Subunit composition and function of GABAA receptors of rat spermatozoa.
GABA triggers mammalian sperm acrosome reaction (AR). Here, evidence is presented, showing that rat spermatozoa contain GABAA receptors, composed of alpha5, beta1 and beta3 subunits. The effects of GABAA receptor agonist and antagonist on the induction of AR in rat spermatozoa were assessed using the chlortetracycline assay. Muscimol, a GABAA receptor agonist, triggered AR; whereas bicuculline, a GABAA receptor antagonist and picrotoxin, a GABAA receptor/Cl- channel blocker, inhibited the ability of GABA or progesterone to induce AR. In conclusion, GABAA receptors appear to mediate the action of progesterone in inducing AR in rat spermatozoa.


[Virological studies in acute polyradiculoneuritis, LGBS type. Various findings in relation to Coxsackie A4 virus].
Studies of isolated virus in LCR and necropsy material were made (medulla roots and rachi ganglia) in acute cases of polyradiculoneuritis. Landry-Gullain-Barré-Strohl type. Serological studies with prepared sera were also made (at three week intervals). The results were discussed based on the isolation of a Coxsackie A virus in four cases and the corresponding serological findings.


Comparative study on drug sensitivity of the TA3/Ha and TA3/St tumor sublines.
TA3/Ha and TA3/St sublines differ from each other in some characteristics, like malignancy, survival time and drug sensitivity. TA3/St exhibited a peculiar response to the Vinca derivatives examined.


Effect of oral clodronate on structural damage and bone turnover in rheumatoid arthritis.
To study the effect of oral clodronate on structural damage and bone metabolism in rheumatoid arthritis (RA). In this 2-year proof-of-concept study, sixty patients with at least moderately active RA were randomised to receive anti-rheumatic therapy alone or together with oral clodronate 1600 mg daily. Radiographs of hands and feet and serum samples for bone biomarkers were studied at baseline and at 24 months. At 24 months, progression of radiographic joint damage was similar in the 2 groups. Clodronate suppressed carboxyterminal cross-linked peptide of type I collagen (p=0.03) and aminoterminal propeptide of type I procollagen (p=0.01). Eight patients (27%) withdrew from clodronate therapy due to adverse drug reactions. Oral clodronate did not retard the focal bone damage in RA despite its beneficial effect on overall bone metabolism, as judged by the decrease in the reference bone biomarkers.


Multivariate prediction of smoking cessation following physician advice to quit smoking: a validation study.
A multivariate predictive model was developed to classify patients with respiratory disease as to their smoking status following physician advice to quit (L.L. Pederson, J. C. Baskerville, and J. M. Wanklin, Prev. Med. 11, 536--549 (1982)). The purpose of this study was to validate this model on a new group of patients by comparing their predicted smoking behavior with their actual behavior. Using a probability of 0.50 as the cutoff for prediction, overall accuracy was 89.6%. However, the sensitivity for detecting those who would actually quit was low. By reducing the cutoff probability to 0.20, overall accuracy remained high and sensitivity was increased. A discussion of the implications of different types of classification errors is presented based on cost-effectiveness considerations. The clinical usefulness of prediction models is discussed.


Liberation of drugs from multi-wall carbon nanotube carriers.
MWCNTs in the 'nanotube-drug' hybrids can play a role of carriers or additives (enhancers) in the more complex formulations. This work reviews qualitative and quantitative analyses of Drug Delivery Systems (DDSs) based on multi-wall carbon nanotubes (MWCNTs) and their chemically modified analogues (mainly oxidised MWCNTs). A special emphasis was placed on the chemical interactions between drug molecules and the nanotube carrier critical both in the stage of preparation/synthesis of the hybrids and liberation of the drug.


Attitudes and Knowledge of Maternal-Fetal Medicine Fellows Regarding Noninvasive Prenatal Testing.
Using cell-free DNA in maternal serum to detect fetal aneuploidy has been shown to have high sensitivity and specificity. The purpose of this study was to assess attitudes and knowledge of Maternal-Fetal Medicine (MFM) fellows regarding noninvasive prenatal testing (NIPT). A 13 question survey was sent via listserv to US-based MFM fellows. One hundred sixteen fellows responded, a 42.3% response rate, with >75% reporting they are comfortable ordering NIPT. Most (82%) preferred that a patient discuss options with a provider or genetic counselor. Three common methods used to learn about NIPT were: formal educational activities (n = 78, 69%), self-review of the literature (n = 76, 67%), and discussions with peers (n = 73, 65%). On questions related to trisomy 21, accuracy was >70%. However, accuracy was lower regarding use in twin pregnancies (42%) and monosomy X screening (50%).


Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis.
The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis. Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe sepsis. ARDS was diagnosed by consensus definitions. Plasma citrulline levels were below normal in all patients (median 9.2 uM, IQR 5.2 - 14.4) and were significantly lower in ARDS compared to the no ARDS group (6.0 (3.3 - 10.4) vs. 10.1 (6.2 - 16.6), P = 0.002). The rate of ARDS was 50% in the lowest citrulline quartile compared to 15% in the highest citrulline quartile (P = 0.002). In multivariable analyses, citrulline levels were associated with ARDS even after adjustment for covariates including severity of illness. In severe sepsis, levels of the NOS substrate citrulline are low and are associated with ARDS. Low NOS substrate levels have been shown in other disease states to lead to NOS uncoupling and oxidative injury suggesting a potential mechanism for the association between low citrulline and ARDS. Further studies are needed to determine whether citrulline supplementation could prevent the development of ARDS in patients with severe sepsis and to determine its role in NOS coupling and function.


Identification of cold-inducible microRNAs in plants by transcriptome analysis.
MicroRNAs are approximately 21-nt long, non-coding RNAs that play critical roles in post-transcriptional gene regulation. Even though a large number of miRNAs have been identified, annotating their functions remains a challenge. We develop a computational, transcriptome-based approach to annotating stress-inducible microRNAs in plants. With this approach, we find that nineteen microRNA genes of eleven microRNA families in Arabidopsis thaliana are up-regulated by cold stress. Our experiments validate that among the eleven microRNAs, eight are differentially induced and three are constantly expressed under low temperature. Our result expands the number of cold-inducible microRNAs from four to eight. A promoter analysis further reveals that the cold-responsive microRNA genes contain many known stress-related cis-regulatory elements in their promoters. Our analysis also indicates that many signaling pathways, such as auxin pathways, may be affected by cold-inducible microRNAs. Our approach can be applied to plant microRNAs responding to other abiotic and biotic stresses. The research demonstrates that machine learning methods, augmented by wet-lab analysis, hold a great promise for functional annotation of microRNAs.


Risk factors for multicentric occurrence of carcinoma in the upper aerodigestive tract-analysis with a serial histologic evaluation of the whole resected-esophagus including carcinoma.
We have reported that both lifestyle and family history might be related to multiplicity of carcinoma in the upper aerodigestive tract (UADT). The aim of this study was to elucidate the relationship between the number of carcinomas and risk factors. A serial histologic evaluation of the entire non-irradiated esophagus was performed in 114 males with esophageal cancer who were divided into three groups (group I: 88 cases with solitary cancer, group II: 11 with double cancers, group III: 15 with three or more cancers). As controls, 228 males with benign diseases were selected. Among group III patients, both the incidence of heavy smoking and that of heavy drinking were 67% and 60%, which were significantly higher than those of group I (28% and 30%) and control subjects (14% and 10%, respectively). Heavy drinkers who were also heavy smokers were observed in 2, 10, 27, and 47% in control subjects, groups I, II, and III, respectively. Regarding family history, 27% of group III had a close relative with UADT or lung cancer, while the incidence was 7% in the control. These findings strongly support the hypothesis that heavy smoking and heavy drinking, as well as a family history of both UADT and lung cancer, might be risk factors for multicentric occurrence of UADT cancer.


Enzymatic activity of a synthetic 99 residue protein corresponding to the putative HIV-1 protease.
A protein corresponding to the putative protease of the human immunodeficiency virus 1 (HIV-1) has been prepared by total chemical synthesis. This 99 residue synthetic enzyme showed specific proteolytic activity on fragments of the natural gag precursor and on synthetic peptide substrates, two of which released fragments corresponding to the N terminus and C terminus of the protease molecule itself. The observed substrate specificity was not restricted to cleavage at Phe/Tyr-Pro bonds. Inhibition studies provided direct evidence that the HIV-1 protease belongs to the family of aspartic proteases. The availability of the HIV-1 protease as a defined molecular species has important implications for the design of specific inhibitors that do not interfere with the host cell metabolism as a possible route to antiviral agents against acquired immunodeficiency syndrome (AIDS).


Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues.
The secretory phospholipase A2 (sPLA2) family in mammals contains more than 10 enzymes. In this study, we examined by immunohistochemistry the localization of six sPLA2s (IIA, IID, IIE, IIF, V and X) in human heart, kidney, liver and stomach. In normal hearts, sPLA2-IIA was detected in coronary vascular smooth muscle cells (VSMC) and sPLA2-V in cardiomyocytes beneath the endocardium. In infarcted hearts, expression of these two enzymes was markedly increased in damaged cardiomyocytes, and expression of sPLA2-IID and-IIE, which was undetectable in normal hearts, was elevated in damaged cardiomyocytes and VSMC, respectively. In infarcted kidneys, sPLA2-IIA and-V were markedly induced in the uriniferous tubular epithelium. In livers affected by viral hepatitis, sPLA2-IIA and-V were expressed in hepatocytes with fatty degeneration. In the gastric glands exhibiting intestinal metaplasia, sPLA2-IIA was localized in the glandular base, sPLA2-IID and-V in the glandular body epithelium, sPLA2-IIE and-IIF in goblet cells in the foveolar epithelium, and sPLA2-X in both glandular body epithelial cells and foveolar epithelial goblet cells. In the gastric submucosal tissues, sPLA2-IIA and-IIE were located in VSMC and sPLA2-V was in the interstitial fibroblasts. In addition, sPLA2-IIA,-IIE,-IIF and-X were highly expressed in gastric signet ring cell carcinoma. Thus, individual sPLA2s exhibit unique cellular localizations in each tissue, suggesting their distinct roles in pathophysiology.


Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap) alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.
The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS) for the treatment of uncomplicated falciparum malaria. Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population using mean time to reduce baseline parasitemia by 90% (PC90). A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT) population. In the Day 3 PP population for the adult group (N = 85), mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5]), 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2]) and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2]) groups. For children in the Day 3 PP population (N = 92), mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0]) and 12.8 h (-7.4 h [95%CI -12.9, -1.8]), respectively. An analysis of mean time to PC90 for the Day 14 PP and ITT populations was consistent with the primary analysis. Treatment emergent, drug-related adverse events were experienced in 35.3% (41/116) of adults and 70.1% (75/107) of children; mostly hematological and gastroenterological. The nature and incidence of adverse events was similar between the groups. No dose-related changes in laboratory parameters were observed. Nine serious adverse events due to any cause occurred in five subjects including two cases of hemolysis believed to be associated with drug treatment (one adult, one child). One adult died of anaphylactic shock, not associated with investigational therapy. CPG-DDS plus artesunate demonstrated advantages over CPG-DDS alone for the primary efficacy endpoint (mean time to PC90) except in children for the 1 mg/kg artesunate dose. Based on a pre-defined decision matrix, the primary endpoint in the child group supported an artesunate dose of 4 mg/kg. Secondary endpoints also supported a 4 mg/kg artesunate dose to take forward into the remainder of the development program. ClinicalTrials.gov NCT00519467.


A stepper motor-driven microelectrode positioner.
The mechanical elements and the electronic control system from a stepper motor-driven microelectrode positioner is described. The unit embodies a high-precision small step angle hybrid motor. The compact, rugged and totally concentric design of the mechanic, by a spindle mechanism achieves the necessary precision by translating the stepwise rotations of the motor into steps of linear movement. The system takes advantage of commercially available low friction parts such as ball bearings, ball bushings and axles with hardened surfaces. The related electronic control unit is designed around the most recent integrated circuitry which is both sophisticated and economical. Though the described system is designed to be built in an average departmental workshop it compares favorably with more expensive commercial units and in some aspects outperforms them.


[19 cases of Paget's disease].
The clinical signs of Paget's disease are similar to those of chronic eczema. The two are often confused, especially extramammary Paget's disease. Only biopsy can help to differentiate them correctly. 19 patients with Paget's disease were reviewed with regard to clinical analysis and treatment from 1987 to 1997. Six patients had breast Paget's disease and 13 had extramammary one. The latter involved scrotum and penis in 11 patients, the groin in 1, and perianal and anal in 1. Follow up showed that 3 patients had recurrences in extramammary patients who had had positive surgical margin biopsy. One patient died of other disease. Surgery is the first choice of treatment for Paget's disease either of breast or of extramammary regions. Negative margins must be achieved to prevent local recurrence.


Oral anticoagulation and self-management: analysis of the factors that determine the feasibility of using self-testing and self-management in primary care.
The skills of patients on oral anticoagulants are critical for achieving good outcomes with this treatment. Self-management, or the capacity of patients to control their INR level and adjust their treatment, is an effective strategy of treatment. Capacity of patients to self manage is determined by a range of factors. The identification of these factors would improve the design of self management programmes and in turn increase the number of patients able to self-manage. The objective of our study is to identify those factors that determine the ability of patients on oral anticoagulant therapy to achieve self-management of their treatment. This will be a three year quasi- experimental prospective study with a control group. 333 patients on anticoagulant therapy from five health centres of the Basque Health Service are to be followed up for a period of six months each after the intervention, to assess their ability to self-test and self-manage. The intervention will consist of a patient training programme involving the provision of information and practical training concerning their condition and its treatment, as well as how to use a portable blood coagulation monitoring device and adjust their anticoagulant dose. The ease-of-use of this technique lead us to believe that self-management is feasible and will represent an innovative advance that should have a substantial impact on the quality of life of this patients and their families as well as on the health care provision systems. Osakidetza Protocol Record ISCIII-11/02285, Oral anticoagulation and self-management, ClinicalTrials.gov Identifier: NCT01878539.


Construction and maintenance costs of mediterranean-climate evergreen and deciduous leaves I. Growth and CO2 exchange analysis.
Gas exchange and leaf growth analysis were used in conjunction to determine leaf-construction and maintenance costs in three co-occurring shrubs of the california chaparral, one evergreen, Heteromeles arbutifolia, and two drougth deciduous species, Lepechinia calycina, and Diplacus aurantiacus. The construction costs per unit of leaf weight were similar among the three species and very close to values reported for other evergreens but considerably higher than leaf construction costs for other deciduous or herbaceous plants. Maintenance costs per unit of leaf weight were significantly greater in one deciduous species, L. calycina, than in the evergreen. Maintenance costs for all species were in the range reported for herbaceous species and considerably above those reported for other evergreens.


Characteristics and management of infectious industrial waste in Taiwan.
Infectious industrial waste management in Taiwan is based on the specific waste production unit. In other countries, management is based simply on whether the producer may lead to infectious disease. Thus, Taiwan has a more detailed classification of infectious waste. The advantage of this classification is that it is easy to identify the sources, while the disadvantage lies in the fact that it is not flexible and hence increases cost. This study presents an overview of current management practices for handling infectious industrial waste in Taiwan, and addresses the current waste disposal methods. The number of small clinics in Taiwan increased from 18,183 to 18,877 between 2003 and 2005. Analysis of the data between 2003 and 2005 showed that the majority of medical waste was general industrial waste, which accounted for 76.9%-79.4% of total medical waste. Infectious industrial waste accounted for 19.3%-21.9% of total medical waste. After the SARS event in Taiwan, the amount of infectious waste reached 19,350 tons in 2004, an increase over the previous year of 4000 tons. Waste minimization was a common consideration for all types of waste treatment. In this study, we summarize the percentage of plastic waste in flammable infectious industrial waste generated by medical units, which, in Taiwan was about 30%. The EPA and Taiwan Department of Health have actively promoted different recycling and waste reduction measures. However, the wide adoption of disposable materials made recycling and waste reduction difficult for some hospitals. It has been suggested that enhancing the education of and promoting communication between medical units and recycling industries must be implemented to prevent recyclable waste from entering the incinerator.


[Changes in production of platelet activating factor by adherent hepatocytes of mice with experimental liver failure].
It is thought that the platelet activating factor (PAF) enhances the immune response and inflammatory reaction. We studied the production of PAF from liver adherent cells. As a result, liver adherent cells produced PAF, when they were stimulated with calcium ionophore. In addition, when mice were treated with heat-killed Propionibacterium acnes and the mononuclear cells were infiltrated into the liver, a significantly larger amount of PAF was produced compared to normal mice.


Responses of growth hormone to desipramine in endogenous and non-endogenous depression.
Desipramine, a monoamine reuptake inhibitor, was used to stimulate release of growth hormone (GH) in 29 DSM-III major depressives and in 10 healthy controls. Eighteen of the depressives showed a blunted response. The GH-stimulation test was unable to distinguish endogenous from non-endogenous patients. The 13 dexamethasone non-suppressors were more likely to have a blunted GH response than the 14 suppressors. The results indicate that at least a subset of non-endogenous depressives have significant neuroendocrine abnormality.


The consequence of delayed neurosurgical care at Tikur Anbessa Hospital, Addis Ababa, Ethiopia.
Tikur Anbessa Hospital (TAH) is the major teaching hospital for Addis Ababa University and the only tertiary referral hospital for neurosurgery in Ethiopia. We explore the consequence of delayed treatment by examining the current system in place for treating patients and the wait times experienced by patients. A retrospective chart review was carried out on patients who received a neurosurgical operation at TAH between January 1 and June 30, 2007. We divided patients into those requiring an elective procedure and those requiring emergency surgical care. Based on data entered in the chart, we determined the length of time from symptom onset to neurosurgical consultation and the time from consultation to receiving an operation. Selective cases were chosen to illustrate the effects of delayed care. A total of 172 neurosurgical operations were performed between January 1 and June 30, 2007, at TAH. Of these, 107 (62.2%) charts were available for retrospective review. Fifty-six elective cases were reviewed. The median time from symptom onset to neurosurgical consultation was 185 days. The median time from neurosurgical consultation to operation was 44 days. Fifty-one trauma/emergency surgical cases were reviewed. The median time from symptom onset or traumatic event to neurosurgical consultation was 3 days. The median time from neurosurgical consultation to operation was 1 day. Delayed neurosurgical care comes with a high personal and social cost. By measuring the time from diagnosis to treatment and taking note of institutional practices, changes can be initiated to improve patient waiting times.


Incorporating Coronary Calcification Into Pre-Test Assessment of the Likelihood of Coronary Artery Disease.
The prevalence of obstructive coronary artery disease (CAD) in symptomatic patients referred for diagnostic testing has declined, warranting optimization of individualized diagnostic strategies. This study sought to present a simple, clinically applicable tool enabling estimation of the likelihood of obstructive CAD by combining a pre-test probability (PTP) model (Diamond-Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score (CACS). The new tool was developed in a cohort of symptomatic patients (n = 41,177) referred for diagnostic testing. The risk factor-weighted clinical likelihood (RF-CL) was calculated through PTP and risk factors, while the CACS-weighted clinical likelihood (CACS-CL) added CACS. The 2 calculation models were validated in European and North American cohorts (n = 15,411) and compared with a recently updated PTP table. The RF-CL and CACS-CL models predicted the prevalence of obstructive CAD more accurately in the validation cohorts than the PTP model, and markedly increased the area under the receiver-operating characteristic curves of obstructive CAD: for the PTP model, 72 (95% confidence intervals [CI]: 71 to 74); for the RF-CL model, 75 (95% CI: 74 to 76); and for the CACS-CL model, 85 (95% CI: 84 to 86). In total, 38% of the patients in the RF-CL group and 54% in the CACS-CL group were categorized as having a low clinical likelihood of CAD, as compared with 11% with the PTP model. A simple risk factor and CACS-CL tool enables improved prediction and discrimination of patients with suspected obstructive CAD. The tool empowers reclassification of patients to low likelihood of CAD, who need no further testing.


Positive and negative impacts of COVID-19, an analysis with special reference to challenges on the supply chain in South Asian countries.
The Coronavirus or COVID-19 is a disease based on an unknown virus. It seems that it started in China and has widely spread in almost all countries in the world. This pandemic situation is one of the widely spread diseases in recent history. However, there was an influenza pandemic in 1918 with the exact number of deaths still unknown. Some believe that the death toll would have been about 50-100 million people. At the time of writing this article, COVID-19 has infected 5,306,928 persons worldwide (when the article was finalised for publication, the number has increased up to 15,947,291). The article is aimed at analysing the positive and negative impacts of COVID-19 in a sociological perspective. It is further focused on possible challenges to the supply chain in South Asia. South Asian countries are highly influenced by the pandemic situation, and the regional representation is about 4% in the later part of May 2020 with an increasing tendency. Also, the article has a proposal for the control of the disease as well as the entire socio-economic, environmental and political atmosphere in a country, whilst particularly giving more weight to South Asia. The proposed actions are analysed in short-term, mid-term and long-term basis, and any expert and social worker who is involved in the pandemic control process can gain an insight into what to do and how to perform their tasks. A sociological analysis on COVID-19 is very important because there is a wing comprising dominant medical experts in the control and management of the disease. The article emphasises the importance of a sociological analysis in a pandemic situation. Naturally, anyone would think of a pandemic situation in very negative terms due to its emotional, socio-economic, environmental, political and cultural factors. However, it is also positive due to certain factors that help to reintegrate and reorganise the social system as a whole.


Referral sources, diagnoses, and service types of youth in public outpatient mental health care: a focus on ethnic minorities.
Racial/ethnic variations in clinical and service delivery characteristics among youth in public outpatient mental health services were examined using data from San Diego County mental health service programs for fiscal year 1996 to 1997 (N = 3,962). Differences in referral sources, primary diagnoses, and service types were investigated for three racial/ethnic groups (African Americans, Asian/Pacific Islander Americans, and Latinos) compared to non-Hispanic whites. Controlling for age, gender, functional impairment, and prior service use, significant differences by race/ethnicity were found for all three variables studied. Possible explanations for these variations and future directions for research are discussed.


Fluoride bioactive glass paste improves bond durability and remineralizes tooth structure prior to adhesive restoration.
The current study aimed at examining a fluoride containing bioactive glass (BiominF®) paste as a temporary filling material capable of remineralizing the demineralized enamel or dentin, and its ability to decrease a simulated dentinal fluids pressure on the resin/dentin interface, without affecting the shear bond strength of a universal bonding agent to enamel and dentin. 60 premolars were utilized for the acid resistance, trans-microradiography (TMR) and shear bond strength (SBS) experiments. Enamel and dentin discs were demineralized for 4 days to create a subsurface demineralized zone followed by applying BiominF® paste, 1.23% acidulated phosphate fluoride, or a temporary filling material for 24 h. 30 extracted human non-carious third molars were utilized for the pulpal pressure experiment in which direct communication to the pulp chamber was created by cutting at a level approximately 1 mm below the cemento-enamel junction while the coronal enamel was ground to expose mid coronal dentin. The dentin surface was exposed to a simulated pulpal pressure. The dentin surfaces had BiominF® paste, an oxalate desensitizing agent, or temporary filling material followed by application of a universal adhesive system. One way ANOVA showed that BiominF® paste remineralized effectively the demineralized enamel or dentin, did not affect the bond strength of the enamel and dentin surfaces to the tested adhesive system p < 0.05, and improved the acid resistance of the demineralized enamel and dentin against a secondary erosive challenge. Moreover, BiominF® paste decreased the nanoleakage expression in the dentin/adhesive interface exposed to a simulated pulpal pressure. BiominF® paste may serve as a temporary filling material that may improve the longevity of adhesive restorations and help to conserve tooth structures by preserving the demineralized enamel and dentin form cutting during cavity preparation.


How telehealth can work best for our patients.
A hybrid model of care embracing office visits and remote consultations may provide the benefits and curtail the disadvantages of both.


[Morphology of the nucleus in bacteria of the Salmonella genus (author's transl)].
Through the use of the Piekarski-Robinow's technique, the Authors have studied the morphology of the nucleus in bacteria of the Salmonella genus and their changes brough about by lithium chloride, tripflavin and penicillin.


Influence of early-life body mass index and systolic blood pressure on left ventricle in adulthood - the Cardiovascular Risk in Young Finns Study.
Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood. We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population (N = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve. After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p < 0.001). Overweight in early-life (age- and sex-specific BMI values corresponding to adult BMI > 25 kg/m2) associated with 4.7% (2.5-6.9%, p < 0.0001) higher LVM regardless of BMI status in adulthood. Overweight in early-life combined with obesity in adulthood (BMI > 30kg/m2) resulted in a 21% (17.3-32.9%, p < 0.0001) increase in LVM. Higher early-life BMI was associated with a risk of developing eccentric hypertrophy. The burden of early-life SPB was not associated with adult LVM or left ventricular remodeling. High BMI in early-life confers a sustained effect on LVM and the risk for eccentric hypertrophy independently of adulthood risk factors. KEY MESSAGES Excess in BMI in early-life has an independent effect on LVM and the risk of developing eccentric hypertrophy regardless of overweight status in adulthood. Systolic blood pressure levels in early-life did not have an independent effect on LVM or LV remodeling. The clinical implication of this study is that primary prevention of obesity in early-life may prevent the development of high LVM and eccentric hypertrophy.


Production of tumor necrosis factor-alpha by microglia and astrocytes in culture.
Stimulation of mouse astrocytes and microglia in enriched culture by lipopolysaccharide (LPS) results in the production of a cytotoxic factor that is functionally similar to macrophage-derived tumor necrosis factor-alpha (TNF). This cytotoxic factor kills murine L929 cells, and is neutralized by a monoclonal anti-mouse TNF. The production of this factor is inhibited by pretreatment of cells by actinomycin D. Microglia are more sensitive to LPS and produce much higher activity of cytotoxicity in lower concentration of LPS than astrocytes. These results suggest that microglia are the major producers of TNF in the brain and may play a role in certain pathological conditions in the brain.


Polymorphisms of interferon-gamma gene CA-repeat and interleukin-10 promoter region (-592A/C) in Japanese type I diabetes.
We investigated the association of the polymorphisms of interferon-gamma gene (IFNG) CA-repeat and IL-10-592A/C with clinical heterogeneity of type I diabetes as well as susceptibility to type I diabetes. Two hundred seven Japanese type I diabetic patients and 160 healthy control subjects were studied in this case-control study. No significant differences of global IFNG allele frequencies were found between controls and type I diabetic patients, and between each subgroup of the patients and controls. When compared with controls, the a12 allele was increased in the patients with age at onset <25 years (p 0.0241, p(c) = 0.1205), and a significant increased frequency of the a12 positive genotype was observed in the patients with age at onset <25 years (p(c) = 0.0121). There were no differences of IL-10-592 genotype and allele frequencies between controls and type I diabetes. However, the frequency of the -592*C allele was significantly increased in the patients with highly positive-GADab compared with controls (p(c) = 0.0060) or compared with the GADab-negative type I patients (p(c) = 0.0276). These results suggest that the IFNG CA-repeat and the IL-10-592A/C polymorphisms are not strong determinants of susceptibility to the development of type I diabetes in Japanese individuals. However, both the IFNG CA-repeat and the IL-10-592A/C polymorphisms are associated with clinical heterogeneity in type I diabetes.


Evidence that dopamine mechanisms in the nucleus accumbens are selectively involved in the effect of desipramine in the forced swimming test.
Bilateral injections of 5 or 1 (but not 0.5) micrograms sulpiride into the nucleus accumbens reduced the effect of a 7-day treatment with 10 mg/kg/day desipramine in the forced swimming test. Bilateral injections of 5 or 1 micrograms sulpiride in the caudate-putamen did not modify the anti-immobility effect of desipramine. The data support the hypothesis that dopamine mechanisms in the limbic regions of the brain of the rat are involved in the effect of repeated treatment with desipramine in the forced swimming test.


Insulin-like growth factors and ovarian physiology.
To review the available information regarding the roles of insulin-like growth factor (IGF)-IGF binding protein (IGFBP) system in ovarian physiology. Studies that specifically relate to the roles of ovarian folliculogenesis, oocyte maturation, and ovulation were identified through the literature and Medline searches. Numerous actions of the IGFs have been demonstrated in the ovary, including an enhancement of cell proliferation, aromatase activity, and progesterone biosynthesis. The ovarian IGF system, comprised of IGF-I and IGF-II peptides, IGFBPs and IGF receptors, plays a significant role in the process of follicular development. In addition, IGF-I stimulates the meiotic maturation of follicle-enclosed oocytes in vitro via the IGF-I receptors. IGFBP-3 significantly inhibit gonadotropin-induced ovulation and oocyte maturation by neutralizing endogenously produced IGF-I. Thus, the intraovarian IGF-IGFBP system play a significant role in the processes of follicular development, oocyte maturation, and ovulation. IGF-IGFBP systems have autocrine/paracrine regulatory actions in ovarian physiology. The disturbance of the IGF-IGFBP system in human ovaries may lead to an ovulation, disorders of androgen excess, and infertility.


A calcium ion-dependent atp pyrophosphohydrolase in Physarum polycephalum.
An activity of ATP Pyrophosphohydrolase (EC 22.214.171.124) was found in the soluble fraction of the plasmodium of Physarum polycephalum. The products of the enzyme reaction were inorganic pyrophosphate and 5'-AMP in equimolar quantities. The enzyme had a pronounced requirement for Ca2+ with high specificity. Mg-2+ was not an essential cofactor but stimulated the enzyme activity about 2.5-fold of the control. The enzyme hydrolyzed ITP, GTP and beta,gamma-methylene ATP at a limited rate. Among inhibitors tested, 3 mM caffeine reduced the activity to about 75% of the control. The enzyme had a broad pH optimum around pH=7.0 and the Km for ATP was 2.0 mM. An Arrhenius plot showed a break at about 18 degrees C and the calculated activation energies were 6.7 and 11.4 kcal/mol above and below the transition temperature, respectively. Disc electrophoresis in dodecyl sulfate and gel filtration on Sephadex -g-200 gave apparent molecular weights of 56 000 and 240 000, respectively, suggesting that the native enzyme was built up from 4 polypeptide chains. The possible role of the enzyme in vivo was discussed.


Synthesis of Phosphachromones by Cyclized Coupling of Ethyl Hydrogen (Phenylethynyl)phosphonate with Arynes.
A straightforward and efficient strategy for the synthesis of phosphachromones has been reported via the insertion of arynes into P-O bonds. This operationally simple reaction is compatible with different functional groups, affording various phosphachromones by the simultaneous formation of C-P and C-O bonds in one step with moderate to good yields, and the Fries rearrangement involving phosphorus atoms is a key step in the reaction.


Enzymatic and non-enzymatic conversion of cystamine to thiotaurine and taurine.
The disulfide-containing molecule cystamine and the thiosulfonate thiotaurine are of interest as therapeutics. Both are precursors of taurine, but the chemistry of their metabolism is not clear. The rates at which these molecules are metabolized is also unknown. The chemistry and rate constants have been determined for a process in which cystamine is converted in four reactions to thiotaurine. Cystamine is oxidized by diamine oxidase with a specificity constant comparable to other diamine substrates. The rapid hydrogen peroxide-mediated oxidation of cystaldimine yields reactive glyoxal and thiocysteamine, which quickly performs transsulfuration with hypotaurine. Thiotaurine reacts spontaneously with hydrogen peroxide to form taurine and sulfite, but it is 15-fold less reactive than hypotaurine as an antioxidant. An estimation of biological rates of reaction indicates that cystamine is likely to be oxidized by diamine oxidase in vivo, but its metabolic products will be diverted to molecules other than thiotaurine.


Exercise performance is regulated during repeated sprints to limit the development of peripheral fatigue beyond a critical threshold.
We hypothesized that exercise performance is adjusted during repeated sprints in order not to surpass a critical threshold of peripheral fatigue. Twelve men randomly performed three experimental sessions on different days, i.e. one single 10 s all-out sprint and two trials of 10 × 10 s all-out sprints with 30 s of passive recovery in between. One trial was performed in the unfatigued state (CTRL) and one following electrically induced quadriceps muscle fatigue (FTNMES). Peripheral fatigue was quantified by comparing pre- with postexercise changes in potentiated quadriceps twitch force (ΔQtw-pot) evoked by supramaximal magnetic stimulation of the femoral nerve. Central fatigue was estimated by comparing pre- with postexercise voluntary activation of quadriceps motor units. The root mean square (RMS) of the vastus lateralis and vastus medialis EMG normalized to maximal M-wave amplitude (RMS.Mmax (-1)) was also calculated during sprints. Compared with CTRL condition, pre-existing quadriceps muscle fatigue in FTNMES (ΔQtw-pot = -29 ± 4%) resulted in a significant (P < 0.05) reduction in power output (-4.0 ± 0.9%) associated with a reduction in RMS.Mmax (-1). However, ΔQtw-pot postsprints decreased by 51% in both conditions, indicating that the level of peripheral fatigue was identical and independent of the degree of pre-existing fatigue. Our findings show that power output and cycling EMG are adjusted during exercise in order to limit the development of peripheral fatigue beyond a constant threshold. We hypothesize that the contribution of peripheral fatigue to exercise limitation involves a reduction in central motor drive in addition to the impairment in muscular function.


Development of a clinical global impression scale for fatigue.
Physical, cognitive, and affective components of fatigue are often associated with depression and other Axis I psychiatric disorders. We developed two, single item global assessment scales to specifically evaluate symptoms of fatigue. 101 subjects visiting a clinical trial site consented to participate in this reliability and validity study. Diagnoses included Major Depressive Disorder, Bipolar disorder, and schizophrenia. There were two clinic visits during which the modified Clinician and Patient Impressions of Fatigue rating instruments were administered in conjunction with the MGH cognitive and physical functioning questionnaire (MGH-CPFQ), a validated patient-rated 7-item scale. CGI-Severity and PGI-Severity for fatigue were well correlated at two separate visits (p < 0.00005). At visit 1, the mean CGI-S for fatigue was 3.33 ± 1.53 (SD) and the PGI-S for fatigue was 3.57 ± 1.70 (r = 0.75; p = 0.000). At visit 1, the total MGH-CPFQ was 21.66 ± 6.92. Both CGI-S and PGI-S measures for fatigue were highly correlated with the MGH-CPFQ: CGI-S (r = 076; p < 0.00005); PGI-S (r = 0.62; p < 0.00005). Both the PGI-S and CGI-S for fatigue revealed temporal stability and convergent validity for the MGH-CPFQ (r = 0.83 for CGI-S and 0.73 for PGI-S). There was high internal consistency between the two independent CGI raters at visit 2 as demonstrated by a kappa statistic = 0.971 (CGI-S) and 0.868 (CGI-I) and Cronbach's alpha = 0.998 (CGI-S) and 0.941 (CGI-I). As shown here, the modified CGI and PGI instruments for fatigue are reliable measures of fatigue and both measures are validated with the MGH-CPFQ instrument.


Determining the mechanism of the root effect on soil detachment under mixed modes of different plant species using flume simulation.
Soil detachment is the separation and dislodgment of soil particles from a soil mass by the force of raindrops and flow, which is also the initial process of soil erosion. Plant roots have significant effects on the soil detachment rate (SDR). Current studies have mainly focused on root effects on the SDR under single species. Because it is difficult to identify the roots of different species in mixed-plant areas, few studies have evaluated the root effects on the SDR under mixed-plants. Natural, undisturbed soil samples containing roots were collected from four natural sampling plots with single plant types, and six natural sampling plots with mixed plant types. Bare soil was used as the control. The samples were subjected to flow scouring through indoor hydraulic flume experiments under six shear stresses (3.65, 7.28, 7.67, 8.59, 10.15, and 12.19 Pa). The results showed that the root reduction effect on the SDR under the mode of tap roots mixed with fibrous roots was 55.54 % weaker than that the mode of fibrous roots mixed with other fibrous roots. When fibrous roots were mixed with tap roots, the fibrous roots indirectly affected the SDR through soil mechanical properties, while the indirect path of the tap roots on the SDR was not unique. However, the indirect effect of roots on the SDR was weaker than the direct effect. The mixed roots affected the SDR mainly by rill erodibility, not critical shear stress. The variation in rill erodibility at the mixed root sites was similar to the SDR variation at those sites. The mode of grasses with fibrous roots mixed with other grasses with fibrous roots was considered as better for soil and water vegetation conservation.


Pharmacokinetic study of 3-in-1 poly(ethylene glycol)-block-poly(D, L-lactic acid) micelles carrying paclitaxel, 17-allylamino-17-demethoxygeldanamycin, and rapamycin.
Concurrent delivery of multiple poorly water-soluble anticancer drugs has been a great challenge due to the toxicities exerted by different surfactants or organic solvents used in solubilizing individual drugs. We previously found that poly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-b-PLA) micelles can serve as a safe delivery platform for simultaneous delivery of paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP) to mice. The high tolerance of this polymeric micelle formulation by mice allowed us to investigate the pharmacokinetics of the 3 co-delivered drugs. In this study, it was shown that 3-in-1 PEG-b-PLA micelle delivering high doses of PTX, 17-AAG, and RAP (60, 60, and 30 mg/kg, respectively) significantly increased the values of the area under the plasma concentration-time curves (AUC) of PTX and RAP in mice compared to the drugs delivered individually, while the pharmacokinetic parameters of 17-AAG were similar in both 3-in-1 and single drug-loaded PEG-b-PLA micelle formulations. Moreover, pharmacokinetic study using 2-in-1 micelles indicated that the augmented AUC value of RAP was due to the co-delivery of 17-AAG, while the increase in AUC of PTX was more likely caused by the co-delivery of RAP. In contrast, when 3-in-1 and single drug-loaded PEG-b-PLA micelles were administrated at modest dose (PTX, 17-AAG, and RAP at 10, 10, and 5 mg/kg, respectively), pharmacokinetic differences of individual drugs between 3-in-1 and single drug formulations were eliminated. These results suggest that 3-in-1 PEG-b-PLA micelles can concurrently deliver PTX, 17-AAG, and RAP without changing the pharmacokinetics of each drug at modest doses, but altered pharmacokinetic profiles emerge when drugs are delivered at higher doses.


MVA-MUC1-IL2 vaccine immunotherapy (TG4010) improves PSA doubling time in patients with prostate cancer with biochemical failure.
TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules of TG4010 on PSA in men with PSA progression. A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than 10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 10(8) pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 10(8) pfu every 3 weeks. The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was well tolerated. Although the primary endpoint was not achieved, there is evidence of biologic activity of TG4010 in patients with PSA progression, further investigation in prostate cancer is warranted.


Hematological predictors and clinical outcomes in cardiac surgery.
The present study was to investigate if five values that are part of the hemogram analysis routinely checked before heart surgeries can be used as a high-quality, quick, low-cost, and easy-to-use outcome predictor. This investigation was a retrospective, observational, cross-sectional study. Univariate and multivariate logistic regression was used to identify independent predictors for combined adverse events. We enrolled 1500 consecutive patients who underwent elective, on-pump, open-heart surgery from 2011 to 2014. Preoperative hemogram evaluation, red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were recorded. We classified combined adverse events (CAE) as (1) myocardial infarction, (2) cardiac reoperation, (3) prolonged mechanical ventilation, (4) prolonged hospital stay, (5) rehospitalization, or (6) mortality. It was found that several parameters obtained as part of the hemogram, namely RDW, MPV, PLR, and NLR, can predict, individually or in combinations, the outcomes in open-heart surgery patients. It was found that the prediction success of NLR (4.8 fold) was higher compared to RDW (1.8 fold) and MPV (1.5 fold). When the prediction success of the combined parameters was investigated, the NLR-RDW (4.7 fold) pair was found higher in the prediction of CAE occurrence. The predictive success of the triple combination of NLR-MPV-RDW (5.5 fold) was higher than other combinations. The triple combination of parameters obtained as part of the hemogram, NLR-RDW-MPV, indicated a much more predictive power than two parameters coupled. This combination of three parameters, NLR-RDW-MPV, is to be considered as a sensitive, high-quality, low-cost outcome prediction marker for cardiac surgery patients that is less time consuming and easy to use.


Management of Diabetes in Patients Undergoing Bariatric Surgery.
The number of bariatric surgeries for patients with type 1 or type 2 diabetes continues to grow. Clinicians are challenged to choose therapies that reach glycemic targets without inducing adverse effects in post-bariatric patients without published guidelines. This review evaluates data supporting the best strategies for diabetes management in patients undergoing bariatric surgery. Though few clinical trials have evaluated the safety and effectiveness of different glucose-lowering therapies following bariatric surgery, remission of diabetes or reduced medications is an established benefit of bariatric surgery. Adverse events including diabetic ketoacidosis in post-bariatric patients on sodium-glucose co-transporter 2 (SGLT2) inhibitors or inadequate insulin have been reported in patient's with both type 1 and type 2 diabetes. Metformin, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, insulin, and sulfonylureas have been used successfully in the perioperative period for other surgeries and guidelines recommend adjusting the doses of these medications especially in the perioperative period. Clinicians should favor weight-neutral or weight-loss promoting therapies in post-bariatric surgery patients such as medical nutrition therapy, metformin, GLP-1 agonists, SGLT2 inhibitors, and DPP-4 inhibitors.


Complete Genome Sequence of the Type Strain Corynebacterium mustelae DSM 45274, Isolated from Various Tissues of a Male Ferret with Lethal Sepsis.
The complete genome of Corynebacterium mustelae DSM 45274 comprises 3,474,226 bp and 3,188 genes. Prominent niche and virulence factors are SpaBCA- and SpaDEF-type pili with similarity to pilus proteins of Corynebacterium resistens and Corynebacterium urealyticum and an immunomodulatory EndoS-like endoglycosidase probably catalyzing the removal of distinct glycans from IgG antibodies.


Is there a probenecid sensitive transport system for monoamine catabolites at the level of the brain capillary plexus?
Probenecid inhibits the transport of the small monocarboxylic acids lactate and propionate from blood to brain but does not affect the transport of 5HIAA or HVA. Neither lactate, 5HIAA, HVA, nor probenecid itself inhibits probenecid uptake into brain from blood and neither lactate nor 5HIAA itself inhibits 5HIAA uptake. These results indicate first that probenecid inhibits the lactate carrier but is itself not transported by that carrier and second that 5HIAA and probenecid are independently transported from blood to brain by a low affinity system, probably by diffusion. Preloading animals with both tryptophan and probenecid increased the apparent transport of lactate, probenecid and 5HIAA but not the transport of glucose. This indicates that the transport of 5HIAA, lactate and probenecid from brain to blood involves a common, saturable carrier. These two sets of data indicate that either the brain capillary transport system is asymmetric or that probenecid-inhibited transport of monoamine catabolites from brain occurs at sites other than the capillary transport system of the blood-brain barrier.


Impact of physical therapists' instructions on function and the perception of post-dry needling soreness in mechanical cervical pain; a randomized clinical trial.
To investigate the impact of physical therapists' instructions on the perception of post dry needling (DN) soreness and function in patients with mechanical neck pain. Seventy-five patients with neck pain were randomly assigned to three groups: "positive" group (n = 25) received positive verbal input; "negative" group (n = 25) received negative verbal input, and control group (n = 25) did not receive any input about post-needling soreness. All three groups received DN of a trigger point in the upper trapezius muscle. The subjective pain experience, pressure pain threshold (PPT), and neck disability Index (NDI) were assessed before and after DN. Patients in all groups showed improvement in pain, PPT and NDI. There were no significant differences in pain (P = 0.41) and PPT (P = 0.68) in the positive and negative groups compared with the control group. Significant difference in function was seen with the NDI after DN of patients in the positive and negative groups compared with the control group (P = 0.011, standard error: 1.08-1.5). Considering that the power of our study may be too low to draw more definitive conclusions, DN appears to be an effective technique to improve pain and mechanical hyperalgesia. The experience of post-needling soreness does not appear to influence the outcome of DN on pain, PPT, and NDI. Post-needling soreness does not seem to be a limiting factor in achieving acceptable outcomes, especially when clinicians offer DN within a therapeutic emphasizing a positive patient response. This study questions whether any treatments need to be offered to patients receiving DN.


Low colorectal anastomoses. An experimental assessment of two sutured and two stapled techniques.
Extraperitoneal colorectal anastomoses were constructed in dogs by four methods: one layer of sutures (N = 10), two layers of sutures (N = 10), EEA staples (N = 10), and SPTU staples (N = 10). Dehiscence occurred in eight sutured and one stapled anastomosis (P less than 0.05). The four leaks following two layer sutured anastomoses caused three deaths, whereas all four leaks following one-layer sutured anastomoses were only detected radiologically (P less than 0.02). In the stapled group, the single leak followed EEA anastomosis and was fatal. Anastomotic narrowing was greater in sutured than stapled groups (P less than 0.05). Two layers of sutures produced gross narrowing compared with one layer (P less than 0.002). Two rows of staples (EEA) produced more narrowing than one row (SPTU) (P less than 0.01). Mean hydroxyproline concentrations and bursting pressures on the seventh postoperative day were higher in stapled than sutured anastomoses (P less than 0.05). Submucosal alignment, mucosal continuity, tissue viability, and stage of healing were all inferior for two-layer sutured anastomoses, reaching statistical significance for tissue viability (P less than 0.05). Stapled anastomoses were completed significantly faster (32.6 +/- 7.3 minutes) than sutured (54.1 +/- 8.4 minutes) (P less than 0.01). This experimental study has demonstrated that stapling is a fast and reliable method of colorectal anastomosis with a low complication rate. The shortcomings of the standard two-layer sutured anastomosis are discussed.


[Subjective decrease of visual acuity after photodynamic therapy: documentation by optical coherence tomography and its correlation with visual acuity].
A 68-year-old patient complained of decreased visual acuity (VA) two days after photodynamic therapy (PDT) had been performed. VA decreased from the pre-operative value of 0.4 to 0.1 on the second postoperative day. With additional + 1.75 diopters, VA was 0.32. Optical coherence tomography (OCT) disclosed a subneuroretinal fluid accumulation causing a serous retinal detachment 600 microm in height. One week postoperatively, neither decreased vision nor retinal elevation were noted. The temporary subjective decreased VA could be predominantly reduced by adequate refraction. OCT and VA measurements excluded ischemia of the neuroretina or the choroid as a causative factor.


Purchase of ultra-processed foods in Norway: a repeated cross-sectional analysis of food sales in 2013 and 2019.
A dietary pattern dominated by ultra-processed foods has been associated with non-communicable diseases in several studies. A previous study from 2013 found a high share of ultra-processed foods in Norwegian food sales. This study aimed to investigate the current share of ultra-processed foods in Norway and the development in expenditure on ultra-processed foods from 2013. A repeated cross-sectional analysis of scanner data from the Consumer Price Index from September 2013 and 2019 and an investigation of the processing degree according to the NOVA classification system. Food sales in Norway. Norwegian grocery stores (n 180, for both time periods). The share of expenditure in 2019 was highest for ultra-processed foods (46·5 %) and minimally or unprocessed foods (36·3 %), followed by processed foods (8·5 %) and processed culinary ingredients (1·3 %). An increasing degree of processing was found for several of the food groups between 2013 and 2019; however, most effect sizes were weak. In 2019, soft drinks became the most frequently purchased food item, surpassing milk and cheese, with the highest expenditure in Norwegian grocery stores. Increases in expenditure on ultra-processed foods were mainly due to increased expenditures on soft drinks, sweets and potato products. A high share of expenditure on ultra-processed food was found in Norway, which may imply a high consumption of these foods. The change in expenditure of NOVA groups between 2013 and 2019 was small. Carbonated and non-carbonated soft drinks were the most frequently purchased products in Norwegian grocery stores and contributed to most of the expenditures.


Binding Aedes aegypti densonucleosis virus to ion exchange membranes.
Experimental and numerical results for binding Aedes aegypti densonucleosis virus (AeDNV) using anion and cation exchange membranes are presented. AeDNV particles are adsorbed by anion and cation exchange membranes providing the virus particles and membranes are oppositely charged. Q membranes which are strongly basic anion exchangers were the most effective. Dynamic and static capacities for Q membranes were found to be similar. A numerical model is proposed which assumes a log normal pore size distribution. By estimating the required parameters from static binding experiments, the model may be used to calculate the breakthrough curve for virus adsorption.


Conception following insemination with a freeze-preserved retrograde ejaculate.
Retrograde ejaculation, an infrequent cause of male infertility, may be the sequela of prostate or bladder neck surgery or the result of interruption in the sympathetic innervation to the bladder neck. The diagnosis is established by history and examination of the urine. In infertile couples artificial insemination homologous (AIH) using retrograde ejaculate recovered from the bladder has been successfully accomplished, but conception has occurred only in isolated cases. A literature review of the subject is presented. The technique of semen recovery from the bladder is time-consuming and uncomfortable to the patient, while the quality of the semen recovered is variable and the risk of iatrogenic urinary tract infection is increased. To avoid the above problems, and to have sperm available for AIH at the time of induced ovulation in an anovulatory wife, we were able to freeze-preserve ejaculate recovered from the bladder for future use. A case of conception following AIH with freeze-preserved retrograde ejaculate is presented.


Does postoperative complication have a negative impact on long-term outcomes following hepatic resection for colorectal liver metastasis?: a meta-analysis.
The negative impact of postoperative complications (POCs) on long-term outcomes is well documented for several cancer surgeries, but conclusive evidence has yet to be provided on the influence of POCs on long-term oncological outcomes after hepatic resection for colorectal liver metastasis (CRLM). Studies published through February 2012 evaluating the oncological impact of POCs after hepatectomy for CRLM were identified by an electronic literature search. Finally, 4 studies were identified and included in the meta-analysis. The main outcome measures were 5-year disease-free survival (DFS) and overall survival (OS). A meta-analysis was performed using the DerSimonian-Laird random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (95 % CI). The outcomes of 2,280 patients were studied. Meta-analysis of 5-year DFS data extracted from three studies demonstrated a significant reduction in 5-year DFS after POCs, with an OR of 1.98 (95 % CI = 1.33-2.96; P = .0008). Meta-analysis of 5-year OS data extracted from four studies demonstrated a significant reduction in 5-year OS after POCs, with an OR of 1.68 (95 % CI = 1.25-2.27; P = .0006). No differences between study heterogeneity were observed in either the DFS or the OS analyses. This study provides persuasive evidence that POCs following hepatic resection for CRLM have significant adverse oncological outcomes. These findings emphasize the need for meticulous surgical technique and careful perioperative management to minimize POCs.


Perioperative Clinical Results of Transcervical and Transhiatal Esophagectomy versus Thoracoscopic Esophagectomy in Patients with Esophageal Carcinoma: A Prospective, Randomized, Controlled Study.
This study assessed the efficacy of transcervical and transhiatal esophagectomy versus thoracoscopic esophagectomy in patients with esophageal carcinoma (EC). A total of 80 patients with EC were enrolled in this study, including 40 cases in the observation group that received transcervical combine transhiatal esophagectomy and the rest 40 cases of the group that underwent thoracoscopic esophagectomy. The preoperative, intraoperative, and postoperative data were analyzed between the two surgeries, regarding perioperative bleeding, the total number of dissected mediastinal lymph nodes, operative time, number of lymph nodes in the left para-recurrent laryngeal nerve (para-RLN) or the right para-RLN, time in the intensive care unit (ICU), postoperative pain score, the length of postoperative stay (LOPS), PO2/fraction of inspired oxygen (PO2/FiO2), pulmonary infection, and lymphatic metastasis. The operations were successfully performed in all 80 patients. The results showed that patients who underwent transcervical and transhiatal esophagectomy had shorter operations than those with transthoracic esophagectomy (200 minutes vs 235 minutes, Kruskal-Wallis test [Z] = -3.700, P < 0.001). The number of dissected mediastinal lymph nodes in the left para-RLN in the observation group was higher than in the control group (25.0% vs 2.5%, Z = 2.568, P = 0.010). The postoperative pain score day 1 (0.0% vs 17.5%, Z = -4.292, P < 0.001), postoperative pain score day 3 (12.5% vs 37.5%, Z = -3.363, P < 0.001) and 48-h PO2/FiO2 (290 minutes vs 255 minutes, Z = 3.747, P < 0.001) were significant between the two groups. The LOPS of patients with EC in the observation group was shorter than the control group (7 vs 8, Z = -2.119, P = 0.034). The number of patients receiving transcervical and transhiatal esophagectomy that developed postoperative pulmonary infections was less than the controls (chi-square [χ 2] = 4.114, P = 0.043). Moreover, the transcervical and transhiatal esophagectomy was an independent protect factor for postoperative pulmonary infection (odds ratio [OR] =7.801, P = 0.037). The transcervical and transhiatal esophagectomy is a good operation for treating patients with EC, which may offer an opportunity to treat cases who cannot have thoracotomy.


Extranodal Rosai-Dorfman disease of bone and nose: a case report and review of literature.
Rosai-Dorfman disease (RDD) is a rare benign condition of unknown origin, which was first described in 1969. By histopathology, the disease is composed of sinusoidal lymph node hyperplasia and abundant histiocytes with haemophagocytosis, particularly lymphocytes. It commonly affects lymph nodes, and rarely has an exclusively extra-nodal clinical presentation. Among the so-called "extranodal" sites, the head and neck region, and in particular the nose and paranasal sinuses, are frequently affected. RDD shows a highly variable clinical course that can be partly modified by medical therapy. We present of a case of extra-nodal RDD, with nasal and osseous involvement, which has been followed-up for 19 years. We also discuss its presentation, the most relevant radiographic findings, treatment options and histological findings.


A proposed screen for evaluating low-molecular-weight chemicals as potential respiratory allergens.
Allergic asthma can result when reactive low-molecular-weight chemicals (LMWCs) haptenate carrier proteins to form immunogenic conjugates, which then induce specific allergic antibodies. As part of an overall assessment process for evaluating the allergenic potential of LMWCs, an in vitro test for detecting the covalent derivatization of proteins by LMWCs was developed. In the assay, globulin-free serum albumins were incubated with increasing concentrations of a given LMWC and the mixtures separated via reversed-phase high-performance liquid chromatography (HPLC). Derivatization was monitored by shifts in the retention time of native versus modified protein. Retention time shifts were seen for most haptens when incubated with human serum albumin at a 50:1 (hapten:protein) starting molar ratio. Some haptens changed the retention time of the protein at a 5:1 initial ratio. Almost all chemicals that non-covalently bind to proteins did not change the protein retention time, even when incubated at 1500:1 molar ratios. The screen correctly identified 12/14 known human allergenic haptens and 23/24 non-allergenic LMWCs. It cannot detect sensitizers which must be metabolized into reactive haptens. This screen can be incorporated into an overall risk assessment approach for evaluating chemicals as respiratory allergens.


Energy loss near edge structure of sulfur in non-stoichiometric CuInS(2)
Non-stoichiometric CuInS(2) is a novel material for thin film solar cells. Electron energy loss spectrometry analysis shows that there are considerable lateral inhomogeneities on a scale of less than 100nm. It is as yet unknown whether the Cu or In surplus comes in nanoprecipitates irregularly distributed in the otherwise stoichiometric matrix, or forms supercells where particular atoms are replaced by their complements. This question bears important consequences for the understanding of the local electronic structure and the mechanism of undesired recombination processes in the cell. Since the energy-loss near edge structure of ionisation edges (ELNES) mirrors the local density of unoccupied states it should be different in the two cases. We compare the sulfur L(2,3) ELNES of a Cu-rich and of an In-rich specimen with simulations of supercells based on the TELNES/WIEN97 code. Faint differences in the edge shape can be made visible using difference spectra. They agree reasonably well with simulations. The results show that the surplus species exists as a separate non-stoichiometric phase and not merely as a precipitate of elemental Cu or In.


Patient-physician communication assessment instruments: 1986 to 1996 in review.
This paper provides a comprehensive review and comparison of instruments used to assess patient-doctor interaction over the past decade. Instruments were identified from papers indexed by MEDLINE from 1986 to 1996 using the medical subject headings 'physician-patient relations', 'physician-patient communication', and 'education, medical', as well as requests for instruments currently in use by colleagues. Each instrument was reviewed under the following categories: name of the instrument; description; number of items; reliability; validity; current use and special notes. Overall, 44 instruments were obtained and reviewed. Of these, 21 were used in only one published study each in the last decade and 15 have never been validated. While most instruments have been shown to be reliable (usually inter-rater reliability), very few instruments have been directly compared with another instrument designed to assess patient-doctor interactions. We suggest that further validation of existing instruments and incorporation of assessment of non-verbal communication between the patient and the doctor are needed.


Tetragonal and helical morphologies from polyferrocenylsilane block polyelectrolytes via ionic self-assembly.
The use of ionic self-assembly, a facile non-covalent approach, to access non-conventional block copolymer morphologies, including tetragonal and helical structures, from a combination of polyferrocenylsilane diblock copolymer polyelectrolytes and AOT-based surfactants, is described.


When the Snake Lost Its Limbs, What Did the Mouse and Lizard Say?
In this issue of Developmental Cell, Infante et al. (2015) compare regulatory DNA sequences in mice, lizards, and limbless snakes to reveal widespread sharing of enhancer activity in developing limbs and genitalia. Genetic deletion of a limb-genital enhancer demonstrates that common regulatory elements affect development of both appendages.


The impact of in-situ balloon occlusion of the renal artery and hypothermic perfusion on renal blood flow.
Unilateral renal blood flow was evaluated in-situ in 13 dogs by cineangiodensitometry and microsphere distribution studies before and after intermittent balloon occlusion with and without hypothermic perfusion of one kidney. The contralateral kidney served as control. No significant difference in renal blood flow and vascular resistance was noted before, and 5, 30 and 60 minutes after unilateral intra-arterial manipulation. Compartmental flow distribution studies in 5 dogs revealed no evidence of alteration of intra-renal haemodynamics. In a clinical pilot study, unilateral renal blood flow measured by cineangiodensitometry showed no change of clinical significance 5 and 60 minutes after intraluminal balloon occlusion of the renal artery for 60 seconds.


[Assisting protective effect of Yiyuan oral solution on mice from irradiation injury].
To study the protective effect of Yiyuan oral solution against radiation injury in mice. Yiyuan oral solution was administered in mice at 10.00, 3.33 and 1.67 ml/kg for 30 days. The mice were then exposed to (60)Co-gamma irradiation at 3 Gy once and the effect of the irradiation on the WBC, bone marrow polychromatic erythrocytes (PEC) micronuclei and serum hemolysin antibody against sheep red cells. Yiyuan oral solution at 10 ml/kg significantly increased WBC counts, decreased bone marrow PEC micronucleus rate and enhanced serum hemolysin antibody in mice, suggesting the protective effect of this preparation against radiation injury.


Cassiae Semen improves non-alcoholic fatty liver disease through autophagy-related pathway.
Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.


Dietary β-Sitosterol Improves Growth Performance, Meat Quality, Antioxidant Status, and Mitochondrial Biogenesis of Breast Muscle in Broilers.
The present study evaluated effects of β-sitosterol on growth performance, meat quality, oxidative status, and mitochondrial biogenesis of breast muscle in broilers. One-day-old chicks were allocated to five treatments of six replicates. Broilers were fed a basal diet supplemented either with 0 (control), 40, 60, 80, or 100 mg/kg β-sitosterol for 42 days. β-sitosterol linearly and quadratically reduced feed/gain ratio, lightness24h and cooking loss24h in breast muscle, whereas 2, 2-diphenyl-1-picrylhydrazyl scavenging activity of breast muscle followed an opposite trend. β-sitosterol linearly decreased drip loss24h and malondialdehyde content, whereas linearly increased pH24h, superoxide dismutase activity, and mRNA abundances of peroxisome proliferator-activated receptor γ coactivator 1α (PCG-1α) and mitochondrial transcription factor A (TFAM) in breast muscle. Compared with control, levels of β-sitosterol higher than 40 mg/kg reduced feed/gain ratio, muscular lightness24h, cooking loss24h, and malondialdehyde level, whereas increased muscular 2, 2-diphenyl-1-picrylhydrazyl scavenging activity, and mRNA abundances (except 60 mg/kg) of PCG-1α and TFAM. Eighty milligram/kilogram β-sitosterol increased muscular pH24h and superoxide dismutase activity, but decreased its drip loss24h. Therefore, β-sitosterol could improve growth performance and meat quality, oxidative status, and mitochondrial biogenesis of breast muscle in broilers. Furthermore, supplementation level of 80 mg/kg β-sitosterol is recommended for broiler diets.


Low oxygen stimulates the immune system.
Changes in tissue oxygen levels trigger molecular signaling pathways that regulate cellular proliferation and differentiation in multiple cell types. The functional role of oxygen signaling in the immune system is not well understood. Rama and colleagues demonstrate that hypoxia induces dendritic-cell maturation; thus they provide a novel mechanistic link between hypoxia/ischemia and the activation of the immune system in the kidney.


Health-related quality of life of Turkish stroke survivors.
Stroke is a major, chronically disabling neurological disease, which often radically and permanently changes the lives of the victims. Improvement of motor coordination and the degree of independence achieved in activities of daily living have been the usual criteria used to measure outcome in stroke rehabilitation. The objective of our study is to compare health-related quality of life (HRQOL) between stroke patients 6 months after rehabilitation and a control group who did not have any major illness. The associations of several factors with the quality of life were also examined. Sixty consecutive stroke patients and 58 healthy control participants were included in the study. Functional independence measure (FIM), Nottingham health profile (NHP) and demographic variables were used as the main outcome measures. There were significant improvements in both motor coordination and functional status as measured by FIM at discharge and also 6 months after stroke and these variables were significantly associated with the HRQOL. The NHP, which is a validated quality-of-life measurement in Turkish patients, was used and the scores were compared with the healthy control participants. The scores of NHP domains (energy level, emotional reactions, sleep, social isolation and physical mobility) of the stroke patients were higher than those of the healthy group (P<0.01). Age, marital status, lesion side and multiple stroke history showed no significant correlation with NHP scores. Being a woman, lower educational status, tendency to depression and the presence of several comorbidities were significantly correlated with the NHP scores. Stroke survivors in our society have lower HRQOL than healthy individuals. HRQOL is correlated with the functional status in the stroke population. Additionally, the reduced HRQOL after stroke appears to be related to several demographic properties such as sex, education, comorbidities and psychological factors.


Vocational adaptation of patients on home dialysis: its relationship to personality, activities and support received.
This analysis identifies, in terms of relative contribution, seven independent variables which appear to be associated with the vocational adaptation of home dialysis patients. The tentative model created by the analysis can be used as a guide for assessing a patient's potential vocational adaptation. It has also identified some conditions associated with adaptation which are amenable to treatment by dialysis staff. Validation of the model, however, requires further testing with other patient groups.


Production efficiency in small mammal populations.
Data from 102 populations of small mammals from 9 ecosystem types in Europe and in North and Central America were analyzed to define the relationship between productivity and respiration in insectivore and rodent populations. Productivity includes addition of new tissue in the form of growth of individual members of the population and new individuals added by reproduction. All data were recalculated to kilojoules per hectare per year. Linear regression was performed on logarithmic transformation of the data to determine the allometric form of the equation relating production to respiration. The relationship for rodents was determined to be: P=0.026 R 1.008 The relationship for shrews was significantly different both in slope and intercept from that for rodents, and was determined to be: P=0.543 R 0.628 The data were also divided according to functional group or trophic level, in addition to taxonomic grouping. Significant differences were found between herbivores and granivores but not among taxonomic divisions other than the Insectivora. Thus, ecological energetics of small mammals is correlated with trophic position but not with taxonomic position.These equations can be used for prediction of production in rodent and shrew populations where the biomass or respiration is known, thereby aiding the evaluation of trophic relationships in terrestrial communities.Production efficiency is lowest for insectivores (0.7%), and is higher for granivores (2.3%), omnivores (2.6%), and for herbivores (3.4%). The three parameters of respiration, production and assimilation define the conditions for existence of individual mammal populations. Population growth characteristics and species strategies are correlated with energetics and moderated through diet selection by the environment.


Development of novel electrospun absorbable polycaprolactone (PCL) scaffolds for hernia repair applications.
Permanent/nonresorbable hernia repair materials rely on profibrotic wound healing, and repair sites are commonly composed of disorganized tissue with inferior mechanical strength and risk of reherniation. Resorbable electrospun scaffolds represent a novel class of biomaterials, which may provide a unique platform for the design of advanced soft tissue repair materials. These materials are simple, inexpensive, nonwoven materials composed of polymer fibers that readily mimic the natural extracellular matrix. The primary goal of the present study was to evaluate the physiomechanical properties of novel electrospun scaffolds to determine their suitability for hernia repair. Based on previous experimentation, scaffolds possessing ≥ 20 N suture retention strength, ≥ 20 N tear resistance, and ≥ 50 N/cm tensile strength are appropriate for hernia repair. Six novel electrospun scaffolds were fabricated by varying combinations of polymer concentration (10-12 %) and flow rate (3.5-10 mL/h). Briefly, poly(ε-caprolactone) (PCL) was dissolved in a solvent mixture and electrospun onto a planar metal collector, yielding sheets with randomly oriented fibers. Physiomechanical properties were evaluated through scanning electron microscopy, laser micrometry, and mechanical testing. Scanning electron micrographs demonstrated fiber diameters ranging from 1.0 ± 0.1 μm (10 % PCL, 3.5 mL/h) to 1.5 ± 0.2 μm (12 % PCL, 4 mL/h). Laser micrometry demonstrated thicknesses ranging from 0.72 ± 0.07 mm (12 % PCL, 10 mL/h) to 0.91 ± 0.05 mm (10 % PCL, 3.5 mL/h). Mechanical testing identified two scaffolds possessing suture retention strengths ≥ 20 N (12 % PCL, 10 mL/h and 12 % PCL, 6 mL/h), and no scaffolds possessing tear resistance values ≥ 20 N (range, 4.7 ± 0.9 N to 10.6 ± 1.8 N). Tensile strengths ranged from 35.27 ± 2.08 N/cm (10 % PCL, 3.5 mL/h) to 81.76 ± 15.85 N/cm (12 % PCL, 4 mL/h), with three scaffolds possessing strengths ≥ 50 N/cm (12 % PCL, 10 mL/h; 12 % PCL, 6 mL/h; 12 % PCL, 4 mL/h). Two electrospun scaffolds (12 % PCL, 10 mL/h and 12 % PCL, 6 mL/h) possessed suture retention and tensile strengths appropriate for hernia repair, justifying evaluation in a large animal model. Additional studies examining advanced methods of fabrication may further improve the unique properties of these scaffolds, propelling them into applications in a variety of clinical settings.


Multi-institutional validation of the ability of preoperative hydronephrosis to predict advanced pathologic tumor stage in upper-tract urothelial carcinoma.
The presence of hydronephrosis (HN) has been implicated as a predictor of poor outcomes for patients diagnosed with bladder cancer. Small, single institution preliminary reports suggest a similar negative relationship may exist for upper-tract urothelial carcinoma (UTUC). Herein, we attempt to validate the prognostic value of preoperative HN in a large, multi-institutional cohort of UTUC patients. Data on 469 patients with localized UTUC from 5 tertiary referral centers who underwent a radical nephroureterectomy (91%) or distal ureterectomy (9%) without neoadjuvant chemotherapy were integrated into a relational database. Preoperative HN data, including presence vs. absence and high vs. low grade, were available in 408 patients. The association of HN with pathologic features was evaluated. A total of 254 men and 154 women with a median age of 69 years (IQR 15) were analyzed. Overall, 192 patients (47%) had ≥pT2 disease, 145 (36%) had non-organ-confined (NOC) cancers (≥pT3 and/or positive lymph nodes), and 298 (73%) had high grade UTUC on final pathology. Forty-six percent of patients had tumors in the renal pelvis, 27% in the ureter, and 27% in both locations. Preoperatively, 223 patients (55%) were noted to have ipsilateral HN (39% low grade and 61% high grade). Hydronephrosis was associated with ≥pT2 stage (P < 0.001), NOC disease (P < 0.001), and high grade cancers (P = 0.04). On multivariate analysis adjusting for gender, age, and tumor location, HN was an independent predictor of muscle invasive (HR 7.4, P < 0.001), NOC (HR 5.5, P < 0.001), and high pathologic grade (HR 1.6, P = 0.03) UTUC disease. The presence of preoperative HN was associated with advanced stage UTUC. This readily available imaging modality may improve preoperative risk stratification for UTUC patients thereby guiding use of endoscopic versus extirpative surgery as well as the need for neoadjuvant chemotherapy regimens.


Pattern approach to MR imaging in patients with end-stage hepatic failure: a proposal for a new disease entity "hepatic encephalopathy continuum".
The purpose of this study was to evaluate the clinical features and the characteristics of MR images of patients with end-stage hepatic failure. We reviewed the MR findings and clinical features of 31 consecutive patients (20 men, 11 women=31, mean age 58.7 years) who had been diagnosed with clinical hepatic encephalopathy. Associations between the lesion locations on each MR sequence were analyzed using a binominal test. The clinical and MR findings were compared in relation to the etiology and clinical status. The most frequently involved site, seen as high signal intensity on T2-W images, was the corpus callosum (20 patients), followed by the dentate nucleus (16 patients) and the globus pallidus (13 patients). Significant associations were seen between the pallidus and the crus cerebri, between the crus cerebri and the red nucleus, between the crus cerebri and the dentate nucleus, and between the red nucleus and the dentate nucleus on the T2-W and DW images (P < 0.004). The crus cerebri, red nucleus, and dentate nucleus were involved concurrently with the corpus callosum more frequently in hepatic encephalopathy grades 3 and 4. Concurrent involvement of the globus pallidus-crus cerebri-red nucleus-dentate nucleus axis was the main MR pattern in end-stage hepatic encephalopathy, which connected with various areas of the brain. We hypothesize that these overlapping MR features could be regarded as an entity denoted as the "hepatic encephalopathy continuum".


Echocardiographic diagnosis of a left atrial thrombus in a patient with normal prosthetic mitral valve.
A 20-year-old male with a Björk-Shiley mitral valve prosthesis on optimal anticoagulation and antiplatelet drug therapy presented with systemic embolization 11 months after mitral valve replacement. Cross-sectional and Doppler echocardiography revealed a left atrial thrombus attached to the posterior wall of the left atrium and normal function of the prosthetic valve. The findings were confirmed at surgery.


Gene expression profiling of individual hypothalamic nuclei from single animals using laser capture microdissection and microarrays.
In order to identify novel genes involved in appetite and body weight regulation we have developed a microarray based method suitable for detecting small changes in gene expression in discrete groups of hypothalamic neurons. The method is based on a combination of stereological sampling, laser capture microdissection (LCM), PCR based amplification (SuperAmp), and one-color cDNA microarray analysis. To validate the method we assessed and compared fasting induced changes in mRNA levels of Neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the hypothalamic arcuate nucleus (ARC) of diet-induced obese rats using cDNA microarrays, quantitative PCR and in situ hybridization. All methods revealed statistically significant fasting-induced changes in NPY and POMC expression. An additional 3480 differentially expressed probes (fold change >1.22, t-test p=0.05) were identified in the microarray analysis. Our findings demonstrate a consistent gene expression pattern across three different gene expression detection methods and strongly suggest that LCM coupled microarray analysis combined with SuperAmp can be used as a semi-quantitative mRNA profiling tool. Importantly, the sensitivity of the method greatly improves the usefulness of the microarray technology for gene expression profiling in non-homogeneous tissues such as the brain.


[Thyrotoxic periodic paralysis: a case series of four patients and literature review].
Periodic thyrotoxic hypokalemic paralysis (TPP) is a neuromuscular complication of hyperthyroidism. It is more common in young Asian males than in Caucasian and African patients. We report four new cases and review the literature. Four consecutive patients were diagnosed with TPP. They were all men with a median age of 34.5 years at presentation. Two patients originated from the Philippines, one was African and one was Caucasian ethnic background. They all presented with a paresis or flaccid paralysis, without respiratory failure. Previous similar episodes in their past medical history, the presence of profound hypokalemia (mean serum potassium level of 2 mmol/L) and the presence of clinical and biological signs of hyperthyroidism led to the diagnosis of TPP. All four patients were diagnosed with Graves' disease. Outcome was favourable in all four patients with the symptomatic treatment of TPP and treatment of Graves' disease. TPP is a severe condition, due to a dysfunction of the Na(+)-K(+) ATPase pump. Initial management relies on β-blocker treatment and careful potassium supplementation. Then, medical or surgical etiological treatment of the thyrotoxicosis is essential to prevent a recurrence. The disease is probably underdiagnosed: it must be suspected when a profound hypokaliema resolves very quickly (<12hours); hyperthyroidism should always be included in the differential diagnosis of a paresis associated with hypokalemia.


Sex differences in symptoms of anxiety, depression, post-traumatic stress disorder, and cognitive function among survivors of out-of-hospital cardiac arrest.
Anxiety, depression, and post-traumatic stress disorder (PTSD) among out-of-hospital cardiac arrest (OHCA) survivors may impact long-term recovery. Coping and perception of symptoms may vary between sexes. The aim was to explore sex differences in psychological consequences following OHCA. This was a prospective observational study of OHCA survivors who attended a structured 3-month follow-up. Symptoms of anxiety/depression were measured using the Hospital Anxiety and Depression Scale, range 0-21, with a cut-off score of ≥8 for significant symptoms; PTSD was measured with the PTSD Checklist for DSM-5 (PCL-5), range 0-80. A score of ≥33 indicated PTSD symptoms. Cognitive function was assessed by the Montreal Cognitive Assessment. From 2016 to 2021, 381 consecutive comatose OHCA survivors were invited. Of these, 288 patients (76%) participated in the follow-up visit [53 (18%) females out of 80 survivors and 235 (82%) males out of 300 alive at follow-up (78%)]. Significant symptoms of anxiety were present in 47 (20%) males and 19 (36%) females (P = 0.01). Significant symptoms of PTSD were present in 30% of males and 55% of females (P = 0.01). Adjusting for pre-specified covariates using multivariable logistic regression, female sex was significantly associated with anxiety [odds ratio (OR): 2.18, confidence interval (CI): 1.09-4.38, P = 0.03]. This difference was especially pronounced among young females (below median age, ORadjusted: 3.31, CI: 1.32-8.29, P = 0.01) compared with young males. No significant sex difference was observed for depression or cognitive function. Symptoms of anxiety and PTSD are frequent in OHCA survivors, and female survivors report significantly more symptoms of anxiety and PTSD compared with males. In particular, young females were significantly more symptomatic than young males.


Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.
Protein phosphatase 2A (PP2A) is a family of serine threonine phosphatases responsible for regulating protein phosphorylation, thus opposing the activity of cellular kinases. PP2A is composed of a catalytic subunit (PP2A Cα/β) and scaffolding subunit (PP2A Aα/β) and various substrate-directing B regulatory subunits. PP2A biogenesis is regulated at multiple levels. For example, the sequestration of the free catalytic subunit during the process of biogenesis avoids promiscuous phosphatase activity. Posttranslational modifications of PP2A C direct PP2A heterotrimeric formation. Additionally, PP2A functions as a haploinsufficient tumor suppressor, where attenuated PP2A enzymatic activity creates a permissive environment for oncogenic transformation. Recent work studying PP2A in cancer showed that its role in tumorigenesis is more nuanced, with some holoenzymes being tumor suppressive, while others are required for oncogenic transformation. In cancer biology, PP2A function is modulated through various mechanisms including the displacement of specific B regulatory subunits by DNA tumor viral antigens, by recurrent mutations, and through loss of carboxymethyl-sensitive heterotrimeric complexes. In aggregate, these alterations bias PP2A activity away from its tumor suppressive functions and toward oncogenic ones. From a therapeutic perspective, molecular glues and disruptors present opportunities for both the selective stabilization of tumor-suppressive holoenzymes and disruption of holoenzymes that are pro-oncogenic. Collectively, these approaches represent an attractive cancer therapy for a wide range of tumor types. This review will discuss the mechanisms by which PP2A holoenzyme formation is dysregulated in cancer and the current therapies that are aimed at biasing heterotrimer formation of PP2A for the treatment of cancer.


Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells.
Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood. We identify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic degradation of mitochondria. The mechanisms of such degradation involve the adenine nucleotide translocator and mitochondrial permeability transition pore opening. We also demonstrate that RCAN1-1L induction can shift cellular bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very little effect on cell division, whereas it has a cumulative negative effect on cell survival. These results shed the light on mechanisms by which RCAN1s can protect or harm cells and by which they may operate in human pathologies. They also suggest that RCAN1s are important players in autophagy and such elusive phenomena as the mitochondrial permeability transition pore.


The effect of various types low molecular weight heparins on fracture healing.
Thromboembolic complications are the most common preventable cause of mortality and morbidity in trauma and arthroplasty patients. Therefore, this group of patients receive a prophylaxis for thromboemboli by mechanical or pharmacological methods. This study was designed to evaluate the effect of enoxaparin, nadroparin, dalteparin and fondaparinux on fracture healing in an experimental rat femur fracture model. Thirty male, Wistar-Albino rats were divided randomly into five groups. A retrograde intramedullary kirschner wire was inserted under general anesthesia and then standard closed femoral shaft fractures were produced. After the production of fractures, treatment groups received enoxaparin, nadroparin, dalteparin and fondaparinux via subcutaneous injections and the control group received placebo injections for four weeks. The formation and healing of the bones were determined by clinical manual evaluation, radiographic and histopathological analyses. Histological callus formation scores were found to be significantly increased in the fondaparinux group when compared to the control group at the end of the fourth week. Other treatment groups' histological scores did not show any significant difference with the control group. The histological scores of all groups were compared and the fondaparinux group histological score was found to be significantly increased. The clinical and radiological scores between the groups did not show any significant difference. A positive histological effect of fondaparinux on fracture healing was observed in this study. This enhancing effect of fondaparinux may be related to its synthetic and selective composition and non-inhibitory effects on osteoblasts and growth factors.