Evaluation of a generic physiologically based pharmacokinetic model for lineshape analysis.
The mechanistic framework of physiologically based pharmacokinetic (PBPK) models makes them uniquely suited to hypothesis testing and lineshape analysis, which help provide valuable insights into mechanisms that contribute to the observed concentration-time profiles. The aim of this article is to evaluate the utility of PBPK models for simulating oral lineshapes by optimizing clearance and distribution parameters through fitting observed intravenous pharmacokinetic profiles. A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of the concentration-time profiles of nine marketed drugs with diverse physicochemical and pharmacokinetic profiles and absorption rates determined solely by transcellular or paracellular permeability and solubility. The model is based on easily available physicochemical properties of compounds such as the log P, acid dissociation constant and solubility, and in vitro pharmacokinetic data such as Caco-2 permeability, the fraction of the compound unbound in plasma, and microsomal or hepatocyte intrinsic clearance. Clearance and distribution parameters optimized through simulation of intravenous profiles were used to simulate their corresponding oral profiles, which are determined by a multitude of parameters, both compound-dependent and physiological. Comparison of the simulated and observed oral profiles was done using goodness-of-fit parameters such as the reduced chi(2) statistic. Fold errors were calculated for the area under the plasma concentration-time curve (AUC), maximum plasma concentration (C(max)) and time to reach the C(max) (t(max)), to assess the accuracy of predictions. The approach of predicting the oral profiles by optimizing the clearance and distribution parameters using the observed intravenous profile seemed to perform well for the nine compounds chosen for the study. The mean fold error for oral pharmacokinetic parameters, such as the C(max), t(max) and AUC, and for lineshape simulation was within 2-fold. The validation of the generic PBPK model built in-house demonstrated that as long as the absorption profile of a compound is determined solely by solubility and paracellular or transcellular permeability, the PBPK simulations of oral profiles using optimized parameters from intravenous simulations provide reasonably good agreement with the observed profile with respect to both the lineshape fit and prediction of pharmacokinetic parameters. Therefore, any lineshape mismatch between PBPK simulated and observed oral profiles can be interpreted suitably to gain mechanistic insights into the pharmacokinetic processes that have resulted in the observed lineshape. A strategy has been proposed to identify involvement of carrier-mediated transport; clearance saturation; enterohepatic recirculation of the parent compound; extra-hepatic, extra-gut elimination; higher in vivo solubility than predicted in vitro; drug-induced gastric emptying delays; gut loss and regional variation in gut absorption.


Mandibular osteotomies in patients with juvenile rheumatoid arthritic disease.
This retrospective study evaluates the results after orthognathic surgery in a group of patients with juvenile rheumatoid arthritis. The material comprised sixteen patients where genioplasty with or without bilateral sagittal split (BSSO) had been performed during a 10-year period between 1991 and 2000. The patients were recalled for follow-up examination and the clinical records and radiographs of the patients were analysed. All patients reported an improved facial esthetics. Sixty-two% reported altered neurosensory dysfunction in the inferior alveolar nerve, but no patients reported altered feelings to interfere with function. Two patients reported reduction in pain in the TMJ from a score 10 and 7 in the VAS-scale preoperatively, to 0 after the orthognathic surgery. Eight of the patients reported this to be less uncomfortable compared to other surgical procedures because of their JRA. Ninety-four% noted a positive social change after the operation. Orthognathic surgical treatment of the JRA patient improves the facial profile. The described procedures are safe and serious complications were not seen in our study.


A "Train-Track" Technique in Anatomic Reconstruction of SVC Bifurcation Complicated by Cardiac Tamponade: An Introspection.
This report describes a stenting technique used to anatomically reconstruct superior vena cava (SVC) bifurcation in a patient with benign SVC syndrome. After recanalizing the SVC bifurcation, we exchanged two 0.035-in. wires for two 0.018-in. wires, deployed the SVC stent over these two wires ("train-track" technique), and stented each innominate vein over one wire. However, our decisions to recanalize both innominate veins, use the "buddy-wire" technique for SVC dilation, and dilate the SVC to 16 mm before stent deployment likely contributed to SVC tear, which was managed by resuscitation, SVC stent placement, and pericardial drainage. Here, we describe the steps of the train-track technique, which can be adopted to reconstruct other bifurcations; we also discuss the controversial aspects of this case.


Suppressive effect of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and dioxin-like polychlorinated biphenyls transfer from feed to eggs of laying hens by activated carbon as feed additive.
In this study, we investigated the suppressive effect of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) transfer from the feed to the eggs of laying hens by using activated carbon as a feed additive. Four groups of six hens (White Leghorn egg-layers; age, 11weeks) were housed as two control groups and two exposure groups for a period of 20weeks. Two control groups were fed with either the basal feed "Control" or basal feed additing activated carbon "Control+C". Another two exposure groups were fed with feed contaminated (about 6ng TEQ kg(-1) feed) by standard solutions of PCDDs/PCDFs and DL-PCBs "Exposure" alone and contaminated feed adding activated carbon "Exposure+C". There was no significant effect on each groups for the growth rate, biochemical blood components, and egg production: these were around the standard levels for poultry in general. Moreover the results in this study showed the availability of activated carbon as a feed additive owing to the reduction in the risk of food pollution by PCDDs/PCDFs and DL-PCBs. The concentration in the eggs of the Exposure group gradually increased following the start of egg-laying but reached a steady state after about 1month. In contrast, the concentration for the Exposure+C group was stationary and below the maximum EU level (6pgTEQg(-1)fat). In comparison to the Exposure group, the Exposure+C group showed a significant decline in the percentage of bioaccumulation into the egg. This reduction due to activated carbon was also observed in the muscle and abdominal fat. The reductions were compound- and congener-dependent for DL-PCBs as follows: PCDDs/PCDFs, non-ortho-PCBs, and mono-ortho-PCBs were more than 90%, 80%, and 50%, respectively, irrespective of the type of tissues. Fat soluble vitamin concentrations in the eggs of the Exposure+C group showed lower trends than the Exposure group. The γ-tocopherol and α-tocopherol concentrations in eggs of Exposure+C group showed a significant reduction of about 40%. However, the addition of activated carbon into animal feed could obviate the remote potential for accidents causing unintentional food pollution with PCDDs/PCDFs and DL-PCBs.


Household organization and the interregional variation of out-migration rates.
Regional out-migration rates may depend on localized conditions, but the range of possibilities for migration decision making in multiperson households includes processes in which the response to variations in localized conditions depends on household size. Analyses of migration rates for households indicate that larger households exhibit more extreme responses to variations in localized conditions and that this is an important source of variation in regional out-migration rates.


Retrospective analysis of population-based causes of death and life expectancy in urban Western China from 2003 to 2012.
Hitherto, a population-based analysis of the cause of death in urban areas of Western China has not been undertaken over an extended period. The aims of this study were to calculate the overall and annual cause-specific mortality rates by age and sex in urban areas of Western China from 2003 to 2012 and to evaluate the quality of the data. We used Excel software, cause-of-death registrations, and International Classification of Diseases, 10th revision, codes to calculate the overall and yearly cause-specific crude mortality rates by age and sex, the Chinese age-standardized mortality rate, and life expectancies. In the Jiulongpo District from 2003 to 2012, there was an increase in the number of death case reports in the census-registered population, a decrease in the number of omitted deaths, and rise in the crude mortality rate. Except for 2003, the Chinese age-standardized mortality rate was the lowest in 2012 (330.83/100,000) and highest in 2005 (390.08/100,000). Life expectancy increased from 78.36 years in 2005 to 81.67 years in 2012. With the development of its social economy, the Chinese government and public attach greater importance to cause-of-death surveillance. The quality of cause-of-death registrations has gradually increased, crude mortality rates have risen, the Chinese age-standardized mortality rate has fallen, and life expectancies have increased.


Halothane and isoflurane in outpatient anaesthesia. A comparison of recovery.
The speed and quality of recovery after anaesthesia were studied in 60 outpatients. Anaesthesia was induced using propofol and maintained by nitrous oxide in oxygen supplemented with either halothane or isoflurane. Initial clinical recovery was significantly faster in the halothane group but no differences were found during subsequent psychomotor testing. Minor postoperative side effects were common in both groups.


Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain.
The effects of developmental lead exposure on the emotional reactivity, contextual fear conditioning and neurogenesis in the dentate gyrus of 60-80 days-old rats were studied. Wistar rat pups were exposed to 0.2% lead acetate via their dams' drinking water from postnatal day (PND) 1 to PND 21 and directly via drinking water from weaning until PND 30. At PND 60 and 80 the level of anxiety and contextual fear conditioning were studied, respectively. At PND 80 all animals received injections of BrdU to determine the effects of Pb on the generation of new cells in the dentate gyrus of hippocampus and on their survival and differentiation patterns. The results of the present study demonstrate that developmental lead exposure induces persistent increase in the level of anxiety and inhibition of contextual fear conditioning. Developmental lead exposure reduced generation of new cells in the dentate gyrus and altered the pattern of differentiation of BrdU-positive cells into mature neurons. A lower proportion of BrdU-positive cells co-expressed with the marker for mature neurons, calbindin. In contrast, the proportions of young not fully differentiated neurons and proportions of astroglial cells, generated from newly born cells, were increased in lead-exposed animals. Our results demonstrate that developmental lead exposure induces persistent inhibition of neurogenesis and alters the pattern of differentiation of newly born cells in the dentate gyrus of rat hippocampus, which could, at least partly, contribute to behavioral and cognitive impairments observed in adulthood.


[Transvenous high frequency current ablation of atrioventricular conduction in therapy refractory tachycardic atrial fibrillation].
We present a case of radiofrequency ablation of the atrioventricular conduction system by means of intravenous catheter technique in a patient with drug-refractory paroxysmal atrial fibrillation. Total AV block was produced. Since the ablation and implantation of a pacemaker this female has had no recurrences. The advantages of this method compared with electrical fulguration are better control of delivered energy and reduction of complications (catheter perforation, thromboembolism). The disadvantage of radiofrequency ablation is the difficulty in positioning the catheter so as to give the most precise contact with the tissue, which is a very time-consuming procedure.


Do nasogastric feeding tubes cause gastro-oesophageal reflux in healthy subjects?
The potential relationship between nasogastric intubation and acid gastro-oesophageal reflux was investigated. Ten healthy volunteers underwent 24h oesophageal pH monitoring following intubation with (i) a pH monitor alone, (ii) a pH monitor plus a Ryles nasogastric tube and (iii) a pH monitor plus a fine-bore nasogastric feeding tube. Neither of the nasogastric intubations were associated with significant reflux.


Identification of substituted cathinones: 3,4-Methylenedioxy derivatives by high performance liquid chromatography-quadrupole time of flight mass spectrometry.
The potential of high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) for screening of synthetic cathinones in legal highs was examined. Samples were analysed by liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometer (Q/TOF). Nanoelectrospray ionisation (nanoESI) was employed. MS and MS/MS spectra were acquired. Six 3,4-methylenedioxy derivatives: methylone, butylone, pentylone, MDPBP, MDPV and BMDP were detected and identified. The fragmentation pattern of 3,4-methylenedioxy derivatives in collision induced dissociation (CID) was derived and described, which will facilitate future screenings and identifications of new synthetic cathinones. For 3,4-methylenodioxy derivative cathinones the loss of neutral groups CH₄O₂, H₂O, amines and imines is observed. The loss of water and the methylenedioxy group does not occur when cyclic amino group - pyrrolidynyl is present in the molecule. Phenyloxazole cations are formed when CH₄O₂ is lost. The formation of the metylenedioxybenzoyloxonium and allyldioxybenzoyloxonium ions is typical for 3,4-methylenodioxy derivatives, however, the formation of the former appears to be inhibited by the presence in the molecule of the group of atoms able to form very stable tropylium carbocation.


4,5-di(2-pyridyl)-1,2,3-triazolate: the elusive member of a family of bridging ligands that facilitate strong metal-metal interactions.
The new click-adduct 4,5-di(2-pyridyl)-1,2,3-triazole acts as a doubly-chelating anionic bridging ligand that forms dinuclear ruthenium(II) complexes which exhibit strong metal-metal interactions.


MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN.
MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development. Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed. miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay. These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease.


The transpososome: control of transposition at the level of catalysis.
Studies of several transposable genetic elements have pinpointed the importance of the transpososome, a nucleoprotein complex involving the transposon ends and a transposon-encoded enzyme--the transposase--as a key in regulating transposition. Transpososomes provide a precise architecture within which the chemical reactions involved in transposon displacement occur. Data are accumulating that suggest they are dynamic and undergo staged conformational changes to accommodate different steps in the transposition pathway. This has been underpinned by recent results obtained particularly with Tn5, Tn10 and bacteriophage Mu.


Risk of antenatal psychosocial distress in indigenous women and its management at primary health care centres in Australia.
This study explored the risk of antenatal psychosocial distress (APD) and associated potential factors and examined management aspects of risk of APD in women attending Aboriginal primary health care services in Australia. Audits of medical records of 797 pregnant women from 36 primary health centres in five jurisdictions (NSW, QLD, SA, WA and NT) were undertaken as part of a quality improvement programme. Information collected included mental health assessed by a standard screening tools, enquiry regarding social and emotional well-being (SEWB), depression management (including antidepressant medications) and referral. Around 18% (n=141) of women were at risk of APD based on assessment using a standard screening tool or by SEWB enquiry. There was a significant association between risk of distress and women's life style behaviours (e.g., alcohol, illicit drug use) and health centre characteristics. Of the 141 women, 16% (n= 22) were prescribed antidepressant drugs during pregnancy. A range of nonpharmaceutical mental health interventions were also recorded, including brief intervention of 61% (n=86), counselling of 57% (n=80) and cognitive behaviour therapy of 5% (n=7). About 39% (n=55) of women with APD were referred to external services for consultations with a psychiatrist, psychologist or social worker or to a women's refuge centre. The higher risk of APD associated with women's life style behaviour indicates that the better understanding of mental health in its cultural context is essential.


Immunoglobulin G4-related periaortitis mimicking an intramural hematoma.
Immunoglobulin G4 (IgG4)-related sclerosing disease in the cardiovascular system is a recently proposed disease entity, which is still unfamiliar to most clinicians. We present a case of IgG4-related periaortitis of the ascending aorta mimicking an intramural hematoma in the computed tomography (CT) scan, which led to an unnecessary surgery. IgG4-related periaortitis needs to be considered in the differential diagnosis in a patient with thickened aortic wall because the disease should be treated medically in light of its good response to steroid therapy.


Right atrial myxoma: case report and anaesthetic considerations.
Primary cardiac tumours occur rarely. Myxoma is the most common of these tumours and 25 per cent of myxoma occur in the right atrium. We present a patient with a right atrial myxoma and hypoxaemia who suffered sudden hypotension upon induction of anaesthesia.


Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain.
Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments.


Psychoform and somatoform dissociation in anorexia nervosa: A systematic review.
Dissociation is a debilitating condition often present as comorbidity in patients with eating disorders, but to date only sparse findings are available on this topic. Additionally, very little data exist on the classification of dissociation, namely, psychoform and somatoform, in anorexia nervosa (AN). This review aimed to provide an updated view on the literature about dissociation in AN, with a focus on AN subtypes (i.e., restricter and binge-purging) as well as dissociation type (i.e., psychoform and somatoform), when available. We screened 304 studies, and after title and abstract selection and full-text reading, 29 of them were included in this review. Most of the studies investigated psychoform dissociation, whereas just four publications considered somatoform dissociation. Dissociation resulted to be present in AN more than in healthy controls and in individuals with other psychiatric disorders, and it was related mostly to the binge-purging subtype of AN. Moreover, dissociation was linked to traumatic events, self-harm and negative treatment outcomes, especially in patients affected by the binge-purging subtype of AN. However, results on these matters are scarce and partially discordant. The methodological assessment we performed revealed an overall fair quality of the included studies, although several flaws emerged as well. The present review reported on one hand the relevance of dissociation in AN, but on the other hand the need to stimulate the scientific debate on (a) a deeper investigation of somatoform dissociation in AN and (b) the relationship between dissociation and both clinical severity and treatment response/resistance in AN.


Correction: Li, et al. LncRNA NEAT1 Silenced miR-133b Promotes Migration and Invasion of Breast Cancer Cells. Int. J. Mol. Sci. 2019, 20, 3616.
The author wishes to make the following correction to this paper [...].


Complications from minimally invasive lumbar interbody fusion: experience from 100 patients.
Minimally invasive lumbar fusion is well described and is reported to offer significant advantages to patients in terms of blood loss, a reduction in post-operative pain and a quicker recovery. However, this technique may expose patients to a greater risk of complications when compared to open lumbar instrumented fusion that may negate these advantages. Between January 2007 and March 2001, we conducted a prospective observational study of 100 consecutive patients (48 males and 52 females, mean age of 54 years) to investigate complications occurring from minimally invasive lumbar interbody fusion surgery using an image-guided technique. All patients underwent post-operative CT scans to assess implant placement. Scanning was repeated at 6 months to assess bony fusion. We observed the following complications: 2.5% (11/435) pedicle screw misplacement, 1.7% (2/120) interbody cage misplacement; 0.8% (1/120) interbody cage migration; 0.8% (1/120) patients requiring a post-operative blood transfusion; 2% (2/100) venous thrombo-embolism and 3% (3/100) patients with complications thought to be related to the use of bone morphogenic protein. There were no occurrences of infection and no cerebrospinal fluid leaks. We concluded that the rate of complications from minimally invasive lumbar interbody fusion is low, and compares favourably with the rates of complication from open procedures. Moreover, computerised navigation systems can be used in place of real-time fluoroscopy to guide implant placement, without an increase in the rate of complications.


Small-diameter titanium grade IV and titanium-zirconium implants in edentulous mandibles: five-year results from a double-blind, randomized controlled trial.
The aim of this study was to compare the 5-year survival and success rates of 3.3 mm dental implants either made from titanium-zirconium (TiZr) alloy or from Grade IV titanium (Ti Grade IV) in mandibular implant-based removable overdentures. The core study had a follow-up period of 36 months and was designed as a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann Bone Level implants (diameter 3.3 mm, SLActive®), one of TiZr (test) and one of Ti Grade IV (control), in the interforaminal region. This follow-up study recruited patients from the core study and evaluated the plaque and sulcus bleeding indices, radiographic crestal bone level, as well as implant survival and success 60 months after implant placement. Of the 91 patients who initially received implants, 75 completed the 36 month follow-up and 49 were available for the 60 month examination. Two patients were excluded so that a total of 47 patients with an average age of 72 ± 8 years were analysed. The characteristics and 36-month performance of the present study cohort did not differ from the non-included initial participants (p > 0.05). In the period since the 36-month follow-up examination, no implant was lost. The cumulative implant survival rate was 98.9 % for the TiZr group and 97.8 % for the Ti Grade IV group. Crestal bone level changes at 60 months were not different in the test and control group (TiZr -0.60 ± 0.69 mm and Ti Grade IV -0.61 ± 0.83 mm; p = 0.96). The cumulative implant success rate after 60 months was 95.8 and 92.6 % for TiZr and Ti Grade IV, respectively. After 60 months, the positive outcomes of the 36 month results for TiZr and Ti Grade IV implants were confirmed, with no significant differences with regard to crestal bone level change, clinical parameters and survival or success rates. TiZr implants performed equally well compared to conventional Ti Grade IV 3.3 mm diameter-reduced implants for mandibular removable overdentures. Registered on www.clinicaltrials.gov: NCT01878331.


Schistosoma japonicum infection in the pig as a model for human schistosomiasis japonica.
Valuable information on human schistosomiasis japonica has been provided using primates and experimental rodent hosts. However, major drawbacks such as high costs and ethical concerns for the primate models and large biological deviations for the rodent models have led to the search for more appropriate models. Recent data on the pig indicate that this natural host for Schistosoma japonicum might be a realistic alternative. As only very few research groups have investigated the S. japonicum/pig model, the present review mainly deals with the experimental methods and the major host/parasite findings obtained from the authors own research group. With emphasis on a critical evaluation of the work, the results are compared to the scarce information existing on human schistosomiasis japonica. Like in humans, S. japonicum establishes mainly in the large intestinal veins, with high faecal egg counts during the acute phase of infection, which varies greatly within and between days. Concomitant resistance is another shared feature, but studies in pigs have indicated that the phenomenon is more complex than generally thought. Clinical signs as eosinophilia and diarrhoea with mucus and blood in the acute phase of infection and hepatomegaly, increased portal diameter, periportal fibrosis and ascites in chronic infections are common findings in both humans and pigs. Low protein diet aggravates the disease in pigs by increasing the establishment rates, the faecal egg excretion and the morbidity. A 100% cure rate is achieved when treating S. japonicum infected pigs with praziquantel at 40 mg/kg, and 4 weeks post treatment pigs remain resistant to reinfection. Lastly, human congenital S. japonicum infection has been confirmed in pigs but the implications of such infections for the pathogenesis of schistosomiasis japonica remain to be investigated.


Ergometer Training in Stroke Rehabilitation: Systematic Review and Meta-analysis.
Ergometer training is routinely used in stroke rehabilitation. Through this meta-analysis, we sought to discover the strength of evidence of its effects. The PubMed database and PEDro database were reviewed prior to January 22, 2019. Randomized controlled trials investigating the effects of ergometer training on stroke recovery were selected. Two reviewers independently selected the studies, performed independent data extraction, and assessed the risk of bias. A total of 28 studies (including 1115 subjects with stroke) were included. The data indicates that (1) ergometer training leads to a significant improvement in walking ability, cardiorespiratory fitness, motor function, muscular force of the lower limbs, balance and postural control, spasticity, cognitive abilities, and the brain's resistance to damage and degeneration; (2) neuromuscular functional electrical stimulation-assisted ergometer training is more efficient than ergometer training alone; (3) high-intensity ergometer training is more efficient that low-intensity ergometer training; and (4) ergometer training is more efficient than other therapies in supporting cardiorespiratory fitness, independence in activities of daily living, and balance and postural control, but less efficient in improving walking ability. Ergometer training can support motor recovery after stroke. However, current data is insufficient for evidence-based rehabilitation. More data is required about the effects of ergometer training on cognitive abilities, emotional status, and quality of life in subjects with a history of stroke.


The influence of the Li+ addition rate during the hydrothermal synthesis of LiFePO4 on the average and local structure.
A hydrothermal method was used to synthesize LiFePO4 to explore the effect of the rate of addition of the Li+ precursor to a mixture of the Fe2+ and PO43- precursors. Both the average and local structures were investigated using powder X-ray diffraction, Mössbauer spectroscopy and X-ray absorption spectroscopy. Slower addition rates led to increased oxidation of Fe2+ to Fe3+ despite purging all solutions constantly, as well as increased defects. The local structure as determined by extended X-ray absorption fine structure displayed far less variation between the samples. The formation of a Li3PO4 impurity appeared to be independent of the Li+ addition rate.


Hepatocyte-Specific β-Catenin Deletion During Severe Liver Injury Provokes Cholangiocytes to Differentiate Into Hepatocytes.
Liver regeneration after injury is normally mediated by proliferation of hepatocytes, although recent studies have suggested biliary epithelial cells (BECs) can differentiate into hepatocytes during severe liver injury when hepatocyte proliferation is impaired. We investigated the effect of hepatocyte-specific β-catenin deletion in recovery from severe liver injury and BEC-to-hepatocyte differentiation. To induce liver injury, we administered choline-deficient, ethionine-supplemented (CDE) diet to three different mouse models, the first being mice with deletion of β-catenin in both BECs and hepatocytes (Albumin-Cre; Ctnnb1flox/flox mice). In our second model, we performed hepatocyte lineage tracing by injecting Ctnnb1flox/flox ; Rosa-stopflox/flox -EYFP mice with the adeno-associated virus serotype 8 encoding Cre recombinase under the control of the thyroid binding globulin promoter, a virus that infects only hepatocytes. Finally, we performed BEC lineage tracing via Krt19-CreERT ; Rosa-stopflox/flox -tdTomato mice. To observe BEC-to-hepatocyte differentiation, mice were allowed to recover on normal diet following CDE diet-induced liver injury. Livers were collected from all mice and analyzed by quantitative real-time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. We show that mice with lack of β-catenin in hepatocytes placed on the CDE diet develop severe liver injury with impaired hepatocyte proliferation, creating a stimulus for BECs to differentiate into hepatocytes. In particular, we use both hepatocyte and BEC lineage tracing to show that BECs differentiate into hepatocytes, which go on to repopulate the liver during long-term recovery. Conclusion: β-catenin is important for liver regeneration after CDE diet-induced liver injury, and BEC-derived hepatocytes can permanently incorporate into the liver parenchyma to mediate liver regeneration.


New recruits. The IRS is changing the rules for hiring doctors.
Will the IRS fix the MD recruitment rules? If hospitals are lucky, the rules on physician recruitment will all change soon. The IRS is about to come out with its first official pronouncement in this area in more than a decade; and hospitals, recruiters and lawyers are looking forward--with some concern--to the change.


Arthrodesis in septic knees using a long intramedullary nail: 17 consecutive cases.
Intramedullary nailing using long or modular nails is the most reliable mean of achieving femorotibial fusion. Here, we report the operative, clinical, functional, and radiological outcomes of 17 long intramedullary nail arthodeses in patients with infection. Clinical and functional outcomes after long intramedullary nailing are at least as good as those obtained using other implants. We retrospectively reevaluated 17 patients after unilateral two-stage knee arthrodesis with a long titanium intramedullary nail and autologous bone grafting. We evaluated satisfaction, leg length discrepancy, and function (Lequesne and WOMAC indices). Radiographs were obtained to assess fusion, time to fusion, and femorotibial angles. No cases of material failure were recorded. One or more complications occurred in seven patients. Mean limb shortening was 27.6mm. Of the 17 patients, 15 were satisfied with the procedure. The mean Lequesne index was 10.5/24 and the mean overall WOMAC score was 26/88. Fusion was achieved in 16 patients, with a mean time to fusion of 5 months. Mean femorotibial angles were 178.6° of varus and 1.9° of flexion. This simple and rapid surgical technique provides functional outcomes similar to those obtained using modular nails. The fusion rate is high. Nail extraction is simple and causes minimal damage, in contrast to modular nails. Increased attention to misalignment is needed. Level IV, retrospective study.


Dizygotic twin pregnancy after transfer of one embryo.
To consider the risk of intercourse without contraception during infertility treatment. Case report. Leiden University Medical Center. An infertile couple underwent IVF for tubal pathology. Transfer of one embryo during a natural cycle. Human leukocyte antigen typing, histochemical analysis of the fetal membranes, neonatal and maternal clinical outcomes. A dizygotic twin pregnancy was confirmed after birth by human leukocyte antigen typing of both fetuses and mother and by histochemical analysis of the dividing fetal membranes. This suggests a pregnancy of concurrent IVF and spontaneous conception. Pregnancy was complicated by preeclampsia and intrauterine growth retardation of both fetuses. We state that couples should abstain from intercourse without contraception during infertility treatment to prevent multiple gestation and its related complications for mother and fetuses.


Protocol to analyze and quantify protein-methylated RNA interactions in mammalian cells with a combination of RNA immunoprecipitation and nucleoside mass spectrometry.
Cellular RNAs are modified by both physiological factors and exogenous agents, such as methyl methanesulfonate (MMS). However, techniques for analyzing how proteins may interact with these modified RNAs are limited. Here, we provide a protocol combining RNA immunoprecipitation (RIP) with mass spectrometry (MS) to analyze the methylation state of the RNAs bound by Flag-tagged proteins in mammalian cells. The approach is highly quantitative and can simultaneously detect several methylated nucleosides in a single experiment. For complete details on the use and execution of this protocol, please refer to Tsao et al. (2021).


Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer.
Cisplatin dosed every 3 weeks (CIS) or weekly cetuximab (CTX) concurrent with radiotherapy are standards of care for locally advanced head and neck squamous cell carcinoma (LAHNC). Retrospective comparisons of CIS and CTX have offered mixed conclusions. We compared outcomes between CIS and CTX in this patient population. Between January 2006 and December 2011, we identified 279 patients who underwent definitive radiotherapy and concurrent systemic therapy for LAHNC. The median age difference between the CIS and CTX groups was relatively small (58 vs. 62 years, respectively) and CIS patients had a slightly higher rate of N2 disease than CTX patients (74% vs. 61%, respectively). Median follow-up was 27 months. Systemic therapy consisted of CIS in 241 (86.4%) and CTX in 38 (13.6%). Actuarial locoregional control of the CIS and CTX groups at 2 years were 91% and 90% (p=0.74), respectively. Actuarial 2 year distant metastasis rates between the groups were 8% and 12%, respectively (p=0.55), and actuarial 2 year overall survival between the groups were 87% and 89%, respectively (p=0.47). We found no difference in locoregional control, distant metastasis rate, or overall survival between patients treated with concurrent CIS or CTX.


Pesticide Sorption to Soilless Media Components Used for Ornamental Plant Production and Aluminum Water Treatment Residuals.
Commercial producers of containerized ornamental plants almost exclusively use soilless media as the substrate for growing the plants. Soilless media are composed primarily of organic materials as opposed to mineral soils. Significant amounts of pesticides can leach from pots containing soilless media to which pesticides have been added as drenches or top-dressings. One of the goals of this project was to identify whether individual components comprising soilless media have differing affinities for the pesticides acephate, imidacloprid, metalaxyl, and plant growth regulator paclobutrazol. One-point 24 h equilibrium sorption assays were conducted to characterize sorption of the pesticides to sand, perlite, vermiculite, coir, peat, pine bark, and aluminum-water treatment residuals (Al-WTRs). Five-point isotherms were then constructed for the more sorptive peat and pine bark substrate components, and for the Al-WTRs. Results indicated significant differences in pesticide behavior with each substrate. Sorption of acephate to most of the substrate components was relatively low, comprising 21-31% of the initial amounts for soilless media components and 63% in Al-WTRs. Al-WTRs were highly sorptive for imidacloprid as evidenced by a partition coefficient of K F = 3275.4 L kg-1. Pine bark was the most sorptive for metalaxyl-M with a measured K F = 195.0 L kg-1. Peat had the highest affinity for paclobutrazol (K F = 398.4 L kg-1). These results indicate that none of component of soilless media has a universally high attraction for all of the pesticides studied.


Changes in renal autacoids and hemodynamics associated with aging and isolated systolic hypertension.
The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.


Hyperfine structure of the photoexcited triplet state 3P680 in plant PS II reaction centres as determined by pulse ENDOR spectroscopy.
The triplet states in plant photosystem II (PS II), 3P680, and from chlorophyll a, 3Chl a, in organic solution have been investigated using pulse ENDOR combined with repetitive laser excitation at cryogenic temperature with the aim to obtain their hyperfine (hf) structure. The large zero field splitting (ZFS) tensor of 3P680 enabled orientation selection via the electron spin resonance (EPR) field setting along the ZFS tensor axes. ENDOR spectra have been obtained for the first time also for the in-plane X- and Y-orientations of the ZFS tensor. This allowed a full determination of the hf-tensors of the three methine protons and one methyl group of 3P680. Based on the orientations of the axes of these hf-tensors, a unique orientation of the axes of the ZFS tensor of 3P680 in the Chl a molecular frame was obtained. These data serve as a structural basis for determining the orientation of 3P680 in the PS II protein complex by EPR on single crystals (see M. Kammel et al. in this issue). The data obtained represent the first complete set of the larger hf-tensors of the triplet state 3P680. They reflect the spin density distribution both in the highest occupied (HOMO) and lowest unoccupied (LUMO) orbitals. The data clearly confirm that 3P680 is a monomeric Chl a species at low temperature (T=10 K) used, as has been proposed earlier based on D- and E-values obtained from EPR and optically detected magnetic resonance (ODMR) studies. Comparison with the hf data for the cation and anion radicals of Chl a indicates a redistribution of spin densities in particular for the LUMO orbital of the triplet states. The electron spin distribution in the LUMO orbital is of special interest since it harbours the excited electron in the excited P680 singlet state, from which light-induced electron transfer proceeds. Observed shifts of hf couplings from individual nuclei of 3P680 as compared with 3Chl a in organic solution are of special interest, since they indicate specific protein interactions, e.g. hydrogen bonding, which might be used in future studies for assigning 3P680 to a particular chlorophyll molecule in PS II.


Involvement of the melanocortin MC4 receptor in stress-related behavior in rodents.
The melanocortin subtype 4 (MC4) receptor has been postulated to be involved in stress and stress-related behavior. We made use of melanocortin MC4 receptor agonists and antagonist to investigate the relationship between the melanocortin MC4 receptor and stress related disorders. The nonspecific melanocortin receptor agonist alpha-melanocyte stimulating hormone (alpha-MSH) and the melanocortin MC4 receptor agonist, Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH-(4-10)-NH2 (MT II) dose-dependently and significantly reduced the number of licking periods in the rat Vogel conflict test, suggesting that stimulation of the melanocortin MC4 receptor causes anxiogenic-like activity in rats. We synthesized a peptidemimetic melanocortin MC4 receptor selective antagonist, Ac-D-2Nal-Arg-2Nal-NH2 (MCL0020), which has high affinity for the melanocortin MC4 receptor with IC50 values of 11.63 +/- 1.48 nM, in contrast, the affinities for melanocortin MC1 and MC3 receptors were negligible. In addition, MCL0020 significantly attenuated the cAMP formation induced by alpha-MSH in COS-1 cells expressing the melanocortin MC4 receptor without affecting basal cAMP contents. Thus, we considered MCL0020 to be a selective melanocrotin MC4 receptor antagonist among melanocortin receptors. Restraint stress significantly reduced food intake in rats, and i.c.v. administration of MCL0020 dose-dependently and significantly attenuated restraint stress-induced anorexia without affecting food intake. Swim stress induced reduction in the time spent in the light area in the mouse light/dark exploration test, and MCL0020 significantly prevented it. Taken together our findings suggest that the melanocortin MC4 receptor might be related to stress-induced changes in behavior, and blockade of the melanocortin MC4 receptor may prevent stress-induced disorders such as anxiety.


Effect of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells.
The effect of natural beta-interferon (beta-IFN) on cell proliferation and steroid receptor level was investigated in CG-5 human breast cancer cell line. beta-interferon determines an appreciable diminution of cell growth, at concentrations ranging from 100 to 1000 IU/ml, which is enhanced when serum content of the culture medium is lowered. Low concentrations of beta-IFN (10-100 IU/ml) produce, after a 5-day treatment, an increase in estrogen receptors (ER) and progesterone receptors (PR). No variation of ER and PR levels is observed when beta-IFN is added directly to the cell homogenate before the assay. Our data suggest that beta-IFN could affect hormone sensitivity through a modification of ER and PR in neoplastic mammary cells.


Linking stroke mortality with air pollution, income, and greenness in northwest Florida: an ecological geographical study.
Relatively few studies have examined the association between air pollution and stroke mortality. Inconsistent and inclusive results from existing studies on air pollution and stroke justify the need to continue to investigate the linkage between stroke and air pollution. No studies have been done to investigate the association between stroke and greenness. The objective of this study was to examine if there is association of stroke with air pollution, income and greenness in northwest Florida. Our study used an ecological geographical approach and dasymetric mapping technique. We adopted a Bayesian hierarchical model with a convolution prior considering five census tract specific covariates. A 95% credible set which defines an interval having a 0.95 posterior probability of containing the parameter for each covariate was calculated from Markov Chain Monte Carlo simulations. The 95% credible sets are (-0.286, -0.097) for household income, (0.034, 0.144) for traffic air pollution effect, (0.419, 1.495) for emission density of monitored point source polluters, (0.413, 1.522) for simple point density of point source polluters without emission data, and (-0.289,-0.031) for greenness. Household income and greenness show negative effects (the posterior densities primarily cover negative values). Air pollution covariates have positive effects (the 95% credible sets cover positive values). High risk of stroke mortality was found in areas with low income level, high air pollution level, and low level of exposure to green space.


EWS-ETS oncoproteins: the linchpins of Ewing tumors.
Ewing tumors, which comprise Ewing's sarcoma and peripheral primitive neuroectodermal tumors, are highly aggressive and mostly affect children and adolescents. Their molecular signature is a chromosomal translocation leading to the generation of EWS-ETS (or very rarely FUS-ETS) fusion proteins that are capable of transforming cells. These oncoproteins act as aberrant transcription factors due to the fusion of an ETS DNA binding domain to a highly potent EWS (or FUS) transactivation domain. Accordingly, many EWS-ETS target genes have been identified whose dysregulation could contribute to the development of tumor formation. Furthermore, EWS-ETS oncoproteins may impact on RNA splicing or affect other proteins through disturbing their ability to form functional complexes. The molecular knowledge gained so far from studying EWS-ETS oncoproteins has not only broadened our understanding of Ewing tumors but also improved the diagnosis of these highly undifferentiated tumors. In addition, several potential prognostic markers have been uncovered and novel therapies are suggested that may improve the still dismal survival rate of Ewing tumor patients.


LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway.
In this study, we aimed to investigate the effects of lncRNA CASC11 on gastric cancer (GC) cell progression through regulating miR-340-5p and cell cycle pathway. Expressions of lncRNA CASC11 in gastric cancer tissues and cell lines were determined by qRT-PCR. Differentially expressed lncRNAs, mRNAs and miRNAs were screened through microarray analysis. The relationship among CASC11, CDK1 and miR-340-5p was predicted by TargetScan and validated through dual luciferase reporter assay. Western blot assay examined the protein level of CDK1 and several cell cycle regulatory proteins. GO functional analysis and KEGG pathway analysis were used to predict the association between functions and related pathways. Cell proliferation was determined by CCK-8 assays. Cell apoptosis and cell cycle were detected by flow cytometry assay. CASC11 was highly expressed in GC tissues and cell lines. Knockdown of CASC11 inhibited GC cell proliferation, promoted cell apoptosis and blocked cell cycle. KEGG further indicated an enriched cell cycle pathway involving CDK1. QRT-PCR showed that miR-340-5p was down-regulated in GC cells tissues, while CDK1 was up-regulated. Furthermore, CASC11 acted as a sponge of miR-340-5p which directly targeted CDK1. Meanwhile, miR-340-5p overexpression promoted GC cell apoptosis and induced cell cycle arrest, while CDK1 overexpression inhibited cell apoptosis and accelerated cell cycle. Our study revealed the mechanism of CASC11/miR-340-5p/CDK1 network in GC cell line, and suggested that CASC11 was a novel facilitator that exerted a biological effect by activating the cell cycle signaling pathway. This finding provides a potential therapeutic target for GC.


The complexity of bacterial transcriptomes.
For eukaryotes there seems to be no doubt that differences on the trancriptomic level substantially contribute to the process of species diversification, whereas for bacteria this is thought to be less important. Recent years saw a significant increase in full transcriptome studies for bacteria, which provided deep insight into the architecture of bacterial transcriptomes. Most notably, it became evident that, in contrast to previous scientific consensus, bacterial transcriptomes are quite complex. There exist a large number of cis-antisense RNAs, non-coding RNAs, overlapping transcripts and RNA elements that regulate transcription, such as riboswitches. Furthermore, processing and degradation of RNA has gained interest, because it has a significant impact on the composition of the transcriptome. In this review, we summarize recent findings and put them into a broader context with respect to the complexity of bacterial transcriptomes and its putative biological meanings.


The TORC1-Nem1/Spo7-Pah1/lipin axis regulates microautophagy induction in budding yeast.
Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase promotes macroautophagy. Macroautophagy is a lipid-consuming process, and Nem1/Spo7 protein phosphatase and Pah1/lipin phosphatidate phosphatase are activated after TORC1 inactivation, supporting macroautophagy induction in the budding yeast Saccharomyces cerevisiae. On the other hand, whether and how microautophagy, which also consumes lipids, is regulated by TORC1 is controversial. Here we show that TORC1 inactivation induces microautophagy in budding yeast. Vps27, but not Atg1, Atg7, or Atg8, was required for TORC1 inactivation-induced microautophagy. Furthermore, the Nem1/Spo7-Pah1 axis was also critical for microautophagy induction. Thus, the TORC1-Nem1/Spo7-Pah1 axis is a master regulator of not only macroautophagy but also microautophagy in budding yeast.


Pulmonary gas exchange during venoarterial bypass with a membrane lung for acute respiratory failure.
In patients with fulminating pulmonary edema not responsive to conventional therapy, venoarterial membrane lung bypass can provide assistance if decreased systemic blood pressure prevents use of high-level positive end-expiratory pressure ventilation. In 10 patients with acute respiratory failure, partial venoarterial bypass provided a rapid and marked improvement of systemic oxygenation. Measurement of pulmonary blood flow (PBF) and intrapulmonary shunting (QS/QP) during bypass via prolonged left heart catheterization showed that left ventricular PaO2 was increased through a rapid and profound reduction of QS/QP. During the first days of bypass, derecruitment of pulmonary vessels is probably the mechanism of improved pulmonary oxygenation. When low pulmonary arterial pressures (PAP) are sustained, resorption of pulmonary edema is favored. Despite the beneficial effects of bypass, death occurred in every case due to diffuse interstitial fibrosis and/or parenchymal damage. The absence of healing, due to prolonged circulatory exclusion, may be detrimental despite immediate improvement. Because of this possibility, venovenous or mixed perfusion should be more extensively explored.


Intravenous immunoglobulin therapy for severe arthritis associated with human parvovirus B19 infection.
Symptoms caused by acute human parvovirus B19 (HPV-B19) infection can vary considerably, from asymptomatic to severely symptomatic. A 39-year-old Japanese woman complained of sudden, severe arthralgia with edematous limbs coincident with an outbreak of HPV-B19 infection at the elementary school attended by her daughter. A diagnosis of acute HPV-B19 infection was made by the detection of serum antibody to HPV-B19 IgM and HPV-B19 DNA. Magnetic resonance imaging revealed bilateral synovitis of the cubital joints. The patient was immunocompetent and suffered from severe arthralgia associated with persistent HPV-B19 viremia for more than 4 months after the diagnosis of acute HPV-B19 infection. The administration of high-dose intravenous immunoglobulin resulted in remission, with little change in the serum HPV-B19 DNA level. Even in our immunocompetent patient, severe and prolonged arthritis was found to be associated with persistent viremia.


A circular polyester platform based on simple gem-disubstituted valerolactones.
Geminal disubstitution of cyclic monomers is an effective strategy to enhance the chemical recyclability of their polymers, but it is utilized for that purpose alone and often at the expense of performance properties. Here we present synergistic use of gem-α,α-disubstitution of available at-scale, bio-based δ-valerolactones to yield gem-dialkyl-substituted valerolactones ([Formula: see text]), which generate polymers that solve not only the poor chemical recyclability but also the low melting temperature and mechanical performance of the parent poly(δ-valerolactone); the gem-disubstituted polyesters ([Formula: see text]) therefore not only exhibit complete chemical recyclability but also thermal, mechanical and transport properties that rival or exceed those of polyethylene. Through a fundamental structure-property study that reveals intriguing impacts of the alkyl chain length on materials performance of [Formula: see text], this work establishes a simple circular, high-performance polyester platform based on [Formula: see text] and highlights the importance of synergistic utilization of gem-disubstitution for enhancing both chemical recyclability and materials performance of sustainable polyesters.


Heme induced oxidative stress attenuates sirtuin1 and enhances adipogenesis in mesenchymal stem cells and mouse pre-adipocytes.
Patho-physiological conditions with high oxidative stress, such as conditions associated with increased denatured heme-proteins, are associated with enhanced adipogenic response. This effect predominantly manifests as adipocyte hypertrophy characterized by dysfunctional, pro-inflammatory adipocytes exhibiting reduced expression of anti-inflammatory hormone, adiponectin. To understand how increased levels of cellular heme, a pro-oxidant molecule, modulates adipogenesis; the following study was designed to evaluate effects of heme on adipogenesis in human mesenchymal stem cells (hMSCs) and mouse pre-adipocytes (3T3L1). Experiments were conducted in the absence and in the presence of a superoxide dismutase (SOD) mimetic (tempol, 100 µM). Heme (10 µM) increased (P<0.05) adipogenesis in hMSCs and mouse pre-adipocytes, where tempol alone (100 µmol/L) attenuated adipogenesis in these cells (P<0.05). Tempol also reversed heme-induced increase in adipogenesis in both hMSCs and mouse pre-adipocytes (P<0.05). In addition, heme exposed 3T3L1 exhibited reduced (P<0.05) expression of transcriptional regulator-sirtuin 1 (Sirt1), along with, increased (P<0.05) expression of adipogenic markers peroxisome proliferators-activated receptor-gamma (PPARγ), C/EBPα, and aP2. These effects of heme were rescued (P<0.05) in cells concurrently treated with heme and tempol (P<0.05) and prevented in cells over-expressing Sirt1. Taken together, our results indicate that heme-induced oxidative stress inhibits Sirt1, thus un-inhibiting adipogenic regulators such as PPARγ and C/EBPα; which in turn induce increased adipogenesis along with adipocyte hypertrophy in pre-adipocytes. Anti-oxidant induced offsetting of these effects of heme supports the role of heme-dependent oxidative stress in mediating such events.


The evaluation of the recovery capacity of media for heat-treated Bacillus stearothermophilus spore strips.
Six media were assessed for their capacity to recover spores of Bacillus stearothermophilus from three commercially available types of spore strip heated for up to 5 min at 121 degrees C in steam. All media recovered similar numbers of spores from unheated strips; however, there was considerable difference in survivor counts when the media were used to recover heated spores. Media containing starch consistently recovered the highest number of spores. The greatest difference in recovery capacity between the media was observed when spore strips were heated for 5 min at 121 degrees C.


Benign submucosal lesions of the stomach and duodenum: imaging characteristics with endoscopic and pathologic correlation.
Benign submucosal lesions of the stomach and duodenum are occasionally encountered during endoscopy. But endoscopy has its limitations in the diagnosis and differentiation of these lesions, because submucosal lesions are often difficult to visualize at endoscopy due to minimal change of the overlying mucosa. Furthermore, endoscopic biopsy may not always yield adequate tissue for diagnosis due to the submucosal location of the lesions. For this reason, the role of radiologic imaging is important in the diagnosis of submucosal lesions of the stomach and duodenum. Recent advances in computed tomography (CT) and sonographic technology are helpful in narrowing the differential diagnosis of gastroduodenal submucosal lesions. In contrast to endoscopy and barium studies, CT or ultrasonography (US) provides information about both the gastric wall and the extragastric extent of the disease. Arterial phase contrast enhanced CT enables us to discriminate a mass of submucosal from that of a mucosal origin in the differential diagnosis of gastric or duodenal lesions. Although endoscopic sonography has been considered the better modality in the diagnosis of gastroduodenal submucosal lesions, transabdominal sonography can still be an alternative method to endoscopic sonography in assessing of the origin and character of the submucosal lesions. Some gastroduodenal submucosal lesions have similar radiologic findings that make differentiation difficult. But despite overlaps in radiologic findings, some lesions have characteristic radiologic features that may suggest a specific diagnosis. Knowledge of the differential diagnosis of benign submucosal lesions in the stomach and duodenum may promote correct diagnosis and appropriate treatment.


Odd-even effect on the thermal conductivity of liquid crystalline epoxy resins.
Rapid developments in high-performance computing and high-power electronics are driving needs for highly thermal conductive polymers and their composites for encapsulants and interface materials. However, polymers typically have low thermal conductivities of ∼0.2 W/(m K). We studied the thermal conductivity of a series of epoxy resins cured by one diamine hardener and seven diepoxide monomers with different precise ethylene linker lengths (x = 2-8). We found pronounced odd-even effects of the ethylene linker length on the liquid crystalline order, mass density, and thermal conductivity. Epoxy resins with even x have liquid crystalline structure with the highest density of 1.44 g/cm3 and highest thermal conductivity of 1.0 W/(m K). Epoxy resins with odd x are amorphous with the lowest density of 1.10 g/cm3 and lowest thermal conductivity of 0.17 W/(m K). These findings indicate that controlling precise linker length in dense networks is a powerful route to molecular design of thermally conductive polymers.


Evaluation of extremely steep residual stress gradients based on a combined approach using laboratory-scale equipment.
Surface treatments characterized by rapid heating and cooling (e.g. laser hardening) can induce very steep residual stress gradients in the direct vicinity of the area being treated. These gradients cannot be characterized with sufficient accuracy by means of the classical sin2Ψ approach applying angle-dispersive X-ray diffraction. This can be mainly attributed to limitations of the material removal method. In order to resolve residual stress gradients in these regions without affecting the residual stress equilibrium, another angle-dispersive approach, i.e. the universal plot method, can be used. A novel combination of the two approaches (sin2Ψ and universal plot) is introduced in the present work. Prevailing limits with respect to profiles as a function of depth can be overcome and, thus, high-resolution surface layer characterization is enabled. The data obtained are discussed comprehensively in comparison with results elaborated by energy-dispersive X-ray diffraction measurements.


Direct health care costs of laryngeal diseases and disorders.
To estimate the annual direct costs associated with the diagnosis and management of laryngeal disorders. Retrospective analysis of data from a large, nationally representative, administrative US claims database. Patients with a laryngeal disorder based on International Classification of Diseases,Ninth Revision-Clinical Modification codes from January 1, 2004 to December 31, 2008 and who were continuously enrolled for 12 months were included. Data regarding age, gender, geographic location, and type of physician providing the diagnosis were collected. Medical encounter, medication, and procedure costs were determined. Total and mean costs per person for 12 months were determined. Of almost 55 million individuals in the database, 309,300 patients with 12 months follow-up, mean age of 47.3 years (standard deviation: 21.3), and 63.5% female were identified. Acute and chronic laryngitis, nonspecific causes of dysphonia, and benign vocal fold lesions were the most common etiologies. The total annual direct costs ranged between $178,524,552 to $294,827,671, with mean costs per person between $577.18 and $953.21. Pharmacy claims accounted for 20.1% to 33.3%, procedure claims 50.4% to 69.9%, and medical encounter claims 16.3% to 8.6% of overall direct costs. Antireflux medication accounted for roughly 10% and antibiotics 6% of annual direct costs. This study establishes the economic impact of the assessment and management of patients with laryngeal disorders and permits cost comparisons with other diseases.


Relationship between the secretor status and the expression of ABH blood group antigenic determinants in human intestinal brush-border membrane hydrolases.
At least six hydrolases of the human intestinal brush-border membrane bear ABH blood group antigenic determinants related to the erythrocyte phenotype: the intestinal glycoproteins of blood group A and B subjects express A or B determinants, respectively, while blood group O subjects express the H determinant identified with Ulex europaeus lectin I. These expressions are under the control of the secretor gene: ABH antigens were not detected in the hydrolases of non-secretor subjects.


Epididymo-orchitis caused by Histoplasma capsulatum.
A 66-year-old man presented with asymptomatic right testicular swelling. He was known to be infected with HIV and was non-adherent to treatment. He was recently treated for nasal leishmaniasis. Surgical drainage was performed and eventually, an orchiectomy was required. A post-mortem diagnosis was made of disseminated histoplasmosis. Testicular infection due to H. capsulatum is rare, with only a few cases being reported. Here we present a case of testicular histoplasmosis, followed by a literature review.


Asymptomatic Leishmania infantum/chagasi infection in blood donors of western Sicily.
The purpose of this study was to evaluate whether the risk of transfusion-transmitted visceral leishmaniasis was present in an area of western Sicily where the incidence of the disease is higher than the regional average. From May to December 2005, 1449 blood donors from Agrigento district (Sicily, Italy) were screened for the presence of anti-Leishmania antibodies by an indirect immunofluorescent antibody test (IFAT). Blood samples from IFAT-positive donors were examined by PCR to detect Leishmania DNA. Anti-Leishmania antibodies were found in 11 (0.75%) cases, among which Leishmania DNA was detected from four (36.4%). Particular techniques to inactivate different pathogens would be considered mandatory in the case of immunosuppressed recipients.


Impact of the COVID-19 Pandemic on Initiation of Antibiotic Treatment After Performing a Blood Culture and Intervention by the Antimicrobial Stewardship Team.
Whether the coronavirus disease 2019 (COVID-19) pandemic had any effect on the time between blood culture collection and administration of antibiotics in the outpatient Department of Emergency Medicine in a single university hospital in Japan was investigated, and the intervention carried out by the antimicrobial stewardship team (AST) to promote the appropriate use of antibiotics was examined. The monthly percentage of patients who visited the outpatient Department of Emergency Medicine between January 2019 and December 2021 and received an intravenous antibiotic within 3 hours of blood culture collection was calculated. The AST calculated a quality indicator (QI) based on the results of the investigation and started QI monitoring and hospital feedback. From January 2020 to March 2021 (the third COVID-19 wave), the implementation rate of antibiotic administration within 3 hours after blood culture collection decreased as the COVID-19 pandemic spread, and the implementation rate tended to increase as the number of COVID-19-positive patients decreased. However, when the AST started monitoring and feedback from April 2021, although there was a temporary decline in the early stages of the fifth wave when the scale of infection was large, the implementation rate rose and was maintained by AST intervention. (the fourth and the fifth COVID-19 waves) (P<0.01). Also, the implementation rate was significantly lower during the COVID-19 pandemic than during the non- pandemic (P<0.05). The early COVID-19 pandemic may have affected the delay in time from blood culture collection to antibiotic administration. Later, in recurring COVID-19 pandemics, AST intervention eliminated this problem. When a bacterial infection such as sepsis is suspected, delayed treatment can be prevented by promptly collecting a blood culture, irrespective of concerns about COVID-19 infection. Calculating the QI may promote AST activities and the appropriate use of antibiotics.


1-Methyl anthraquinones and their biogenetic precursors from Stereospermum personatum.
Two novel 1(17)-methyl anthraquinones, sterequinone-A and -D, their biogenetic precursors sterequinone-B, -C, and a new naphthoquinone sterequinone-E along with a known naphthoquinone, sterekunthal-B, have been isolated from the petroleum ether extract of stem bark of Stereospermum personatum. Their structures were established using spectroscopic methods.


IGF receptor function and regulation in autocrine human neuroblastoma cell growth.
Insulin-like growth factor-II (IGF-II) and its receptors (type I and II IGF receptors) are expressed in the nervous system in a tissue and developmentally specific manner. We have previously shown that SH-SY5Y human neuroblastoma cells synthesize and secrete high levels of IGF-II, and respond to it with increased neuritic outgrowth, DNA synthesis, and cell proliferation. SH-SY5Y cells also produce type I IGF and IGF-II/M6P receptors; however, it is not known whether these receptors mediate the observed growth promoting effects of IGF-II. In this study, we assayed the role of type I IGF receptor and IGF-II/M6P receptor expression in mediating autocrine IGF-II induced growth. Using anti-receptor antibodies, we found that IGF-II stimulates cell proliferation via the type I IGF receptor but not via the IGF-II/M6P receptor. By Northern analysis, we detected increased mRNA expression of both receptors, with more dramatic changes in type I IGF receptor expression. Collectively, our results indicate a role for the type I IGF receptor in mediating IGF-II induced autocrine neuroblastoma cell growth.


RADIATION DOSE DETERMINATION IN ABDOMINAL CT EXAMINATIONS OF CHILDREN AT SUDANESE HOSPITALS USING SIZE-SPECIFIC DOSE ESTIMATES.
In this study, we thought to estimate the radiation exposure of children undergoing multi-detector CT examinations using size-specific dose estimates (SSDE). Console-displayed volume computed tomography dose index (CTDIvol) were recorded for a total of 78 paediatric abdominal CT examinations performed in six hospitals. Measurements of the patient diameters were taken from the mid-slice location on the transverse and scout CT images. Size-specific conversion coefficients were used to translate CTDIvol to the SSDE, according AAPM Report 204. For children aged 0-1 y, CTDIvol, SSDEtrans (from transverse images) and SSDEsco (from scout images) were: 12.80 ± 16.10, 14.43 ± 13.22; and 14.37 ± 13.03 mGy; respectively. For children aged 1-5 y, CTDIvol, SSDEtrans and SSDEsco were: 12.11 ± 14.47, 18.8 ± 18.61 and 16.51 ± 13.55 mGy; respectively. The obtained doses are higher than the corresponding diagnostic reference levels. SSDE increase with patient size as results of tube current modulation and is therefore a valuable tool for dose optimisation.


Regional disparity in the provision of rehabilitation services using the open data from the Japanese national claims database: an ecological study.
There are few reports on regional differences in the supply/utilisation balance and provision of rehabilitation services. This study analysed those regional differences in Japan to help policymakers provide more uniform and efficient rehabilitation services and optimally allocate related resources. An ecological study. 47 prefectures and 9 regions in Japan in 2017. Primary measures were 'supply/utilisation (S/U) ratio', calculated by dividing rehabilitation supply converted to service units, by rehabilitation utilisation and 'utilisation/expected utilisation (U/EU) ratio', calculated by dividing utilisation by EU. The EU was defined as utilisation expected from the demography in each area. Data required to calculate these indicators were collected from open sources such as the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan. The S/U ratios were higher in Shikoku, Kyusyu, Tohoku and Hokuriku regions, and lower in Kanto and Tokai regions. The number of rehabilitation providers per population was higher mostly in the western part of Japan and lower mostly in the eastern part. The U/EU ratios were also higher mostly in the western part, and lower mostly in the eastern part such as Tohoku and Hokuriku regions. The same trend was seen for cerebrovascular disease and musculoskeletal disorder rehabilitation, which accounted for approximately 84% of rehabilitation services. For disuse syndrome rehabilitation, such a trend did not exist, and the U/EU ratio differed by prefectures. The large surplus in rehabilitation supply in the western part was attributed to the greater number of providers, while the smaller surplus in Kanto and Tokai regions was due to the smaller amount of supply. The number of rehabilitation services used was lesser in the eastern part such as Tohoku and Hokuriku regions, indicating regional differences in the provision of rehabilitation services.


Trends in total elbow arthroplasty in patients with rheumatoid arthritis receiving disease-modifying antirheumatic drug therapy based on payer status.
Total elbow arthroplasty (TEA) is often used to manage advanced arthropathies of the elbow caused by inflammatory conditions such as rheumatoid arthritis (RA). Recent literature has shown that use of TEA is decreasing in patients with RA, part of which can be attributed to early medical management involving disease-modifying antirheumatic drugs (DMARDs). However, there is a significant economic barrier to accessing DMARD therapy. The purpose of this study was to compare the use of TEA between patients with and without DMARD therapy from 2010 to 2020. A retrospective cohort analysis was performed using a national insurance claim database to investigate the trends of patients with RA undergoing TEA from 2010-2020. Patients who underwent TEA and had a diagnosis of RA were identified using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD)-9 and ICD-10 codes between 2010 and 2020. These patients were then stratified into 2 cohorts: those with DMARD prescription claims and those without. A linear regression, compound annual growth rate (CAGR) analysis, and χ2 analysis were conducted to compare trends and demographic variables, including insurance type, between cohorts. Additionally, a multivariable logistic regression was subsequently performed to observe odds ratios (ORs) and 95% confidence intervals. From 2010 to 2020, there has been no significant change in the incidence of TEA in RA patients without DMARD prescriptions, whereas there has been a statistically significantly decreasing rate of TEA observed in RA patients with DMARD prescription claims. The analysis showed that there was a CAGR of -4%. For patients with a diagnosis of RA and DMARD prescription claims, the highest incidence of undergoing TEA was seen in the age group of 60-69 years, whereas patients with a diagnosis of RA and no DMARD prescription claims had the highest incidence of undergoing TEA in the age group of 70-79 years. The incidence of patients undergoing TEA with a diagnosis of RA and DMARD prescription claims has shown a statistically significant decrease from 2010 to 2020, whereas no significant difference was observed for patients without DMARD prescription claims. There were no statistically significant differences in the insurance plans between cohorts.


Isolation and characterization of membrane proteins responsible for attachment of polyribosomes to rough microsomal fraction of rat liver.
A protein fraction which has a high affinity for polyribosomes was isolated from rough microsomal membranes of rat liver. The mode of polyribosome binding to this fraction (R-fraction) was studied by using CsCl equilibrium centrifugation and compared with that for stripped rough microsomal membranes. The following were found. (1) The polyribosome-binding cpacity of the R-fraction was heat-labile and sensitive to trypsin, and was suppressed by increasing KCl concentration and addition of 0.1 mM-aurintricarboxylic acid. (2) Of the four subfractions obtained by gel filtration of the R-fraction on a Sephadex G-200, only the R1-fraction, eluted at the void volume, showed a high affinity for polyribosomes. The polyribosome-binding capacity of the R1-fraction decreased with time on storage at 4 degrees C. (3) The R1-fraction contained three major proteins with mol. wts. 108,000, 99,000 and 65,000.


A 15-year followup of a nonmicrosurgical technique for vasovasostomy.
A 15-year followup was summarized for patients who had nonmicrosurgical vasectomy reversal. Over-all pregnancy rates were 45 per cent (43 per cent for the first 8 years and 49 per cent for the next 7 years) and 73 per cent of the pregnancies occurred within 1 year after vasectomy reversal. Patients who achieved pregnancy compared to those who did not had significantly better sperm motility and a lower incidence of antisperm antibodies. The data indicate that nonmicrosurgical techniques can be used successfully to reverse vasectomy more economically and more rapidly than the microsurgical approach, while contributing to a reasonable pregnancy rate.


Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes.
In Escherichia coli, the miniF plasmid CcdB protein is responsible for cell death when its action is not prevented by polypeptide CcdA. We report the isolation, localization, sequencing and properties of a bacterial mutant resistant to the cytotoxic activity of the CcdB protein. This mutation is located in the gene encoding the A subunit of topoisomerase II and produces an Arg462----Cys substitution in the amino acid sequence of the GyrA polypeptide. Hence, the mutation was called gyrA462. We show that in the wild-type strain, the CcdB protein promotes plasmid linearization; in the gyrA462 strain, this double-stranded DNA cleavage is suppressed. This indicates that the CcdB protein is responsible for gyrase-mediated double-stranded DNA breakage. CcdB, in the absence of CcdA, induces the SOS pathway. SOS induction is a biological response to DNA-damaging agents. We show that the gyrA462 mutation suppresses this SOS activation, indicating that SOS induction is a consequence of DNA damages promoted by the CcdB protein on gyrase-DNA complexes. In addition, we observe that the CcdBS sensitive phenotype dominates over the resistant phenotype. This is better explained by the conversion, in gyrA+/gyrA462 merodiploid strains, of the wild-type gyrase into a DNA-damaging agent. These results strongly suggest that the CcdB protein, like quinolone antibiotics and a variety of antitumoral drugs, is a DNA topoisomerase II poison. This is the first proteinic poison-antipoison mechanism that has been found to act via the DNA topoisomerase II.


Uterine allograft removal by total laparoscopic hysterectomy after successful cesarean delivery in a living-donor uterus recipient with uterovaginal agenesis (MRKHS).
To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). A 37-year-old woman with uterovaginal agenesis due to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.


Ultrasound mediated delivery of drugs and genes to solid tumors.
It has long been shown that therapeutic ultrasound can be used effectively to ablate solid tumors, and a variety of cancers are presently being treated in the clinic using these types of ultrasound exposures. There is, however, an ever-increasing body of preclinical literature that demonstrates how ultrasound energy can also be used non-destructively for increasing the efficacy of drugs and genes for improving cancer treatment. In this review, a summary of the most important ultrasound mechanisms will be given with a detailed description of how each one can be employed for a variety of applications. This includes the manner by which acoustic energy deposition can be used to create changes in tissue permeability for enhancing the delivery of conventional agents, as well as for deploying and activating drugs and genes via specially tailored vehicles and formulations.


Ixekizumab 80 mg Every 2 Weeks Treatment Beyond Week 12 for Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis.
In 2018, ixekizumab (80 mg every 2 weeks [Q2W] beyond Week 12) received approval in Japan for patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). This open-label study evaluated the efficacy and safety of ixekizumab (80 mg Q2W from Week 12 to Week 20) in Japanese patients with GPP and EP. Seven patients with GPP and five patients with EP were enrolled. An initial dose of 160 mg (subcutaneous [SC] injection) was followed by 80 mg Q2W SC until Week 12. Primary endpoint assessed global improvement score (GIS) by comparing psoriatic findings, Static Physician Global Assessment, Psoriasis Area and Severity Index score, and other evaluations with those at the baseline and were graded as 1 = resolved, 2= improved, 3 = unchanged, and 4 = worsened. Patients who showed GIS = 1 (resolved) at Week 12 completed the study. Patients with GIS ≥ 2 continued to receive ixekizumab 80 mg Q2W until Week 20. At Week 12, four of seven patients with GPP showed "resolved," two showed "improved," and one showed "worsened." Of five patients with EP, one showed "resolved" and four showed "improved." Two patients with GPP and four patients with EP continued ixekizumab treatment until Week 20. At Week 20, one of the two patients with GPP showed "resolved" and one patient showed "improved." All four patients with EP showed "improved." One non-drug related serious adverse event was reported by one patient with EP at Week 12. From Week 12 to Week 20, no adverse events (AEs) were reported in patients with GPP, but two mild AEs were reported in one of the four patients with EP. This study indicates that ixekizumab continuous Q2W dosing is efficacious and safe for patients with GPP and EP. NCT03942042.


Safety and Efficacy of High-Dose Unfractionated Heparin for Prevention of Venous Thromboembolism in Overweight and Obese Patients.
To determine the safety and efficacy of high-dose subcutaneous unfractionated heparin (UFH) for prevention of venous thromboembolism (VTE) in overweight and obese patients. Single-center retrospective observational cohort study. Large academic tertiary care medical center. A total of 1335 adults who weighed more than 100 kg on admission and received either subcutaneous UFH 7500 units every 8 hours (751 patients [high-dose group]) or 5000 units every 8 hours (584 patients [low-dose group]) for VTE prophylaxis during their hospitalization between January 1, 2013, and August 31, 2014. The incidences of VTE and bleeding complications were assessed in each group. Each group was further divided into four groups based on their body mass index (BMI): overweight (BMI 25-29.9 kg/m(2) ), obese class I (BMI 30-34.9 kg/m(2) ), obese class II (BMI 35-39.9 kg/m(2) ), and obese class III (BMI ≥ 40 kg/m(2) ). The incidence of VTE was similar for patients in the high-dose group versus those in the low-dose group for all BMI categories. Bleeding complications were significantly higher for patients in the high-dose group. The proportion of patients with at least a 2-g/dl hemoglobin drop from admission was higher in patients in the high-dose groups in obese classes II and III: obese class II, 46 (30%) of 152 patients in the high-dose group versus 30 (18%) of 171 patients in the low-dose group (p<0.01); obese class III, 109 (25%) of 432 patients in the high-dose group versus 31 (12%) of 249 patients in the low-dose group (p<0.01). In addition, the proportion of patients who received at least 2 units of packed red blood cell transfusion was significantly higher in patients in the high-dose group who were in obese class III: 47 (11%) of 432 in the high-dose group versus 13 (5%) of 249 in the low-dose group (p<0.01). Administering a higher dose of heparin to patients weighing more than 100 kg may not impart additional efficacy in reducing the incidence of VTE. However, it may increase the risk for bleeding.


Plasma prorenin in normal, hypertensive, and anephric subjects and its effect on renin measurements.
We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by shaking plasma at -5 degrees C for 4 days. Circulating prorenin averaged 5.6 +/- 0.8 (SE) ng/ml per hour in a group of 30 normal subjects and 5.1 +/- 1.0 ng/ml per hour in 25 hypertensive subjects during random sodium intake. In these two groups, prorenin ranged from zero to 36 times the endogenous renin level, averaging 2.5-fold in normal subjects and 3.4-fold in hypertensive subjects. During sodium deprivation prorenin more than doubled in 12 hypertensive subjects from a mean of 2.8 to 6.3 ng/ml per hour. In 25 anephric subjects, circulating prorenin was slightly lower than in normal subjects, averaging 3.4 +/- 0.9 ng/ml per hour (P less than 0.05). In contrast to our findings in nephric subjects, the low level of PRA measured in anephric subjects ((0.26 +/- 0.04 ng/ml per hour) was almost always a constant fraction of the measured prorenin. This led to the demonstration that prorenin can be inadvertently activated by chilling blood during processing for renin measurement and this often accounts for the small amount of renin measured in plasmas from anephric subjects. The error in routine PRA measurements due to inadvertent activation averaged +48% in anephric subjects and +17% in those with kidneys. Evaluation of the effect of processing bloods at room temperature revealed that net angiotensin I accumulation is less than 2% of that generated during incubation and can be ignored. Accordingly, to avoid the inadvertent activation of prorenin which can at times lead to a sizable and variable overestimation of PRA we recommend collecting and processing blood samples at room temperature and then storage of plasma completely frozen until the time for analysis.


The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial.
In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. Patients were randomly assigned at a median of 4.4 [3.0-5.8] days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74-0.99], P=0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. URL: https://www. gov; Unique identifier: NCT02924727.


Renotropic activity of lutropin: direct stimulation of DNA synthesis of cultured rat renal cortical cells.
Two differently purified ovine lutropin (LH) preparations were studied to see if they stimulated [3H] thymidine incorporation into cultured rat renal cortical cells. Both preparations showed a dose-dependent (0.11-1 ng/ml), time-dependent (peaking at 18 h), serum-dependent (7.5% of fetal calf serum or 10% castrated-hypo-physectomized rat serum) renotropic effect. Ovine TSH and FSH failed to mimic this specific, renotropic effect. We concluded that LH directly stimulates renal DNA synthesis in cooperation with other serum factor's.


A new delay technique with application to ultrasound phased-array imaging systems.
In ultrasound phased-array imaging systems the receiver directivity pattern is steered by controlling the delay of echoes from the array elements. A new processing technique is introduced that provides the required delay first by properly phasing the echo carrier, and successively by delaying the echo envelope. This latter operation is based on a new analogue sampled-data delay-line. Independent control of phase delay offers a simple means of compensating for random phase errors due to non-uniformity of the array elements response.


Child and Adolescent Psychiatric Screening Inventory-Retrospect (CAPSI-R): a questionnaire for adults concerning child and adolescent mental disorders.
This study examines the properties of the Child and Adolescent Psychiatric Screening Inventory-Retrospect, CAPSI-R, a self-report 146-item questionnaire for adults concerning earlier child psychiatric symptoms, comprising both DSM-IV categories and functional impairment. The instrument was mailed to 359 former child psychiatric patients born between 1951 and 1977 (164 of whom responded) and to a matched control group (193 of whom responded). There was good internal consistency (Cronbach's alpha ranged between 0.62-0.93, and between 0.76-0.93 after elimination of one item). The lifetime prevalence of a mental disorder was 87.8% in the former patients' without considering impairment and 76.8% when impairment was considered. The corresponding figures for the control group were 49.7% and 10.4%, respectively. When the former patients' CAPSI-R diagnoses (with incorporation of the impairment criterion) were validated against the DSM-IV diagnoses based on information in their medical records, generally, an acceptable sensitivity and specificity were obtained. The overall kappa between CAPSI-R diagnoses and those from medical records was 0.79. The CAPSI-R shows promise for further evaluation and may be useful in recognising child and adolescent mental disorders in adults.


Title VII--Nutrition Program for the Elderly. I. Contribution to one day's dietary intake.
Food records kept by 466 individuals participating in the federally funded Nutrition Program for the Elderly show that those eating at the meal site on the day of the food record consumed more energy, protein, and calcium than non-participants and participants who did not eat there on the day of the record. Dietary ratings, which included eight nutrients and energy, indicated they also had better overall diets than non-participants. Non-participants consumed more iron than participants. The daily intake of all nutrients, except calcium, of those eating at the meal site reflected what was offered. Between 40 and 50 per cent of the total daily intake was consumed at the meal center. Women consumed a significantly greater proportion of their daily intake of most nutrients from the food provided by program than the men. The desirability of providing a high proportion of the recommended allowances for protein and other nutrients through the meal program menus is emphasized. The results of the study demonstrated the importance of nutritionists in administrative roles at the state and area levels in determining the effectiveness of a meal program, since food intake reflected menu planning.


Search for genes responsible for UV susceptibility of human cells: involvement of syndecan-1 in UV resistance.
UVr-1 UV-resistant cells were established from UV-sensitive human RSa cells. We looked for genes expressed differentially between UVr-1 and RSa cells using PCR-based mRNA differential display to elucidate the molecular mechanisms underlying UV resistance. The transcription levels of syndecan-1 mRNA were increased in UVr-1 cells compared with those of RSa cells. Syndecan-1 is a transmembrane heparan sulfate proteoglycan and associates with cell adhesion and the cytoskeleton. Flow cytometric analysis using anti-syndecan-1 monoclonal antibody revealed that syndecan-1 was more abundant in UVr-1 cells than in RSa cells. The MTT method revealed that UVr-1 cells treated with the antibody showed higher sensitivity to UV cell killing than mock-treated cells. Studies using antisense oligonucleotides for syndecan-1 showed that antisense-treated UVr-1 cells became sensitive to UV cell killing. Thus, syndecan-1 might be involved in UV resistance in UVr-1 cells.


Premature menopause and low back pain. A population-based study.
The association between premature menopause and low back pain was examined among 5325 women surveyed in the second National Health and Nutrition Examination survey. Nearly 49% of the women were postmenopausal. In a multiple logistic regression model that included age, postmenopausal women were approximately twice as likely to report low back pain compared to premenopausal women (odds ratio = 2.1; 95% confidence interval: 1.4-3.0). Among postmenopausal women, significant positive trends in low back pain were observed with decreasing age at menopause (P = 0.005) and increasing years since menopause (P = 0.004). The prevalence odds ratio for women who had their menopause before the age of 30 was 3.2 (1.8-5.4); and for women who had their menopause for 15 or more years the odds ratio was 3.0 (1.7-5.3). These findings suggest that premature menopause is associated with low back pain. Further studies appear warranted to confirm these findings, assess possible explanations, and examine the circumstances in which premature menopause occurs.