Conventional Chemoembolization Plus Radiofrequency Ablation versus Surgical Resection for Single, Medium-Sized Hepatocellular Carcinoma: Propensity-Score Matching Analysis.
To retrospectively compare long-term outcomes of conventional chemoembolization plus radiofrequency (RF) ablation vs those of surgical resection in patients with a single 3-5-cm hepatocellular carcinoma (HCC). From January 2008 to December 2017, 139 of 623 patients who underwent surgical resection and 60 of 186 patients who underwent chemoembolization/RF ablation in a single center were compared with respect to local tumor progression (LTP), intrahepatic distant recurrence (IDR), disease-free survival (DFS), overall survival (OS), major complications, and hospital stay before and after propensity-score matching. Mean follow-up periods were similar in the chemoembolization/RF ablation and surgical resection groups (41.9 mo vs 48.4 mo). Three (5%) and 17 (28.3%) patients in the chemoembolization/RF ablation group and 12 (8.6%) and 57 (41.0%) patients in the surgical resection group showed LTP and IDR (P = .366 and P =.114, respectively). At 1, 3, and 5 years, respective DFS rates were 88.1%, 65.3%, and 49.0% for chemoembolization/RF ablation and 84.2%, 58.2%, and 46.5% for surgical resection (P = .294). Moreover, respective OS rates were 95.0%, 73.5%, and 54.0% for chemoembolization/RF ablation and 97.1%, 87.4%, and 75.0% for surgical resection (P = .055). After matching (n = 52), therapeutic outcomes remained similar (P = .370, P = .110, P = .230, and P = .760, respectively). Surgical resection was associated with higher complication rates (P = .015) and longer hospital stays (8.4 d ± 3.7 vs 16.9 d ± 7.0; P < .001). Conventional chemoembolization combined with RF ablation may be feasible for single 3-5-cm HCCs, with comparable therapeutic outcomes vs surgical resection and shorter hospital stays.


circNR3C1 Suppresses Bladder Cancer Progression through Acting as an Endogenous Blocker of BRD4/C-myc Complex.
Bromodomain-containing protein 4 (BRD4), the core component of transcriptional regulatory elements, plays a significant role in tumorigenesis and aggressiveness. However, the mechanisms regulating the functions of BRD4 in bladder cancer (BC) still remain elusive. Herein, we identify one exonic circular RNA (circRNA) generated from NR3C1 gene (circNR3C1) as a regulator of BRD4/C-myc complex. Our previous study indicated that BRD4 and C-myc promoter region form a complex, allowing C-myc to function as a transcription factor for BC progression. In the present study, mechanism studies reveal that circNR3C1 could interact with BRD4 protein, dissociating the formation of BRD4/C-myc complex. In vivo, ectopic expression of C-myc partly reverses the tumorigenesis of xenografts circNR3C1-induced in nude mice. Conclusively, these results demonstrate that circNR3C1 inhibits BC progression through acting as endogenous blocker of BRD4/C-myc complex.


Identification of an intracellular β-glucosidase in Aspergillus niger with transglycosylation activity.
Aspergillus niger is featured with its copious amount of extracellular β-glucosidase which is generally used to balance the cellulolytic enzyme cocktails for lignocellulose saccharification. However, whether or not A. niger produces any intracellular β-glucosidase remains obscure. In this study, we analyzed a total of fifteen putative β-glucosidase genes (bgls) in A. niger CBS 513.88 genome and the five of them were predicted as intracellular bgls due to the lack of signal peptide of extracellular proteins. After further characterization of these five genes through a Saccharomyces cerevisiae in vivo system, only An03g03740 (designated bgl1B) was confirmed to be a β-glucosidase gene. Western blot and mass spectrometry analysis confirmed BGL1B protein localization inside the cell. BGL1B exhibited the maximal activity at 40 °C and pH 5.6. The Km for p-nitrophenyl-β-D-glucopyranoside and Ki for glucose were 0.233 ± 0.058 mM and 119.8 ± 4.35 mM, respectively. BGL1B showed a strong transglycosylation activity while hydrolyzing cellodextrins with sophorose, laminaribiose, and cellotriose formed from cellobiose, and sophorose and laminaribiose formed from cellotriose. The confirmation of the intracellular β-glucosidase BGL1B in A. niger further extends our understanding of how A. niger utilizes lignocellulose. KEY POINTS: • Identification of putative genes revealed a novel β-glucosidase in Aspergillus niger. • Newly identified β-glucosidase BGL1B was an intracellular enzyme of A. niger. • BGL1B exhibited a strong transglycosylation activity.


A post hoc pooled analysis of exacerbations among US participants in randomized controlled trials of tiotropium.
Exacerbations are a defining outcome of chronic obstructive pulmonary disease (COPD). We evaluated the effect of tiotropium on COPD exacerbations and related hospitalizations among patients from the USA enrolled in clinical trials. Data were pooled from six randomized, double-blind, placebo-controlled trials (6 to ≥ 12 months' duration) of tiotropium in patients with COPD. Exacerbations were defined retrospectively as an increase in or new onset of >1 respiratory symptom lasting for ≥ 3 days and requiring treatment with systemic corticosteroids and/or antibiotics. Time to first exacerbation or hospitalization and exacerbation rates were analyzed at 6 months, and at 1 year for studies ≥ 1 year. In total, 4355 patients (tiotropium, 2268, placebo, 2087; mean age 66.5 years; forced expiratory volume in 1 s [FEV1] 1.03 L [35.5% predicted]) were analyzed at 6 months and 2455 at 1 year (tiotropium 1317, placebo 1138; mean age 65.5 years; FEV1 1.03 L [37.0% predicted]). Tiotropium delayed time to first exacerbation or first hospitalized exacerbation at 6 months (hazard ratios [HRs], 0.80, 0.65, respectively; p < 0.001 vs placebo) and 1 year (HRs, 0.73 and 0.55; p < 0.001 vs placebo) and reduced exacerbation rates and hospitalization rates (6 months: HRs, 0.79, 0.64; 1 year: HRs, 0.78, 0.56, respectively; all p < 0.01 vs placebo). Tiotropium significantly reduced exacerbations, irrespective of inhaled corticosteroid use at baseline. Tiotropium was not associated with an increased risk of cardiac-related events. Tiotropium significantly reduced the risk and rates of exacerbations and hospitalizations among US patients with COPD.


Transition and transfer from pediatric to adult health care in epilepsy: a families' survey on Dravet syndrome.
We used a questionnaire to ascertain the perception of transition and transfer from pediatric to adult health-care system in patients with Dravet syndrome and their families. Sixty families received the questionnaire. We had a response rate of 85%. Sixty-one percent of patients experienced a transfer. Factors that positively impacted transfer were the quality of transition preparation (p<.000001), a longer duration of follow-up by the same child neurologist (p<.001), the availability of the child neurology staff (p<.01), a transfer into the adult health-care system after the age of 18 (p<.01), and a stable medical condition before transfer (p<.05). All families reported a positive experience in the pediatric health-care system. Child neurologists were considered as welcoming, available, and helpful. Their experience in the adult health-care system was similar to pediatric care. Almost all patients who experienced "transfer" reported no gap in this process.


Novel derivatives of 6-mercaptopurine: synthesis, characterization and antiproliferative activities of S-allylthio-mercaptopurines.
Biologically active S-allylthio derivatives of 6-mercaptopurine (6-MP) and 6-mercaptopurine riboside (6-MPR) were synthesized. The products, S-allylthio-6-mercaptopurine (SA-6MP) and S-allylthio-6-mercaptopurine riboside (SA-6MPR) were characterized. The antiproliferative activity of the new prodrugs was tested on human leukemia and monolayer cell lines, and compared to that of their parent reactants. The new prodrugs acted by a concentration-dependent mechanism. They inhibited cell proliferation and induced-apoptosis more efficiently than the parent molecules. Leukemia cell lines were more sensitive to the new prodrugs than monolayer cell lines. Higher hydrophobicity of the derivatives improves their penetration into cells, where upon reaction with glutathione, S-allylthioglutathione (GSSA) is formed, and 6-MP or 6-MPR is released for further processing.


Proteasome activation as a novel anti-aging strategy.
Aging and longevity are two multifactorial biological phenomena whose knowledge at molecular level is still limited. We have studied proteasome function in replicative senescence and cell survival (Mol Aspects Med 35, 1-71, 2014). We have observed reduced levels of proteasome content and activities in senescent cells due to the down-regulation of the catalytic subunits of the 20S complex (J Biol Chem 278, 28026-28037, 2003). In support, partial inhibition of proteasomes in young cells by specific inhibitors induces premature senescence which is p53 dependent (Aging Cell 7, 717-732, 2008). Stable over-expression of catalytic subunits or POMP resulted in enhanced proteasome assembly and activities and increased cell survival following treatments with various oxidants. Importantly, the developed "proteasome activated" human fibroblasts cell lines exhibit a delay of senescence by approximately 15% (J Biol Chem 280, 11840-11850, 2005; J Biol Chem 284, 30076-30086, 2009). Our current work proposes that proteasome activation is an evolutionary conserved mechanism, as it can delay aging in various in vivo systems. Moreover, additional findings indicate that the recorded proteasome activation by many inducers is Nrf2-dependent (J Biol Chem 285, 8171-8184, 2010). Finally, we have studied the proteolysis processes of various age-related proteins and we have identified that CHIP is a major p53 E3 ligase in senescent fibroblasts (Free Rad Biol Med 50, 157-165, 2011).


Case report: Bilateral emphysematous pyelonephritis with pneumatosis intestinalis.
Emphysematous pyelonephritis is a severe and rare gas producing infection in the renal parenchyma or collecting system. Diabetes mellitus is an established risk factor. Treatment options include antibiotics, minimally invasive management such as percutaneous drainage, or nephrectomy. This case report describes a 40-year-old female with newly diagnosed diabetes and cirrhosis who presented with left sided emphysematous pyelonephritis. After initial management with intravenous antibiotics and drainage of the collecting system, this patient's clinical condition worsened, and subsequent repeat imaging revealed bilateral emphysematous pyelonephritis as well as pneumatosis intestinalis.


Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry.
Patients with Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or secondary prophylaxis. On the other hand, disease-related bleeding complications (i.e., from esophageal varices) are common in patients with MPN. This analysis was performed to define the frequency of such events, identify risk factors, and assess antiplatelet/anticoagulant therapy in a cohort of patients with MPN. The MPN registry of the Study Alliance Leukemia is a non-interventional prospective study including adult patients with an MPN according to WHO criteria (2008). For statistical analysis, descriptive methods and tests for significant differences as well as contingency tables were used to identify the odds of potential risk factors for vascular events. MPN subgroups significantly differed in sex distribution, age at diagnosis, blood counts, LDH levels, JAK2V617F positivity, and spleen size (length). While most thromboembolic events occurred around the time of MPN diagnosis, one third of these events occurred after that date. Splanchnic vein thrombosis was most frequent in post-PV-MF and MPN-U patients. The chance of developing a thromboembolic event was significantly elevated if patients suffered from post-PV-MF (OR 3.43; 95% CI = 1.39-8.48) and splenomegaly (OR 1.76; 95% CI = 1.15-2.71). Significant odds for major bleeding were previous thromboembolic events (OR = 2.71; 95% CI = 1.36-5.40), splenomegaly (OR = 2.22; 95% CI 1.01-4.89), and the administration of heparin (OR = 5.64; 95% CI = 1.84-17.34). Major bleeding episodes were significantly less frequent in ET patients compared to other MPN subgroups. Together, this report on an unselected "real-world" cohort of German MPN patients reveals important data on the prevalence, diagnosis, and treatment of thromboembolic and major bleeding complications of MPN.


Estimation of the Ideal Lumbar Lordosis to Be Restored From Spinal Fusion Surgery: A Predictive Formula for Chinese Population.
A prospective, cross-sectional study. To determine the independent variables associated with lumbar lordosis (LL) and to establish the predictive formula of ideal LL in Chinese population. Several formulas have been established in Caucasians to estimate the ideal LL to be restored for lumbar fusion surgery. However, there is still a lack of knowledge concerning the establishment of such predictive formula in Chinese population. A total of 296 asymptomatic Chinese adults were prospectively recruited. The relationships between LL and variables including pelvic incidence (PI), age, sex, and body mass index were investigated to determine the independent factors that could be used to establish the predictive formula. For the validation of the current formula, other 4 reported predictive formulas were included. The absolute value of the gap between the actual LL and the ideal LL yielded by these formulas was calculated and then compared between the 4 reported formulas and the current one to determine its reliability in predicting the ideal LL. The logistic regression analysis showed that there were significant associations of LL with PI and age (R = 0.508, P < 0.001 for PI; R = 0.088, P = 0.03 for age). The formula was, therefore, established as follows: LL = 0.508 × PI - 0.088 × Age + 28.6. When applying our formula to these subjects, the gap between the predicted ideal LL and the actual LL was averaged 3.9 ± 2.1°, which was significantly lower than that of the other 4 formulas. The calculation formula derived in this study can provide a more accurate prediction of the LL for the Chinese population, which could be used as a tool for decision making to restore the LL in lumbar corrective surgery. 3.


Epitope mapping with ELISA of an antibody against oxytocin used for the characterization of an oxytocin-like epitope in the sex segmental ganglia of the leech Erpobdella octoculata.
1. Using direct, inhibiting and competitive enzyme-linked immunosorbent assay (ELISA), two steps were involved in the mapping of the recognition site of a polyclonal antibody against oxytocin (OT). 2. The percentage of cross-reactivity between OT and the N-terminal or the C-terminal fragment of OT demonstrated that the C-terminal fragment is the antigenic part of OT. 3. The percentage of cross-reactivity between OT and other molecules of the OT family indicated that the amino acid in the 8-position and the C-terminal amide of the OT molecule contribute to the recognition. 4. In the two sex segmental ganglia of the leech Erpobdella octoculata, where cells immunoreactive to the anti-OT are detected, the antibody has allowed to characterize an epitope close to the mammalian OT by its C-terminal part.


Chronic inflammatory demyelinating polyneuropathy with anti-NF155 IgG4 in China.
Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) seropositive for autoantibodies against nodal and paranodal proteins display distinct clinical presentations. We herein tested for autoantibodies against neurofascin (NF) 155, NF186, contactin-associated protein 1 and contactin-1 and investigated the autoantibody-related clinical features in 29 patients with CIDP from China. Six patients with anti-NF155 IgG4 antibodies displayed younger age of onset and poor response to intravenous immunoglobulin than seronegative patients. One patient had anti-NF186 IgG antibody and no patients had anti-contactin-associated protein 1 or anti-contactin-1 antibodies. Clinical features of CIDP patients with anti-NF155 antibodies in China were similar to those reported in other countries.


Recent Advances in Isolation, Synthesis and Biological Evaluation of Terrein.
Terrein is a small-molecule polyketide compound with a simple structure mainly isolated from fungi. Since its discovery in 1935, many scholars have conducted a series of research on its structure identification, isolation source, production increase, synthesis and biological activity. Studies have shown that terrein has a variety of biological activities, not only can inhibit melanin production and epidermal hyperplasia, but also has anti-cancer, anti-inflammatory, anti-angiopoietic secretion, antibacterial, insecticidal activities, and so on. It has potential application prospects in beauty, medicine, agriculture and other fields. This article reviews the process of structural identification of terrein since 1935, and summarizes the latest advances in its isolation, source, production increase, synthesis, and biological activity evaluation, with a view to providing a reference and helping for the in-depth research of terrein.


[Brucellosis with hepatic lesions: A diagnosis to keep in mind].
Brucellosis is a rare infection in France and its wide spectrum of clinical presentation can be a diagnostic challenge. We report here the case of a 76-year-old Tunisian-born woman referred for fatigue, weight loss, intermittent fever, and pain in the right upper quadrant, along with hepatic lesions on CT-scan, MRI and PET-FDG suggesting malignant lesions. However blood cultures were positive to Brucella melitensis leading to a diagnosis of hepatic brucelloma. Hepatic abscesses are rare in brucellosis. This infection has to be evoked in patients coming from endemic areas even with atypical manifestations.


Diagnostic accuracy of REM sleep behaviour disorder screening questionnaire: a meta-analysis.
A screening tool can greatly facilitate the identification of individuals with rapid eye movement (REM) sleep behaviour disorder (RBD). Currently, the REM sleep behaviour disorder screening questionnaire (RBDSQ) is widely used, but its diagnostic accuracy has varied across previous studies. The aim of the present study was to systematically assess the diagnostic performance of the RBDSQ. We comprehensively searched for studies that evaluated the diagnostic performance of the RBDSQ. A bivariate mixed-effects model was used to summarize the diagnostic accuracy of the RBDSQ. Subgroup analyses were performed according to the study design and the different populations included in the studies. Ten studies were included. Using a cutoff value of 5, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.91 (95% CI 0.85-0.95), 0.77 (95% CI 0.66-0.85), 4.00 (95% CI 2.60-6.10), 0.12 (95% CI 0.07-0.19), and 34 (95% CI 16-71), respectively. A subgroup analysis revealed that the RBDSQ had excellent diagnostic accuracy for RBD screening in the general population. However, its performance in specific patient populations, especially patients with Parkinson's disease, was less satisfactory. In conclusion, the RBDSQ is an effective diagnostic screening tool for RBD in the general population, but its performance in subjects with specific neurological disorders requires more comprehensive assessments.


Single doses of ofloxacin in uncomplicated gonorrhoea.
The clinical efficacies of 2 different single-dose oral treatments of ofloxacin were evaluated in a double-blind, randomised study of 60 males with gonococcal urethritis. 30 patients received a single dose of ofloxacin 100mg and 30 received a single dose of ofloxacin 200mg. The minimal inhibitory concentrations of ofloxacin against all isolates were less than or equal to 0.25 mg/L. Neisseria gonorrhoeae was eradicated from all 50 patients evaluated and clinical cure was achieved in 84%. In total, 8 patients developed post-gonococcal urethritis, although there was a significantly (p less than 0.05) lower rate of post-gonococcal urethritis in the group treated with ofloxacin 200mg. In conclusion, a single oral dose of ofloxacin 100mg could be an alternative treatment for uncomplicated gonorrhoea.


Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant -7m8.
Recently, we described a modified AAV2 vector-AAV2-7m8-having a capsid-displayed peptide insertion of 10 amino acids with enhanced retinal transduction properties. The insertion of the peptide referred to as 7m8 is responsible for high-level gene delivery into deep layers of the retina when virus is delivered into the eye's vitreous. Here, we further characterize AAV2-7m8 mediated gene delivery to neural tissue and investigate the mechanisms by which the inserted peptide provides better transduction away from the injection site. First, in order to understand if the peptide exerts its effect on its own or in conjunction with the neighboring amino acids, we inserted the 7m8 peptide at equivalent positions on three other AAV capsids, AAV5, AAV8, and AAV9, and evaluated its effect on their infectivity. Intravitreal delivery of these peptide insertion vectors revealed that only AAV9 benefited from 7m8 insertion in the context of the retina. We then investigated AAV2-7m8 and AAV9-7m8 properties in the brain, to better evaluate the spread and efficacy of viral transduction in view of the peptide insertion. While 7m8 insertion led to higher intensity gene expression, the spread of gene expression remained unchanged compared to the parental serotypes. Our results indicate that the 7m8 peptide insertion acts by increasing efficacy of cellular entry, with little effect on the spread of viral particles in neural tissue. The effects of peptide insertion are capsid and tissue dependent, highlighting the importance of the microenvironment in gene delivery using AAV. Biotechnol. Bioeng. 2016;113: 2712-2724. © 2016 Wiley Periodicals, Inc.


Transcatheter interventions for valvular heart diseases in liver cirrhosis patients.
There is an increasing prevalence of patients who have both liver cirrhosis (LC) and severe valvular heart disease. This combination typically poses prohibitive risk for liver transplantation. LC related malnourishment, hypoalbuminemia and hyperdynamic circulation places patients with severe LC at higher rates for significant bleeding and/or thrombosis, as well as infectious and renal complications, after either surgical or transcatheter valvular interventions. Although there remains scarce comparative evidence, the preponderance of data suggest that percutaneous strategies are preferred over surgical ones. A multidisciplinary team is ideal for identifying those patients with LC who would benefit from transcatheter valvular heart interventions.


Review of self-administration.
The reinforcing properties of drugs can be evaluated pre-clinically using self-administration procedures in laboratory animals. This paper reviews self-administration studies of the four opioid agonist/antagonist analgesics pentazocine, butorphanol, nalbuphine and buprenorphine, and compares these results to those from studies of morphine and cyclazocine. All four agonist/antagonists possess reinforcing properties under at least some test conditions. In this respect they more resemble morphine than cyclazocine. These results suggest that they all may have some potential for recreational use. On the other hand, some data point to a lower reinforcing efficacy for these agonist/antagonists than for the pure agonists such as morphine. Studies comparing the reinforcing efficacy among the agonist/antagonists are also reviewed, however more data are needed before definitive conclusions can be drawn within the class.


Live virus vaccination following pediatric liver transplantation: Outcomes from two academic children's hospitals.
Pediatric liver transplant (LT) recipients are often transplanted at a young age, precluding them from receiving live virus vaccinations (LVV) such as varicella (VZV) vaccine and measles, mumps and rubella. This places them at profound risk for vaccine preventable illness. We sought to detail safety of vaccination. This was a retrospective cohort study of pediatric LT recipients at two children's hospitals. Among 204 LT recipients included in the study, 97 received at least one LVV after LT. Six patients who did not receive LVV after transplant had evidence of vaccine-preventable infection following vaccination (one disseminated VZV disease, five VZV-related rash), while one patient who received LVV after transplant developed a diffuse VZV-related rash. Rejection rates were the same between those that did and did not receive a live virus vaccine post-transplant. There were no serious adverse events caused by vaccination post-transplant. LVV following LT was safe at our two institutions, although there exist limitations in our study due to its retrospective study design. Larger scale studies should be performed to evaluate the effectiveness of LVV in relation to immunosuppression.


Neurodevelopment in school-aged children after intrauterine exposure to antipsychotics.
Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long-term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school-aged children. We performed a cross-sectional neurodevelopmental assessment of 91 children aged 6-14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy. Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report. No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school-aged children (6-14 years).


[The long-term results of treatment of Ménière's disease with intratympanic injections of gentamicin].
To estimate the results of treatment of Ménière's disease with intratympanic injections of gentamicin. 37 patients with defined, pharmacological treatment resistant Ménière's disease treated in Department of Otolaryngology and Laryngological Oncology of University of Medical Sciences in Poznań with intratympanic injections of gentamicin from 2001 to 2010 year. Patients were injected intratympanic with 0.3 ml (12 mg) of gentamicin once or few times with 7 days or longer breaks and a number of injections depended on the reaction of the inner ear. We estimated the patients' subjective feelings and results of equilibrium and hearing organ examination in early (3 months) and late (2 years) period after treatment. Complete control of vertigo (class A) was achieved in 84.6%, and complete and essential control (class A and B) in 96.1%. Hearing deterioration usually mild or moderate was observed directly after treatment in 16.2% and after 2 years in 23% patients. The results of pure tone audiometry showed deterioration of hearing in 16.2% (early) and 26.9% (late). In 1 patient hearing deterioration was essential. Intratympanic injections of gentamicin are effective and not troublesome method of treatment of pharmacological treatment resistant Ménière's disease. In most of patients hearing can be preserved, but they should be always informed about possible risk of hearing deterioration. The number of injections and breaks between them depends on the effect of therapy and of expectations of patients.


The Diagnosis of α-Thalassaemia: A Case of Hemoglobin H -α Deletion.
We report a case of hemolytic anemia that was subsequently identified to be a case of α-thalassaemia harboring the common rightward 3.7 kb deletion/HbH. The diagnosis was based on sequential analyses using BioRad D10 HPLC, Alkaline gel electrophoresis, GPO α THAL-IC strips and the identification of the specific genetic lesion using an α Globin reverse dot blot hybridization assay. Supravital stain of RBCs helped in identifying classical HbH inclusions. In a background of a variable clinical presentation, lack of definitive hematological markers, and general under-diagnosis of α-thalassaemias we have used this case to highlight the features and sequence of techniques involved in identifying and characterizing an α-globin chain mutation, starting from a diffuse clinical history and presentation up to the identification of a specific genetic lesion involved.


Tolerance, physical dependence and changes in muscarinic receptor binding sites after chronic ethanol treatment in the rat.
Rats were treated with ethanol in the drinking water for 73-75 weeks. The daily drinking periods were restricted to only 2x1 h to get significant ethanol blood concentrations. After the end of the ethanol treatment (last day of treatment denoted day 0 of the abstinence) tolerance to sedatives were recorded with a hexobarbital threshold method, convulsions recorded with jiggle cages, and muscarinic receptor binding sites determined with 3H-quinuclidinyl benzilate. Tolerance to hexobarbital was found to have a maximum on day 8 in the abstinence while convulsions recorded from the rats participating in the hexobarbital threshold determinations had a maximum on day 14. Atropine administered as a single dose on day 8 decreased the tolerance to hexobarbital on that day and seemed to reduce the number of convulsions on the following days. Muscarinic receptor sites were significantly increased in the striatum on day 8 of the abstinence at the time of maximal tolerance, This increase in muscarinic receptors was less in rats which had had convulsions during the abstinence before sacrifice. Thus the results indicate that cholinergic mechanisms are involved in the changes seen during the abstinence after chronic ethanol exposure.


Psychometric properties of the Coronavirus Anxiety Scale based on Classical Test Theory (CTT) and Item Response Theory (IRT) models among Chinese front-line healthcare workers.
Since March 2022, the COVID-19 epidemic has rebounded widely and frequently in China. Healthcare workers have faced grand challenges such as soaring COVID-19 patients, being busy with the nucleic acid screening of all the populations in the epidemic areas every day, and testing positive for COVID-19, all of which contributed to anxiety easily according to the Conservation of Resources theory. However, anxiety among healthcare workers is not only associated with personal health but also adversely affects the quality of health services. Therefore, it is crucial to search for suitable tools to monitor the anxiety related to COVID-19 among healthcare workers. The current study aimed to test the Coronavirus Anxiety Scale (CAS) in Chinese healthcare workers. The current study employed a cross-sectional design. The CAS was translated into Chinese. Then, according to Classical Test Theory (CTT) and Item Response Theory (IRT) models, the psychometric properties of the Chinese version were measured among 811 healthcare workers. The split-half reliability was 0.855. The Cronbach's α coefficient was 0.895. The retest coefficient was 0.901 with 10 days as the retest interval. The content validity index was 0.920. In exploratory factor analysis, one common factor was extracted and explained 72.559% of the total variance. All item load values on the common factor ranged from 0.790 to 0.885, and the communality of each item ranged from 0.625 to 0.784. With confirmatory factor analysis, the single factor model showed an excellent goodness-of-fit, chi-square/degree of freedom (χ2/df) = 3.339, goodness of fit index (GFI) = 0.992, adjusted goodness of fit index (AGFI) = 0.975, root-mean-square error of approximation (RMSEA) = 0.054, root mean square residual (RMR) = 0.005, incremental fit index (IFI) = 0.967, Tucker-Lewis index (TLI) = 0.932, and comparative fit index (CFI) = 0.966. The multiple-group confirmatory factor analysis revealed the invariance measuring anxiety of COVID-19 was in similar ways across ages, hospital degrees, and professional titles. With convergent validity, the CAS was positively correlated with post-traumatic stress disorder (r = 0.619, P < 0.001), fear of COVID (r = 0.550, P < 0.001), and depression (r = 0.367, P < 0.001). According to IRT models, the results showed that all item discrimination parameters were higher than 1.70 and difficulty parameters ranged from 1.13 to 2.83. The Chinese version of CAS has good psychometric properties in healthcare workers after China adjusted the COVID-19 management measures during the COVID-19 Omicron epidemic, and can be used for assessing the anxiety associated with COVID-19 in Chinese healthcare workers.


Successful outcome of preoperative prism adaptation for decompensated microtropia in an adult.
A 27-year-old myopic female presented with a recurrence of constant horizontal diplopia secondary to a decompensated microtropia. Following prism adaptation the patient underwent strabismus surgery for the prism adapted angle. A successful outcome ensued; the patient's alignment remains stable and she continues to be symptom free 12 months postoperatively.


Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity.
Adaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat. The present study identified totally 1870 miRNAs differentially expressed in HUVEC under MG condition when compared to the cells subjected to unitary G conditions. The functional association of identified miRNAs targeting specific mRNAs revealed that miRNAs, hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsa-miR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p differentially regulated the genes involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways. Further, the q-PCR based experimental studies of upregulated and downregulated miRNA and mRNAs demonstrate that the above reported miRNAs influence the cell proliferation and vascular functions of the HUVEC in MG conditions effectively. Consensus on the interactome results indicates restricted fluctuations in the transcriptome of the HUVEC exposed to short-term MG that could lead to higher levels of endothelial functions like angiogenesis and vascular patterning.


Decreased gene expression of neuropeptide Y and its receptors in hippocampal regions during ethanol withdrawal in rats.
Ethanol withdrawal is associated with neuronal hyperexcitability and increased hippocampal glutamate release. Neuropeptide Y (NPY) appears to play an important role in regulation of hippocampal neuronal excitability by inhibiting glutamate release. Expression of NPY and its receptors Y1, Y2, and Y5 was studied in hippocampal areas of rats during ethanol withdrawal after repeated intragastric ethanol administration for 2 or 4 days using in situ hybridization. Withdrawal was associated with decreased hippocampal expression of NPY and each of its receptors, particularly Y2, after 2 and/or 4 days of ethanol compared to control rats. These data suggest that the hippocampal NPY system is downregulated during ethanol withdrawal and these neuroadaptational changes could play a role in mediating withdrawal hyperexcitability.


Plant-mediated synthesis of silver-doped zinc oxide nanoparticles and evaluation of their antimicrobial activity against bacteria cause tooth decay.
In this research, silver-doped zinc oxide (SdZnO) nanoparticles (NPs) were synthesized in an environmental-friendly manner. The synthesized NPs were identified by UV-vis spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Finally, the antimicrobial activity of synthesized ZnO and SdZnO NPs was performed. It was observed that by doping silver, the size of ZnO NPs was changed. By adding silver to ZnO NPs, the antimicrobial effect of ZnO NPs was improved. Antibacterial test against gram-positive bacterium Streptococcus mutants showed that SdZnO NPs with a low density of silver had higher antibacterial activity than ZnO NPs; Therefore, SdZnO NPs can be used as a new antibacterial agent in medical applications. RESEARCH HIGHLIGHTS: Silver-doped zinc oxide nanoparticles were prepared using an eco-friendly synthesis method and their antimicrobial activity against bacteria causing tooth decay was studied.


Effects of storage time and temperature on lipid oxidation of egg powders enriched with natural antioxidants.
The lipid fraction of egg powder may be affected by storage conditions due to the development of oxidative rancidity caused by polyunsaturated fatty acids. This study evaluated egg powders enriched with antioxidants [tocopherol, catechin, lycopene, and butylated hydroxyanisole (BHA)] for conjugated dienes (during a 90-day period) and for malonaldehydes (during a 210-day period) at 25±2 and 4±1°C. The presence of lycopene and BHA increases the total phenolic compounds in the enriched egg powders, and BHA exhibits the most antioxidant activity, as quantified by an ABTS assay. Egg powders enriched with antioxidants do not show any reduction in conjugate diene production compared to controls, and no effect of storage temperature is observed; however, in the production of malonaldehyde, greater stability is observed at 4°C, and catechin is more effective in reducing oxidation during storage. The results show that natural antioxidants can be used in egg powder instead of synthetic compounds to reduce malonaldehyde production during storage.


Determinants of prolonged mechanical ventilation in patients with chronic obstructive pulmonary diseases and acute hypercapnic respiratory failure.
The aim of the present study was to identify early risk factors for prolonged mechanical ventilation (PMV) in chronic obstructive pulmonary disease (COPD) patients admitted to respiratory intensive care units (RICU) for acute hypercapnic respiratory failure. PMV was defined as invasive ventilation lasting longer than 7 days. Between January 1, 2000 and December 31, 2005, epidemiological and clinical data on RICU admission day were retrospectively analyzed for eligible patients. Univariate and multiple stepwise logistic regression analyses were used for statistical analysis. A total of 152 patients were eligible for evaluation during the 6-year study period and their mean age was 63+/-12 years. Fifty-one patients died before day 7 after the onset of MV (early death group). Of the remaining 101 patients who survived until day 7, 56 had been weaned successfully (non-PMV group) and 45 continued to receive MV (PMV group). Logistic regression analysis showed that age above 65 (OR=1.98, 95% CI=0.96-4.17, P=0.011), a pH of 7.30 or less measured 12 h after ventilation (OR=2.09, 95% CI=1.17-5.64, P=0.002), an APACHE II score above 20 (OR=3.25, 95% CI=1.58-7.10, P<0.001), development of non-respiratory organ failure (OR=4.67, 95% CI=1.54-9.71, P<0.001), and the presence of shock (OR=4.71, 95% CI=2.14-10.09, P<0.001) were independently associated with PMV. The presence of two factors predicted PMV with a sensitivity of 86% and a specificity of 94%. Age, APACHE II score, refractory acidosis, presence of non-respiratory organ failure, and shock on RICU admission day were early determinants of PMV in patients with COPD and acute hypercapnic respiratory failure.


Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications.
To determine whether the measurement of pleural fluid pH in malignant effusions has diagnostic use, predicts survival, and has therapeutic implications. A prospective comparison of cytologic examinations and pleural biopsy results, survival, and response to chemical pleurodesis with tetracycline in patients with normal-pH (7.30 or greater) and low-pH (less than 7.30) malignant pleural effusions. Academic medical center, university referral hospital, city hospital, and Veterans Administration hospital. Sixty patients with malignant pleural effusions, proven at either initial thoracentesis by cytologic examination or within 4 months of initial thoracentesis by repeat thoracentesis, thoracotomy, or autopsy, were followed until death. Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. The 20 patients with low-pH malignant effusions had a significantly greater positivity on initial pleural fluid cytologic evaluation, a shorter mean survival, and a poorer response to tetracycline pleurodesis compared with 40 patients with normal-pH malignant effusions. Determination of pleural fluid pH in malignant effusions provides a rational approach to further diagnostic testing, prognostic information, and a rationale for palliative treatment.


Segmental and Circumferential Acetabular Labral Reconstruction Have Comparable Outcomes in the Treatment of Irreparable or Unsalvageable Labral Pathology: A Systematic Review.
To perform a systematic review comparing outcomes of segmental versus circumferential arthroscopic labral reconstruction as a treatment for symptomatic irreparable or unsalvageable acetabular labral pathology. A systematic review was conducted according to PRISMA guidelines using defined inclusion and exclusion criteria. The study groups were divided into segmental and circumferential labral reconstructions. Studies with <2 years follow up, overlapping patient populations, or indications for labral reconstruction other than irreparable or unsalvageable pathology were excluded. The literature search resulted in nine included publications. Five studies presented data on segmental labral reconstruction (166 hips in 164 patients), and seven studies presented data on circumferential labral reconstruction (261 hips in 253 patients). All circumferential reconstruction studies used allograft only, while segmental studies used a combination of autograft and allograft. The range of conversion to total hip arthroplasty was 9.1% to 26.8% in the segmental studies and 3.1% to 9.9% in the circumferential studies. The modified Harris Hip Score (mHHS) was the only patient-reported outcome measure reported in three or more studies in both groups. The mean change from preoperative to postoperative mHHS ranged from 17.8 to 29 in the segmental group and from 20.4 to 31.7 in the circumferential group. Weighted estimates were not calculated due to significant heterogeneity for both the segmental and circumferential groups (I2 = 63.9% and 72.9%, respectively). Segmental and circumferential reconstructions are both reasonable options for arthroscopic treatment of irreparable or unsalvageable labral pathology. Articles in both groups demonstrated improvement in patient-reported outcomes (mHHS). Because of study heterogeneity, low level of evidence, and high risk of bias, the scores were unable to be directly compared. Although there are theoretical biomechanical and technical advantages of one technique over another, this systematic review did not demonstrate clinical superiority of either technique. Level IV, systematic review of level III and IV studies.


[Serum cholinesterase activity (CHE) in different classes of chronic liver diseases (author's transl)].
ChE activity was studied in a series of 193 patients of different classes of chronic hepatitis. CAH and much more cirrhosis showed a mean value significantly lower than normal controls. In CAH, no difference was found between HBsAg positive and HBsAg negative cases. Alcoholic cirrhotics had serum cholinesterase levels more lowered than non alcoholic patients. Finally, the follow-up of serum cholinesterase levels could be useful in assessing the prognosis of cirrhotic patients.


Predictive value of median-SSEP in early phase of stroke: a comparison in supratentorial infarction and hemorrhage.
To compare the prognostic value of median somatosensory evoked potentials (M-SSEP) changes in the early phase of supratentorial infarction and hemorrhage. This study includes 130 patients (mean age 62+/-11.4 years, 43 women, large middle cerebral artery territory infarction in 36 patients, restricted/lacunar in 55, massive supratentorial hemorrhage in 10, small/medium size hemorrhage in 31). M-SSEP were recorded early (0-7 days in ischemia, 0-21 days in hemorrhage) and patients stratified into groups with absent, abnormal, normal response. Clinical state was determined by the Medical Research Council (MRC) scale, Barthel Index and Rankin score and followed for at least 6 months. Moderate prognostic correlation was established between N20-P25 amplitudes (r=0.34, p<0.05) and N20-P25 amplitude ratio (r=0.45, p<0.01) and Barthel Index at 6 months in patients with ischemic stroke. Moderate relationship (r=-0.34, p<0.05) exists also between N20-P25 ratio and Rankin score at 6 months in patients with small/medium size hemorrhage. In large infarctions and small/medium size cerebral hemorrhages correlations with all clinical indices of outcome are weak. In massive hemorrhage, only a weak correlation (r=-0.19, p<0.05) between amplitude ratio and Rankin score was found. The combination of initial MRC and N20-P25 amplitude ratio has 10% (in hemorrhage) to 15% (in infarction) greater prognostic value (p<0.05) than initial alone. M-SSEP have independent predictive value regarding functional recovery in ischemic stroke and small/medium size cerebral hemorrhage. Combined assessment of initial MRC and M-SSEP substantially improves prognosis in acute stroke.


Long-term measurements of energy expenditure in severe burn injury.
The objective of this study was to evaluate resting energy expenditure (REE) in spontaneously breathing and artificially ventilated burn patients during the entire intensive care period. In 27 patients with 51 +/- 20% body surface area burned (BSAB) the REE was determined via indirect calorimetry. Three groups were formed according to the mortality prognosis index of Zawacki et al. In groups A, B, and C the predicted mortality rates were <20%, 20% to 80%, and >80%, respectively. The frequency of acute respiratory distress syndrome (ARDS), sepsis, renal failure, and mortality increased from group A toward group C. The REE test revealed wide individual variation and was usually overestimated by all tested formulas. The mean REE was comparable in groups A, B, and C during the first 20 days (49 +/- 16% vs. 59 +/- 21% vs. 57 +/- 18% above the REE calculated by the Harris-Benedict equation, or HBEE). The REE of patients in groups A and B declined after this period, whereas the long-term ventilated patients in the prognostically unfavorable group C showed a high REE up to the 45th day, usually accompanied by severe organ dysfunction and major metabolic disorders. During this time a nutritional regimen meeting the actual REE could not be achieved. In the clinical situation when indirect calorimetry is not available, REE can be stated to be 50% to 60% above HBEE in patients with >20% BSAB for at least 20 days. Expecting a stable clinical course in patients with a predicted mortality of <20% (group A), oral nutrition usually seems sufficient after a short period of artificial nutritional support (1 week). Patients with a predicted mortality of more than 20% have a complication-burdened clinical course and a prolonged period of ventilation (groups B and C). These patients need parenteral and enteral nutrition for at least 20 days after trauma to prevent severe malnutrition.


Patient-perspective quality of life after laparoscopic and open hernia repair: a controlled randomized trial.
Laparoscopic hernia repair accounts for 10% of all hernia surgery. Potential benefits include reduction in postoperative pain, rapid recovery, lower recurrence rate, and fewer complications. The outcomes of health-related quality of life and patient perspective after hernia repair are our aim. Consecutive patients treated for unilateral uncomplicated groin hernia were enrolled after evaluation for inclusion. Participants were randomly distributed to receive either laparoscopic transabdominal preperitoneal repair (TAPP) (group I) or Lichtenstein repair (group II). Operative and postoperative complications, operative time, hospital stay, and late complications were assessed early postoperatively, at 4 weeks, and every 6 months thereafter. Quality of life was assessed using Short Form-36 questionnaire in the first visit (after 4 weeks). One hundred and eighty-five patients of unilateral uncomplicated groin hernia were included; 88 patients (group I) were treated by TAPP, and 97 patients were treated by Lichtenstein repair (group II) with median follow-up of 17.9 months. Mean hospital stay, mean operative time, operative and postoperative complications were similar in the two groups. Quality of life showed better and significant outcomes in group I for physical function (p ≤ 0.001), role physical (p ≤ 0.011), bodily pain (p ≤ 0.017), general health (p ≤ 0.047), and total physical health (p ≤ 0.008). However, mental health showed no statistical significance in its four scales, but with better outcomes in group I. Total quality outcomes showed significantly better outcomes in group I (p ≤ 0.031). TAPP hernia repair technique is a safe technique with low complication rate, less postoperative body pain, and better quality-of-life outcomes compared with open technique, being well accepted from the patient's perspective for quality of life.


Is growing old a disease? A study of the attitudes of elderly people to physical symptoms.
In a survey of people living at home, aged 77 years and over, a total of 126 women and 77 men were interviewed concerning their attitudes to their physical symptoms. For each organ system the subjects indicated whether their symptoms were considered to be a normal condition for elderly people or a manifestation of a disease. To a large extent symptoms were accepted as a normal condition, however, a highly significant difference in their attitudes to symptoms stemming from different systems was found (p less than 0.001). Generally, compared with severe symptoms, mild symptoms were accepted more readily as a normal condition in old age. Although most of the elderly people had seen a doctor because of their symptoms, a highly significant difference was found in consultation rates among elderly persons with symptoms from different organ systems (p less than 0.001). The attitudes to symptoms influenced the tendency of the subjects to consult a doctor (p less than 0.05). The need for education of elderly people and health professionals is discussed.


The Media as a Source of Weight Stigma for Pregnant and Postpartum Women.
The media often contain weight-stigmatizing material. However, little is known about pregnant and postpartum women's experiences with media-based weight stigma. Two studies investigated weight stigma in the media from multiple perspectives. Study 1 analyzed open-response examples of weight-stigmatizing experiences coming from the media, broadly defined, from 123 pregnant and postpartum women (from a larger sample of 501). Study 2 identified online news-media articles about pregnancy and weight published during the study 1 data collection period (August to November 2017). Study 1 revealed that weight stigma was common and frequent in media, manifesting across three themes: (1) ideal appearance of pregnant bodies, (2) pressure to quickly "bounce back" after birth to a prepregnancy appearance, and (3) media praising celebrities for achieving either of the previous themes. Study 2 identified 33 articles. A content analysis revealed that women with overweight or obesity were rarely portrayed in images. Additionally, discussion of weight was often negative, focusing on adverse maternal-child health consequences. Finally, media-communicated ideals for weight and weight loss were often unrealistic and did not reference medical guidelines. This work is the first to document that online news media are a pervasive and potentially distressing source of pregnancy-related weight stigma, suggesting much-needed reform in media guidelines.


Ring-like distribution of IgG-containing cells around the lymph follicle in the human intestine.
Immunoglobulin (Ig)-containing cells were studied in the lamina propria of the normal human large bowel and around the lymph follicle, including Peyer's patches, in the normal intestine. Ig-containing cells were identified by the indirect immunoperoxidase staining method, using mouse anti-human Ig monoclonal antibodies. In the lamina propria in the large bowel, the mean percentage of IgA+ (IgA1+ cells and IgA2+ cells), IgM+, IgD+, IgG+ and IgE+ cells was 75.9, 8.5, 7.3, 5.8, 2.5, respectively (total 100), namely there was a marked preponderance of IgA+ cells in comparison to IgG+ cells. However, IgG+ cells were observed not only on the epithelial but also in the serosal side of lymph follicles, showing a ring-like pattern. Ig+ cells of the other four classes did not show such a pattern. The ring-like distribution of IgG+ cells around lymph follicles was observed in both the large and small intestine including Peyer's patches. This tendency was observed in 9 out of 14 follicles (64.3 per cent). A large number of IgG+ cells were observed outside lymph follicles, while a small number of IgG+ cells were observed at the most outer rim of lymph follicles which suggested a local maturation of IgG+ cells. The significance and the role of the newly recognized IgG+ cells in the vicinity of lymph follicles remain to be resolved.


Isolation by flow cytometry of a human ovarian tumor cell subpopulation exhibiting a high glutathione content phenotype and increased resistance to adriamycin.
We have used monochlorobimane as a quantitative marker by which cells of naturally high or low GSH contents were purified by fluorescence-activated cell sorting (FACS). The cell line chosen for this purpose, MLS, was a human ovarian tumor cell line established from a patient who had received extensive chemotherapy and showed evidence of 'multidrug' resistance. Cells of a specified volume were sorted into subpopulations containing the 1% most dim (low GSH) and 1% most bright (high GSH) cells. With an increasing number of sortings, cell subpopulations emerged with progressively lower (dim) and higher (bright) GSH content as compared to the parent population. After 4 sortings, GSH contents were 10.6 +/- 0.8, 5.1 +/- 0.4, and 7.2 +/- 0.7 X 10(-18) moles/micron3 for MLS/bright, MLS/dim and MLS/parent respectively. The high and low GSH phenotypes were of limited stability reverting to the parent phenotype by the sixth week following the last FACS. Cells with high GSH content were more resistant to adriamycin than cells with low GSH content, for example, at 1 log cell kill MLS/bright was 1.6 fold more resistant than MLS/dim. An ADR resistant variant of the MLS line, designated MLS/ADRR/2, established by twice treating MLS cells with 1 microgram/ml ADR for 2 hr, also showed increased GSH content (1.3-fold) and ADR resistance as compared with the parent line. These results illustrate the possible importance of tumor cell GSH status in determining the response to chemotherapy of a heterogenous population of tumor cells with diverse GSH contents.


Breakthrough candidaemia in the era of broad-spectrum antifungal therapies.
We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.


NETosis markers: Quest for specific, objective, and quantitative markers.
More than 10years have passed since the discovery of neutrophil extracellular traps (NETs) in 2004. NETs are extracellular web-like DNA decorated with antimicrobial proteins, which are released from activated neutrophils. The state of neutrophils with NET formation is called NETosis. It has been realized that NETosis includes suicidal NETosis and vital NETosis. The former state means cell death of neutrophils, whereas the latter state preserves living neutrophilic functions. Although both suicidal and vital NETosis play essential roles in elimination of microorganisms, excessive formation of NETs, especially the ones derived from suicidal NETosis, can harm the hosts. Therefore, the discovery of NETosis markers and development of evaluation methods are important. In this review, we compare the methods for evaluating NETosis, including immunocytological and immunohistological detection of co-localized neutrophil-derived proteins and extracellular DNA, and citrullinated histones, detection of NET remnants in fluid samples, and flow cytometric detection of cell-appendant NET components, with focus on the specificity, objectivity, and quantitativity. Since the gold standard marker of NETosis or method of NET detection has not been established yet, researchers should choose the most appropriate marker or method in each situation based on the knowledge of the respective virtues and faults.


Genotyping of human class I alcohol dehydrogenase. Analysis of enzymatically amplified DNA with allele-specific oligonucleotides.
Large inter-individual differences are noted in the susceptibility to alcohol-related problems. Part of this variation may be due to the different isoenzyme patterns of the alcohol-metabolizing enzymes and, consequently, different pharmacokinetics of alcohol degradation. We have used the polymerase chain reaction and oligonucleotide hybridization to amplify and analyze class I alcohol dehydrogenase isoenzyme-specific genomic DNA. The method unambiguously distinguishes between different allelic variants and thus provides a new means of elucidating the alcohol dehydrogenase isoenzyme pattern of humans.


Cor triatriatum dexter with anomalous pulmonary venous drainage and sinus venosus atrial septal defect.
The atypical location of a membrane in a case of cor triatriatum dexter prompted successful repair of accompanying anomalies, with in situ use of the membrane. The anatomy is described with a review of the literature.


Perineal skin bridge and levator muscle preservation in neutral sagittal anorectoplasty (NSARP) for vestibular fistula.
The incision in limited posterior sagittal anorectoplasty for vestibular fistula (VF) extends from the coccyx to the fistula with the rectum identified by partial sagittal division of the levator muscle. In anterior sagittal anorectoplasty, the perineal incision extends from the fistula opening to the posterior margin of the external sphincter complex while preserving intact the levator muscle. We describe a modification of the operation for repair of VF, the neutral sagittal anorectoplasty (NSARP), which preserves both a perineal skin bridge between the neo-anus and the posterior fourchette and the levator muscle. Leaving the perineal skin bridge and the levator muscle intact could be important both from the aspects of perineal wound-healing and functional outcome. The skin incision in NSARP extends from the coccyx to the anterior limit of the external sphincter muscle complex as defined by muscle stimulation. An artery forceps passed through the VF facilitates the location and exposure of the rectum. The levator muscle is left intact. The dissection and closure of the VF is done entirely from within the opened rectum. There is an intact perineal skin bridge between the neo-anus and the posterior fourchette at the completion of the NSARP. In 12 consecutive patients with VF, NSARP prevented the risk of wound complications occurring between the neo-anus and the posterior fourchette. A diverting colostomy was safely avoided in our last five patients. NSARP does not involve any division of the levator muscle and it also retains an undisturbed wad of tissue that could function as the perineal body. All five patients who are 3 years or older demonstrate voluntary bowel movements. Preserving the perineal skin bridge and the levator muscle in NSARP have contributed to the improvement of aesthetic appearance of the perineum and faecal continence in our patients.


Delayed pressure sore healing can be prevented.
Delayed pressure sore healing is still a costly problem despite the advances in knowledge on wound healing.


Luffa cylindrica and phytosterols bioconversion: from shake flask to jar bioreactor.
Bioconversion of lipophilic compounds poorly soluble in water, such as sterols, required the use of chemicals and solubilizing agents. On the other hand, it was shown that immobilization of Mycobacterium species on the dried fruit of Luffa cylindrica (DFLC) allows a close interaction between immobilized cells and cholesterol particles and increases by then the product's yield. In this work, the use of DFLC in a 5-l jar bioreactor with phytosterols mixture (1 g/l) as substrate was assessed without addition of any chemicals or solubilizing agents. DFLC increased by a factor of four the volumetric productivity of androstenones (0.08 g/l day). Products were accumulated in the aqueous medium while substrates remained on the fibers of DFLC. This observation lets envisage a green semi-continuous process of androstenone production. DFLC has no influence on cell growth, and is moreover natural, inexpensive, non-toxic, and mechanically strong.


Ureterocele causing anhydramnios successfully treated with percutaneous decompression.
Ureteroceles are congenital cystic dilatations of the submucosal segment of the distal ureter. We present a case of an intravesical ureterocele causing anhydramnios at 31 weeks' gestation. A primiparous woman near 20 weeks' gestation had ultrasound evidence of a fetal duplicated right collecting system. At 31 weeks, an intravesical ureterocele was seen along with bilateral hydroureteronephrosis and anhydramnios. A single percutaneous needle decompression of the bladder and ureterocele successfully restored amniotic fluid volume. Follow-up ultrasounds are indicated when either a duplicated renal collecting system or a ureterocele is identified. In utero treatment is indicated only when amniotic fluid is compromised. Needle decompression should be first-line treatment, with more invasive methods reserved for failures of decompression.


Glyceryl triacetate feeding in mice increases plasma acetate levels but has no anticonvulsant effects in acute electrical seizure models.
Acetate has been shown to have neuroprotective and anti-inflammatory effects. It is oxidized by astrocytes and can thus provide auxiliary energy to the brain in addition to glucose. Therefore, we hypothesized that it may protect against seizures, which is investigated here by feeding glyceryl triacetate (GTA), to provide high amounts of acetate without raising sodium or acid levels. CD1 male mice were fed controlled diets with or without GTA for up to three weeks. Body weights, blood glucose levels, plasma short-chain fatty acid levels, and other hematological parameters were monitored. Seizure thresholds were determined in 6 Hz and maximal electroshock seizure threshold (MEST) tests. Antioxidant capacities were evaluated in the cerebral cortex and plasma using a ferric reducing antioxidant power (FRAP) assay and Trolox equivalent antioxidant capacity assay. Body weight gain was similar with both diets with and without GTA in two experiments. Glyceryl triacetate-fed groups showed 2-3- and 1.6-fold increased acetate and propionate levels in plasma, respectively. Glucose levels were unaltered in blood collected from the tail tip but increased in trunk blood. No differences were found in the activity of cerebral cortex acetyl-CoA synthetase. In the 6 Hz threshold test, seizure thresholds were lower by 3 mA and 2.4 mA after 8 and 14 days, respectively, in the GTA compared to the control diet-fed group, but showed no difference on day 16, showing that GTA has small, but inconsistent proconvulsant effects in this model. In MEST tests, a slightly increased seizure threshold (1 mA) was found on day 19 in the GTA-fed group, but not in another experiment on day 21. There were no differences in antioxidant capacity in plasma or cortex between the two groups. Glyceryl triacetate feeding showed no antioxidant effects nor beneficial changes in acute electrical seizure threshold mouse models, despite its ability to increase plasma acetate levels.


Labeling of RNA in young and adult rat brain: evidence for different RNA processing.
The labeling of RNA in young and adult rat brain has been studied by measuring in vitro (tissue slices incubation) the incorporation of labeled uridine into RNA of total tissue and of the various subcellular fractions purified from cerebral hemispheres of 1- and 10-month-old rats. Gel electrophoretic analysis of the newly synthesized nuclear and microsomal RNA was also accomplished. An active metabolism of RNA in adult animals was found; moreover, distinct differences in ribosomal RNA processing in cerebral hemispheres of 1- and 10-month-old rats, with a more rapid processing in the brain of adult animals, were obtained.


Prostate Cancer Spheroids: A Three-Dimensional Model for Studying Tumor Heterogeneity.
Prostate cancer is one of the main causes of cancer and the sixth cause of death among men worldwide. One of the major challenges in prostate cancer research is cell heterogeneity defined as the different genomic and phenotypic characteristics in each individual cell making more difficult to assess the proper prostate cancer diagnosis and therapy. Tumor 3D spatial arrangement allow a strong interaction between the different cellular lineages and components which modulate cell proliferation, differentiation, and morphology. Prostate cancer spheroids are a cellular model which is capable to mimic the mechanical tensions of tumor tissue, providing a more representative pathophysiological model than the use of conventional 2D culture. Here, we describe a protocol to develop a 3D model of spheroids using prostate cancer cell lines (LNCaP, PC3, VCaP) which can be used to improve research considering tumoral heterogeneity role in cancer development, prognosis, and therapy.


Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas. An immunohistochemical study.
We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland.


Ureteric stent in renal transplantation.
Several techniques can be used to accomplish the ureteroneocystostomy in kidney transplantation. A ureteral catheter is a prophylactic measure to avoid urological complications (UC) of stenosis and/or fistula. In this study we evaluate the influence of using a ureteral stent upon the rate of UC in renal transplantation. Retrospective review of 2061 kidney transplants (75 living and 1986 cadaveric donors) for 1360 male and 684 female recipients, from July 14, 1991, to January 13, 2012, with a minimum follow-up of 6 months A double J stent (JJ) was used in 1890 an external tumor (ET) catheter in 52 and no catheter (NC) in 119 cases. Mean recipient age was 44.66 ± 13.66 years. UC occurred in 5.9% among which ET showed 17.3%, 8.4% for NC, and 5.4% for JJ (P < .0005). Urological complications were more frequent when surgery duration exceeded 3 hours (8.8% vs 5.3% ≤ 3 hours; P = .003), using older donors organs (P = .048) and with higher donor weight (P = .009). No differences were observed related to recipient age, gender, or weight; donor gender; pretransplant dialysis time; cold ischemia time; type of donor (living vs cadaveric); number of HLA matches; or initial immunosuppression (mammalian target of rapamycin inhibitor vs other). On multivariate analysis, donor weight (odds ratio [OR]: 1.023; P = .015), use of a JJ vs ET (OR: 0.280; P = .005), and surgery time exceeding 3 hours (OR: 3.270; P < .0005) were independently associated with UC. Catheterization of the urinary anastomosis with a JJ was associated with fewer UC. This is especially important for grafts from heavier donors. The use of an external catheter which was associated with an high rate of UC, should be avoided.


Clonal analysis of the specificity of alloreactive cells: "dominance" of E beta reactive clones.
The present experiments analyze the specificity of cells proliferating in murine mixed lymphocyte cultures (MLC). Lymphocytes from the B10.A(5R) strain, enriched by repeated restimulations with B10.A cells, proliferate specifically in response to B10.BR, B10.A and [B10.A(4R) X B10.A(5R)]F1 stimulators, while showing very limited responsiveness to B10.A(4R) cells. The preferential recognition of determinants on molecules other than Kk or I-Ak was directly proven by isolating 21 T-cell clones, all of which were Ek beta specific. This "dominance" seems to reflect a high frequency of Ek beta reactive T cells in the unselected B10.A(5R) repertoire because: (1) it is already observed in blasts isolated in a primary MLC, (2) it is typical of several independently raised B10.A(5R) anti-B10.A cultures, and (3) it is not found in parallel C57BL/6 anti-B10.BR MLCs that show dominant I-A specificity. Results showing the importance of determinant concentrations expressed by stimulator cells suggest that uncloned T-cell lines are heterogeneous in their "affinities" and that our cloning conditions select cells with high "functional affinity".


Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure.
This observational study enrolled adult patients with bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) who were treated at the emergency department of a teaching hospital from 2001 to 2007. MRSA isolates with type IV and type V staphylococcal cassette chromosome mec (SCCmec) genes (SCC IV/V-MRSA) were included in the final analysis. Healthcare-associated SCC IV/V-MRSA (HA-SCC IV/V-MRSA) and community-acquired SCC IV/V-MRSA (CA-SCC IV/V-MRSA) were defined as the identification of an SCC IV/V-MRSA isolate from a patient with and without healthcare-associated risk factors, respectively. Thirty-four cases of CA-SCC IV/V-MRSA (20 SCCmec type IV, 14 SCCmec type V) and 81 cases of HA-SCC IV/V-MRSA (59 SCCmec type IV, 22 SCCmec type V) bacteremia were identified. Vascular device-associated infections were a significant infection source in HA-SCC IV/V-MRSA bacteremia cases. SCCmec type IV HA-SCC IV/V-MRSA isolates (3.4%) were significantly less likely to carry the Panton-Valentine leukocidin (PVL) gene than SCCmec type IV CA-SCC IV/V-MRSA isolates (35.0%, p = 0.001). The 90-day cumulative probability of survival was 76% for patients with CA-SCC IV/V-MRSA bacteremia and 66% for patients with HA-SCC IV/V-MRSA bacteremia (p = 0.247, by the Wilcoxon rank-sum test). Significant differences in antimicrobial susceptibility were observed between bacterial isolates from patients with CA-SCC IV/V-MRSA bacteremia and HA-SCC IV/V-MRSA bacteremia.


Treatment of salivary stones by intraductal pneumatic lithotripsy: A preliminary presentation of the StoneBreaker with sterile bag covering.
Sialendoscopy has changed the management of obstructive sialadenitis. Nowadays, minimally invasive techniques evolve to preserve salivary gland function. Intraductal lithotripsy allows stones fragmentation and retrieval without opening the salivary duct. We report our experience with the StoneBreaker (SB), a new lithotripter with improvement using a sterile bag that permits reuse of the SB without passing to sterilization. The non-sterilized SB was used into a sterile camera sleeve in 5 patients, 3 submandibular lithiases and 2 parotid lithiases. Technique and outcomes were described with a review of the literature. An explanatory video of the procedure was performed. Complete fragmentation was achieved and all fragments were extracted without any ductal damage. Utilization of the sterile sleeve did not change the SB efficiency and the procedure duration. The use of a sterile bag allowed several consecutive procedures with a single non-sterilized handpiece. However, the gas cartridge change may be more delicate when more than 80 impacts are needed. Patients remained symptoms and stones free one month after surgery.


Hypothermia may reduce mortality and improve neurologic outcomes in adult patients treated with VA-ECMO: A systematic review and meta-analysis.
VA-ECMO can greatly reduce mortality in critically ill patients, and hypothermia attenuates the deleterious effects of ischemia-reperfusion injury. We aimed to study the effects of hypothermia on mortality and neurological outcomes in VA-ECMO patients. A systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from the earliest available date to 31 December 2022. The primary outcome was discharge or 28-day mortality and favorable neurological outcomes in VA-ECMO patients, and the secondary outcome was bleeding risk in VA-ECMO patients. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Based on the heterogeneity assessed by the I2 statistic, meta-analyses were performed using random or fixed-effects models. GRADE methodology was used to rate the certainty in the findings. A total of 27 articles (3782 patients) were included. Hypothermia (33-35 °C) lasting at least 24 h can significantly reduce discharge or 28-day mortality (OR, 0.45; 95% CI, 0.33-0.63; I2 = 41%) and significantly improve favorable neurological outcomes (OR, 2.08; 95% CI, 1.66-2.61; I2 = 3%) in VA-ECMO patients. Additionally, there was no risk associated with bleeding (OR, 1.15; 95% CI, 0.86-1.53; I2 = 12%). In our subgroup analysis according to in-hospital or out-of-hospital cardiac arrest, hypothermia reduced short-term mortality in both VA-ECMO-assisted in-hospital (OR, 0.30; 95% CI, 0.11-0.86; I2 = 0.0%) and out-of-hospital cardiac arrest (OR, 0.41; 95% CI, 0.25-0.69; I2 = 52.3%). Out-of-hospital cardiac arrest patients assisted by VA-ECMO for favorable neurological outcomes were consistent with the conclusions of this paper (OR, 2.10; 95% CI, 1.63-2.72; I2 = 0.5%). Our results show that mild hypothermia (33-35 °C) lasting at least 24 h can greatly reduce short-term mortality and significantly improve favorable short-term neurologic outcomes in VA-ECMO-assisted patients without bleeding-related risks. As the grade assessment indicated that the certainty of the evidence was relatively low, hypothermia as a strategy for VA-ECMO-assisted patient care may need to be treated with caution.


Shwachman-Diamond syndrome presenting in a premature infant as pancytopenia.
Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized by bone marrow dysfunction, exocrine pancreatic insufficiency, failure to thrive, and skeletal abnormalities. It is most commonly diagnosed in early childhood after the development of hematologic abnormalities. We report a premature infant born at 33 weeks gestation who was small for gestational age and displayed persistent cytopenias requiring transfusion. Genetic testing confirmed a diagnosis of Shwachman-Diamond syndrome (SDS).


Reversible activation of the ATP-dependent potassium current with dialysis of frog atrial cells by micromolar concentrations of GDP.
We studied the effects of internal and external solutions on potassium currents in frog atrial cells. Experiments were carried out in whole cell recording in the presence of tetrodotoxin and cobalt in the bath to suppress the inward currents. In the absence of pyruvate and glucose in the external solution, a time-independent current increased progressively in a few minutes till the death of the cell. This current had the properties of the ATP-sensitive potassium current IK(ATP) in mammalian cells. In the presence of pyruvate and glucose in the external solution, the membrane current stayed low for 30 min. Addition of guanosine monophosphate (GMP, 40 microM), guanosine triphosphate (GTP, 40 to 1000 microM), adenosine diphosphate (ADP, 40 microM) or adenosine triphosphate (ATP, 3000 microM) to the internal solution had no major effect on the current amplitude. In contrast, addition of GDP (20 or 40 microM) produced a loss of rectification in a few minutes. The current activated by GDP was time independent as was the current observed in the absence of glucose and pyruvate. It was sensitive to cesium and barium, it was blocked when ATP was added to GDP in the internal solution, and it was suppressed by the sulphonylurea glibenclamide (1 microM). We suggest that GDP produced a local depletion of ATP, by displacement of the equilibrium between ATP, GDP, ADP and GTP. This hypothesis is supported by the fact that the current activated by GDP was rapidly suppressed when adding GTP in excess to the internal solution.


Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection.
Five hundred twelve (373 men, 139 women) patients, aged 1-75 yr, with chronic hepatitis B virus infection seen during a 5-yr period were analyzed. Of these, 43.8% were hepatitis B e antigen (HBeAg)-positive, 49.2% were positive for hepatitis B e antibody, and 7% were negative for both HBeAg and hepatitis B e antibody at presentation. The cumulative probability of clearing HBeAg at the end of the first, second, and third years was 17%, 30%, and 34%, respectively. The probability of clearing HBeAg increased with the age of the patients. Reversion to HBeAg occurred in 7.8% of patients who were HBeAg-negative at presentation and 32.3% of HBeAg-positive patients who cleared HBeAg. In 70.6% of these patients, serum hepatitis B virus-deoxyribonucleic acid was persistently positive or became detectable at the time of HBeAg reversion. Most reversions occurred during the "e-window" phase. The reversions were transient in 31.8% of the cases. Recognition of the dynamics of these serologic changes is important in the evaluation of therapeutic regimens aimed at suppression of HBV replication and call for controlled trials with adequate duration of follow-up. Biochemical exacerbation of liver disease accompanied 38.7% of HBeAg to hepatitis B e antibody seroconversions and 34.8% of reversions. Such exacerbations may be mistaken for acute attacks of hepatitis B in patients not previously recognized to be hepatitis B surface antigen carriers and, in the absence of serial serologic data, are indistinguishable from superimposed non-A, non-B hepatitis.


Swallowing analysis for semisolid food texture in poststroke dysphagic patients.
Our objective was to determine the texture of semisolid foods that are appropriate for poststroke dysphagic patients. Subjects included 52 poststroke dysphagic patients (72 ± 8 years of age) who were trained with semisolid foods and required the evaluation of swallowing function. Fifty-two homogeneous semisolid foods not requiring mastication were given. Texture were measured twice using a rheometer (TPU-2S; Yamaden Co. Ltd., Tokyo, Japan). Texture characteristics were as follows: hardness, 1873 to 19,510 N/m(2) (mean 9,129 N/m(2)); cohesiveness, 0.13 to 0.67 (mean 0.32); adhesiveness, 2 to 878 J/m(3) (mean 209 J/m(3)); and gumminess, 546 to 8781 N/m(2) (mean 2908 N/m(2)). Patients sat during fiberoptic endoscopic evaluation and ingested a single semisolid food. The patients were asked to swallow 4 g of food, and the texture, pharyngeal residue, penetration into the larynx, and aspiration were evaluated. We observed and noted the association between the texture of foods and swallowing movements by videoendoscopy. Evaluating food texture by endoscopy revealed significant differences in adhesiveness according to residue deposition and significant differences in gumminess according to aspiration. We identified the textures of different semisolid foods as being either appropriate or inappropriate for poststroke dysphagic patients.


A Promising Future: Comparable Imaging Capability of MRI-Compatible Silicon Photomultiplier and Conventional Photosensor Preclinical PET Systems.
We recently completed construction of a small-animal PET system-the MiniPET-3-that uses state-of-the-art silicon photomultiplier (SiPM) photosensors, making possible dual-modality imaging with MRI. In this article, we compare the MiniPET-3 with the MiniPET-2, a system with the same crystal geometry but conventional photomultiplier tubes (PMTs). The standard measurements proposed by the National Electrical Manufacturers Association NU 4 protocols were performed on both systems. These measurements included spatial resolution, system sensitivity, energy resolution, counting rate performance, scatter fraction, spillover ratio for air and water, recovery coefficient, and image uniformity. The energy windows were set to 350-650 keV on the MiniPET-2 and 360-662 keV on the MiniPET-3. Spatial resolution was approximately 17% better on average for the MiniPET-3 than the MiniPET-2. The systems performed similarly in terms of peak absolute sensitivity (∼1.37%), spillover ratio for air (∼0.15), spillover ratio for water (∼0.25), and recovery coefficient (∼0.33, 0.59, 0.81, 0.89, and 0.94). Uniformity was 5.59% for the MiniPET-2 and 6.49% for the MiniPET-3. Minor differences were found in scatter fraction. With the ratlike phantom, the peak noise-equivalent counting rate was 14 kcps on the MiniPET-2 but 24 kcps on the MiniPET-3. However, with the mouselike phantom, these values were 55 and 91 kcps, respectively. The optimal coincidence time window was 6 ns for the MiniPET-2 and 8 ns for the MiniPET-3. Images obtained with the SiPM-based MiniPET-3 small-animal PET system are similar in quality to those obtained with the conventional PMT-based MiniPET-2.


The genomic sequence for Prader-Willi/Angelman syndromes' loci of human is apparently conserved in the great apes.
Chromosomal changes through pericentric inversions play an important role in the origin of species. Certain pericentric inversions are too minute to be detected cytogenetically, thus hindering the complete reconstruction of hominoid phylogeny. The advent of the fluorescence in situ hybridization (FISH) technique has facilitated the identification of many chromosomal segments, even at the single gene level. Therefore the cosmid probe for Prader-Willi (PWS)/Angelman syndrome to the loci on human chromosome 15 [q11-13] is being used as a marker to highlight the complementary sequence in higher primates. We hybridized metaphase chromosomes of chimpanzee (PTR), gorilla (GGO), and orangutan (PPY) with this probe (Oncor) to characterize the chromosomal segments because the nature of these pericentric inversions remains relatively unknown. Our observations suggest that a pericentric inversion has occurred in chimpanzee chromosome (PTR 16) which corresponds to human chromosome 15 at PTR 16 band p11-12, while in gorilla (GGO 15) and orangutan (PPY 16) the bands q11-13 complemented to human chromosome 15 band q11-13. This approach has proven to be a better avenue to characterize the pericentric inversions which have apparently occurred during human evolution. "Genetic" divergence in the speciation process which occurs through "chromosomal" rearrangement needs to be reevaluated and further explored using newer techniques.


Observations on the removal of brood inoculated with Tropilaelaps mercedesae (Acari: Laelapidae) and the mite's reproductive success in Apis mellifera colonies.
This study assessed the response of Apis mellifera to brood deliberately infested with Tropilaelaps mercedesae. The reproductive success of T. mercedesae in mite-inoculated and naturally infested brood was also compared. The presence of T. mercedesae inside brood cells significantly affected brood removal. Thai A. mellifera removed 52.6 ± 8.2 % of the brood inoculated with T. mercedesae as compared to 17.2 ± 1.8 and 5.7 ± 1.1 % removal rates for the groups of brood with their cell cappings opened and closed without mite inoculation and the control brood (undisturbed, no mite inoculation), respectively. Brood removal peaked during the second and third days post inoculation when test brood was at the prepupal stage. Overall, non-reproduction (NR) of foundress T. mercedesae was high. However, when NR was measured based on the criteria used for Varroa, the naturally infested pupae (NIP) supported the highest NR (92.8 %). Newly sealed larvae inoculated with Tropilaelaps collected from newly sealed larvae (NSL) had 78.2 % NR and those inoculated with Tropilaelaps collected from tan-bodied pupae (TBP) had 76.8 % NR. Since Tropilaelaps is known to have a short development period and nearly all progeny reach adulthood by the time of host emergence, we also used two Tropilaelaps-specific criteria to determine NR. Foundresses that did not produce progeny and those that produced only one progeny were considered NR. Using these two criteria, NR decreased tremendously but showed similar trends with means of 65, 40 and 33 % for NIP, NSL and TBP, respectively. High NR in the NIP group may indicate increased hygienic behavior in Thai A. mellifera colonies. The removal of infested prepupae or tan-bodied pupae will likely decrease the reproductive potential of Tropilaelaps. Our study suggests that brood removal may be one of the resistance mechanisms towards T. mercedesae by naturally adapted Thai A. mellifera.


Novel nitroxide-bile acid conjugates inform substrate requirements for human bile acid transporters.
Transport of bile acids within the enterohepatic circulation from the liver to the intestines via the gallbladder and back to the liver via the portal vein plays a critical role in bile acid regulation and homeostasis. Deficiency of fibroblast growth factor 19 (FGF19), a hormone whose role is to suppress de novo hepatic bile acid synthesis to maintain homeostatic levels, results in bile acid diarrhea (BAD). FGF19 also modulates gallbladder motility so that bile acids are concentrated in the gallbladder until postprandial contraction. To assess bile acid transport and diagnose ailments like BAD that are associated with altered bile acid synthesis and transport, we created bile acid conjugates with nitroxide radicals. Because nitroxides are paramagnetic and can promote proton relaxation, we reasoned that these paramagnetic conjugates should act as contrast agents in in vivo magnetic resonance imaging (MRI). We tested substrate capability by assessing the inhibitory potential of these novel agents against taurocholate uptake by the apical sodium dependent bile acid transporter (ASBT) and the Na+/taurocholate cotransporting polypeptide (NTCP). Surprisingly, neither the paramagnetic compounds CA-Px-1 and CA-Px-2, nor their reduced forms, CA-Px-1H and CA-Px-2H, inhibited hASBT- or hNTCP-mediated taurocholate uptake. Therefore, the new conjugates cannot serve as contrast agents for MRI in vivo. However, our findings identify important structural constraints of transportable bile acid conjugates and suggest potential modifications to overcome these limitations.


Microbiota-governed microRNA-204 impairs endothelial function and blood pressure decline during inactivity in db/db mice.
An impaired decline in blood pressure at rest is typical in people with diabetes, reflects endothelial dysfunction, and increases the risk of end-organ damage. Here we report that microRNA-204 (miR-204) promotes endothelial dysfunction and impairment in blood pressure decline during inactivity. We show that db/db mice overexpress miR-204 in the aorta, and its absence rescues endothelial dysfunction and impaired blood pressure decline during inactivity despite obesity. The vascular miR-204 is sensitive to microbiota, and microbial suppression reversibly decreases aortic miR-204 and improves endothelial function, while the endothelial function of mice lacking miR-204 remained indifferent to the microbial alterations. We also show that the circulating miR-122 regulates vascular miR-204 as miR-122 inhibition decreases miR-204 in endothelial cells and aorta. This study establishes that miR-204 impairs endothelial function, promotes impairment in blood pressure decline during rest, and opens avenues for miR-204 inhibition strategies against vascular dysfunction.


Racial disparities in ordering laboratory and radiology tests for pediatric patients in the emergency department.
The objective of this study was to examine the association of race and language on laboratory and radiological testing in the pediatric emergency department (ED). This retrospective, case-cohort study examined laboratory and radiological testing among patients discharged home from 2 urban, pediatric EDs between March 2, 2009, and March 31, 2010. There were 75,254 visits among 49,164 unique patients, of whom 31.0% had laboratory and 30.5% had radiological testing. African American (adjusted odds ratio [aOR], 0.93; confidence interval [CI], 0.89-0.98; P = 0.004) and biracial racial categories (aOR, 0.91; CI, 0.86-0.98; P = 0.007) were associated with decreased odds of laboratory testing compared with non-Hispanic whites. Similarly, Native American (aOR, 0.82; CI, 0.73-0.94), African American (aOR0.81; CI, 0.72-0.81), biracial (aOR, 0.82; CI, 0.77-0.88), Hispanic (aOR.76; CI, 0.72-0.81), and "other" (aOR, 0.84; CI, 0.73-0.97) racial categories were each associated with lower odds of radiological testing compared with non-Hispanic whites. Subgroup analysis of visits with a final diagnosis of fever and upper respiratory tract infection, conditions for which there were few treatment protocols, confirmed the racial differences. Subgroup analysis in visits for head injury, for which there is an established evaluation protocol, did not find a lower odds of laboratory or radiological testing by race compared with non-Hispanic whites. Racial disparities in laboratory and radiological testing were present in pediatric ED visits. No racial differences were seen in the radiological and laboratory charges in the head injury subgroup, suggesting that evaluation algorithms can ameliorate racial disparities in pediatric ED care.


Label-free proteomic analysis reveals the differentiation between unfertilized and fertilized Beijing-You chicken eggs.
Egg fertilization is a dynamic process, including varieties of biochemical changes. To better understand the molecular mechanisms during the egg embryo development, the objective of this study was to quantify protein expression changes between fertilized and unfertilized Beijing-You chicken eggs using label-free liquid chromatography-tandem mass spectrometry method. The results showed that a total of 1241 proteins were identified from fertilized and unfertilized eggs, 229 proteins were observed difference in fertilized eggs (p < 0.05) compared with that in unfertilized eggs. The expressions of 86 proteins were up-regulated and 48 proteins were down-regulated in fertilized eggs. STRING database analysis and Gene Ontology analysis results showed that these differentially expressed proteins significantly interacted and were involved in lipid transport and inflammatory response biological processes. The mRNA and protein expression levels of most differentially expressed proteins Apolipoprotein B, Fibrinogen alpha chain, Transferrin receptor protein 1, Phospholipid transfer protein and Vimentin were validated by RT-PCR and western blot. These results could provide possible novel insights for the molecular mechanism of egg fertilization.


[Decompression technique for ileus: emptying of the intestine with the fingers (author's transl)].
Intestinal obstruction and distension with stasis of the intestinal contents have to be dealt with simultaneously. Opening of the small intestine for aspiration may cause infection and is not necessary. Aspiration via a Miller-Abbot tube is complicated and time consuming. Beginning at the proximal end of the jejunum the contents of the small intestine can be emptied without risk into the stomach by digital pressure. The contaminated intestinal contents can be aspirated via a gastric tube, relieving distension and restoring intestinal circulation and motility. The simplicity of this method, its immediate effect, and its lack of complications are evident.


Monitoring of organochlorine pesticides using PFU systems in Yunnan lakes and rivers, China.
Polyurethane foam unit (PFU) systems were collected from 11 lakes and three rivers in the Yunnan Plateau, China and, the PFU extrusion liquids were analyzed for organochlorine pesticides (OCPs) by gas chromatography with electron capture detection (GC-ECD). The concentrations of pp'-DDE, HCB and HCHs were undetectable to 1.86 microgl-1 (mean 0.27 microgl-1), undetectable to 0.72 microgl-1 (mean 0.11 microgl-1), and 0.24-21.95 microgl-1 (mean 7.39 microgl-1) respectively in lakes; and those in rivers were undetectable to 0.23 microgl-1 (mean 0.08 microgl-1), 0.68-2.93 microgl-1 (mean 1.70 microgl-1), and 2.71-37.56 microgl-1 (mean 17.01 microgl-1) respectively. Notably, some residue levels of OCPs exceeded the US National Recommended Water Quality Criteria, implying Yunnan has levels of OCPs potentially harmful to human health. Further, the contamination by OCPs showed an obvious spatial distribution pattern. Amongst the lakes, Dianchi, Xingyun, Lugu and Yangzonghai had the highest OCP levels dominated by beta-HCH, whereas among rivers, Nujiang and Lancang Rivers had the highest contents of OCPs dominated by alpha-HCH. This demonstrates that HCHs are the predominant contaminants and some point sources of HCHs may still exist in Yunnan. The pollution levels in Yunnan were compared with other studies, suggesting the PFU method is suitable for long-term on-line monitoring of trace OCPs in aquatic ecosystems. Therefore, continuous studies monitoring OCPs in lakes and rivers are needed to further understand the future trend of contamination.