores of 0, 1, 2, and 3 or greater had shunt failure rates of 4%, 50%, 75%, and 100%, respectively. Using the shunt score derived from late encounters, patients with scores of 0, 1, and 2 or greater had shunt failure rates of 8%, 38%, and 100%, respectively. In children, certain symptoms and signs that occur during the first several months following shunt insertion are strongly associated with shunt failure; however, the individual absence of these symptoms and signs offers the clinician only a limited ability to rule out a shunt malfunction. Combining them in a weighted scoring system improves the ability to predict shunt failure based on clinical findings.


Characteristics and predictors of adult frequent emergency department users in the United States: A systematic literature review.
We conducted a systematic literature review to identify and to update patient characteristics and contextual factors for adult frequent emergency department users (FEDUs) compared with non-FEDU in an era where the US health care system underwent substantial changes. We searched MEDLINE, CINAHL, and EMBASE to identify all relevant articles after 2010 through July 2018 that describe FEDU. We included US studies on adult FEDU only and excluded studies on specific subgroups of FEDU. We included demographic, clinical, and health care utilization information, and two reviewers independently evaluated the studies using the Joanna Briggs Institute Critical Appraisal tool. The 11 studies included in the review indicated that FEDU were 4% to 16% of total ED users but accounted for 14% to 47% of ED visits, with six to nine visits per year on average. The majority of FEDU were young or middle-aged adults, females, of low socioeconomic status and high school or less education, with public insurance, multiple primary care provider visits, and chronic conditions. Fair or poor self-perceived health status, unemployment, unmet needs from primary care providers (PCPs), mental health, and substance abuse were predictors of FEDU. FEDUs are disproportionally sicker and are also heavy users of non-ED health care service providers. The limited data for non-ED health services use in facility-specific studies of FEDU may contribute to findings in such studies that complex and unmet needs from PCPs contributed to ED visits. This suggests the need for more comprehensive data analysis beyond a few sites that can inform systemic management approaches.


Efficacy of zerumbone against dual-species biofilms of Candida albicans and Staphylococcus aureus.
Candida albicans and Staphylococcus aureus are the most common opportunistic pathogens that co-exist as mixed biofilms. Dual-species biofilms of C. albicans and S. aureus cause nosocomial medical device-related infections that are strongly resistant to antibiotics and host immune responses compared with mono-species biofilms. The purpose of this study was to describe the efficacy of zerumbone derived from Zingiber zerumbet (L.) Smith, on dual-species biofilm formation. This study examined the inhibitory effects of zerumbone on planktonic cell growth, adhesion and biofilm formation. The results demonstrated that zerumbone remarkably inhibited mono- and dual-species biofilms formed by C. albicans and S. aureus using the XTT [2,3-bis(2-smethoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide]-reduction assay. Furthermore, a significant decrease in biomass and cell density of dual-species biofilms following zerumbone treatment was confirmed using confocal laser scanning microscopy (CLSM). Therefore, our study suggests that zerumbone is a potential antimicrobial and antibiofilm agent indicated for the therapeutic management of nosocomial medical device-related infections induced by dual-species biofilms of C. albicans and S. aureus.


Appendicitis, 2002: relationship between payors and outcome.
As the status of health-care insurance changes in the United States, studies have indicated that uninsured patients are less likely to receive timely and quality health care. Previous studies of appendicitis have shown that insurance status may effect the stage of presentation and outcome. However, these studies were based on databases lacking information regarding stage of presentation, timeliness of diagnosis and treatment, and character of hospitalization (length of stay, duration of antibiotic therapy, hospital costs). We accomplished a case control study, retrospective analysis of 975 patients treated for acute appendicitis between January 1996 and December 1999. Times to operation, number of preoperative outpatient visits, number of studies, severity of presentation, length of antibiotics and hospital stay, and hospital costs were analyzed [analysis of variance (ANOVA) techniques, P < 0.05 significant]. We sought answers to the following: (1) Did insurance status affect the timeliness of diagnosis and treatment? (2) Did insurance status affect the stage of presentation? (3) Did insurance status affect hospitalization, as measured by length of stay, duration of antibiotic therapy, and hospital costs? (4) Did age affect outcome independent of insurance status? There were no correlations between insurance status and timeliness of diagnosis or severity of presentation. Length of stay and hospital costs were also not different between insurance categories. Pediatric patients (< 12 years old) and the elderly (> 65 years old) presented with more advanced appendicitis, independent of insurance category. In contrast to previously published data, the treatment of acute appendicitis is not affected by insurance coverage in the sample community. Age and timeliness of presentation were the only factors correlating to outcomes.