[Effects of rho-kinase inhibitor on cardiac hypertrophy of left ventricle in spontaneously hypertensive rats].
To explore the effects of Rho-kinase inhibitor on cardiac hypertrophy of left ventricle in spontaneously hypertensive rats (SHR). SHRs (n = 30) were randomly divided into 5 groups (n = 6 each): SHR control group, 5 mg/kg fasudil group (SHRL), 10 mg/kg fasudil group (SHRM), 20 mg/kg fasudil group (SHRH) and nifedipine group (XBDP, 10 mg/kg). Six male Wistar-Kyoto rats were selected as normal control group (WKY group). Systolic blood pressure (SBP) was measured before and after treatment every 2 weeks. The hypertrophic parameters of left ventricular weight index (LVWI) and cardiomyocyte transverse diameter (TDM) were measured. In addition, the expression levels of Rho kinase mRNA and protein in cardiomyocytes were observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The levels of LVWI and TDM in WKY group were significantly lower than those in SHR control group [(2.98 ± 0.05) vs (3.16 ± 0.08) mg/g, (18.18 ± 0.75) vs (21.32 ± 1.25) µm, P < 0.01]. After 8 weeks, the levels of LVWI and TDM in three fasudil groups were markedly lower than those in SHR control group [SHRL group: (3.12 ± 0.05) mg/g, SHRM group: (3.10 ± 0.07) mg/g, SHRH group: (3.08 ± 0.09) mg/g vs SHR control group: (3.16 ± 0.08) mg/g, SHRL group: (20.11 ± 1.15) µm, SHRM group: (19.63 ± 1.62) µm, SHRH group: (18.91 ± 1.05) µm vs SHR control group: (21.32 ± 1.25) µm, P < 0.05 or P < 0.01]. But the levels of LVWI and TDM were not different between SHR control and XBDP groups [(3.14 ± 0.08) mg/g,(21.42 ± 1.23) µm, P > 0.05]. Compared with SHR control group, the expression of Rho kinase mRNA and protein in cardiomyocytes significantly decreased in three fasudil groups [SHRL group mRNA: (0.45 ± 0.08), SHRM group mRNA: (0.37 ± 0.07), SHRH group mRNA: (0.32 ± 0.07) vs SHR control group mRNA: (0.63 ± 0.07), SHRL group protein: 0.78 ± 0.11), SHRM group protein: (0.73 ± 0.10), SHRH group protein: (0.68 ± 0.10) vs SHR control group protein: (0.90 ± 0.1), P < 0.05 or P < 0.01], but showed no obvious change in XBDP group [mRNA: (0.56 ± 0.07), protein: (0.85 ± 0.10), P > 0.05]. Rho kinase inhibitor may significantly down-regulate the expression of Rho kinase in cardiomyocytes of SHR. The mechanism is probably due to the favorable effects of Rho kinase inhibitor in the prevention of cardiac hypertrophy of left ventricle.


The envelope protein encoded by the A33R gene is required for formation of actin-containing microvilli and efficient cell-to-cell spread of vaccinia virus.
The vaccinia virus (VV) A33R gene encodes a highly conserved 23- to 28-kDa glycoprotein that is specifically incorporated into the viral outer envelope. The protein is expressed early and late after infection, consistent with putative early and late promoter sequences. To determine the role of the protein, two inducible A33R mutants were constructed, one with the late promoter and one with the early and late A33R promoter elements. Decreased A33R expression was associated with small plaques that formed comets in liquid medium. Using both an antibiotic resistance gene and a color marker, an A33R deletion mutant, vA33delta, was isolated, indicating that the A33R gene is not essential for VV replication. The plaques formed by vA33delta, however, were tiny, indicating that the A33R protein is necessary for efficient cell-to-cell spread. Rescue of the large-plaque phenotype was achieved by inserting a new copy of the A33R gene into the thymidine kinase locus, confirming the specific genetic basis of the phenotype. Although there was a reduction in intracellular virus formed in cells infected with vA33delta, the amount of infectious virus in the medium was increased. The virus particles in the medium had the buoyant density of extracellular enveloped viruses (EEV). Additionally, amounts of vA33delta cell-associated extracellular enveloped viruses (CEV) were found to be normal. Immunogold electron microscopy of cells infected with vA33delta demonstrated the presence of the expected F13L and B5R proteins in wrapping membranes and EEV; however, fully wrapped vA33delta intracellular enveloped viruses (IEV) were rare compared to partially wrapped particles. Specialized actin tails that propel IEV particles to the periphery and virus-tipped microvilli (both common in wild-type-infected cells) were absent in cells infected with vA33delta. This is the first deletion mutant in a VV envelope gene that produces at least normal amounts of fully infectious EEV and CEV and yet has a small-plaque phenotype. These data support a new model for VV spread, emphasizing the importance of virus-tipped actin tails.


[Referral to elective and emergency coronary investigation from a medium-size central hospital].
Little is known about regional differences in the incidence of acute and elective invasive coronary procedures in Norway. Such information is important in the planning of new invasive centres. In this prospective study all patients referred to coronary angiography at the Rikshospitalet University Hospital in Oslo (100 km remote) from the county of Vestfold (218,000 inhabitants) from 1 December 2002 to 30 November 2003 were included. Referrals were categorised as acute or elective. Based upon the discharge summaries from Oslo, all coronary angiographies, percutaneous interventions and coronary artery bypass grafts were registered. A total of 760 patients were referred, of whom 746 (98 %) underwent coronary angiography (19 % acutely). They were treated as follows: percutaneous coronary intervention, n = 295 (31 % acutely); coronary artery bypass grafting, n = 123 and conservative treatment, n = 342. Based upon these results, the incidence figures for 100,000 inhabitants per year in 2003 were similar to the nation-wide average for percutaneous interventions per year in Norway in 2001 and approximately 30 % below that average for 2003. Therefore, in the planning of an optimal peripheral catheterisation laboratory, the population basis has to be calculated from the local incidence of procedures, since there are obviously significant regional differences in the use of such procedures.


High flow rate nanofluidics for in-liquid electron microscopy and diffraction.
We introduce a nanofluidic platform that can be used to carry out femtosecond electron diffraction (FED) and transmission electron microscopy (TEM) measurements in liquid samples or in-liquid specimens, respectively. The nanofluidic cell (NFC) system presented herein has been designed to withstand high sample refreshing rates (over one kilohertz), a prerequisite to succeed with FED experiments in our lab. Short beam paths, below 1 μm, in combination with ultrathin membranes (less than 100 nm thick) are necessary conditions for in-liquid FED and TEM studies due to the strongly interacting nature of electrons. Depending on the application, the beam path in our NFC can be tuned between 50 nm and 10 μm with ultrathin stoichiometric silicon nitride (Si3N4) windows as thin as 20 nm. Stoichiometric Si3N4 has been selected to reduce membrane bulging owing to its higher tensile stress and transparency in the UV-vis-NIR region to allow for laser excitation in FED experiments. Key design parameters and improvements made over previous NFC systems are discussed, and some preliminary electron images obtained by 200 kV scanning TEM are presented.


General base-tuned unorthodox synthesis of amides and ketoesters with water.
We discovered a highly reactive λ(3)-hypervalent iodane species using an inorganic/organic base for the unorthodox synthesis of amides and ketoesters through grafting terminal alkynes. In contrast to the metal-catalyzed dehydrative approaches the in situ generated nonmetallic reagent efficiently created C-N/C-O and C[double bond, length as m-dash]O bonds with amines/alkynes and water at rt.


Clinical classification of hepatoma in Japan according to serial changes in serum alpha-fetoprotein levels.
Quantitative determinations of serum alpha-fetoprotein (AFP) in 96 patients with hepatomas have demonstrated three main groups based on changes in the serial levels: 1) patients with more than 10 000 ng/ml during most of their clinical course, and with an increase of 10 000 ng/ml or more in a week (Group A); 2) patients with levels varying from 200 to 10 000 ng/ml and with an increase of 1000 ng/ml in three to four months (Group B); and 3) patients with serum AFP level below 200 ng/ml during most of their clinical course (Group C). The patients in Group A had a mean survival time of 7.62 +/- 3.97 months, and those in Group B, 16.18 +/- 12.18 months. The patients in Group C were subdivided into two groups according to whether survival time was long (33.92 +/- 28.22 months) or short (3.75 +/- 0.87 months). Histologic findings revealed poorly differentiated carcinoma in patients in Group A, moderately differentiated carcinoma in those in Group B, and well differentiated carcinoma in those with long survival in Group C and anaplastic carcinoma in those with short survival in Group C.


[Measurement of inflammatory activity in chronic rheumatism by blood pretein levels].
Seventy six patients with chronic inflammatory rheumatism were treated with various non-steroid anti-inflammatory drugs for 5 to 7 days. The average variations of several serum proteins were studied. The variation of haptoglobin remained nil. Those of other serum proteins remained negative and significantly different from zero, distributed from the greatest to the smallest value of the degree of statistical significance as follow : ceruloplasmin (p < 0.0001), orosomucoide (p < 0.02), fibrinogen (p < 0.02) alpha-2-macroglobulin (p < 0.04) and alpha-1-antitrypsin (p < 0.05). The study of the partial results showed the variability of the degree of significance of the serum proteins in relation to the non-steroid anti-inflammatory drugs. The practical interest of these serum protein seemed low to measure in the short term, the efficacy of non-steroid anti-inflammatory drugs. Their interest in long term studies remains to be demonstrated compared with that of the measurement of the sedimentation rate by the technic of the sigma E.S.R.


The Columbia-Suicide Severity Rating Scale (C-SSRS): Has the "Gold Standard" Become a Liability?
The Columbia- Suicide Severity Rating Scale has become the gold standard for the assessment of suicidal ideation and behavior in clinical trials. Criticism of the instrument has been mounting. We examine whether the instrument meets widely accepted psychometric standards and maps to the United States Food and Drug Administration's most recent 2012 algorithm for assessment of suicidal phenomena. Our goal is to determine if the Columbia-Suicide Severity Rating Scale should be retained as the preferred instrument for assessment of suicidal ideation and behavior. Standard psychometric criteria dictate that categorizations to avoid type I and type II errors should be comprehensive and address the full spectrum (i.e., all dimensions) of a phenomenon. The criteria should also be well defined and consistent, and the wording throughout should be unambiguous. We examine the Columbia-Suicide Severity Rating Scale in terms of these criteria. The Columbia-Suicide Severity Rating Scale does not address the full spectrum of suicidal ideation or behavior. As a result, it has the potential to miss many combinations of suicidal ideation and behavior that present to clinicians in practice (type II error). Potential misclassifications (type I and II errors) are compounded by flawed navigation instructions; mismatches in category titles, definitions, and probes; and wording that is susceptible to multiple interpretations. Further, the Columbia-Suicide Severity Rating Scale in its current form does not map to the 2012 Food and Drug Administration's draft classification algorithm for suicidal ideation and behavior. The evidence suggests that the Columbia-Suicide Severity Rating Scale is conceptually and psychometrically flawed and does not map to the Food and Drug Administration's new standards. A new gold standard for assessment of suicidality may be warranted.


The Impact of EBM-Manufactured Ti6Al4V ELI Alloy Surface Modifications on Cytotoxicity toward Eukaryotic Cells and Microbial Biofilm Formation.
Electron beam melting (EBM) is an additive manufacturing technique, which allows forming customized implants that perfectly fit the loss of the anatomical structure of bone. Implantation efficiency depends not only on the implant's functional or mechanical properties but also on its surface properties, which are of great importance with regard to such biological processes as bone regeneration or microbial contamination. This work presents the impact of surface modifications (mechanical polishing, sandblasting, and acid-polishing) of EBM-produced Ti6Al4V ELI implants on essential biological parameters. These include wettability, cytotoxicity toward fibroblast and osteoblast cell line, and ability to form biofilm by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Obtained results indicated that all prepared surfaces exhibited hydrophilic character and the highest changes of wettability were obtained by chemical modification. All implants displayed no cytotoxicity against osteoblast and fibroblast cell lines regardless of the modification type. In turn, the quantitative microbiological tests and visualization of microbial biofilm by means of electron microscopy showed that type of implant's modification correlated with the species-specific ability of microbes to form biofilm on it. Thus, the results of the presented study confirm the relationship between such technological aspects as surface modification and biological properties. The provided data are useful with regard to applications of the EBM technology and present a significant step towards personalized, customized implantology practice.


Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury.
No FDA approved pharmacological therapy is available that would reduce cell death following traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective agonist of alpha-2 adrenergic receptors and has demonstrated neuroprotective effects in hippocampal slice cultures undergoing direct impact. However, no one has tested whether Dex, in addition to its sedative action, has neuroprotective effects in an animal model of TBI. Thus, in the present study, we investigated the effects of Dex on an animal model of TBI. Mice received different doses of Dex (1, 10, or 100 µg/kg bodyweight, n = 10 each group) or saline as control at 1 hour and 12 hours following TBI. The mice treated with Dex lost less cortical tissue than the control mice. Further analysis found that Dex treatment reduced cell death in the cortex and the hippocampus measured by Fluoro-Jade B (FJB) staining, prevented axonal degeneration detected by immunostaining with antibody against β-amyloid precursor protein (β-APP), and protected synapses from elimination with synaptophysin staining. Taken together, in an in vivo murine model of TBI, Dex at the dose of 100 µg/kg not only prevented tissue lesion and cell death, but also reduced axonal injury and synaptic degeneration caused by TBI.


Prevalence and Associated Factors of Diabetes Mellitus Type 2 Among Tuberculosis Patients in Muscat, Oman, 2017-2020.
Diabetes mellitus (DM) and tuberculosis (TB) are global public health concerns and leading causes of mortality and morbidity worldwide. Coinfection is known to complicate TB control and outcomes. However, there is no national study regarding the prevalence of DM among TB patients in Oman. The objective of the current study was to assess the prevalence of DM and its associated factors among TB patients in Muscat, Oman. We conducted an analytical cross-sectional study using secondary data from the electronic system of the Ministry of Health (Al-Shifa 3+). It includes all adult TB patients in Muscat, from 2017-2020. Sociodemographic data, clinical characteristics, and comorbidities of TB patients were collected. SPSS with 95% CI and p-value ≤ 0.05 was used for statistical analysis. Of 426 TB cases, the prevalence of DM was 27.0%. The associated factors of DM were age group 40-54 years (odds ratio (OR) = 9.08, 95% CI: 4.16-19.84) and ≥ 55 years (OR = 11.35, 95% CI: 5.19-24.82), male (OR = 2.35, 95% CI: 1.45-3.81), being married (OR = 13.18, 95% CI: 4.72-36.84), being employed (OR = 2.30, 95% CI: 1.19-4.47), and Bangladeshi (OR = 7.08, 95% CI: 2.50-20.12) or Indian (OR = 6.14, 95% CI: 2.40-15.70) nationality. The absence of Bacillus Calmette-Guérin scar (OR = 2.06, 95% CI: 1.19-3.56), death (OR = 7.08, 95% CI: 1.26-7.82), and cured after TB treatment (OR = 3.02, 95% CI 1.71-5.31) showed significant association. Also, smoking (OR = 2.93, 95% CI: 1.81-4.76), drinking alcohol (OR = 1.79, 95% CI: 1.10-2.91), hypertension (OR = 10.45, 95% CI: 5.29-20.64), heart disease (OR = 8.50, 95% CI: 1.69-42.77), and renal disease (OR = 4.84, 95% CI: 1.71-13.64) contributed to the study's comorbidities. Old age (adjusted OR = 2.30, 95% CI: 1.72-3.06) and hypertension (adjusted OR = 5.21, 95% CI: 2.28-11.87) were found to be predictors of DM among TB patients. The prevalence of DM among TB patients in Muscat is high. Integrated systematic bidirectional TB-DM screening is needed. Furthermore, special attention is required for associated factors when managing these comorbidities.


Prenatal Imaging Diagnosis of Suprarenal Lesions.
Prenatal suprarenal lesions represent diverse pathologies. This study investigated prenatal imaging features and regression patterns associated with specific lesion diagnoses. This is a multicenter retrospective review of fetuses with prenatally diagnosed suprarenal lesions between 2001 and 2019. Prenatal ultrasound and MRI characteristics, postnatal imaging, and clinical course were reviewed. Prenatal imaging findings were compared by the most common diagnoses and regression patterns. Forty-four fetuses were prenatally diagnosed with suprarenal lesions. Diagnoses included pulmonary sequestration (n = 12; 27.3%), adrenal hemorrhage (n = 12; 27.3%), upper quadrant cyst (including 2 duplication cysts, 1 splenic cyst, and 3 indeterminate cysts), neuroblastoma (n = 4), adrenal hyperplasia (n = 3), bilateral adrenal calcifications (n = 1), and indeterminate lesions (n = 6). Sequestrations were uniformly left-sided (100 vs. 50%; p = 0.014) and diagnosed earlier in gestation than adrenal hemorrhages (p = 0.025). Sequestrations were also significantly more likely to have a prenatal feeding vessel (p = 0.005), low T1 MRI signal (p = 0.015), and no MRI blood products (p = 0.018) compared to adrenal hemorrhages. When comparing all 44 patients, a prenatal feeding vessel and low T1 signal on prenatal MRI were significantly associated with lesion persistence (p = 0.003; p = 0.044). Imaging findings on prenatal ultrasound and MRI aid in the diagnosis of suprarenal lesions, including differentiating pulmonary sequestrations and adrenal hemorrhages.


Suppression of cytotoxic T cell induction in vivo by prodigiosin 25-C.
Prodigiosin 25-C (PrG25-C) was discovered as an immunosuppressant in the course of our screening for immunomodulating substances. In this system, PrG25-C inhibited T lymphocytes proliferation and was less suppressive against B lymphocytes. PrG25-C was also a powerful inhibitor of cytotoxic T cell induction by mixed lymphocyte reaction and completely suppressed induction of H-2 specific cytotoxic cells at 12.7 nM. PrG25-C also inhibited in vivo induction of H-2 restricted cytotoxic T lymphocytes at a dose of 0.5 mg/kg but had little myelotoxicity because numbers of blood leukocytes and splenocytes of PrG25-C-treated mice were comparable to those of nonsensitized mice. No inhibitory effects of PrG25-C were observed on the production of anti-SRBC antibody. These results indicate that PrG25-C is a T-lymphocyte-specific immunosuppressant.


Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome.
Andersen-Tawil syndrome is a skeletal and cardiac muscle disease with developmental features caused by mutations in the inward rectifier K+ channel gene KCNJ2. Patients harboring these mutations exhibit extremely variable expressivities. To explore whether these mutations can be correlated with a specific patient phenotype, we expressed both wild-type (WT) and mutant genes cloned into a bi-cistronic vector. Functional expression in human embryonic kidney 293 cells showed that none of the mutant channels express current when present alone. When co-expressed with WT channels, only construct V302M-WT yields inward current. Confocal microscopy fluorescence revealed three patterns of channel expression in the cell: 1) mutations D71V, N216H, R218Q, and pore mutations co-assemble and co-localize to the membrane with the WT and exert a dominant-negative effect on the WT channels; 2) mutation V302M leads to channels that lose their ability to co-assemble with WT and traffic to the cell surface; 3) deletions Delta 95-98 and Delta 314-315 lead to channels that do not traffic to the membrane but retain their ability to co-assemble with WT channels. These data show that the Andersen-Tawil syndrome phenotype may occur through a dominant-negative effect as well as through haplo-insufficiency and reveal amino acids critical in trafficking and conductance of the inward rectifier K+ channels.


Binocular vision and foraging in ducks, geese and swans (Anatidae).
Wide variation in visual field configuration across avian species is hypothesized to be driven primarily by foraging ecology and predator detection. While some studies of selected taxa have identified relationships between foraging ecology and binocular field characteristics in particular species, few have accounted for the relevance of shared ancestry. We conducted a large-scale, comparative analysis across 39 Anatidae species to investigate the relationship between the foraging ecology traits of diet or behaviour and binocular field parameters, while controlling for phylogeny. We used phylogenetic models to examine correlations between traits and binocular field characteristics, using unidimensional and morphometric approaches. We found that foraging behaviour influenced three parameters of binocular field size: maximum binocular field width, vertical binocular field extent, and angular separation between the eye-bill projection and the direction of maximum binocular field width. Foraging behaviour and body mass each influenced two descriptors of binocular field shape. Phylogenetic relatedness had minimal influence on binocular field size and shape, apart from vertical binocular field extent. Binocular field differences are associated with specific foraging behaviours, as related to the perceptual challenges of obtaining different food items from aquatic and terrestrial environments.


Biomaterial implants induce the inflammation marker CRP at the site of implantation.
Following implantation of biomaterial patches into the gastrointestinal tract, we analyzed the host's response towards the foreign material. Asymmetric patches of polydioxanone covered Vicryl or poly-3-hydroxybutyrate were sutured onto the rat stomach. Tissue samples were generated at distinct time intervals after surgery, and RNA profiles were compared by Differential Display. RT-PCR analysis of gene candidates that seemed differentially expressed showed that vitamin D binding protein mRNA was induced in stomach tissue after implantation of the biomaterial patches. In parallel, the amount of C-reactive protein mRNA was found to be increased transiently as well. Implants induce a tissue response that is specific for a given material.


At risk drinking in primary care: report from a survey in Sao Paulo, Brazil.
This article describes the prevalence of at risk drinking among patients attending the primary health care sector in the city of Sao Paulo, Brazil. Five percent of the screened population answered positively to two or more questions on the CAGE questionnaire; 12% of male and 3% of female subjects were considered to be at risk drinking. Patients socio-demographic characteristics were analysed by means of logistic models. Variables sex, age, employment status and years living in Sao Paulo had significant effects on the risk of being a CAGE high-scorer.


Dynamic kinetic resolution of secondary alcohols combining enzyme-catalyzed transesterification and zeolite-catalyzed racemization.
Hydrophobic zeolite beta containing low concentrations of Zr or Al was found to be a good catalyst for the racemization of 1-phenylethanol. The formation of styrene as a side product could be minimized by reducing the metal concentration in the zeolite beta. Combined with an immobilized lipase from Candida antarctica, the dynamic kinetic resolution of 1-phenylethanol to the (R)-phenylethylester can be achieved with high yield and selectivity. The reaction was best conducted in toluene as solvent at 60 degrees C, with higher temperatures leading to a loss in the enantioselectivity of the formed ester. By using high-molecular-weight acyl-transfer reagents, such as vinyl butyrate or vinyl octanoate, a high enantiomeric excess of the product esters of 92 and 98 %, respectively, could be achieved. This is attributed to a steric effect: the bulky ester is less able to enter the pore space of the zeolite catalyst where the active sites for racemization are localized. Close to 100 % conversion of the alcohol was achieved within 2 h. If the more common acyl donor, isopropenyl acetate, was used, the enantiomeric excess (ee) of the formed ester was only 67 %, and the reaction was considerably slower.


Early glucose normalization does not improve outcome in the critically ill trauma population.
Strict control of serum glucose in critically ill patients decreases morbidity and mortality. The objective of this study was to evaluate the effect of early normalization of glucose in our burn and trauma intensive care unit. From January 2002 to June 2005, 290 patients were admitted with serum glucose 150 mg/dL or greater and 319 patients with serum glucose less than 150 mg/dL. The patients with hyperglycemia were more severely injured and more often required operative intervention within the first 48 hours. The patients with hyperglycemia were at increased risk for infection and mortality. Of those 290 patients in the hyperglycemic cohort, 125 patients had early normalization of serum glucose, whereas 165 patients required more than 24 hours to normalize. The early normalization cohort was younger in mean age than the late group, but these 2 groups were similar in injury severity. Correspondingly, there was no difference in the rate of infection. Although hyperglycemia on admission appears to correlate with a worse outcome, early glucose normalization did not affect morbidity and mortality in our critically ill population.


Assessment of junior doctors' admission notes: do they follow what they learn?
To assess the completeness of history-taking and physical-examination notes of junior doctors at King Abdulaziz University Hospital per the approach they learned in medical school. In this retrospective study, we reviewed 860 admission notes written by 269 junior doctors (interns and residents) in an academic tertiary-care medical centre in Jeddah, Saudi Arabia, over a two-month period. Notes were evaluated for completeness using a checklist developed with reference to relevant medical textbooks. The checklist included 32 items related to history-taking and physical examination. Based on the review of the notes, checklist items were evaluated as complete, incomplete, not present, or not applicable according to set criteria. Data were analysed and summarised for information on the frequency and relative frequency of these types. The history items varied in completeness. At the high end, asking about chief complaint and duration, associated symptoms, aggravating and relieving factors, and conducting systemic review were marked 'complete' in 74.2%, 81.7%, 80.4%, and 79.7% of notes, respectively. At the low end, asking about previous episodes, allergies, medications, and family history were complete in 5.3%, 1.9%, 4.8%, and 2.9% of notes, respectively. All physical examination items were poorly documented, especially breast examination, which was 'not present' in 95.8% of the notes. Junior doctors' history and physical-examination notes are often incomplete and do not follow the approach taught in medical school. The reasons for this must be studied via focus-group discussions with junior doctors.


Microleakage of composite resin restoration in cavities prepared by Er,Cr:YSGG laser irradiation and etched bur cavities in primary teeth.
In this in vitro study, the surface alterations of enamel and dentin in cavities prepared by Er,Cr:YSGG laser irradiation was investigated by scanning electron microscopy and compared to the microleakage degree after composite resin restoration with etched bur cavities in human primary teeth. The results confirmed that laser cavity surface facilitated a good adhesion with the restorative materials; the acid etch step can be easily avoided with the laser treatment.


Menu labeling implementation in dine-in restaurants: the Public's knowledge, attitude and practices.
The practice of menu labeling is gaining popularity worldwide as a potential policy to reduce energy intake as a means to decrease the prevalence of obesity. So the purpose of the present study is to identify the knowledge, attitudes, and practices of adults regarding the implementation of menu labeling in dine-in restaurants. A cross sectional survey included 2020 male or female adults (aged ≥ 18 years old) participants was collected from two cities in the United Arab Emirates(UAE). The participants filled a validated questionnaire in public places in two cities. A chi-squared test was conducted to compare responses for differences in proportions. Most participants were knowledgeable about energy requirements for moderately active men (60%) and women (59%), but underestimated energy requirements for inactive adults (34%). The majority of the respondents favored the requirement to post calorie information on menus of dine-in restaurants at the point of purchase (76%). About half the respondents (48%) were more likely to visit restaurants with labeled menus. The results from this study may form the basis for future strategies in mandating calorie labeling of restaurant menu items in UAE. Menu labeling may be a useful policy tool for promoting appropriate caloric consumption.


Supplementation with Ashitaba (Angelica keiskei) Yellow Stem Exudate Prevents Aging-Induced Thrombotic Tendencies and Systemic Inflammation Without Affecting Body Weight Gain in Mice.
Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine and health supplement in Japan. Ashitaba yellow stem exudate (AYE) contains abundant chalcones and thus has the potential to treat and prevent many pathological states such as cancer, inflammation, obesity, diabetics, thrombosis, and hypertension. Levels of plasminogen activator inhibitor 1 (PAI-1), a key regulator of the fibrinolytic system, increase with age in mouse plasma. Therefore, we aimed to determine the effects of AYE on plasma thrombotic parameters in aging mice. Long-term (52 weeks) AYE supplementation significantly decreased age-induced increases of PAI-1 in mouse plasma. Supplementation with AYE decreased levels of the acute-phase and fibrinolytic protein plasma plasminogen, and significantly decreased those of tumor necrosis factor α. These results suggested that continuous intake of AYE throughout life decreases age-induced systemic inflammation and prevents thrombotic tendencies without affecting body weight gain in aged mice. Our findings showed that supplementing diets with AYE might help to prevent thrombotic diseases in elderly individuals.


Studies of an Fe9 tridiminished icosahedron.
The synthesis and structural characterization of a nonanuclear FeIII cage complex is reported. The nine iron centers in [Fe9(mu3-O)4(O3PPh)3(O2CCMe3)13] lie on the vertices of an incomplete icosahedron, with the P atoms of triphenylphosphonate at the other three vertices. The paramagnetic core therefore describes a tridiminished icosahedron. Magnetic studies suggest an S=1/2 ground state for the molecule. Analysis of exchange paths and the susceptibility data point to the interpretation that the cluster can be divided into two nearly decoupled sections: an {Fe6O3} section, with an S=0 ground state, in which three oxo-centered triangles bound a central triangle that is not oxo-centered; and an {Fe3O} triangle with S=1/2. The analysis of the susceptibility data leads to a Heisenberg model based on three significant antiferromagnetic exchange interactions, with values of 173.7 cm-1 in the {Fe3O} triangle, and 30.9 and 19.1 cm-1 within the {Fe6O3} section, while the exchange between them is <1 cm-1. With these assignments, the theoretical low-temperature differential susceptibility is also in very good agreement with measurements up to 50 T. Magnetic measurements in the milli-kelvin range reveal striking hysteresis loops and magnetization reversals associated with a Landau-Zener-Stückelberg (LZS) transition as enhanced by the occurrence of a phonon bottleneck.


Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression.
Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy.


UVA protection labeling and in vitro testing methods.
The importance of adequate UVA protection is apparent with improved understanding of UVA-induced skin damage. This has led to the development of new sunscreen ingredients. A number of regulatory bodies or experts from the industry and academia have proposed methods to assess the efficacy of sunscreens against UVA radiation. In addition different proposals have been made regarding the labeling for UVA protection. The purpose of this paper is to describe several in vitro methods for measuring UVA protection of sunscreen products and to consider their validity. The different proposals in terms of UVA labeling are also presented and discussed. This review illustrates the need for standardization of the measurement conditions and harmonization to convey to consumers the most appropriate information on UVA protection.


[Phosphorus magnetic resonance in studying energy metabolism in skeletal muscles].
The present study objective involved evaluation of possibilities of magnetic resonance spectroscopy with phosphorus (31P-MRS) in diagnosis of metabolic disorders of skeletal muscles in patients with intermittent claudication, chronic heart failure and varicose disease of the lower extremities. In 20 patients with intermittent claudication, 10 patients with chronic heart failure, 10 patients with varicose disease and 10 volunteers, 31P-MRS was performed with 1.5 T MR system (Magnetom SP 63, Siemens). The following parameters were computed: phosphorus-creatinine index, intracellular pH in calf muscle, and time of half-recovery of the phosphorus-creatinine index. At rest, the phosphorus-creatinine indexes were similar in all groups; pH values at rest did not vary either. During isotonic exercise the phosphorus-creatinine index in the control group remained uncharged. In patients with intermittent claudication, the phosphorus-creatinine index at peak of exercise was decreased by 26.1% (p < 0.001), in patients with varicose disease--by 25.6% (p < 0.001), in patients with chronic heart failure by 8% (p < 0.001). PCr recovery half-time was increased in all patients. The patient group with intermittent claudication showed a reverse correlation between the pressure index and the degree of phosphorus-creatinine index decrease. 31P-MRS makes it possible to carry out non-invasive diagnosis of energy metabolic disorders of skeletal muscles in patients with impaired peripheral hemodynamics.


[Association between aerobic capacity and quality of life in older adults in Colombia].
The objective of this study was to determine the association of aerobic capacity with health-related quality of life in 121 subjects using the modified Bruce protocol as a predictor of maximum oxygen consumption (VO2 maximum) and the SF-36 quality of life questionnaire. The average maximum VO2 was 26.56 ± 12.67 mL/kg/min for men and 25.36 ± 10.72 mL/kg/min for women. There was a significant association between sex and maximum VO2 (p = 0.018). Physical function and social function were the variables with the highest average values in the total sample, and aerobic capacity explained 15.3% of the physical function. In conclusion, low maximum VO2 was found in both sexes, and there was a significant association of maximum VO2 with physical function, physical performance, general health, vitality, and social function.


Dermoscopy for the Diagnosis of Creeping Hair Caused by Ingrowing Hair: A Case Report.
Creeping hair is a rare condition characterized by creeping eruption with a black line at the advancing end, mimicking cutaneous larva migrans. The condition is also referred to as cutaneous pili migrans, migrating hair, and embedded hair. A total of 52 cases have been reported since 1957 and most cases were published in English. Herein, we report a case in which creeping hair occurred in the iliac region and review the literature from 1957 to February 2021. A 35-year-old Chinese female presented with a black moving linear eruption that had migrated from the lower abdomen to the iliac region without causing any symptoms during a 3-year period. Cutaneous examination showed a 6.5-cm-long black linear lesion beneath the skin that was revealed to be a hair shaft. After removal of the hair, the eruption diminished and no recurrence occurred in 3 months of follow-up. The creeping hair that had migrated with its lower end forward was confirmed by observation under dematoscopy and light microscopy. A review of the literature revealed that creeping hair occurs most frequently in young and middle-aged patients and the reported cases are mainly from Asia. The top locations involve the foot. The causative hair includes head hair, beard, pubic hair, body hair, and one case of dog hair. A close-up examination and dermoscopic inspection are helpful for the diagnosis of creeping hair.


Prospective study of catheter-related infection during prolonged arterial catheterization.
Ninety-six arterial catheters from 75 different anatomical sites in 56 surgical ICU patients were studied prospectively to determine the rate of catheter-related infection associated with prolonged arterial catheterization (defined as greater than 96 h). Every 96 h, all catheters were semiquantitatively (SQ) cultured and the percutaneous entry site was swab cultured. Sites were used indefinitely by exchanging the catheters over a guide-wire every 96 h as long as arterial monitoring was necessary and SQ cultures remained negative (less than or equal to 15 colonies). No sites used less than 96 h developed skin colonization, while 14/51 (27%) sites used greater than 96 h developed positive swab cultures. No SQ cultures were positive in sites with negative swab cultures (p less than .001). Catheter-related infection (a positive SQ culture) developed in 4/42 (9.5%) radial or femoral sites compared to 4/9 (44%) axillary sites used greater than 96 h (p less than .01). It is concluded that arterial catheter-related infection develops in less than 10% of radial or femoral sites used greater than 96 h, and 90% of radial and femoral sites may be used safely for prolonged periods if skin colonization at the percutaneous sites is controlled and SQ catheter cultures remain negative. Skin site swab cultures may be useful for determining when arterial catheters should be removed and SQ cultured.


Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities.
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer in the United States by 2025, with 5-year survival at less than 10%. In other recalcitrant cancers, immunotherapy has shown unprecedented response rates, including durable remissions after drug discontinuation. However, responses to immunotherapy in PDAC are rare. Accumulating evidence in mice and humans suggests that this remarkable resistance is linked to the complex, dueling role of the immune system in simultaneously promoting and restraining PDAC. In this review, we highlight the rationale that supports pursuing immunotherapy in PDAC, outline the key barriers that limit immunotherapy efficacy, and summarize the primary preclinical and clinical efforts to sensitize PDAC to immunotherapy.


Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation.
Sulfation is a common final step in the biotransformation of xenobiotics and is traditionally associated with inactivation. However, the sulfate group is electron-withdrawing and may be cleaved off heterolytically in some molecules, leading to an electrophilic cation. The stable heterologous expression of sulfotransferases in indicator cells of standard mutagenicity tests has substantially improved the accessibility of this activation pathway. Sulfotransferase-mediated genotoxic effects have been demonstrated for numerous benzylic alcohols derived from polycyclic aromatic hydrocarbons and various aromatic hydroxylamines. Also, hycanthone (a benzylic alcohol), alpha-hydroxytamoxifen (an allylic alcohol), 1'-hydroxysafrole (an allylic/benzylic alcohol), and 2-nitropropane are activated to genotoxicants by sulfotransferases. Various reactive sulfate conjugates show strong mutagenic effects only when they are generated directly within the indicator cell, due to their inefficient penetration of cell membranes. In other cases, secondary membrane-penetrating reactive species are formed from sulfuric acid esters by displacement reactions with medium components, such as chloride or amino acids. Reaction with water regenerates the alcohol, which becomes available for a new cycle of activation. Different sulfotransferases from the same species as well as related forms from rat and human differ in their substrate specificities and tissue distributions. These characteristics and reactivities of the sulfate conjugates formed may explain organotropic effects of the compounds activated via sulfotransferases.


Normalization of microarray data: single-labeled and dual-labeled arrays.
DNA microarray is a powerful tool for high-throughput analysis of biological systems. Various computational tools have been created to facilitate the analysis of the large volume of data produced in DNA microarray experiments. Normalization is a critical step for obtaining data that are reliable and usable for subsequent analysis such as identification of differentially expressed genes and clustering. A variety of normalization methods have been proposed over the past few years, but no methods are still perfect. Various assumptions are often taken in the process of normalization. Therefore, the knowledge of underlying assumption and principle of normalization would be helpful for the correct analysis of microarray data. We present a review of normalization techniques from single-labeled platforms such as the Affymetrix GeneChip array to dual-labeled platforms like spotted array focusing on their principles and assumptions.


Is the use of hypnotics, sedatives and minor tranquilizers really a major health problem?
An analysis has been made of individual purchases of hypnotics, sedatives and minor tranquilizers made during 1973 by patients who had bought such drugs either only once (group S, n= 417) or regularly (group R, n=76) during a 16-month period five years earlier from pharmacies in the town of Ostersund, county of Jmtland, Sweden. By 1973, 17% of the patients in each group had either died or moved out of the country and were therefore excluded from the comparison. In group S, 81 patients (23%) bought the above drugs once or more in 1973, while the corresponding figure for group R was 55 (87%). Compared with 1968-69, there was a decrease in the number of prescriptions and also in the number of tablets obtained per individual. Furthermore, the number of tablets per prescription was lower in 1973. Among the drugs prescribed, benzodiazepines dominated during both periods, followed by barbiturates. In 1973 there was a substantial increase in the use of nitrazepam, mostly at the expense of diazepam and combined products. One patient in group S and one in group R showed a tendency to decrease the interval between purchases. The latter was already known to be a drug abuser five years earlier. Without knowing the reason why the drugs were prescribed and to what extent they were actually taken, it is impossible to say whether the other patient should be classified as drug abuser or not. Although the number of patients in this study is limited, it might be concluded that the risk of an occasional user of hypnotics, sedatives and minor tranquilizers living in this area becoming an abuser of such drugs within a five-year period is less than 1/345.


Draft Genome Sequence of Citrobacter freundii Strain A47, Resistant to the Mycotoxin Deoxynivalenol.
Here, we present the draft genome sequence of Citrobacter freundii strain A47 with a length of 4,878,242 bp, which contains 4,357 putative protein coding genes, including 270 unique genes. This work is expected to assist in obtaining novel gene(s) that code for deoxynivalenol (DON) de-epoxidation enzyme(s).


Use of prescription drug samples and patient assistance programs, and the role of doctor-patient communication.
Cost-related underuse of medications is common among older adults, who seldom discuss medication costs with their physicians. Some older adults may use free drug samples or industry-sponsored patient assistance programs (PAP) in hopes of lowering out-of-pocket costs, although the long-term effect of these programs on drug spending is unclear. To examine older adults' use of industry-sponsored strategies to reduce out-of-pocket drug costs and the association between doctor-patient communication and use of these programs. Cross-sectional analysis of a 2006 nationally representative survey of Medicare beneficiaries. 14,322 community-dwelling Medicare beneficiaries age ≥65. We conducted bivariate and multivariate analyses of the association between receipt of free samples and participation in PAPs with sociodemographic characteristics, health status, access to care, drug coverage, medication cost burden, and doctor-patient communication. 51.4% of seniors reported receiving at least one free sample over the last 12 months and 29.2% reported receiving free samples more than once. In contrast, only 1.3% of seniors reported participating in an industry-sponsored PAP. Higher income respondents were more likely to report free sample receipt than low-income respondents (50.8% vs. 43.8%, p < 0.001) and less likely to report participating in a PAP (0.42% vs. 2.2%, p < 0.001). In multivariate analyses, those who reported talking to their doctor about the cost of their medications had more than twice the odds of receiving samples as those who did not (OR 2.17, 95% CI 1.95-2.42). In 2006, over half of seniors in Medicare received free samples, but only 1.3% reported receiving any medications from a patient assistance program. Doctor-patient communication is strongly associated with use of these programs, which has important implications for clinical care regardless of whether these programs are viewed as drivers of prescription costs or a remedy for them.


Development of a plaque assay for a cytopathic, rapidly replicating isolate of hepatitis A virus.
Most hepatitis A virus (HAV) replication in cell culture has been reported to be nonlytic and relatively slow. A rapidly replicating isolate of strain HM-175 from persistently infected, serially passed cell cultures (pHM-175) was found to induce a cytopathic effect. This observation allowed the development of a classic plaque assay for pHM-175 in FRhK-4 cells. The plaques were neutralized by polyclonal and monoclonal antisera to HAV.


Molecular Modelling reveals the inhibition mechanism and structure-activity relationship of curcumin and its analogues to Staphylococcal aureus Sortase A.
Previous studies found that the activity of Sortase A, a bacterial surface protein from Staphylococcus aureus, was inhibited by curcumin and its analogues. To explore this inhibitory mechanism, Sortase A and its inhibitors in complex systems were studied by molecular docking, molecular modelling, binding energy decomposition calculation and steered molecular dynamics simulations. Energy decomposition analysis indicated that PRO-163, LEU-169, GLN-172, ILE-182 and ILE-199 are key residues in Sortase A-inhibitor complexes. Furthermore, interactions between the methoxyl group on the benzene ring in the conjugated molecule (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and VAL-168, LEU-169 and GLN-172 induce the inhibitory activity based on the energy decomposition and distance analyses between the whole residues and inhibitors. However, because of its coiled structure, the non-conjugated molecule, tetrahydrocurcumin, with key residues in the binding sites of Sortase A, interacted weakly with SrtA, leading to the loss of inhibitory activity. Based on these results, the methoxyl group on the benzene ring in the conjugated molecule largely influenced the inhibitory activity of the Sortase A inhibitors.


Escape from T-cell targeting immunotherapies in acute myeloid leukemia.
Single-cell and spatial multimodal technologies have propelled discoveries of the solid tumor microenvironment (TME) molecular features and their correlation with clinical response and resistance to immunotherapy. Computational tools are incessantly being developed to characterize tumor-infiltrating immune cells and to model tumor immune escape. These advances have led to substantial research into T-cell hypofunctional states in the TME and their reinvigoration with T cell-targeting approaches, including checkpoint inhibitors (CPI). Until recently, we lacked a high-dimensional picture of the acute myeloid leukemia (AML) TME, including compositional and functional differences in immune cells between disease onset and post-chemotherapy or post-transplantation relapse, and the dynamic interplay between immune cells and AML blasts at various maturation stages. AML subgroups with heightened interferon (IFN)-g signaling were shown to derive clinical benefit from CD123 x CD3 bispecific DART molecules and CPI, whilst being less likely to respond to standard-of-care cytotoxic chemotherapy. In this Review, we first highlight recent progress into deciphering immune effector states in AML (including T-cell exhaustion and senescence), oncogenic signaling mechanisms that could reduce the susceptibility of AML cells to T cell-mediated killing and the dichotomous roles of type I and II IFN in anti-tumor immunity. In the second part, we discuss how this knowledge could be translated into opportunities to manipulate the AML TME with the aim to overcome resistance to CPI and other T-cell immunotherapies, building on recent success stories in the solid tumor field, and we provide an outlook for the future.


Temporal and spatial comparisons of the reproductive biology of northern Gulf of Mexico (USA) red snapper (Lutjanus campechanus) collected a decade apart.
In studies done a decade apart, we provide evidence of a recent shift toward a slower progression to sexual maturity as well as reduced egg production, especially among young, small female red snapper, in the Gulf of Mexico (Gulf). Slower maturation rates (among fish ≤6 years old), lower GSI values and decreased spawning frequency were observed, and were especially pronounced in the northwestern Gulf. Furthermore, an Index of Reproductive Importance showed that young fish (ages 2-7) are contributing far less to the spawning stock in recent years, while older fish (>8 years) are contributing more, when compared to fish from the same age groups sampled in the previous decade. Coincident with these changes in reproductive output, fishing pressure has steadily declined gulf-wide, and spawning stock biomass and spawning potential ratio have increased. Thus, it is possible that the age structure of the red snapper stock is becoming less truncated, or that reproductive effort observed is due to the temporary influence of recent strong year classes produced in 2004 and 2006 as they begin to reach full reproductive potential. If the latter is true, careful documentation of the stock's reproductive dynamics during a time of population growth provides new understanding at the meta-population spatial and decadal temporal scales. In contrast, if the former is true, a truncated age structure due to overharvest can limit the productivity of the Gulf red snapper stock. In addition, we have learned that red snapper females in the northwestern Gulf collected on natural reefs and banks have much higher reproductive output than those on artificial reefs in the form of standing and toppled oil and gas platforms, thus making the need to know the relative abundance of females found on these disparate habitats an important next step toward better-understanding factors impacting the reproductive dynamics of this species.


Increased cAMP levels in stimulated neutrophils inhibit their adhesion to human bronchial epithelial cells.
Bronchial epithelial cells express the intercellular adhesion molecule-1 that mediates binding of activated neutrophils via interaction with Mac-1 and/or leukocyte function-associated antigen-1. In this study, we examined whether increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) affected neutrophil adhesion to the human bronchial epithelial cells. It was found that the N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was concentration dependently inhibited when the cAMP analogs dibutyryl adenosine 3',5'-cyclic monophosphate or 8-bromoadenosine 3',5'-cyclic monophosphate were present. The beta-adrenergic receptor agonists isoprenaline and salmeterol, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), were also able to inhibit the fMLP-stimulated adhesion of neutrophils to bronchial epithelial cells. These agonists in combination with IBMX significantly increased the intracellular cAMP level in both neutrophils and epithelial cells. Preincubation of neutrophils with the long-acting beta2-adrenergic receptor agonist salmeterol (in the presence of IBMX) inhibited their fMLP-stimulated adhesion to epithelial cells, whereas pretreatment of epithelial cells did not influence the adhesion process. When ethanol-fixed epithelium was used, salmeterol pretreatment also diminished the adhesion of stimulated neutrophils. Moreover, combinations of salmeterol or isoprenaline with IBMX inhibited fMLP-upregulated Mac-1 expression. Therefore, we conclude from these data that elevation of intracellular cAMP in the neutrophil inhibits stimulated neutrophil adhesion to bronchial epithelial cells via Mac-1.


[A preliminary study on the changes of calcium (Ca) and phosphorus (P) contents in serum following intravenous administration of lead acetate (author's transl)].
We investigated the mechanisms of interaction between lead acetate (Pb-Ac) and bone minerals. One hundred and eighteen male rats were used and the following experiments were carried out: (1) determination of changes in serum Ca and P following intravenous injection of Pb-Ac or sodium acetate(Na-Ac) as the control for acetate, (2) to ascertain the deposition of lead at the calcifying site of bone immediately after Pb-Ac administration. The serum Ca and P levels increased with time after Pb-Ac administration and the maximum values were noted after 1 hour in Ca (17 mg%) and 30 minutes in P (13.5mg%), respectively. Both Ca and P levels reverted to the normal range within 12 hours. The net increasing rates in both Ca and P were calculated from each value in the Pb-Ac and Na-Ac groups. Those maximum rates were found immediately after the Pb-Ac administration (0 approximately 30 sec). At the same time, deposition of lead was evident at the calcifying site of bone and insicor dentine.


Relationship between sigma-like site and progesterone-binding site of adult male rat liver microsomes.
An increasing amount of evidence suggests that the sigma (sigma) sites, putative targets for a variety of psychotomimetic and antipsychotic drugs, exist not only in the brain but also in various peripheral organs. However, there are many ambiguities as to their biological roles, subcellular distributions, endogenous ligands and so on. We therefore performed our study for clarification of some of these ambiguities. As a result, we demonstrated that adult male rat liver microsomes, especially smooth endoplasmic reticulum, possessed a saturable haloperidol-binding site closely resembling the sigma site, with a high affinity (Kd 1.0 +/- 0.3 nmol/L) and high capacity (Bmax 9.3 +/- 1.5 pmol/mg protein) and with the rank order of affinity of the ligands: haloperidol > reduced haloperidol > clorgyline > ifenprodil > 1,3-di(2-tolyl)guanidine, (-)-butaclamol > GBR-12909 > SKF-525A > progesterone > 5 alpha-dihydrotestosterone > R(+)-3- (hydroxyphenyl)-N-propylpiperidine > testosterone >> corticosteroids, estradiol-17 beta, cholesterol and neuroactive compounds displaying high affinities for other neurotransmitter receptors such as dopamine D2, serotonin (5-HT1A and 5-HT2) and alpha 1-adrenergic and GABAA receptors. This rank order showed a high correlation (r = 0.908) with that of a large portion (approximately 85%) of specific progesterone-binding site (Kd 31.0 +/- 3.5 nmol/L, Bmax 5.7 +/- 0.2 pmol/mg protein) of the same source. Therefore, these two sites were suggested to be the same or closely related. Furthermore, we provide a strong suggestion that these sites neither are identical with some subforms of the microsomal cytochromes P-450 or other steroid/drug-metabolizing enzymes nor participate universally and directly in the progesterone-metabolizing processes.


Aberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instability.
To account for the accumulation of genomic alterations required for tumor progression, it has been suggested that the genomes of cancer cells are unstable and that this instability results from defective mutators (the "mutator phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators act as the mutators contributing to genomic instability, the present study, based on primary tumor tissues from 71 patients with breast cancer, was performed to determine whether there was an association between aberrant expression of cell-cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and chromosomal instability. Comparative genomic hybridization was used to measure chromosomal changes, reflecting genomic instability in individual tumors, whereas immunohistochemistry was used to detect aberrant expression of cell-cycle regulators. Overexpression of cyclin D1 was found to be significantly correlated with increased chromosomal instability (defined as harboring more than 7 chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05). Interestingly, this relationship was independent of cell outgrowth (as detected by the proliferation marker Ki-67) and was particularly significant in tumors not expressing p27 or in tumors with detectable RB1. These results suggest that cyclin D1 plays an alternative role in the regulation of genomic stability.


GluN3-Containing NMDA Receptors in the Rat Nucleus Accumbens Core Contribute to Incubation of Cocaine Craving.
Cue-induced cocaine craving progressively intensifies (incubates) after withdrawal from cocaine self-administration in rats and humans. In rats, the expression of incubation ultimately depends on Ca2+-permeable AMPARs that accumulate in synapses onto medium spiny neurons (MSNs) in the NAc core. However, the delay in their accumulation (∼1 month after drug self-administration ceases) suggests earlier waves of plasticity. This prompted us to conduct the first study of NMDAR transmission in NAc core during incubation, focusing on the GluN3 subunit, which confers atypical properties when incorporated into NMDARs, including insensitivity to Mg2+ block and Ca2+ impermeability. Whole-cell patch-clamp recordings were conducted in MSNs of adult male rats 1-68 d after discontinuing extended-access saline or cocaine self-administration. NMDAR transmission was enhanced after 5 d of cocaine withdrawal, and this persisted for at least 68 d of withdrawal. The earliest functional alterations were mediated through increased contributions of GluN2B-containing NMDARs, followed by increased contributions of GluN3-containing NMDARs. As predicted by GluN3-NMDAR incorporation, fewer MSN spines exhibited NMDAR-mediated Ca2+ entry. GluN3A knockdown in NAc core was sufficient to prevent incubation of craving, consistent with biotinylation studies showing increased GluN3A surface expression, although array tomography studies suggested that adaptations involving GluN3B also occur. Collectively, our data show that a complex cascade of NMDAR and AMPAR plasticity occurs in NAc core, potentially through a homeostatic mechanism, leading to persistent increases in cocaine cue reactivity and relapse vulnerability. This is a remarkable example of experience-dependent glutamatergic plasticity evolving over a protracted window in the adult brain.SIGNIFICANCE STATEMENT "Incubation of craving" is an animal model for the persistence of vulnerability to cue-induced relapse after prolonged drug abstinence. Incubation also occurs in human drug users. AMPAR plasticity in medium spiny neurons (MSNs) of the NAc core is critical for incubation of cocaine craving but occurs only after a delay. Here we found that AMPAR plasticity is preceded by NMDAR plasticity that is essential for incubation and involves GluN3, an atypical NMDAR subunit that markedly alters NMDAR transmission. Together with AMPAR plasticity, this represents profound remodeling of excitatory synaptic transmission onto MSNs. Given the importance of MSNs for translating motivation into action, this plasticity may explain, at least in part, the profound shifts in motivated behavior that characterize addiction.


A Preclinical Study of Cell-seeded Tubularized Scaffolds Specially Secreting LL37 for Reconstruction of Long Urethral Defects.
We constructed a new artificial, long tubular acellular matrix, seeded with autologous progenitor cells transfected with the sequence to produce the antibiotic peptide LL37 and another two common seeding cells, which might be adopted for patients requiring repair of long segment of the urethra. Autologous endothelial progenitor cells transfected by lentiviral vectors expressing antibiotic peptide LL37, as well as urothelial and smooth muscle cells from New Zealand white male rabbits, were cultured and seeded onto preconfigured acellular collagen-based tubular matrices (3 cm in length). Artificial conduits were created again in New Zealand white male rabbits and, then, evaluated by immunohistochemistry after 8 weeks. Cell-seeded tubularized collagen scaffolds were found to be effective in repairing long urethral defects, whereas scaffolds without cells led to poor tissue development and structures. The artificial tissue engineered tubularized scaffolds combined with genetic methods resulted in vascularized autologous grafts, which may potentially be used for urethroplasty in patients requiring repair of a long segment of the urethra.


Impacts of variation in the human genome on gene regulation.
Recent advances in fast and inexpensive DNA sequencing have enabled the extensive study of genomic and transcriptomic variation in humans. Human genomic variation is composed of sequence and structural changes including single-nucleotide and multinucleotide variants, short insertions or deletions (indels), larger copy number variants, and similarly sized copy neutral inversions and translocations. It is now well established that any two genomes differ extensively and that structural changes constitute a prominent source of this variation. There have also been major technological advances in RNA sequencing to globally quantify and describe diversity in transcripts. Large consortia such as the 1000 Genomes Project and the ENCODE (ENCyclopedia Of DNA Elements) Project are producing increasingly comprehensive maps outlining the regions of the human genome containing variants and functional elements, respectively. Integration of genetic variation data and extensive annotation of functional genomic elements, along with the ability to measure global transcription, allow the impacts of genetic variants on gene expression to be resolved. There are several well-established models by which genetic variants affect gene regulation depending on the type, nature, and position of the variant with respect to the affected genes. These effects can be manifested in two ways: changes to transcript sequences and isoforms by coding variants, and changes to transcript abundance by dosage or regulatory variants. Here, we review the current state of how genetic variations impact gene regulation locally and globally in the human genome.


Cu-Catalyzed Hydrocarbonylative C-C Coupling of Terminal Alkynes with Alkyl Iodides.
A Cu-catalyzed hydrocarbonylative C-C coupling of terminal alkynes with unactivated alkyl iodides has been developed, enabling highly chemo- and regioselective synthesis of unsymmetrical dialkyl ketones. A variety of functional groups are tolerated, and both primary and secondary alkyl iodides react well. An autotandem sequence of two Cu-catalyzed processes is proposed: first hydrocarbonylative coupling of the alkyne and the alkyl iodide, followed by reduction of the intermediate unsaturated ketone to the saturated product. Mechanistic experiments indicate that an alkenylcopper intermediate activates the alkyl iodide by single electron transfer to enable a radical carbonylation pathway.


Mechanoresponsive Behavior of a Polymer-Embedded Red-Light Emitting Rotaxane Mechanophore.
A red light-emitting photoluminescent supramolecular mechanophore based on an interlocked molecular motif is presented. The rotaxane-based mechanophore contains a cyclic compound featuring a π-extended 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye as a red emitter that was threaded onto a dumbbell-shaped molecule containing an electron-poor 1,4,5,8-naphthalenetetracarboxylic diimide quencher at its center. Through two aliphatic hydroxyl groups attached to the dumbbell and the cycle, the mechanophore was covalently embedded into the backbone of a thermoplastic polyurethane elastomer. The mechanophore is only weakly photoluminescent in solution, indicating that the BODIPY's emission is efficiently quenched. Solution-cast films of the rotaxane-containing polymer, by contrast, show an appreciable photoluminescence, which suggests that during film formation, some of the emitting cycles are trapped in positions away from the quencher. Interestingly, the emission intensity could be significantly reduced by swelling the films with an organic solvent and the emission increased again upon drying, suggesting that such solvent plasticization causes a reversible rearrangement. In both dry and solvent-swollen films, uniaxial deformation caused a significant, reversible increase of the emission intensity, on account of mechanically induced shuttling of the emitters away from and back to the quenchers. It is shown that the properties of the polymer can be tuned by the solvent, and that such plasticizing extends the small palette of approaches that allow modification of the activation stress of a given material system.


Costs of multiple sclerosis in Panama from societal, patient perspectives and health-related quality of life.
The purpose of this work is to estimate the costs associated with managing patients with MS in Panama and evaluating the impact of the disease on their health-related quality of life (HRQoL). Multicentric observational, retrospective, cross-sectional study. The costs were estimated from societal and patient perspectives and expressed in USD, 2015. The focus of the study is based on prevalence and on a "bottom-up" approach. To estimate the total cost per patient, annual reported use for each resource was multiplied by its unit cost. To evaluate HRQoL, patients completed the EQ-5D-3L questionnaire. 108 patients took part in the study. 82.41% were women with 44.78 (SD: 12.27) years. 61.11% presented mild (EDSS = 0-3.5), 25.93% moderate (EDSS = 3.5-6) and 12.96%, severe disability (EDSS≥6.5). The mean annual cost from the patient's perspective was estimated at 777.99 USD (SD: 1,741.45) per patient. The mean cost from a societal perspective was estimated at 23,803.21 USD (SD: 13,331.83) per patient. Disease-modifying therapies (DMT) accounted for the main component of the cost. A deterioration in HRQoL was observed as the disease advances and as disability increases, with mobility and usual activities being the areas most affected by its progression. From both perspective, the cost per MS patient in Panama is high. In addition to the high economic impact, MS also exerts a negative impact on patient HRQoL, which increases as the disease advances.


Autologous unpurged bone marrow transplantation for acute non-lymphoblastic leukaemia in first complete remission.
Twenty-five patients with acute non-lymphoblastic leukemia (ANLL) in first complete remission underwent autologous bone marrow transplantation (ABMT) between March 1984 and March 1988. The high-dose therapy employed included cyclophosphamide followed by total body irradiation (10 Gy), administered as a single dose. The median time from complete remission to ABMT was 5 months (range 2-9 months). Thirteen (52%) patients remain in complete remission 10-51 months (median 25 months) after ABMT and 14-60 months (median 32 months) after achieving complete remission. Causes of death were recurrent leukemia (five patients), parenchymal toxicities (acute respiratory distress syndrome, veno-occlusive disease) (three patients), cerebral haemorrhage (one patient), cerebral aspergillosis (one patient) and viral hepatitis (one patient). Six patients relapsed at a median of 5 months after ABMT (range 4-10 months). In conclusion, this study has resulted in survival data comparable to those of other institutions and the best reported outcomes of conventional chemotherapy.


Myhre Syndrome Misdiagnosed as Marfan Syndrome: an Educational Presentation.
A 32-month-old girl with patent ductus arteriosus, false tendon of left ventricle, mild pulmonary hypertension, and chronic cardiac insufficiency (cardiac function level I-II) was misdiagnosed with Marfan Syndrome and there was no improvement in her physical growth after operation for this disease. The preterm baby was finally diagnosed with Myhre Syndrome by clinical phenotypes and mutation of SMAD4 gene.


Inertial measurement unit-based pose estimation: Analyzing and reducing sensitivity to sensor placement and body measures.
Inertial measurement units have been proposed for automated pose estimation and exercise monitoring in clinical settings. However, many existing methods assume an extensive calibration procedure, which may not be realizable in clinical practice. In this study, an inertial measurement unit-based pose estimation method using extended Kalman filter and kinematic chain modeling is adapted for lower body pose estimation during clinical mobility tests such as the single leg squat, and the sensitivity to parameter calibration is investigated. The sensitivity of pose estimation accuracy to each of the kinematic model and sensor placement parameters was analyzed. Sensitivity analysis results suggested that accurate extraction of inertial measurement unit orientation on the body is a key factor in improving the accuracy. Hence, a simple calibration protocol was proposed to reach a better approximation for inertial measurement unit orientation. After applying the protocol, the ankle, knee, and hip joint angle errors improved to 4 . 2 ∘ , 6 . 3 ∘ , and 8 . 3 ∘ , without the need for any other calibration. Only a small subset of kinematic and sensor parameters contribute significantly to pose estimation accuracy when using body worn inertial sensors. A simple calibration procedure identifying the inertial measurement unit orientation on the body can provide good pose estimation performance.


Regulation of liver regeneration.
Hepatocyte regeneration proceeds along a sequence of distinctive phases and results in a precise reconstitution of the lost tissue mass. The molecular mechanisms regulating liver regeneration have recently been elucidated. Important aspects of the regulatory steps of hepatocyte proliferation during regeneration are summarized. Hepatocytes normally remain in proliferative quiescence. Regeneration requires priming of hepatocytes to achieve competence for proliferation. This is the initiation phase, which is regulated by cytokines, including interleukin-6 and tumour necrosis factor-alpha. During the subsequent proliferation, the hepatocyte population is expanded (the expansion phase), it being chiefly regulated by hepatocyte growth factor and transforming growth factor-alpha. Upon sensing of the required cell mass, the proliferation response is terminated (termination phase) and is mainly mediated by transforming growth factor-beta and activins. These structured processes go in line with a remodelling response, resulting in the reconstruction of a vascularized liver lobule. Liver regeneration proceeds in a highly ordered fashion, critical steps being regulated by several molecular mechanisms acting in a characteristic timely sequence.


Estimating Lean Body Weight in Adults With the PAWPER XL-MAC Tape Using Actual Measured Weight as an Input Variable.
Introduction Accurate drug dose calculation in obese patients requires an estimation of lean body weight (LBW) for dosing hydrophilic medications. Inaccurate weight estimates during the management of critically ill obese adults may contribute to inaccurate drug doses and consequential poor outcomes. Existing methods of LBW estimation or measurement may be very difficult or impossible to use during emergency care. A point-of-care model that could provide rapid, accurate estimates of LBW would, therefore, be of significant clinical value. Methods A model was derived based using the adult version of the PAWPER XL-MAC tape. This derived model used recumbent length and measured total body weight (TBW) to estimate LBW. The derived model was used to generate LBW estimations in a random sample from National Health and Nutrition Examination Survey (NHANES) datasets (n=33,215). The benchmark outcome measure was to achieve >95% of LBW estimations within 20% of DXA-measured fat-free mass (P20>95%) and >70% of estimations within 10% of DXA-measured fat-free mass (P10>70%). Results The new model achieved a P20 of 99.7% and a P10 of 86.4% for LBW in the pooled sample and exceeded the minimum accuracy standards. This accuracy was maintained in both sexes, all ages, all ethnic groups, all lengths and in all habitus types. Conclusions The modified PAWPER XL-MAC model, using TBW as an input variable, proved to be an accurate method of LBW estimation. It could potentially have an important role in facilitating emergency drug dose calculations in critically ill or injured obese adult patients.


[Progress on detection and analysis method of endocrine disrupting compounds].
EDCs are new generation of environmental pollutions which are globally concerned. They may cause adverse effect mainly to the endocrine system and nervous system, etc. To assess the EDCs' hazard to the health exactly, we should know about the distribution and level of EDCs in the environment. In this paper, the technique of pretreatment in different matrices, the method of detection and analysis about EDCs were reviewed, and the future's prospect on the study of detection and analysis method were talked about also.


Variation and information in white blood cell differential counts.
The magnitude and sources of variation in the white blood cell (WBC) count and differential count affect their information content and clinical value. This study describes components of variation in the WBC count and differential, estimates the magnitude of each component, and uses computer simulations to compare the information conveyed by the total WBC count and by the WBC differential count, expressed as the number of each type of cell and as the percentage of each cell type. Biologic variation is much greater than statistical sampling variation in differential WBC counts, even when a relatively small number of cells is classified. The commonly reported neutrophil percentage is inferior both to the neutrophil count and to the total WBC count in its ability to detect neutrophilia and to detect recovery from elevated levels. This conclusion holds for single as well as for sequential WBC differential determinations and regardless of the level of test result at which the clinician considers disease to be present. The total WBC count and the neutrophil count differ little in performance, so a neutrophilic patient's return to normal levels can safely be detected and monitored by relying on the less expensive total WBC count and foregoing repeated requests for differential counts.


Noninvasive three-state sleep-wake staging in mice using electric field sensors.
Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were attached to the exterior of each chamber to record respiration and other movement simultaneously with EEG, EMG, and video. A sleep-wake scoring method based on EF sensor data was developed with reference to EEG/EMG and then validated by three expert scorers. Additionally, novice scorers without sleep-wake scoring experience were self-trained to score sleep using only the EF sensor data, and results were compared to those from expert scorers. Lastly, ability to capture three-state sleep-wake staging with EF sensors attached to traditional mouse home-cages was tested. EF sensors quantified wake, rapid eye movement (REM) sleep, and non-REM sleep with high agreement (>93%) and comparable inter- and intra-scorer error as EEG/EMG. Novice scorers successfully learned sleep-wake scoring using only EF sensor data and scoring criteria, and achieved high agreement with expert scorers (>91%). When applied to traditional home-cages, EF sensors enabled classification of three-state (wake, NREM and REM) sleep-wake independent of EEG/EMG. EF sensors score three-state sleep-wake architecture with high agreement to conventional EEG/EMG sleep-wake scoring 1) without invasive surgery, 2) from outside the home-cage, and 3) and without requiring specialized training or equipment. EF sensors provide an alternative method to assess rodent sleep for animal models and research laboratories in which EEG/EMG is not possible or where noninvasive approaches are preferred.


Temporal response of post-activation performance enhancement induced by a plyometric conditioning activity.
To better understand the post-activation performance enhancement (PAPE) effect promoted by a plyometric conditioning activity (CA), the aim of this study was to investigate the temporal response of PAPE after a plyometric CA. Fourteen healthy and active adults visited the laboratory 3 times, with an interval of 7 days between each visit. On the first day they were familiarized with the countermovement jump (CMJ) test and plyometric CA. In the second and third visits, participants performed either plyometric CA or control (remaining seated) in a crossover design. The CMJ test was performed pre and 1-, 3-, 6-, and 9-min post the plyometric CA or control. The comparisons were performed using the repeated measure two-factor ANOVA and Bonferroni adjustment (significance level adopted P ≤ 0.05). Time (P < 0.01), condition (P < 0.01), and interaction (P < 0.01) effects were reported for CMJ comparisons. For the control condition, CMJ increased at 3 min compared to pre (P = 0.03) and at 3 min compared to 1 min (P = 0.03). For the plyometric CA, CMJ increased at 1- (P < 0.01), 3- (P < 0.01), and 6-min (P = 0.02) compared to pre. For condition comparisons, CMJ was different at 1- (P < 0.01), 3- (P < 0.01), 6- (P < 0.01), and 9-min (P = 0.02). The Effect size of the comparisons of all moments compared to pre was null (d < 0.20) for control and small (d < 0.50) for plyometric CA. It is possible to conclude that the plyometric CA promoted a PAPE effect for up to 9-min. Strength and conditioning coaches and practitioners may consider multiple sets of plyometric CA to produce immediate enhancement of power in the lower limbs.


Implementation of TeamSTEPPS in the emergency department.
Team training and practice is an essential part of emergency department workflow. TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) is a teamwork and communication systems model that has the potential to improve patient safety while also addressing aspects of staff satisfaction and morale. This article describes the experience of one emergency department's implementation of TeamSTEPPS, with a focus on methods of training faculty and staff, progression of implementation over a period of time, and evaluation of the process with recommendations for future growth. Background, history, and specific tools used within the department are described, with an emphasis on "briefs," "huddles," and "debriefs" or team "wrap-ups."


Utilisation of corn (Zea mays) bran and corn fiber in the production of food components.
The milling of corn for the production of food constituents results in a number of low-value co-products. Two of the major co-products produced by this operation are corn bran and corn fiber, which currently have low commercial value. This review focuses on current and prospective research surrounding the utilization of corn fiber and corn bran in the production of potentially higher-value food components. Corn bran and corn fiber contain potentially useful components that may be harvested through physical, chemical or enzymatic means for the production of food ingredients or additives, including corn fiber oil, corn fiber gum, cellulosic fiber gels, xylo-oligosaccharides and ferulic acid. Components of corn bran and corn fiber may also be converted to food chemicals such as vanillin and xylitol. Commercialization of processes for the isolation or production of food products from corn bran or corn fiber has been met with numerous technical challenges, therefore further research that improves the production of these components from corn bran or corn fiber is needed.


[Hypothyroid myopathy in a young adult].
We describe here the case of a young man admitted to our department for asthenia and diffuse myalgia. Because of persistently increasing aminotransferase levels over the preceding 2 years, he had undergone a number of diagnostic procedures to evaluate liver function. On admission to our department, the patient suffered from asthenia, myalgia, notable hair loss and sinus bradycardia. Laboratory examinations confirmed severe primary hypothyroidism with high serum levels of aminotransferase, aldolase and creatine-phosphokinase attributable to thyroprivic myopathy. The thyroid deficit was caused by autoimmune atrophic thyroiditis. Treated with levothyroxine, the patient recovered fully from his illness, his normal metabolic state was restored, and his serum aminotransferase level returned to normal.


Iron status of adults in the capital area of Finland.
Enrichment of wheat flour with iron, which commenced in Finland in the mid-1970s, ceased in 1994. No data on iron status among adults have been published since 1993. To assess the iron status, adequacy of iron intake and dietary sources of iron in Finnish adults. A random sample of adults aged 25-64 years in the capital area of Finland was stratified for sex and 10-year age groups. Food consumption was measured with 24-h recall and a 38-item food frequency questionnaire. Iron status was evaluated by haemoglobin (Hb) concentration and other haematological variables from venous blood samples in both genders (n = 239 men and 190 women), and serum ferritin (SF) for women (n = 137). The mean Hb concentration was 133+/-12 g/l and 137 +/- 10 g/l for women aged < 50 years and >/= 50 years, respectively, and 150 +/- 10 g/l for men. In younger women, the mean SF level was 32 +/- 30 micro g/l and 20% of women showed iron depletion (SF < 12 micro g/l),whereas in older women, the respective results were 62 +/- 59 micro g/l and 11 %. The prevalence of anaemia was 5.8 % for women (Hb < 120 g/l) and 1.3 % for men (Hb < 130 g/l). The respective mean intakes of iron were 10 mg/d and 13 mg/d. Cereals and meat were the major dietary sources of iron. While iron status is fairly good among Finnish males, especially in younger women it is suboptimal,with iron intake failing to reach recommended levels. Food consumption was poorly associated with iron status.


Re-weighted inference about hepatitis C virus-infected communities when analysing diagnosed patients referred to liver clinics.
To project national hepatitis C virus (HCV) burden, unbiased estimation of HCV progression to liver cirrhosis is required for the whole community of HCV-infected individuals. However, widely varying estimates of progression rates to cirrhosis have been produced. This disparity is partly associated with the statistical methods applied, but is mainly due to the differing types of study cohort. We use an inverse probability weighted estimation method to recover the true parameters for the (Weibull regression) model that determines the incubation period from infection to cirrhosis for the community of HCV-infected individuals, when there is cirrhosis-related recruitment bias to the studied cohort. We apply the method to simulated data for a liver clinic which attracts patients from a community of 1000 HCV-infected individuals under different event-biased referral patterns. We investigate how well the method performs in recovering the true community parameters, and then apply it to Edinburgh Royal Infirmary's liver clinic series. The results obtained are compared to those from a Weibull survival analysis which ignores the selection bias.


Caring for young adolescent sexual abuse victims in a hospital-based children's advocacy center.
This study compared health care assessments, referrals, treatment, and outcomes for young adolescent sexual assault/sexual abuse victims seen at a hospital-based Child Advocacy Center (CAC), to that provided to similar victims evaluated by other community providers. A second purpose was to document how common DNA evidence is found among such cases. A retrospective matched case-comparison design matched index CAC cases diagnosed with extra-familial sexual assault to non-CAC cases referred for prosecution in the same county, matched by age and sex of victim, age and sex of perpetrator, and type of assault (N=128 pairs). Since the case-comparison design produces paired data, analyses used paired t-tests, McNemars test, and Wilcoxon signed-rank tests. Health care outcomes included whether victims received a health exam, indicated tests, findings of trauma on genital exams and counseling referrals; legal outcomes included whether cases were prosecuted, verdicts, and length of sentences. CAC cases were significantly more likely to receive a physical exam, a genital exam when indicated, and referral for counseling (all p<.001). In the CAC group 26.7% vs. 4.8% had positive genital trauma findings, and only 6.3% of CAC cases failed to get indicated sexually transmitted infection (STI) tests or prophylactic treatment for STIs vs. 80% of the comparisons (p<.001). There were no differences in decisions to prosecute, convictions, or sentence lengths between the groups. DNA was documented in only 27.3% of acute cases, although evidence kits were completed. Young adolescent sexual abuse victims received markedly different health care in a hospital-based CAC compared to elsewhere. DNA is not commonly found in acute cases. Community health care providers and law enforcement should be encouraged to refer victims to hospital-based CACs for specialized examinations and treatment.


Idiopathic interstitial lung disease: anatomoradiologic pathogenesis.
Interstitial lung disease encompasses a large number of clinical disorders that affect the epithelium, the endothelium or both cell surfaces of alveolar wall and satellite structures including terminal and respiratory bronchioles. Causative factors are over 200 from bacteria, fungi, viruses, protozoans, to collagen disease, hypersensitivity and inorganic pneumoconiosis. Clinical and histological findings of open lung and transbronchial biopsies from 50 patients are reported, 18 patients were affected by diffuse alveolar damage (DAD), 15 patients by usual interstitial pneumonia (UIP), 8 patients by non specific interstitial pneumonia-fibrosis (NSIP-F), 9 patients by bronchiolitis obliterans organizing pneumonia (BOOP) correlated with conventional chest radiography in 30 patients and with HRCT in 31 patients. Interstitial lung disease other than histiocytosis X share anatomoradiologic features indicative for activity, chronic progression, chronic quiescence, chronic advanced and irreversible disease. In general, the histologic features correlate with radiographic patterns and even if radiologic findings do not always supply definitive diagnosis, some HRCT patterns are highly suggestive and usually classified into 4 categories: normal; with ground glass attenuation; linear, nodular or reticulo-nodular; honeycombing, suggestive for end-stage fibrosis. Correlation of HRCT with histologic findings in 31 patients with idiopathic interstitial fibrosis (IIF) allowed assessment of disease activity, follow-up and therapeutic result. HRCT definitely better than conventional radiology detects the presence, type and extent of parenchymal alterations, differentiating potential reversible lesions (inflammatory) from potentially irreversible (fibrotic) lesions. In IIF, for diagnostic accuracy the specimen of open lung (the gold standard), transbronchial or video-thoracoscopic biopsy must be preoperative, HRCT-assisted and centered on ground glass opacties (or nodules in suspected histiocytosis X) since a diagnostically reliable biopsy correlates with HRCT morphology of histologic specimen. Interstitial lung disease includes benign as well as malignant forms, thus only a multidisciplinary approach can prevent long term hazardous effects as severe cor pulmonale or a fatal outcome. The histologic HRCT-assisted assessment of "active" lesions is crucial for correct careful treatment of these patients.


Initiation specificity of the poly(cytidylic acid)-dependent Qbeta replicase activity.
The initiation specificity of RNA synthesis catalysed by the poly(C)-dependent Qbeta replicase activity was investigated with various synthetic ribopolymers as template. It was found that the initiation efficiency of a series of oligo(C) with various chain lengths is proportional to the template size. Synthetic riboheteropolymers containing cytidylic acid were accepted as templates only if they contained at their 3' end a cytidylic acid sequence of more than 5 nucleotides. Such an oligocytidylate sequence served also as an initiator sequence for copying the non-cytidylic-acid-containing part of the heterotemplate. RNA synthesis always began with the incorporation of GTP, even if the 3'-terminating nucleotide of the template was not cytidylic acid.


Nitric oxide transport in normal human thoracic aorta: effects of hemodynamics and nitric oxide scavengers.
Despite the crucial role of nitric oxide (NO) in the homeostasis of the vasculature, little quantitative information exists concerning NO transport and distribution in medium and large-sized arteries where atherosclerosis and aneurysm occur and hemodynamics is complex. We hypothesized that local hemodynamics in arteries may govern NO transport and affect the distribution of NO in the arteries, hence playing an important role in the localization of vascular diseases. To substantiate this hypothesis, we presented a lumen/wall model of the human aorta based on its MRI images to simulate the production, transport and consumption of NO in the arterial lumen and within the aortic wall. The results demonstrated that the distribution of NO in the aorta was quite uneven with remarkably reduced NO bioavailability in regions of disturbed flow, and local hemodynamics could affect NO distribution mainly via flow dependent NO production rate of endothelium. In addition, erythrocytes in the blood could moderately modulate NO concentration in the aorta, especially at the endothelial surface. However, the reaction of NO within the wall could only slightly affect NO concentration on the luminal surface, but strongly reduce NO concentration within the aortic wall. A strong positive correlation was revealed between wall shear stress and NO concentration, which was affected by local hemodynamics and NO reaction rate. In conclusion, the distribution of NO in the aorta may be determined by local hemodynamics and modulated differently by NO scavengers in the lumen and within the wall.


Pleuroparenchymal Fibroelastosis of the Lung: A Review.
Described in Japan by Amitani et al in 1992, the entity of idiopathic upper lobe fibrosis was subsequently given the name pleuroparenchymal fibroelastosis (PPFE) in the English-speaking world. Pleuroparenchymal fibroelastosis is believed to be a rare disease characterized by a fibrosing process affecting the pleura and the subpleural lung parenchyma, with a predilection for the upper lobes. Uniquely, the fibrosing process is elastotic in nature, being associated with intra-alveolar fibrosis. The etiology of PPFE is unclear at this juncture, with many cases being considered as idiopathic forms of the disease. Conditions associated with PPFE include infections, bone marrow transplantation, and autoimmunity. In this review, we explore the clinical, radiologic, and pathologic features associated with PPFE in light of current understanding of the disease. Recent studies implicated that PPFE may not be as uncommon as claimed. The various differential diagnoses and implications of diagnosing PPFE are discussed.


Mus musculus: Experimental Induction of Territory Formation.
In groups of house mice (Mus musculus) an experimentally imposed sequence of experience led to the establishment of male territories in suitably designed observation pens. This sequence consisted of familiarization with the area followed by combat with and social dominance over another male who was then removed, and a final step in which defeat on the home ground of a similarly experienced male was coupled with victory over the latter on familiar ground.


Visian Implantable Collamer Lens Behavior in Descemet Membrane Endothelial Keratoplasty Surgery.
Endothelial damage is one of the leading causes for anterior chamber phakic intraocular lens (AC-pIOL) explantation. In young patients, where the pIOL is explanted alone without lensectomy, an important anisometropia is left, unless an exchange with a posterior chamber (PC) pIOL is performed. However, in the event of corneal decompensation, there is no published evidence about the potential influence of a collamer-based PC-pIOL [implantable collamer lens (ICL)] on endothelial keratoplasty surgery. We report a case of severe endothelial damage after AC-pIOL implantation managed by the exchange of the AC-pIOL by an ICL, followed by Descemet membrane endothelial keratoplasty. Collamer-based PC-pIOLs seem to not affect Descemet membrane endothelial keratoplasty outcomes. ICL did not show any transparency loss. These results cannot be extrapolated to other non-collamer-based PC-pIOLs. Further studies with larger samples are necessary to confirm these outcomes.