Predictors of high healthcare resource utilization and liver disease progression among patients with chronic hepatitis C.
Since hepatitis C virus therapy is typically prioritized for patients with more advanced disease, predicting which patients will progress could help direct scarce resources to those likely to benefit most. This study aims to identify demographics and clinical characteristics associated with high healthcare resource utilization (HRU) and liver disease progression among CHC patients. Using health insurance claims (January 2001-March 2013), adult patients with ≥2 CHC claims (ICD-9-CM: 070.44 or 070.54), and ≥6 months of continuous insurance coverage before and ≥36 months after the first CHC diagnosis were included. Patients with human immunodeficiency virus were excluded. Generalized estimating equations were used to identify the demographic and clinical characteristics of being in the 20% of patients with the highest HRU. Factors predicting liver disease progression were also identified. In the study population (n = 4898), liver disease severity and both CHC- and non-CHC-related comorbidities and conditions were strong predictors of high healthcare costs, with odds ratios (ORs; 95% confidence interval [CI]) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities/conditions of 2.78 (2.48-3.12) and 2.19 (1.76-2.72), respectively. CHC- and non-CHC-related comorbidities and conditions were also strong predictors of liver disease progression with ORs (95% CI) for ≥2 CHC-related and ≥2 non-CHC-related comorbidities and conditions of 2.18 (1.83-2.60) and 1.50 (1.14-1.97), respectively. Potential inaccuracies in claims data, information or classification bias, and findings based on a privately insured population. This study suggests that CHC patients with high healthcare resource utilization have a high level of comorbidity at baseline and also that non-CHC comorbidities and conditions are strong predictors of high HRU. Non-cirrhotic CHC patients with one or more comorbidities are at high risk of progressing to cirrhosis or end-stage liver disease.


Age- and function-related regional changes in cortical folding of the default mode network in older adults.
Healthy aging is accompanied by changes in the functional architecture of the default mode network (DMN), e.g. a posterior to anterior shift (PASA) of activations. The putative structural correlate for this functional reorganization, however, is largely unknown. Changes in gyrification, i.e. decreases of cortical folding were found to be a marker of atrophy of the brain in later decades of life. Therefore, the present study assessed local gyrification indices of the DMN in relation to age and cognitive performance in 749 older adults aged 55-85 years. Age-related decreases in local gyrification indices were found in the anterior part of the DMN [particularly; medial prefrontal cortex (mPFC)] of the right hemisphere, and the medial posterior parts of the DMN [particularly; posterior cingulate cortex (PCC)/precuneus] of both hemispheres. Positive correlations between cognitive performance and local gyrification indices were found for (1) selective attention and left PCC/precuneus, (2) visual/visual-spatial working memory and bilateral PCC/precuneus and right angular gyrus (AG), and (3) semantic verbal fluency and right AG and right mPFC. The more pronounced age-related decrease in local gyrification indices of the posterior parts of the DMN supports the functionally motivated PASA theory by correlated structural changes. Surprisingly, the prominent age-related decrease in local gyrification indices in right hemispheric ROIs provides evidence for a structural underpinning of the right hemi-aging hypothesis. Noticeably, the performance-related changes in local gyrification largely involved the same parts of the DMN that were subject to age-related local gyrification decreases. Thus, the present study lends support for a combined structural and functional theory of aging, in that the functional changes in the DMN during aging are accompanied by comparably localized structural alterations.


The Coronavirus Disease 2019 Pandemic's Effect on Critical Care Resources and Health-Care Providers: A Global Survey.
The coronavirus disease 2019 (COVID-19) pandemic has severely affected ICUs and critical care health-care providers (HCPs) worldwide. How do regional differences and perceived lack of ICU resources affect critical care resource use and the well-being of HCPs? Between April 23 and May 7, 2020, we electronically administered a 41-question survey to interdisciplinary HCPs caring for patients critically ill with COVID-19. The survey was distributed via critical care societies, research networks, personal contacts, and social media portals. Responses were tabulated according to World Bank region. We performed multivariate log-binomial regression to assess factors associated with three main outcomes: limiting mechanical ventilation (MV), changes in CPR practices, and emotional distress and burnout. We included 2,700 respondents from 77 countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%). The reported lack of ICU nurses was higher than that of intensivists (32% vs 15%). Limiting MV for patients with COVID-19 was reported by 16% of respondents, was lowest in North America (10%), and was associated with reduced ventilator availability (absolute risk reduction [ARR], 2.10; 95% CI, 1.61-2.74). Overall, 66% of respondents reported changes in CPR practices. Emotional distress or burnout was high across regions (52%, highest in North America) and associated with being female (mechanical ventilation, 1.16; 95% CI, 1.01-1.33), being a nurse (ARR, 1.31; 95% CI, 1.13-1.53), reporting a shortage of ICU nurses (ARR, 1.18; 95% CI, 1.05-1.33), reporting a shortage of powered air-purifying respirators (ARR, 1.30; 95% CI, 1.09-1.55), and experiencing poor communication from supervisors (ARR, 1.30; 95% CI, 1.16-1.46). Our findings demonstrate variability in ICU resource availability and use worldwide. The high prevalence of provider burnout and its association with reported insufficient resources and poor communication from supervisors suggest a need for targeted interventions to support HCPs on the front lines.


Ethnic density, urbanicity and psychosis risk for migrant groups - A population cohort study.
Rates of psychotic disorder are raised for many migrant groups. Understanding the role played by the social context in which they live may help explain why. This study investigates the effect of both neighbourhood ethnic density and urbanicity on the incidence of non-affective psychosis for migrant groups. Population based cohort of all those born 1965 or later followed from their 15th birthday (2,224,464 people) to 1st July 2013 (37,335,812 person years). Neighbourhood exposures were measured at age 15. For all groups incidence of non-affective psychosis was greater in lower ethnic density neighbourhoods. For migrants of African origin there was a 1.94-fold increase (95% CI, 1.17-3.23) comparing lowest and highest density quintiles; with similar effects for migrants from Europe (excluding Scandinavia): incidence rate ratio (IRR) 1.99 (95% CI, 1.56-2.54); Asia: IRR 1.63 (95% CI, 1.02-2.59); and the Middle East: IRR 1.68 (95% CI, 1.19-2.38). This initial analysis found no evidence for an urbanicity effect for migrant groups. Adjusting for ethnic density revealed a positive association between level of urbanicity and psychosis for two groups, with a statistically significant linear trend (average effect of a one quintile increase) for migrants from Europe: IRR 1.09 (95% CI, 1.02-1.16) and the Middle East: IRR 1.12 (95% CI, 1.01-1.23). In this first nationwide population-based study of ethnic density, urbanicity and psychosis we show that lower ethnic density is associated with increased incidence of non-affective psychosis for different migrant groups; masking urban/rural differences in psychosis for some groups.


Stability studies of tetracycline in methanol solution.
The stability of tetracycline in methanol solution was investigated by UV-visible spectroscopy, HPLC and TLC methods. After dissolution in methanol, tetracycline decomposed rapidly under the influence of light and atmospheric oxygen, forming more than fourteen different degradation products. None of the previously reported degradation products, such as the epi- and anhydro-compounds, were detected as the final degradation products. The molecular structures for eight of the compounds were suggested by their product-ion mass spectra. A degradation sequence was proposed for the reactions of tetracycline with methanol. A new HPLC-MS mobile phase was developed, which solved the clogging problem at the interface between the HPLC and MS chamber and enabled a high separation efficiency.


It takes two to Tango: Two gates orchestrate the opening of human TRPM2.
TRPM2 is a calcium permeable non-selective cation channel involved in many important physiological processes and has divergent gating mechanisms across species. Structural studies have revealed that TRPM2 is gated by adenosine 5'-diphosphoribose that binds to the cytosolic domains of TRPM2 and calcium ions that are coordinated by residues in the transmembrane domain. However, the selectivity filter of human TRPM2 remains elusive due to the poor resolution in this region. In a recent manuscript published in Cell Reports, Yu et al. present unexpected dual roles of the selectivity filter in human TRPM2 by determining a high-resolution structure of human TRPM2 in lipid nanodiscs. This study provides unprecedented insights into the gating mechanism of human TRPM2.


Familial haemophagocytic lymphohistiocytosis: survival of a premature twin with immuno-chemotherapy and bone marrow transplantation from an HLA-identical unrelated donor.
We describe a premature twin born at 30 wk of gestational age, affected with familial haemophagocytic lymphohistiocytosis. Two different mutations were identified in his DNA: one inherited from the mother and one from the father. Haemophagocytosis had been confirmed in his twin brother, who died soon after birth, as well as in the re-evaluation of the autopsy of his older sister, who died 1 y earlier. At 26 d of age, chemotherapy and immune-suppressive treatment were started according to the HLH-94 protocol. At 6 mo of age, a bone marrow transplant from an HLA-identical, unrelated volunteer was performed. Now at 32 mo of age, the infant is healthy and without signs of graft-versus-host disease. This case report shows that immuno-chemotherapy and allogenic bone marrow transplant are feasible even in premature infants affected with familial haemophagocytic lymphohistiocytosis, which should be ruled out in unknown bleeding disorders of neonates.


Pregnancy in patients with thalassemia major: a cohort study and conclusions for an adequate care management approach.
An improvement in quality of life and survival occurred among thalassemia major (TM) patients: pregnancy in such patients has become a reality. Safe pregnancy and delivery require efforts to ensure the best outcomes. Between 2007 and 2016, 30 TM patients had 37 pregnancies. We analyzed the hematological parameters before, during, and after pregnancies and in 19 patients a cardiovascular magnetic resonance (CMR) T2* was performed. The mean age at first pregnancy was 30 ± 4 years; the current mean age is 35 ± 5 years. Twenty-four patients (80%) had a single pregnancy, five patients (17%) had two pregnancies, and one patient (3%) became pregnant three times. Seventeen pregnancies (46%) were spontaneous, 20 (64%) needed gonadotrophin-induced ovulation and/or reproductive technologies. All pregnancies resulted in live births. Seven were twin pregnancies (19%). The mean gestational hemoglobin was 9.2 ± 0.5 g/dl, lower than pre- and postpregnancy (9.8 ± 1 g/dl, p = ns and 9.6 ± 1 g/dl, p = 0.02, respectively). Median ferritin levels increased progressively (1071, range 409-5724 ng/ml, before pregnancy vs 2231, range 836-6918 ng/ml, after pregnancy, p < 0.0001). CMR before pregnancy showed a normal cardiac T2* (mean 35.34 ± 8.90 ms) and a mean liver iron concentration (LIC) of 3.37 ± 2.11 mg/g dry weight (dw). After pregnancy, the mean cardiac T2* was 31.06 ± 13.26 ms and the mean LIC was significantly increased (9.06 ± 5.75 mg/g dw, p = 0.0001). Pregnancy is possible and safe in thalassemia major. During pregnancy, iron accumulates, especially in the liver; a prompt resumption of chelation after delivery is mandatory.


[Electromyographic investigations about operative and conservative treatment after rupture of the long tendon of m. biceps brachii (author's transl)].
After conservative respectively operative treatment of two exactly comparable patients who suffered from rupture of the long head of the biceps tendon of the arm, the myoelectric activity of both muscle heads was investigated on the injured arm and compared to the uninjured side. There was a significant diminution of activity in the ruptured long head as well as a reactive hyperactivity in the short head after conservative treatment in contrast to the operative treated patient, where these alterations in muscle activity were less marked. The operative treatment therefore shows a better functional result when compared with the conservatively treated rupture.


Risk factors and clinical outcomes of cytomegalovirus disease occurring more than one year post solid organ transplantation.
Cytomegalovirus (CMV) disease typically occurs during the first year after solid organ transplantation, after cessation of antiviral prophylaxis. CMV occurring after the first year is uncommon and not well described. We conducted a case-control study to identify potential risk factors and a retrospective cohort study to evaluate 1-month mortality in solid organ transplant (SOT) recipients who developed CMV disease after the first year post transplant, or "very late CMV" (VLCMV), compared with those developing CMV within the first year (CMV Y1), adjusting for demographics, donor and recipient CMV serostatus, immunosuppression, rejection, and co-morbidities. We identified 85 SOT recipients with CMV disease at a single transplant center between January 2006 and October 2008: 23 (27%) had VLCMV and 62 (73%) had CMV Y1. Heart transplantation was independently associated with increased risk (adjusted odd ratio [OR] 4.11; 95% confidence interval [CI] 1.34-12.61; P = 0.01) for VLCMV. Patients with VLCMV had increased 1-month mortality (unadjusted OR 5.39; 95% CI 1.06-27.48; P = 0.02). Mortality was uncommonly attributable to CMV. CMV disease continues to occur after the first year post solid organ transplantation, particularly in heart transplant recipients, and can be associated with poor outcomes. CMV should be suspected in patients with symptoms or laboratory findings consistent with CMV, even if the patients present >1 year post transplant.


Brief report: The sensitivity of motor responses for detecting catheter-nerve contact during ultrasound-guided femoral nerve blocks with stimulating catheters.
We determined the sensitivity of motor responses evoked by stimulating catheters in determining catheter-nerve contact using ultrasonography as reference. Femoral nerves were contacted using stimulating catheters under ultrasonography scanning in 25 patients. The output current was increased from its minimum until quadriceps muscle contraction occurred. The sensitivity of the motor response in determining catheter-nerve contact was calculated using 0.5 mA as current threshold. The current required for catheter stimulation to evoke a motor response ranged between 0.18 and 2.0 mA. Muscle contraction in response to 0.5 mA occurred in 16 of 25 subjects. The sensitivity of motor response for nerve stimulation was 64% (95% confidence interval: 0.43, 0.82). The absence of muscle responses at a stimulating current≤0.5 mA does not necessarily indicate the absence of catheter-nerve contact.


RHAMM regulates MMTV-PyMT-induced lung metastasis by connecting STING-dependent DNA damage sensing to interferon/STAT1 pro-apoptosis signaling.
RHAMM is a multifunctional protein that is upregulated in breast tumors, and the presence of strongly RHAMM+ve cancer cell subsets associates with elevated risk of peripheral metastasis. Experimentally, RHAMM impacts cell cycle progression and cell migration. However, the RHAMM functions that contribute to breast cancer metastasis are poorly understood. We interrogated the metastatic functions of RHAMM using a loss-of-function approach by crossing the MMTV-PyMT mouse model of breast cancer susceptibility with Rhamm-/- mice. In vitro analyses of known RHAMM functions were performed using primary tumor cell cultures and MMTV-PyMT cell lines. Somatic mutations were identified using a mouse genotyping array. RNA-seq was performed to identify transcriptome changes resulting from Rhamm-loss, and SiRNA and CRISPR/Cas9 gene editing was used to establish cause and effect of survival mechanisms in vitro. Rhamm-loss does not alter initiation or growth of MMTV-PyMT-induced primary tumors but unexpectedly increases lung metastasis. Increased metastatic propensity with Rhamm-loss is not associated with obvious alterations in proliferation, epithelial plasticity, migration, invasion or genomic stability. SNV analyses identify positive selection of Rhamm-/- primary tumor clones that are enriched in lung metastases. Rhamm-/- tumor clones are characterized by an increased ability to survive with ROS-mediated DNA damage, which associates with blunted expression of interferon pathway and target genes, particularly those implicated in DNA damage-resistance. Mechanistic analyses show that ablating RHAMM expression in breast tumor cells by siRNA knockdown or CRISPR-Cas9 gene editing blunts interferon signaling activation by STING agonists and reduces STING agonist-induced apoptosis. The metastasis-specific effect of RHAMM expression-loss is linked to microenvironmental factors unique to tumor-bearing lung tissue, notably high ROS and TGFB levels. These factors promote STING-induced apoptosis of RHAMM+ve tumor cells to a significantly greater extent than RHAMM-ve comparators. As predicted by these results, colony size of Wildtype lung metastases is inversely related to RHAMM expression. RHAMM expression-loss blunts STING-IFN signaling, which offers growth advantages under specific microenvironmental conditions of lung tissue. These results provide mechanistic insight into factors controlling clonal survival/expansion of metastatic colonies and has translational potential for RHAMM expression as a marker of sensitivity to interferon therapy.


HLA class I typing in Egyptian childhood minimal change nephrotic syndrome.
Reports on the association between human leukocyte antigens (HLAs) and childhood minimal change nephrotic syndrome (MCNS) are variable. The association between HLA class I and MCNS has not been tested among Egyptian children. We studied such associations in a group of steroid-responsive MCNS Egyptian children (n=37) in comparison to a group of healthy Egyptians (n=100). Typing was performed using standard lymphocytotoxicity assay. The frequency of HLA-B27 was remarkably higher among MCNS children (18.9%) compared with the control group (1%) (p<0.001, risk ratio [RR] = 3.76, 95% confidence interval [95% CI], 2.5-5.66). Additionally, MCNS children had a significantly higher frequency of HLA-A11 (16.2% vs. 3%) and HLA-B13 (13.5% vs. 2%) (p=0.012 and p=0.016; RR=2.75 and RR=2.9; 95% CI, 1.58-4.79 and 1.66-5.06; respectively). With multivariate analysis, the previous 3 loci were still significant in addition to HLA-B12 (p=0.001, p=0.005, p=0.013 and p=0.033, for HLA-B27, HLA-B13, HLA-A11 and HLA-B12, respectively). The frequency of HLA haplotypes was comparable in both groups. We concluded that associations of HLA class I with childhood MCNS in Egypt have both similarities and dissimilarities to those in other populations. HLA-B27, which has not been reported before, has the strongest association. However, similar to studies from other populations, HLA-A11, HLA-B13 and HLA-B12 loci were also associated with MCNS.


Usefulness of intraoperative transesophageal echocardiography for hemodynamic management of liver transplantation in a patient with massive polycystic liver disease: a case report.
Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation. A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver. TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management.


mu-Opioid receptor modulates peptide release from rat neurohypophysial terminals by inhibiting Ca(2+) influx.
The activation of opioid receptors in neurones of the central nervous system leads to a variety of effects including the modulation of diuresis and parturition, processes that are directly controlled by the hypothalamic-neurohypophysial system (HNS). The effects of mu-opioid receptor activation on peptide release, voltage-gated Ca2+ currents and intracellular calcium levels ([Ca2+]i) were studied in isolated nerve terminals of the HNS. The mu-receptor agonist, DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin) inhibited high K+-induced peptide release in a dose-dependent manner, with oxytocin release being more sensitive to block than vasopressin release at all concentrations tested. The addition of the mu-receptor antagonist CTOP (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide) was able to overcome the inhibitory effects of DAMGO. By contrast to previous results, voltage-gated Ca2+ currents were sensitive to blockage by DAMGO and this inhibition was also prevented by CTOP. Furthermore, [Ca2+]i measurements with Fura-2 corroborated the inhibition by DAMGO of calcium entry and its reversal by the micro -receptor antagonist in these nerve terminals. Thus, the decrease in neuropeptide release, particularly for oxytocin, induced by the activation of mu-opioid receptors in neurohypophysial terminals is mediated, at least in part, by a corresponding decrease in Ca2+ entry due to the inhibition of voltage-gated Ca2+ channels.


Mutagenicity of hydrogen peroxide in V79 Chinese hamster cells.
Hydrogen peroxide (H2O2) was investigated for its potential to induce gene mutations in V79 Chinese hamster cells. Exposure of 2-3 X 10(6) cells/100-mm dish to 0.5-4.0 mM H2O2 for 1 h resulted in a concentration-dependent increase in the frequency of 6-thioguanine-resistant clones. At 4 mM H2O2 the mutation frequency was increased about 6-fold above that in controls and survival of the cells was reduced by 50%. Cytotoxicity was markedly increased at lower cell densities. When only 100-200 cells/100-mm dish were exposed to H2O2 for 1 h, 50% were killed at an H2O2 concentration as low as 60 microM. The results show that mutagenicity of H2O2 in mammalian cells in vitro has escaped attention previously because the concentrations tested were too low, presumably because the likely toxicity of H2O2 to V79 cells treated at high cell densities was overestimated.


Feasibility and outcome of substitution treatment of heroin-dependent patients in specialized substitution centers and primary care facilities in Germany: a naturalistic study in 2694 patients.
In many countries, buprenorphine and methadone are licensed for the maintenance treatment (MT) of opioid dependence. Despite many short-term studies, little is known about the long-term (12-month) effects of these treatments in different settings, i.e. primary care-based (PMC) and specialized substitution centers (SSCs). To describe over a period of 12 months: (1) mortality, retention and abstinence rates; (2) changes in concomitant drug use, somatic and mental health; and (3) to explore differences between different types of provider settings. 12-Month prospective-longitudinal naturalistic study with four waves of assessment in a prevalence sample of N=2694 maintenance patients, recruited from a nationally representative sample of N=223 substitution physicians. The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. When controlling for initial severity, small PMC settings revealed better retention, abstinence and concomitant drug use rates. The study underlines the overall 12-month effectiveness of various forms of agonist MT. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life. PMC settings appear to be a good additional option to improve access to MTs.


Ethanolaminephosphate cytidylyltransferase. Purification and characterization of the enzyme from rat liver.
Ethanolaminephosphate cytidylyltransferase (EC 18.104.22.168), which catalyzes a central step in phosphatidylethanolamine synthesis, has been purified 1000-fold from a postmicrosomal supernatant from rat liver. The enzyme, which requires a reducing agent, like dithiothreitol, for activity, is stable for weeks at 0-4 degrees when stored in the presence of dithiothreitol and in the pH range 7.5 to 9.0. A molecular weight of 100 to 120 X 10(3) was estimated by gel chromatography on Sephadex G-200. Gel electrophoresis in the presence of sodium dodecyl sulfate gave only one protein band with an apparent molecular weight of 49 to 50 X 10(3). The reaction catalyzed by the enzyme is reversible with a Keq for the forward reaction of 0.46 under the assay conditions. Michaelis constants of 53 and 65 muM were determined for CTP and ethanolaminephosphate, respectively. From the product inhibition pattern an ordered sequential reaction mechanism is proposed, in which CTP is the first substrate to add to the enzyme and CDP-ethanolamine is the last product to be released. The possible role of this reaction in the regulation of phosphatidylethanolamine synthesis in liver is discussed.


Differentiation between vaccine and wild-type varicella-zoster virus genotypes by high-resolution melt analysis of single nucleotide polymorphisms.
The analysis of single nucleotide polymorphisms (SNPs) of varicella-zoster virus (VZV) has enabled differentiation between wild-type genotypes from the Oka vaccine strain (V-Oka). To genotype VZV strains in Australia using high-resolution melt (HRM) analysis of SNPs in five gene targets. Extracted DNA from 78 samples obtained from patients with chickenpox and zoster were genotyped by HRM analysis of SNPs in five open reading frames (ORFs): 1 (685 G>A), 21 (33725 C>T), 37 (66288 G>A), 60 (101464 C>A) and 62 (106262 T>C) using a double-stranded (ds) DNA saturating dye, LC Green Plus. For each genotype, melt curve temperature (Tm) shifts differentiated the nucleotide present at that locus (P<0.0001) with melting curve shifts between alleles ranging from 0.56 degrees C (ORF 37) to 3.34 degrees C (ORF 62). The most common genotypes detected were the European Type C (59%) and B (18%) strains. This was followed by the African/Asian Type A (14%) and Japanese J1 (9%), strains, both prevalent in the Northern Territory and Western Australia. HRM analysis of SNPs showed that the European B and C genotypes were most prevalent in Australia, with genotypes A and J strains also present. HRM analysis using a dsDNA dye provides a useful tool in classifying varicella-zoster viruses.


Evaluation of diaphragm ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD.
To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. All included patients with COPD received mechanical ventilation (MV) and were ready to wean from MV. After patients passed the 30 min spontaneous breathing trail (SBT), extubation was considered to be feasible, and the right DE measured by ultrasound at 0 min, 5 min, and 30 min of SBT were named as DE0, DE5, and DE30, respectively. Twenty-five patients succeeded extubation; 12 patients failed. The area under receiver operator characteristic curve (AUCROC) of DE30 and ΔDE30-5 (the variation between 30 and 5 min) were 0.762 and 0.835; a cutoff value of DE30 > 1.72 cm and ΔDE30-5 > 0.16 cm were associated with a successful extubation with a sensitivity of 76% and 84%, a specificity of 75% and 83.3%, respectively. The predictive probability equation of the DE30 plus ∆DE30-5 was P = 1/[1 + e-(-5.625+17.689×∆DE30-5+1.802×DE30)], a cutoff value of P > 0.626 was associated with a successful extubation with the AUCROC of 0.867, a sensitivity of 92%, and a specificity of 83.3%. The combination of DE30 and ∆DE30-5 could improve the predictive value and could be used as the predictor of extubation outcome in mechanically ventilated patients with COPD.


Long-chain fatty acid acylated derivatives of isoflavone glycosides from the rhizomes of Iris domestica.
Six undescribed long-chain fatty acid esters of isoflavone glycosides were obtained from the rhizomes of Iris domestica (L.). Their structures were elucidated by comprehensive spectroscopic data, alkaline hydrolysis, and acid hydrolysis. This is the first report of the long-chain (C14-C18) fatty acid derivatives of isoflavone glycosides from natural products. Belamcandnoate B and D exhibited moderate cytotoxic activities against HCT-116, HepG2, and BGC823 cell lines with IC50 values of 1.69-6.86 μM. Belamcandnoate B and E exhibited 72.27 and 58.98% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 μM.


Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold.
Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were prepared as potential dual antithrombotic compounds. Fluorine scan (3-fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4-difluorobenzyl)amino compound (9i) as the most potent compound with balanced dual activity (K(i(Thr))=0.33±0.07μM, IC(50(GP IIb/IIIa))=1.1±0.6μM).


Tricarbonyldichlororuthenium(II) dimer, the lipid-soluble carbon monoxide-releasing molecule, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.
Carbon monoxide (CO) is increasingly being appreciated as an important mediator that has pleiotropic biological properties and appears to have a possible therapeutic application for a variety of disorders. Nevertheless, whether this gaseous molecule may be utilized as a therapeutic intervention for periodontal disease is unclear. Here, we examined the potential beneficial effect of CO-releasing molecule-2 (CORM-2), a tricarbonyldichlororuthenium(II) dimer, against the elaboration of proinflammatory mediators by murine macrophages challenged with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogenic bacterium implicated in inflammatory periodontal disease. We found that NO and IL-1β production, iNOS protein expression and mRNA expressions of iNOS and IL-1β were significantly down-regulated when LPS-challenged RAW264.7 cells were exposed to CORM-2. In addition, HO-1 expression was upregulated by CORM-2 in cells activated with P. intermedia LPS, and the inhibitory influence of CORM-2 upon NO production was attenuated by tin protoporphyrin IX, an inhibitor of HO activity. PPAR-γ did not function in the attenuation of NO and IL-1β by CORM-2. JNK and p38 phosphorylation caused by LPS was not altered by CORM-2. CORM-2 reduced NF-κB reporter activity and IκB-α degradation elicited by P. intermedia LPS. Additionally, CORM-2 inhibited LPS-induced phosphorylation of STAT1/3. In conclusion, CORM-2 suppresses NO and IL-1β production caused by P. intermedia LPS. CORM-2 exerts its effect by a mechanism involving anti-inflammatory HO-1 induction and attenuation of NF-κB and STAT1/3 activation, independently of PPAR-γ as well as JNK and p38. CORM-2 may hold promise as host response modulation agent for periodontal disease, though further research is indicated to verify the therapeutic effect.


Hydrolysis of phosphatidylinositol 3,4-bisphosphate by inositol polyphosphate 4-phosphatase isolated by affinity elution chromatography.
Inositol polyphosphate 4-phosphatase is a monomeric 110-kDa protein that hydrolyzes two substrates in the inositol phosphate pathway. Inositol 3,4-bisphosphate is converted to inositol 3-phosphate, and inositol 1,3,4-trisphosphate is converted to inositol 1,3-bisphosphate. We have exploited the fact that inositol hexasulfate inhibits the enzyme to devise an affinity elution scheme from a Mono S cation exchange column that resulted in an 11,300-fold purified preparation of rat brain 4-phosphatase. The resulting 4-phosphatase hydrolyzed phosphatidylinositol 3,4-bisphosphate to phosphatidylinositol 3-phosphate with a first order rate constant 120-fold greater than that for inositol 3,4-bisphosphate and 900-fold greater than that for inositol 1,3,4-trisphosphate. This is now the third example wherein the same enzyme hydrolyzes both an inositol lipid and its analogous inositol phosphate.


Phase I and pharmacokinetic trial of liposome-encapsulated doxorubicin.
A total of 21 patients with advanced cancer were entered into a phase I study to determine the maximum tolerable dose (MTD) of liposome-encapsulated doxorubicin (LED) given weekly for 3 consecutive weeks at doses of 20, 30, or 37.5 mg/m2 per week. For a comparison of the pharmacokinetic behavior of LED with that of standard-formulation doxorubicin, 13 patients received a dose of standard-formulation doxorubicin 2 weeks prior to the first dose of LED. All doses were given by 1-h infusion through a central vein. Toxicity was evaluated in 22 courses delivered to 17 patients. The MTD with this schedule was 30 mg/m2 per week x 3. The single patient treated at 37.5 mg/m2 weekly could not complete the entire course due to myelosuppression. At the dose of 30 mg/m2 per week, three of eight patients had grade > or = 3 leukopenia. Other toxicities included mild to moderate thrombocytopenia, nausea, vomiting, fever, alopecia, diarrhea, fatigue, stomatitis, and infection. At the dose of 30 mg/m2 per week, the total doxorubicin AUC and peak total doxorubicin concentrations in plasma were 8.75 +/- 8.80 microM h (mean +/- SD) and 3.07 +/- 1.45 microM, respectively, after LED administration. The total doxorubicin AUC and peak total doxorubicin concentrations in plasma were 3.92 +/- 2.47 microM h and 2.75 +/- 2.70 microM, respectively, after the infusion of standard-formulation doxorubicin. The total body clearance of doxorubicin was 18.42 +/- 11.23 l/h after the infusion of LED and 31.21 +/- 15.48 l/h after the infusion of standard-formulation doxorubicin. The mean elimination half-lives of doxorubicin were similar: 8.65 +/- 5.16 h for LED and 7.46 +/- 5.16 h for standard-formulation doxorubicin. Interpatient variability in pharmacokinetic parameters as demonstrated by the percentage of coefficients of variation was 33%-105%. There was no relationship between the percentage of WBC decrease or the duration of WBC suppression and the total doxorubicin or doxorubicinol AUC. There was no correlation between the duration of leukopenia and drug exposure as reflected by the AUC of liposome-associated doxorubicin. LED can be given in doses similar to those of standard-formulation doxorubicin and produces acute toxicities similar to those caused by standard doxorubicin.


Shift from farm to dairy tank milk microbiota revealed by a polyphasic approach is independent from geographical origin.
Detailed information on the natural microbial community present in raw milk, especially on the non-cultivable part of the milk microbiota, is rather limited as research in the past mainly focused on the detection of bacterial pathogens or microorganisms responsible for the deterioration of raw milk. In frame of the EU project BIOtracer raw milk samples from three different European countries were analyzed to gain a deeper insight into the diversity of the natural bacterial flora of raw milk by combining culture-dependent and -independent methods. Fourier-transform infrared (FTIR) spectroscopy was used as rapid and cost efficient metabolic fingerprinting technique to monitor the cultivable microbiota of raw milk. In addition, direct sequencing was applied to acquire additional information on the non-cultivable part of the bacterial raw milk flora. Subsequent performed biostatistical analysis revealed a high correlation between the data gathered by culture-dependent and independent methods. Both methods revealed significant differences between the microbiota of farm and dairy tank milk, which appeared to be rather independent from geographical regions. Based on the results from FTIR and direct sequencing, the predominant bacterial raw milk flora was determined, representative isolates were selected and two model floras, representative for farm tank milk and dairy bulk tank milk, were compiled. These bacterial model floras for raw milk are now available for the Biotracer partners and can be used for validation purposes or contamination scenarios. The knowledge gained on the variation range of the normal raw milk microbiota will help to identify raw milk with divergent microbiota, pointing towards potential pathogen contaminations.


A highly active ubiquinol-cytochrome c reductase (bc1 complex) from the colorless alga Polytomella spp., a close relative of Chlamydomonas. Characterization of the heme binding site of cytochrome c1.
The alga Polytomella spp. offers extraordinary advantages in the preparation of mitochondria since it lacks chloroplasts and a cell wall. In this work the mitochondrial bc1 complex from Polytomella spp. was solubilized and purified by ion exchange chromatography. The complex was found to be composed of 10 polypeptides and exhibited high rates of ubiquinol-cytochrome c oxidoreductase activity (> 300 s-1) sensitive to antimycin and myxothiazol. The molecular mass of the bc1 complex from Polytomella spp. was assayed by gel filtration and estimated to be of 256,300 Da. Therefore, this complex exhibits the unique property of behaving as a monomer. Amino-terminal sequencing of cytochrome c1 identified 7 residues, from which a deoxyoligonucleotide was designed. A second deoxyoligonucleotide was constructed based on a highly conserved region of the c1 type cytochromes. With these probes, a fragment of the cytochrome c1 gene was amplified by polymerase chain reaction and sequenced. The deduced sequence of the apoprotein exhibited a consensus binding site CXXCH. The data suggest that the cytochrome c1 from Polytomella spp. differs from other protoctists like Crithidia and Euglena, i.e. it exhibits a heme binding domain structurally related to the bovine, yeast, and Neurospora c1 type cytochromes.


Fast acquisition of NMR spectra using Fourier transform of non-equispaced data.
Rapid acquisition of high-resolution 2D and 3D NMR spectra is essential for studying biological macromolecules. In order to minimize the experimental time, a non-linear sampling scheme is proposed for the indirect dimensions of multidimensional experiments. These data can be processed using the algorithm proposed by Dutt and Rokhlin (Appl. Comp. Harm. Anal. 1995, 2, 85-100) for fast Fourier transforms of non equispaced data. Examples of 1H-(15)N HSQC spectra are shown, where crowded correlation peaks can be resolved using non-linear acquisition. Simulated data have been used to analyze the artefacts produced by the Lagrange interpolation. As compared to non-linear processing methods, this algorithm is simple and highly robust since no parameters need to be adjusted by the user.


Systemic spread of tuberculosis after surgery for a splenic tuberculous abscess without postoperational antituberculosis treatment: a case report.
Solitary splenic tuberculosis (TB) is rare, with less than ten cases ever being reported. The diagnosis is established by the pathological analysis of a biopsy from a surgical operation or from a fine-needle aspiration sample. Manifestations of splenic TB include low-grade fever, weight loss, abdominal pain, and diarrhea. This case, however, has no obvious symptoms, and multiple splenic tubercles were discovered during a routine physical examination. Splenic abscesses from TB were diagnosed after the operation. Postoperative spread of TB lead to cerebral tuberculous abscesses and pulmonary TB. Resolution was achieved with anti-TB therapy.


Off-Label Use of Cardiovascular Drugs in the Home Therapy of Children With Congenital or Acquired Heart Disease.
Most medications are not labeled for use in the pediatric population because they have not been formally studied in children. Data on off-label use of cardiovascular (CV) drugs in the home therapy of children with CV disease are scanty. The study included 325 pediatric patients with CV disease and on ≥1 CV medication who underwent ≥1 visit during 2019 at the Pediatric Cardiology outpatient clinic of Giovanni XXIII Pediatric Hospital in Bari, Italy. A total of 287 patients (88.3%) received ≥1 off-label medication, whereas 113 patients (34.7%) received ≥2 off-label medications, and 22 patients (6.7%) ≥3 off-label medications. In CV medications (n = 27) 85% were used off-label in all cases, and 92.5% were used off-label in ≥50% of patients. Adverse events occurred in 8 patients, leading to drug discontinuation in 2 of them. In all 8 cases, medications were used off-label. In multivariate analysis, congenital heart disease patients with single-ventricle physiology (odds ratio 8.4, 95% confidence interval 2.25 to 54.4) and those with heart failure (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) were at higher risk for receiving ≥2 off-label drugs. The off-label use of CV drugs in the home therapy of children with congenital or acquired heart disease is common and adverse events may occur. Patients with congenital heart disease with single-ventricle physiology and those with heart failure have a higher probability to receive ≥2 off-label medications. This study highlights the need for larger safety and efficacy trials in this specific cohort of pediatric patients.


Rapid screen for truncating ATM mutations by PTT-ELISA.
Mutations in the ataxia-telangiectasia mutated (ATM) gene are responsible for the autosomal recessive genetic disorder, ataxia-telangiectasia (A-T). Approximately 80% of ATM mutations found in A-T patients results in truncations, which can be detected by Protein Truncation Test (PTT). Conventional PTT uses SDS-PAGE electrophoresis to detect mobility of radiolabeled truncated protein fragments. In this study, we developed a non-radioactive Protein Truncation Test which utilizes an enzyme-linked immunosorbent assay (PTT-ELISA) to detect ATM mutations in eight overlapping fragments. N- and C-terminal epitopes (c-myc and V5, respectively) were introduced into transcription/translation products, which could then be detected by Sandwich ELISA. Using this assay, we screened 9 newly diagnosed A-T patients consecutively. Of the 18 expected mutations, 14 truncating mutations were independently identified by cDNA direct sequencing and/or DNA dHPLC analysis. PTT-ELISA detected all of these 14. Four mutations were novel. The PTT-ELISA provides a rapid method for detecting truncating mutations in large genes and should be considered prior to using more laborious or costly methods, such as direct sequencing.


Childhood passive smoke exposure is associated with adult head and neck cancer.
Passive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain. We conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression. CPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01-1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80-1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at non-oropharyngeal sites (OR, 2.02; 95% CI, 1.01-4.06, N=52 cases vs. OR, 1.04; 95% CI, 0.68-1.60, N=132 cases; P-for-heterogeneity=0.08). Data from this large US-based case control study suggest a role for CPSE in HNSCC etiology.


Oct-6 transcription factor.
A variety of neurological disorders may have their origin during development of the central nervous system. Defects consistent with abnormal brain development have been reported in schizophrenia. These include faulty neuronal migration,altered spatial neuronal distribution, and the absence of significant gliosis. These abnormalities in the adult are allocated to developmental processes and thus indicate a developmental basis for schizophrenia. Our way toward understanding schizophrenia pathology has been to consider the genes that regulate normal brain development. One such family of genes is the POU family of homeobox transcription factors. This chapter reviews POU domain proteins, focusing on the POU III domain gene, Oct-6, along with its potential relevance to schizophrenia.


Antithrombotic strategies in children receiving long-term Berlin Heart EXCOR ventricular assist device therapy.
Thromboembolic events while receiving ventricular assist device (VAD) support remain a significant cause of morbidity and mortality despite standard anti-coagulation and anti-platelet therapies. The use of bivalirudin and epoprostenol infusions as an alternate anti-thrombotic (AT) regimen in pediatric VAD patients was reviewed. This was a retrospective record review of 6 pediatric patients (aged ≤17 years) at 2 institutions treated with bivalirudin and epoprostenol infusions while being supported with the Berlin Heart EXCOR (Berlin Heart GmbH, Berlin, Germany) VAD. Six patients (age, 0.8-14 years; weight, 6.7-29.7 kg) were treated. Diagnoses included cardiomyopathy in 2 and congenital heart disease in 4. VAD support was left VAD in 2 and bi-VAD in 4, with duration of support of 21 to 155 days. Three patients required extracorporeal membrane oxygenation before VAD support. Bivalirudin/epoprostenol was used after recurrent thromboses on conventional medication in 3 patients, heparin-induced thrombocytopenia in 2, and in 1 patient considered high risk with a prosthetic mitral valve. The bivalirudin dose was titrated to partial thromboplastin time (PTT) of 1.5- to 2-times baseline (0.1-0.8 mg/kg/hour); the epoprostenol dose was 2 to 10 ng/kg/min. Additional anti-platelet agents included acetylsalicylic acid, dipyridamole, and clopidogrel in 5 patients each. No bleeding complications occurred. One patient sustained a cerebrovascular infarct on therapy, with subsequent complete recovery. No other complications occurred. Five patients underwent successful transplantation, and 1 patient died of multisystem organ failure. This report provides data on estimated safety and efficacy of bivalirudin and epoprostenol as an AT strategy in pediatric patients on extended VAD support. The short drug half-life and predictable AT response facilitated conversion to standard AT regimens at the time of transplantation (heparin-induced thrombocytopenia-negative patients). These agents should be considered for management of pediatric VAD patients when standard regimens fail.


Allovectin-7 therapy in metastatic melanoma.
Patients with metastatic melanoma are immunosuppressed by the growing tumor. Allovectin-7 therapy is a form of active immunotherapy that aims at immunization of the host with substances designed to elicit an immune reaction that will eliminate or slow down the growth and spread of the cancer. to describe the rationale for immunotherapy with Allovectin-7 and assess its safety profile and efficacy based on the results of completed melanoma clinical trials. we reviewed both the published medical literature and the results of trials pending publication. Allovectin-7 is a safe and active immunotherapeutic agent. It induces local and systemic durable responses in patients with metastatic melanoma.


Comparison of different grinding procedures on the flexural strength of zirconia.
The surface of zirconia ceramic is damaged during grinding, which may affect the mechanical properties of the material. The purpose of this study was to compare the biaxial flexural strength of zirconia after different grinding procedures and to measure the temperature rise from grinding. Forty disk-shaped zirconia specimens (15 × 1.2 mm) with a smaller disk in the center of each disk (1 × 3 mm) were divided into 4 groups (n=10). The specimens were ground with a high-speed handpiece and micromotor with 2 different grinding protocols, continual grinding and periodic grinding (10 seconds grinding with 10 seconds duration), until the smaller disk was removed. Control specimens without the center disk (n=10) were analyzed without grinding. The biaxial flexural strengths of the disks were determined in a universal testing machine at a crosshead speed of 0.5 mm/min. The fracture strength (MPa) was recorded, and the results were analyzed using a 1-way ANOVA, Tukey HSD test, Student's t test, and Pearson correlation test (α=05). All grinding procedures significantly decreased flexural strength (P<.01). The mean flexural strength of the high-speed handpiece groups was higher (815 MPa) than that of the micromotor groups (718 MPa). The temperature values obtained from micromotor grinding (127°C) were significantly higher than those from high-speed handpiece grinding (63°C) (P<.01). Grinding zirconia decreased flexural strength. Zirconia material ground with a high-speed handpiece run continually caused the least reduction in flexural strength.


Idiopathic recurrent acute pancreatitis.
Idiopathic recurrent acute pancreatitis is clinically challenging and has substantial socioeconomic consequences. Investigations are expensive and often reveal little about the cause of the disease. Little is known about the interaction between genetic, environmental, anatomical, and other factors that contribute to the disease. Data on the efficacy, safety, and long-term outcomes of endoscopic therapies are scarce. The effect of idiopathic recurrent pancreatitis on quality of life is often underestimated. A more thorough examination of the causes of the disease and the roles of other associated risk factors is needed, as are well designed clinical studies with robust and objectively measurable outcomes. Ideally, evaluation of the causes of disease and therapy should be done only in specialised centres, should follow a protocol, and all outcomes should be formally assessed.


Natural Good Theories and the Value of Human Dignity.
One of the widely recognized facts about human dignity is its vastly divergent applicability-from highly controversial issues in bioethics to broader topics in political philosophy. A group of theories that this article subsumes under the header "natural good theories" appears to be especially fitted for normatively multifaceted notions like dignity. However, the heavy normative weight the concept of dignity has to bear due to the central position it occupies within these theories creates its own difficulties. As is shown in a discussion of Martha Nussbaum's capability conception of dignity, dignity appears to be unable to mirror the special normative relevance people want to assign to it in cases of great moral misconduct. The article provides a suggestion on how to solve this problem by means of paradigmatic cases that work as material constraints regarding the exact boundaries of dignity violations.


Electromagnetic Navigation Bronchoscopy: Where Are We Now? Five Years of a Single-Center Experience.
Electromagnetic navigation (ENB) is a guidance tool used in the diagnosis of solitary pulmonary nodules (SPNs) and masses. Its diagnostic yield is highly variable (38-71%) and a recent study has put in doubt the role of ENB in sampling SPNs in a real-life setting. The aim of this study is to describe the 5-year experience of our center with ENB, analyzing the population, possible confounding factors, and the diagnostic yield and accuracy of this technique. We conducted a retrospective observational study including all consecutive patients who underwent ENB for SPNs and masses from January 2011 to December 2015. We included 113 patients; 79% had SPNs, 21% masses. The majority were localized in the upper and middle lobes (80%) and 61% presented a bronchus sign. 54% of the patients had a previous negative fluoroscopy-guided bronchoscopy. ENB achieved the diagnosis in 78 patients (69%) with 64 malignant and 14 were benign lesions. The diagnostic yield and accuracy of ENB were respectively 0.69 and 0.76. The only factor influencing the ability to reach a diagnosis was the presence of bronchus sign (p = 0.002). No procedural complications were reported. ENB is a safe procedure with a similar diagnostic yield in the real-life and research setting. Bronchus sign is an important factor in determining the diagnostic yield. ENB efficacy can be maximized by expertise and by a careful selection of each case.


Perspectives of Kennedy's disease.
Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare, adult-onset, X-linked, recessive trinucleotide, polyglutamine (poly-G) disorder, caused by expansion of an unstable CAG-tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome Xq11-12. Poly-Q-expanded AR accumulates in nuclei, undergoes fragmentation and initiates degeneration and loss of motor neurons and dorsal root ganglia. Phenotypically, patients present with weakness and wasting of the facial, bulbar and extremity muscles, sensory disturbances, and endocrinological disturbances, such as gynecomastia and reduced fertility. In the limb muscles weakness and wasting may be symmetric or asymmetric, proximal or distal, or may predominate at the lower or upper limb muscles. There may be mild to severe hyper-CK-emia, elevated testosterone or other sexual hormones, abnormal motor and sensory nerve conduction studies, and neuropathic or rarely myopathic alterations on muscle biopsy. BSMA is diagnosed if the number of CAG-repeats exceeds 40. No causal therapy is available but symptomatic therapy may be beneficial for weakness, tremor, endocrinological abnormalities, muscle cramps, respiratory failure, or dysphagia. The course is slowly progressive and the ability to walk lost only late in life. Only few patients require ventilatory support and life expectancy is only slightly compromised.


Acute Liver Failure Secondary to Drug-Induced Liver Injury.
Drug-induced liver injury (DILI) is the most common cause of acute liver failure (ALF) in Western countries. Without liver transplantation, the mortality rate for ALF approaches greater than 80%. Acetaminophen-related ALF may be associated with a rapid progression but fortunately has a high chance for spontaneous survival compared with idiosyncratic DILI-related ALF. Several prognostic scoring systems for severe DILI have been developed to aid clinicians in selecting patients who require urgent liver transplantation. Patients who undergo liver transplantation for ALF are at risk for early graft loss and death and should be closely followed.


Elevated tear IgG and conjunctival plasma cell infiltrate in a graft versus host disease patient.
Two patients developed graft versus host disease (GvHD) following allogeneic bone marrow transplantation for leukemia. One patient developed acute GvHD 12 days after transplantation, and the second developed chronic GvHD 100 days after transplantation. Tear analysis and conjunctival impression cytology were performed. The results were compared to a normal control and to another patient who was 18 months status post bone marrow transplantation with successfully treated GvHD. Tear sampling on the patient with chronic GvHD revealed greatly elevated IgG levels with an inverse IgG to IgA ratio, as compared with normals. In addition, two of three leukemia patients demonstrated decreased mucin levels in tears. Conjunctival impression cytology from the patient with chronic GvHD revealed an abundance of plasma cells.


Determination of noradrenaline and adrenaline in plasma by a radioenzymatic assay using high pressure liquid chromatography for the separation of the radiochemical products.
Plasma catecholamines are determined by a radioenzymatic assay using high pressure liquid chromatography for the separation of the labelled radiochemical products. Noradrenaline and adrenaline are converted to their O-methylated analogues, normethanephrine and metanephrine, by the enzyme catechol O-methyltransferase in the presence of tritiated S-adenosyl-L-methionine. Non-radioactive carriers are added, whereupon the metanephrines are extracted in an organic phase and re-extracted in an aqueous phase. The aqueous phase is dried, the residue taken up in a phosphate solution and chromatographed. The normetanephrine and metanephrine peaks are collected, converted to vanillin and assayed for radioactivity. The detection limit for noradrenaline is 32 ng/l plasma and for adrenaline 16 ng/l plasma. Intra- and interassay variables are respectively 6.2 and 10% for noradrenaline and 5.3 and 8.8% for adrenaline. The mean supine levels of noradrenaline and adrenaline in normal subjects are 355 and 61 ng/l plasma, respectively. This highly specific procedure takes two days for one person to assay 45 blood samples and can be reduced to one day if the chromatography step is automated.


Finite element analysis of maxillary bone stress caused by Aramany Class IV obturator prostheses.
The retention of an Aramany Class IV removable partial dental prosthesis can be compromised by a lack of support. The biomechanics of this obturator prosthesis result in an unusual stress distribution on the residual maxillary bone. This study evaluated the biomechanics of an Aramany Class IV obturator prosthesis with finite element analysis and a digital 3-dimensional (3-D) model developed from a computed tomography scan; bone stress was evaluated according to the load placed on the prosthesis. A 3-D model of an Aramany Class IV maxillary resection and prosthesis was constructed. This model was used to develop a finite element mesh. A 120 N load was applied to the occlusal and incisal platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis were expressed in MPa. Under posterior load, tensile and compressive stresses were observed; the tensile stress was greater than the compressive stress, regardless of the bone region, and the greatest compressive stress was observed on the anterior palate near the midline. Under an anterior load, tensile stress was observed in all of the evaluated bone regions; the tensile stress was greater than the compressive stress, regardless of the bone region. The Aramany Class IV obturator prosthesis tended to rotate toward the surgical resection when subjected to posterior or anterior loads. The amount of tensile and compressive stress caused by the Aramany Class IV obturator prosthesis did not exceed the physiological limits of the maxillary bone tissue. (J Prosthet Dent 2012;107:336-342).


Paraplegia caused by spinal infection after acupuncture.
Case report of a 64-year-old man with psoas abscesses, epidural abscess and spondylitis after acupuncture. To report a case of paraplegia caused by spinal infection after acupuncture. Seoul, Korea. A 64-year-old man came to an emergency room because of severe back pain. At 3 days prior to visit, the patient received acupuncture therapy to the low back with a needle about 10 cm in length because of back pain. Pain was aggravated gradually for 3 days. Escherichia coli sepsis developed with altered mentality during admission. At hospital day 9, he regained his consciousness and was found to have paraplegia. Abdominal computerized tomography (CT) and lumbar spine magnetic resonance imaging (MRI) revealed abscesses of bilateral psoas muscles and spondylitis with epidural abscess. After conservative management with intravenous administration of antibiotics, infection was controlled but the patient remained paraplegic (ASIA scale C L1 level) without neurological recovery. Paraplegia might result from complications of an acupuncture therapy.


Attitudes Toward Mandatory COVID-19 Vaccination in Germany.
Adequate immunity to COVID-19 apparently cannot be attained in Germany by voluntary vaccination alone, and therefore the introduction of mandatory COVID-19 vaccination is still under consideration. We present findings on the potential acceptance of such a requirement by the German population, and we report on the reasons given for accepting or rejecting it and how these reasons vary according to population subgroup. We used representative data from the Socio-Economic Panel for the period January to December 2021. We linked the respondents' answers concerning mandatory COVID-19 vaccination to information about their sociodemographic characteristics, state of health, political attitudes, and degree of confidence in the judicial and political systems. We analyzed these data using univariate, bivariate, and multivariate statistical methods. Just over half of the respondents (50.44% [49.08%; 51.79%]) favored mandatory COVID-19 vaccination. Among the supporters, the reason most frequently given (95.22% [94.45; 96.00]) was that, without such a requirement, not enough people would be vaccinated. Among the opponents of mandatory COVID-19 vaccination (49.56% [48.21%; 50.92%]), by far the most common reason given for opposing it was a desire to uphold individual freedom (91.36% [90.31%; 92.40%]). Persons supporting mandatory COVID-19 vaccination, on average, older than those who opposed it; they less commonly had an education beyond secondary school, were less healthy, tended to have no children, had centrist political views, and expressed more confidence in the political system. The largest difference between the two groups was that about 90% of supporters of mandatory COVID-19 vaccination were themselves vaccinated, compared to only about 62% of opponents. The lack of consensus on this issue among politicians and physicians in Germany is reflected in a similar lack of consensus in the German population as a whole. A discussion of the appropriate understanding of individual freedom would be the most promising way to widen the acceptance of mandatory COVID-19 vaccination. A commonly expressed conception of freedom that permits the deliberate endangerment of other people's health seems morally questionable.


Degradation of the 34 amino acid gastrin by rat tissue homogenates.
Extracts of rat kidney contain an enzyme (gastrinase) that is highly specific for degradation of the 34 amino acid gastrin (G34). The Michaelis constant (Km) for kidney is 0.36 +/- 0.04 microM and the Vmax is 9.5 +/- 2.4 nmol X g-1 X min-1. Extracts of liver and brain also have gastrin degrading activity but the enzymes responsible appear to be different from the kidney gastrinase. Km for the liver enzyme is 0.08 +/- 0.02 microM but its Vmax (0.10 +/- 0.02 nmol X g-1 X min-1) is only 1% of the kidney gastrinase; Km for the brain enzyme is 0.10 +/- 0.03 microM but its Vmax (0.023 +/- 0.007 nmol X g-1 X min-1) is even lower than for the liver enzyme. The liver and brain enzymes appear to be less specific than the kidney enzyme with respect to competitive inhibition by insulin and glucagon. Cholecystokinin octapeptide is less inhibitory than the other peptides even though it shares a common C-terminal pentapeptide with G34. These findings are consistent with in vivo studies which have demonstrated that the dog kidney is an important site for extraction and degradation of endogenous dog gastrin but there is little or no hepatic removal of G34.


A dye-photosensitized reaction that generates stable protein-protein crosslinks.
Irradiation of fibrinogen with visible light for 30 s in the presence of 1-1000 microM fluorescein was found to crosslink fibrinogen both inter- and intramolecularly. Optimum crosslinking was achieved at dye concentrations of around 100 microM and the amount of crosslinking was shown to increase with pH. Crosslinking was inhibited in the presence of 50 microM tryptophan or tyrosine and enhanced in the presence of 5 mM histidine. Twice as much crosslinking was found to take place under anaerobic conditions. These observations are consistent with a dye-photosensitized reaction following the hydrogen abstraction pathway. The subunits of eukaryotic ribosomes and those of phosphorylase a were also crosslinked by the method described.


Foliar application of sodium selenate induces regulation in yield formation, grain quality characters and 2-acetyl-1-pyrroline biosynthesis in fragrant rice.
Selenium (Se) is a beneficial element for higher plants and essential for mammals. To study the effect of the foliar application of sodium selenate on fragrant rice performance, a pot experiment was conducted in Guangdong, China. At the initial heading stage, one-time foliar application of sodium selenate with concentrations of 0, 10, 20, 30, 40 and 50 μmol·L- 1 (named CK, Se1, Se2, Se3, Se4 and Se5, respectively) were foliar applied on two fragrant rice varieties, 'Meixiangzhan-2' and 'Xiangyaxiangzhan'. Selenate application at the initial heading stage not only improved the grain yield of fragrant rice by increasing the seed-setting rate and grain weight, but also promoted the grain quality by increasing crude protein contents and lowering the chalky rice rate. Furthermore, Se applications enhanced the biosynthesis of 2-acetyl-1- pyrroline (2-AP), the main aromatic compound, by increasing the contents of precursors (△1- pyrroline, proline and pyrroline-5-carboxylic acid (P5C)) and the activities of enzymes (proline dehydrogenase (PRODH), △1-pyrroline-5-carboxylic acid synthetase (P5CS), and ornithine aminotransferase (OAT)) in fragrant rice. The results also showed that foliar application of sodium selenate enhanced the antioxidant system of both varieties by promoting the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and reducing the contents of malondialdehyde (MDA). Furthermore, the real-time PCR analyses depicted that foliar application of selenate up-regulated the GPX1, GPX4 and CATC transcripts. The higher antioxidative enzymatic activities might strength the stress resistant to ensure the stability of yield in fragrant rice form abiotic stress. Foliar applications of sodium selenate at the initial heading stage increased the grain 2-AP content by enhancing the biosynthesis-related enzymes and precursors. The grain yield and quality of fragrant rice also increased due to selenate application. Furthermore, foliar application of selenate promoted the activities of enzymes such as POD, SOD and CAT and up-regulated the expression of gene GPX4, GPX1 and CATC.


Anhydride structures affect the acylation modification and emulsion stabilization ability of mammalian and fish gelatins.
In this work, ring-like anhydrides (C4, C5, and C6) with different sizes and succinic anhydrides (C4, C10, C12, C14, and C16) with different side chain lengths were used to modify bovine bone gelatin (BBG) and cold-water fish skin gelatin (CFG), and the effect of acylated gelatins on fish oil-loaded emulsions stability was explored. The results showed that the degree of N-acylation decreased with increased ring sizes or side chain lengths, and the surface hydrophobicity of acylated gelatins increased with increased anhydride carbon numbers. Acylated CFGs had higher droplet stability and lower liquid-gel transition time than acylated BBGs. Only BBG-C12 had a slight increase on the creaming stability among these acylated gelatins. These results demonstrated that the gelatins could be modified by all the anhydrides and their emulsion stabilization ability was dependent on the gelatin type and anhydride structure. The results could be beneficial for protein-based emulsifier development and application.


Quality of life and voice outcome of patients treated with transoral CO2 laser microsurgery for early glottic carcinoma (T1-T2): a 2-year follow-up study.
Longitudinal studies in laryngeal cancer can provide clinicians information about short-term and long-term functional outcomes, like quality of life (QoL) and voice outcome. This information is important when counseling patients or choosing a primary treatment modality. The present study assessed long-term (2 years) QoL and voice outcome in patients with extended T1 and limited T2 glottic carcinoma treated with transoral CO2 laser microsurgery (TLM) (unilateral type III or bilateral type II resections). Three questionnaires were administered: the Voice Handicap Index (VHI), the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ)-C30, the EORTC QLQ-HN35. A perceptual voice evaluation at six different time points was conducted: preoperatively, and postoperatively at 6 weeks, 3 months, 6 months, 1 year, and 2 years. Fluctuations over time were investigated. Sixty-one patients were included in the analysis. Patients reported high-level functioning and low symptom scores 2 years postoperatively. Gender significantly affected the VHI scores at 2 years (mean VHI scores: female 8.7 vs. male, 23.9; p = 0.023). The major improvement in VHI scores was observed within the first 6 months. The tumor stage (T1a, T1b, and T2) significantly impacted the grade (mean scores at 2 years: 1.0, 1.9, and 1.7; p = 0.001). These scores stabilized at 6 months. Patients show good long-term QoL with low symptom scores, a low voice handicap, and mild to moderate dysphonia, 2 years postoperatively. Scores stabilize at 6 months and provide a clear indication of status at 1 and 2 years.


Feasibility study for production of I-131 radioisotope using MNSR research reactor.
A feasibility study for (131)I production using a Low Power Research Reactor was conducted to predict the yield of (131)I by cyclic activation technique. A maximum activity of 5.1GBq was achieved through simulation using FORTRAN 90, for an irradiation of 6h. But experimentally only 4h irradiation could be done, which resulted in an activity of 4.0×10(5)Bq. The discrepancy in the activities was due to the fact that beta decays released during the process could not be considered.


Calcitonin and bone mass status in congenital hypothyroidism.
Calcitonin (CT) deficiency and its possible repercussions on bone mass were studied in a group of 9 adult patients (7 females, 2 males) with congenital hypothyroidism of dysgenetic origin. Using a new extraction method (exCT) which considerably improves the sensitivity and the specificity of the assay for CT-monomer, we measured CT levels before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 minutes) to evaluate C-cell secretory reserve. Mean basal plasma CT concentrations were lower in the hypothyroid women (mean +/- SEM: 0.6 +/- 0.1 pg/ml) than in 30 normal female controls (1.7 +/- 0.2 pg/ml, P less than 0.001). Serum calcium increased similarly in the two groups, but postinfusion CT levels were lower in the hypothyroid women, (1.7 +/- 0.2 pg/ml) than in normal women (16.8 +/- 2.9 pg/ml), P less than 0.001. Hypothyroid women showed a 10% reduction in bone mineral content at the diaphyseal site in the radius, 0.840 +/- 0.037 g/cm, compared with normal age-matched controls, 0.930 +/- 0.020 g/cm, (P less than 0.05). Our study demonstrates the existence of a profound CT-monomer deficiency in adult patients with thyroid agenesis or dysgenesis. Both calcitonin deficiency and thyroid hormone treatment could play a role in the observed bone loss. Attention should therefore be paid to bone metabolism during treatment of congenital hypothyroidism to avoid further bone loss.


Tissue levels of N-n-propylnorapomorphine after treatment with (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally long-acting prodrug active at central dopamine receptors.
High performance liquid chromatography with electrochemical detection was used to assay N-n-propylnorapomorphine (NPA) and other aporphines. Pretreatment of rats with (-)10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) yielded dose-dependent increases in tissue levels of NPA after oral or parenteral administration. Cerebral levels of NPA significantly paralleled the stereo-typed behavioral effects produced by MDO-NPA at several doses and times. Pretreatment with the microsomal oxidase inhibitor SKF-525A (see Methods) prevented these behavioral effects of MDO-NPA and blocked the formation of NPA in vitro. These results support the suggestion that MDO-NPA is a uniquely orally effective and relatively long-acting aporphine which acts at cerebral dopamine receptors as a prodrug of NPA.


Natural and synthetic peptides (other than neuropeptides) endowed with immunomodulating activities.
A large number of peptides, in most cases of low or relatively low molecular weight, exert immunomodulating activities, i.e., they interact in vitro with various cell populations of the immune system and, in vivo, enhance or depress, according to the case, cell-mediated and humoral immune functions. Immunomodulating peptides include glycopeptides from the bacterial cell wall, natural acyloligopeptide ciclosporin, peptidic hormones from the thytide cyclosporine, peptidic hormones from the thymus, peptidic fragments of immunoglobulins and other plasma proteins, as well as peptides isolated from food proteins. An amazing diversity of structure exists among the various immunomodulating peptides. The molecular mechanisms of interaction between these peptides and the cells of the immune system remain, in most cases, to be elucidated. Possibilities of therapeutic applications exist for many of these immunomodulating peptides: one of them (ciclosporin) is widely used as an immunosuppressive drug, several others (glycopeptides, lipopeptides, tuftsin, thymic peptides) are under clinical investigation as immunostimulating and/or immunorestoring agents.


Adapting a feedforward heteroassociative network to Hodgkin-Huxley dynamics.
Using the original McCulloch-Pitts notion of simple on and off spike coding in lieu of rate coding, an Anderson-Kohonen artificial neural network (ANN) associative memory model was ported to a neuronal network with Hodgkin-Huxley dynamics. In the ANN, the use of 0/1 (no-spike/spike) units introduced a cross-talk term that had to be compensated by introducing balanced feedforward inhibition. The resulting ANN showed good capacity and fair selectivity (rejection of unknown input vectors). Translation to the Hodgkin-Huxley model resulted in a network that was functional but not at all robust. Evaluation of the weaknesses of this network revealed that it functioned far better using spike timing, rather than spike occurrence, as the code. The algorithm requires a novel learning algorithm for feedforward inhibition that could be sought physiologically.


Periappendicular Abscess Presenting within an Inguinal Hernia.
The presence of the appendix within an inguinal hernia is a rare finding. We present the case of an elderly woman who developed appendicitis within an inguinal hernia, complicated by a supervening periappendicular abscess. She was successfully treated with a combination of antibiotics and percutaneous drainage.


Using case-control studies for prescribing research.
In this review, the principles of design, analysis and interpretation of case-control studies are illustrated by considering the evidence from case-control studies that link hormone replacement therapy to venous thromboembolism.


The comparative gastric ulcerogenic activities of non-steroid anti-inflammatory drugs.
A new gastric assay was employed to screen for the ulcerogenic activity of non-steroid anti-inflammatory (NSAI) analgesic drugs. The technique involves exposing rats to brief periods of cold stress, which is not itself sufficient to cause mucosal damage, but does specifically sensitize the stomach to irritant or ulcerogenic actions of NSAI drugs. The assessment of gastric ulcerogenicity of some well-known anti-inflammatory/analgesic drugs using this new assay was shown to agree well with clinical reports of the occurrence of gastric ulceration and haemorrhage. This assay was employed to screen for the ulcrogenicity of some new anti-inflammatory drugs and for potential drug interactions resulting from administration of certain frequently used combinations of these drugs.


Characterization of nasal irrigation flow from a squeeze bottle using computational fluid dynamics.
Nasal saline irrigation has become standard of care in various sinonasal conditions, including allergic and nonallergic rhinitis, chronic rhinosinusitis, and in the postoperative patient. Evidence regarding the mechanisms and dynamics of liquid flow through the sinonasal cavity remains limited due to inadequate experimental models (cadaveric, 3-dimensional [3D] printed, imaging of labeled dyes and radioisotopes). We aimed to develop a computational fluid dynamics (CFD) model of nasal irrigation to demonstrate sinonasal surface coverage, residence times across the mucosal surfaces, and shearing force of irrigation. A nasal cavity geometry derived from high-resolution paranasal sinus computed tomography (CT) scans of a healthy, unoperated, 25-year-old patient was created. CFD analysis was performed to assess the distribution of nasal irrigation from a tapered nozzle bottle at a forward head-tilt position of 45 degrees with a 2-second burst at 35 mL/second. The model demonstrates nasal irrigation from ipsilateral to contralateral with precise measures of velocity, pressure, wall shear stress, and mapping of surface coverage and residence times at specific locations and times. The nasal cavity experiences almost complete coverage of irrigation, while overflow from the nasal cavity facilitates moderate coverage of the ipsilateral maxillary (40%) and anterior ethmoid sinuses (30%). Negligible coverage of the sphenoid and frontal sinuses was noted. Detailed physical mechanisms of liquid irrigation injected from a commonly used squeeze bottle were shown. Ipsilateral maxillary and ethmoid sinus penetration are primarily due to overflow rather than direct jet entry, confirming the recommendation of larger volumes of irrigation to "flood" the sinus ostia.


Objections to the proposition of the new genera Protaetiibacter and Pseudolysinimonas.
Our principal conclusions state that Lysinimonas kribbensis and Lysinimonas soli strains, actually constitute a single coherent group at 16S rRNA gene level, and Protaetiibacter intestinalis is phylogenetically and genomically consistent with the genus Leifsonia and its nomenclature must be amended.


Parental bonding after preterm birth: child and parent perspectives in the Helsinki study of very low birth weight adults.
To examine whether parenting behavior recalled by very low birth weight (VLBW) adults or their parents differs from that of term-born control subjects or their parents. A total of 164 VLBW and 172 control adults (mean age 22.5 years, SD 2.2) assessed retrospectively the parenting behavior of their parents by the Parental Bonding Instrument, which includes dimensions of care, protectiveness, and authoritarianism. A subgroup of 190 mothers and 154 fathers assessed their own parenting behavior by the Parent Behavior Inventory, which includes dimensions of supportive and hostile parenting. The VLBW women assessed their mothers as more protective and authoritarian than the control women. The VLBW and control men did not differ from each other. Both mothers and fathers of the VLBW adults assessed their own parenting as more supportive than those of the control subjects. Preterm birth at VLBW may promote a more protective, as well as more supportive, parenting style.


CuO nanoparticles doping recovered the photocatalytic antialgal activity of graphitic carbon nitride.
In this work, graphitic carbon nitride (g-C3N4) and CuO nanoparticles doped g-C3N4 (Cu-g-C3N4) was synthesized, and the mechanisms of humic acid (HA) impact on the photocatalytic antialgal activities of g-C3N4 and Cu-g-C3N4 to harmful algae were investigated. The 72 h median effective concentrations of g-C3N4 and Cu-g-C3N4 to two algae (Microcystis aeruginosa, Chlorella vulgaris) were (56.4, 89.6 mg/L) and (12.5, 20.6 mg/L), respectively. Cu-g-C3N4 exhibited higher photocatalytic antialgal activity than g-C3N4 because that: I) Cu-g-C3N4 was easier to aggregate with algal cells due to its lower surface potential and higher hydrophobicity than g-C3N4; II) Cu-g-C3N4 generated more O2-, OH*, and h+ due to its higher full-wavelength light utilization efficiency and higher electron-hole pairs separation efficiency than g-C3N4. HA (10 mg/L) inhibited the photocatalytic antialgal activity of g-C3N4, however, HA had no effect on that of Cu-g-C3N4. The mechanisms were that: I) doped CuO nanoparticles occupied the adsorption sites of HA on g-C3N4, which alleviated the inhibition of HA on the g-C3N4-algae heteroaggregation; II) HA adsorbed on CuO nanoparticles enhanced the oxygen reduction rate of Cu-g-C3N4. This work provides new insight into the inhibition mechanisms of NOM on g-C3N4 photocatalytic antialgal activity and addresses the optimization of g-C3N4 for environmental application.


Selective processing of linguistic and pictorial food stimuli in females with anorexia and bulimia nervosa.
This study investigated subjects with eating disorders' selective attention to linguistic and pictorial representations of food stimuli in a version of the Stroop color-naming task. If subjects with eating disorders' attention really are biased by food stimuli, one would expect equally delayed color-naming latencies to food pictures as previous studies have found to food words. Twenty females with eating disorders (anorexia nervosa, bulimia nervosa, or a combination of both) and 24 female controls identified the color of Stroop versions of linguistic and pictorial representations of color, food, emotional, and neutral stimuli. The eating disorder group was slower than the controls in identifying the color of all words (including the food words) and the pictures depicting food stimuli (but not any of the other pictures). The eating disorder group was also slower in identifying the color of both food and emotional than neutral stimuli, both for the linguistic and pictorial stimuli. These findings indicate that females with bulimia and anorexia nervosa's biased attention to food stimuli are not restricted to linguistic representations. The delayed responses to the emotional words and pictures suggest that processing of negative emotional stimuli, in addition to dysfunctional concerns about stimuli related to food and eating, is important in the maintenance of eating disorders.


Noninvasive assessment of cardiomyopathy in normotensive diabetic patients between 20 and 50 years old.
To further the understanding of diabetic heart disease, we tested the hypothesis that an asymptomatic group of normotensive diabetic patients between 20 and 50 years old had a restrictive cardiomyopathy independent of clinically significant coronary artery disease. Quantitative two-dimensional echocardiography and stress myocardial perfusion scintigraphy were performed to detect and characterize the cardiac abnormalities in this study group comprising 88 patients with rigorously classified diabetes and 65 volunteer control subjects. Diabetic patients were shown to have a mildly reduced left ventricular end-diastolic volume index: 50.1 +/- 8.2 and 52.1 +/- 14.7 mL/m2 for patients with type I and type II diabetes, respectively, versus 58.9 +/- 11.7 mL/m2 for control subjects. The left ventricular diastolic filling was also impaired in diabetic patients as reflected by a lower atrial emptying index: 0.73 +/- 0.24 and 0.76 +/- 0.3 for type I and type II diabetics, respectively, compared with 1.14 +/- 0.24 for control subjects. Exercise tolerance was normal in subjects with type I diabetes and slightly reduced in subjects with type II diabetes. Only one patient developed regional ischemia on thallium exercise testing. Using a comprehensive, noninvasive approach, we have shown that asymptomatic normotensive patients with type I or type II diabetes who were between 20 and 50 years old had a restrictive cardiomyopathy characterized by mildly reduced left ventricular end-diastolic volume and altered left ventricular compliance independent of critical coronary artery disease.


A review of 79 cases of eyelid dermatitis.
Seventy-nine patients with eyelid dermatitis and 1012 patients with dermatitis at other sites were assessed with patch tests. Eighty-nine percent of the eyelid cases involved women. Only the eyelids were involved in 78.5% of cases. Of the patients with eyelid dermatitis 46% had allergic contact dermatitis, 15% had irritant contact dermatitis, and 23% had atopic dermatitis. Only 13% were work related. Positive reactions to patch tests for cinnamic alcohol, diazolidinyl urea, and neomycin sulfate occurred more frequently, whereas those for cobalt and nickel occurred less frequently, in patients who had eyelid dermatitis when compared to the reactions of patients who did not have eyelid dermatitis.


Use of exercise thallium-201 imaging for risk stratification of elderly patients with coronary artery disease.
Although coronary artery disease (CAD) may be asymptomatic, it is the most common cause of death in elderly patients in the U.S. This study examined the prognosis of 449 patients with a mean age of 65 years using exercise thallium-201 imaging. At a follow-up of 25 months, 45 patients underwent coronary artery revascularization, 8 died of cardiac causes and 10 had nonfatal acute myocardial infarctions (AMIs). Thus the total of patients with "hard" events was 18. The events included 12 of 276 patients with atypical or non-anginal symptoms versus 6 of 128 with typical angina (p = not significant); 7 of 51 patients (14%) with Q-wave AMI versus 11 of 353 (3%) without Q-wave AMI (p less than 0.001); 1 of 183 patients (1%) with normal versus 17 of 221 (8%) with abnormal exercise thallium-201 images (p less than 0.002); 10 of 76 patients (13%) with multi vessel thallium-201 abnormality vs 8 of 328 (2%) with no or 1-vessel thallium-201 abnormality (p less than 0.001) and 10 of 96 patients (10%) with greater than or equal to 3 abnormal segments by thallium-201 imaging (total segments = 9) versus 8 of 308 patients with no or less than 3 abnormal segments (p less than 0.001). The number of segments with thallium-201 defects was 1 +/- 2 patients without and 3 +/- 2 in patients with hard events (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)


Integrating buprenorphine maintenance therapy into federally qualified health centers: real-world substance abuse treatment outcomes.
Few studies have examined real-world effectiveness of integrated buprenorphine maintenance treatment (BMT) programs in federally qualified health centers (FQHCs). Opioid dependent patients (N=266) inducted on buprenorphine between July 2007 and December 2008 were retrospectively assessed at Connecticut's largest FQHC network. Six-month BMT retention and opioid-free time were collected longitudinally from electronic health records; 136 (51.1%) of patients were followed for at least 12 months. Participants had a mean age of 40.1 years, were primarily male (69.2%) and treated by family practitioners (70.3%). Co-morbidity included HCV infection (59.8%), mood disorders (71.8%) and concomitant cocaine use (59%). Retention on BMT was 56.8% at 6 months and 61.6% at 12 months for the subset observed over 1 year. Not being retained on BMT at 12 months was associated with cocaine use (AOR=2.18; 95% CI=1.35-3.50) while prescription of psychiatric medication (AOR=0.36; 95% CI 0.20-0.62) and receiving on-site substance abuse counseling (AOR=0.34; 95% CI 0.19, 0.59) improved retention. Two thirds of the participants experienced at least one BMT gap of 2 or more weeks with a mean gap length of 116.4 days. Integrating BMT in this large FQHC network resulted in retention rates similarly reported in clinical trials and emphasizes the need for providing substance abuse counseling and screening for and treating psychiatric comorbidity.


Insulin sensitivity: gender-related differences in subjects with normal glucose tolerance.
To verify whether age and the perimenopausal state may herald the onset of the metabolic syndrome (MS) in females as compared to age-matched males, we studied subjects with normal glucose tolerance, according to ADA definition. In 368 eligible subjects subdivided into three age groups we measured insulin sensitivity by ISI-glycaemia, resistance by HOMA-IR, computed, during OGTT, from fasting and 2-h post-load plasma insulin and glucose concentrations. The significance of differences was tested between different age groups and between males and females within corresponding age groups. Insulin sensitivity fell slightly and insulin resistance rose significantly in the perimenopausal group as compared to younger and older female patients, and compared to men of the same age. This pattern remains after excluding patients with high blood pressure, and after adjusting for WHR and BMI by multivariate analysis. HOMA-IR averaged 2.9+/-1.8 in females, 2.2+/-1.2 in men aged 45-54 years (p<0.02), while in the other age groups insulin resistance was higher in men. The onset of MS during the menopause is associated with a physiological shift in insulin resistance occurring even in normal glucose tolerant subjects, suggesting that it may depend upon critical metabolic changes occurring specifically in that age period.


Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients.
Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG.


Almost anyone can have home therapy but can we overcome the barriers?
Home dialysis, including both peritoneal and haemodialysis, has been shown to improve patient wellbeing as well as being an economically beneficial alternative to hospital-based therapies. This paper discusses the major barriers to home therapies, particularly in relation to home haemodialysis (HHD) and systems that can be used to overcome them. The use of HHD varies considerably between and within countries. The major limitation is lack of experience and education. A well-planned pre-dialysis education programme seems to be one essential key to the growth of home therapies. Key points in providing a successful home therapy programme are a highly motivated multidisciplinary team including a dedicated nephrologist and high-level nursing expertise. In addition, an effective pre-dialysis education programme for identifying suitable patients is required.


Transpiration rates decline under limited moisture supply along hillslopes in a humid karst terrain.
Topographic positions can mediate subsurface water availability, but its effects on tree transpiration are controversial. In humid karst regions, climax forests are usually not limited by moisture supply, even at the summit, through absorbing water from deep layers. However, little is known on the transpiration pattern and its limiting factor on the shrubland widely distributed along the karst hillslopes. In the current study, Rhus chinensis, a widely spread constructive species in natural restoration was selected. Meteorological factors, 0-300 cm soil-epikarst moisture, sap flow, and root water uptake were studied during an entire growing season to assess how hillslope positions affected transpiration. We found the mean water content in uphill was only around 60 % of that in downhill, indicating a contrasting water supply along the slope. However, there were no significant differences in the xylem isotopic composition and lc-excess which suggested the similar water uptake strategies in both uphill and downhill. R. chinensis primarily relied on the soil water rather than epikarst water (groundwater) along the hillslope because of the MixSIAR model results and more negative lc-excess values (-13.18 ‰). R. chinensis exhibited decreases of nearly half in the transpiration rate and amount in uphill compared to those in downhill. In downhill with sufficient water availability, transpiration followed the variation in atmospheric water demand. In uphill, a poor moisture supply limited tree transpiration and its response to atmospheric water demand. Our findings revealed that the early successional species did not entirely depend on atmospheric water demand, absorbing deep epikarst water as the mature forest. The transpiration rates of those species declined by nearly half to adapt to the water-limited environment along the hillslope in the humid karst region. This study can contribute to the evaluation of eco-hydrological functions during natural restoration.


Prognosis and response to therapy in colorectal cancer.
Colorectal cancer is Europe's second biggest cancer killer. Yet despite advances in knowledge and changes in chemotherapy practice, we have not seen great strides in improved survival. Histopathological staging is at present the most accurate prognostic factor for survival and recurrence. Improvements in staging have led to the recognition of the importance of the circumferential resection margin (CRM) and how the quality of surgery influences local recurrence rates. Further refinements in staging and increasing knowledge of tumour biology will have a large contribution to play in the future.


Feline restrictive orbital myofibroblastic sarcoma treated with toceranib phosphate (Palladia) as adjuvant chemotherapy: A case study of one cat.
This is the first case report of treatment with toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS. This reported case highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS. Feline restrictive orbital myofibroblastic sarcoma (FROMS) is a rare aggressive tumor in cats. We explored the effectiveness of using toceranib phosphate as postsurgical adjuvant chemotherapy for advanced FROMS in a 7-year-old cat. Despite treatment, the cat died 4 months after surgery. This report highlights the need for further studies on the efficacy of toceranib phosphate as adjuvant chemotherapy for FROMS.


Performance characteristics of an automated PCR assay for the quantification of cytomegalovirus DNA in plasma.
The COBAS Amplicor CMV Monitor test (Roche Diagnostics), an automated polymerase chain reaction (PCR) assay for the quantification of cytomegalovirus (CMV) DNA in plasma samples, was evaluated in a routine diagnostic laboratory. Using cell culture-derived CMV and CMV-negative human plasma, the linear detection range of the assay as well as its intra-and inter-assay variabilities were assessed. The study design allowed distinguishing variations in results related to amplification and detection from those caused by differences in the efficiency of DNA extraction. The assay was able to identify the majority of samples correctly as positive with CMV DNA concentrations above the limit of detection. However, the reported values were often twofold or more different from the (theoretical) input, which could be explained partly by inefficient DNA extraction. The following values were computed for the coefficients of determination R(2): inter-assay variability excluding DNA extraction, R(2)=0.982; including DNA extraction, R(2)=0.977; intra-assay variability excluding DNA extraction, R(2)=0.992; including DNA extraction, R(2)=0.992. On balance, the test has acceptable within-run and between-run reproducibility. It therefore allows the comparison of results obtained at different time-points as well as in different laboratories, e.g. in multi-centre studies.