Triglyceride glucose index for the detection of asymptomatic coronary artery stenosis in patients with type 2 diabetes.
Triglyceride Glucose (TyG) index has been associated with an increased risk in cardiovascular events. Silent coronary disease is common in patients with type 2 diabetes. In Vietnam, a low-middle income country, the burden of cardiovascular disease is growing simultaneously with the epidemiologic transition. Our aim was to assess the prevalence of coronary stenoses (CS) in patients with type 2 diabetes and no history or symptom of cardiovascular disease and to investigate the association between TyG index and cardiovascular risk factors and both the presence and severity of CS. Futhermore, we assessed the value of TyG index in predicting subclinical CS. This was a cross-sectional observational study. We recruited 166 patients at Ninh Thuan General Hospital, Vietnam. TyG index and HOMA-IR were calculated, and a coronary computed tomography angiography (CCTA) was performed. The population was classified according to tertiles of TyG index. The highest TyG values were associated with higher BMI, waist circumference, total cholesterol, LDL-cholesterol, triglycerides, plasma glucose, HbA1c levels and HOMA-IR, lower HDL-cholesterol, a higher incidence of metabolic syndrome and less frequent physical activity (p < 0.05 to < 0.0001). TyG index correlated with logHOMA-IR (p < 0.0001). CS ≥ 50% were present in 60 participants and 32 had coronary artery stenosis ≥ 70%. TyG index and HOMA-IR were significantly higher in patients with CS ≥ 70%. The number of narrowed coronary arteries and the degree of stenosis were associated with higher TyG index levels (p = 0.04 and < 0.005 respectively). A TyG index ≥ 10 was significantly associated with an increased risk of multiple coronary artery disease and of more severe CS. After adjusting for confounding factors, including logHOMA-IR, these risks remained mostly significant. A TyG index threshold at 10 resulted in 57% sensitivity and 75% specificity for predicting the presence of CS ≥ 70%. In subgroup analysis TyG index ≥ 10 was associated with an increased risk in CS ≥ 70% in patients treated with statin or antiplatelet therapy. More than one third of asymptomatic patients with type 2 diabetes had significant CS on CCTA. TyG index may be considered as a marker for insulin resistance and increased TyG index could identify patients with high risk of coronary artery stenoses and is associated with the number and the severity of artery stenoses.


Children's processing of written irony: An eye-tracking study.
Ironic language is challenging for many people to understand, and particularly for children. Comprehending irony is considered a major milestone in children's development, as it requires inferring the intentions of the person who is being ironic. However, the theories of irony comprehension generally do not address developmental changes, and there are limited data on children's processing of verbal irony. In the present pre-registered study, we examined, for the first time, how children process and comprehend written irony in comparison to adults. Seventy participants took part in the study (35 10-year-old children and 35 adults). In the experiment, participants read ironic and literal sentences embedded in story contexts while their eye movements were recorded. They also responded to a text memory question and an inference question after each story, and children's levels of reading skills were measured. Results showed that for both children and adults comprehending written irony was more difficult than for literal texts (the "irony effect") and was more challenging for children than for adults. Moreover, although children showed longer overall reading times than adults, processing of ironic stories was largely similar between children and adults. One group difference was that for children, more accurate irony comprehension was qualified by faster reading times whereas for adults more accurate irony comprehension involved slower reading times. Interestingly, both age groups were able to adapt to task context and improve their irony processing across trials. These results provide new insights about the costs of irony and development of the ability to overcome them.


Ansa pancreatica: an anatomic variation and a rare cause of acute pancreatitis.
The ansa pancreatica is a rare anatomic variation of the pancreatic ducts. It is a communication between the main pancreatic duct (Wirsung) and the accessory pancreatic duct (Santorini). Recently, the ansa pancreatica has been considered as a predisposing factor in patients with idiopathic acute pancreatitis. \We report a case of non-alcoholic and non-biliary acute pancreatitis, in a 53-year-old patient. An ansa pancreatica was discovered in a post-operative cholangiography. A pancreatic duct variation, as the ansa pancreatica, can be diagnosed during a severe acute pancreatitis. It is still not clear whether the presence of these two pathologies is a coincidence or if the ansa pancreatica is the cause of the acute pancreatitis. New studies are necessary to clarify these points.


Inactivation of Bacteria by γ-Irradiation to Investigate the Interaction with Antimicrobial Peptides.
The activity of antimicrobial peptides (AMPs) has been investigated extensively using model membranes composed of phospholipids or lipopolysaccharides in aqueous environments. However, from a biophysical perspective, there is a large scientific interest regarding the direct interaction of membrane-active peptides with whole bacteria. Working with living bacteria limits the usability of experimental setups and the interpretation of the resulting data because of safety risks and the overlap of active and passive effects induced by AMPs. We killed or inactivated metabolic-active bacteria using γ-irradiation or sodium azide, respectively. Microscopy, flow cytometry, and SYTOX green assays showed that the cell envelope remained intact to a high degree at the minimal bactericidal dose. Furthermore, the tumor-necrosis-factor-α-inducing activity of the lipopolysaccharides and the chemical lipid composition was unchanged. Determining the binding capacity of AMPs to the bacterial cell envelope by calorimetry is difficult because of an overlapping of the binding heat and metabolic activities of the bacteria-induced by the AMPs. The inactivation of all active processes helps to decipher the complex thermodynamic information. From the isothermal titration calorimetry (ITC) results, we propose that the bacterial membrane potential (Δψ) is possibly an underestimated modulator of the AMP activity. The negative surface charge of the outer leaflet of the outer membrane of Gram-negative bacteria is already neutralized by peptide concentrations below the minimal inhibitory concentration. This proves that peptide aggregation on the bacterial membrane surface plays a decisive role in the degree of antimicrobial activity. This will not only enable many biophysical approaches for the investigation between bacteria and membrane-active peptides in the future but will also make it possible to compare biophysical parameters of active and inactive bacteria. This opens up new possibilities to better understand the active and passive interaction processes between AMPs and bacteria.


[Current situation of the Aedes aegypti mosquito in the metropolitan area of Panama city].
Ae. aegypti was reintroduced into Panama in 1985; control was unsuccessful and by 1988 Ae. aegypti larvae were detected in every borough of Panama Metropolitan Area. Only 3% of the Panama City population has dengue antibody (against DEN 2) and virtually no one is immune to other serotypes. The relative risk of the introduction of Dengue virus into Panama is discussed.


Participation and conflict in the decision-making process for endoscopic resection or surgical gastrectomy for early gastric cancer.
This study was to evaluate the participation role and conflict of patients during the decision-making process for endoscopic or surgical treatment for early gastric cancer (EGC). In this prospective observational study, the sequential survey for patients under consideration for treatment of differentiated EGC was performed at the tertiary referral center. Among the 82 responders, 63.4% preferred endoscopic resection. The total decisional conflict scores were high and significantly different between groups that preferred endoscopic resection or surgical treatment (44.8 vs. 51.6, P = 0.016). Values assigned to the two treatment attributes "preservation of stomach (OR = 0.51)" and "bother in case of incomplete resection (OR = 2.13)" clearly discriminated between patients reaching a final decision of surgical gastrectomy or endoscopic resection. Regarding the participation role, a shared role was more frequent in the group with preference for endoscopic treatment before consultation (42.3% vs. 24.0%, P = 0.045). However, at the time of therapeutic decision, the passive role was most remarkable, both for the endoscopic (53.2%) and surgical (71.4%) groups. Despite the high overall decisional conflict, patients with preference for endoscopic treatment tended to be more autonomous. After consultation, all patients exhibited a passive participation role in the decision-making process.


Functional similarities between the P1 component and alpha oscillations.
The present study attempts to demonstrate functional similarities between the P1 component of event-related potentials and alpha oscillations that are predicted by the 'alpha inhibition-timing' hypothesis. On the basis of findings showing that the frequency characteristic of the P1 component lies in the alpha range and that alpha oscillation is functionally associated with inhibition, we predict that the P1 component also reflects inhibitory processes. This hypothesis is tested in two experiments, a spatial-cuing task and a visual-semantic categorization task. The results of the cuing task demonstrate that in a similar way as alpha power, the P1 component is larger over task-irrelevant ipsilateral sites. For the categorization task, we found that the P1 component, in a similar way to alpha oscillations, is larger for task-irrelevant, distorted pictures. We conclude that the P1 component may be generated at least in part by evoked alpha oscillations and reflects inhibition in the sense of suppressing task-irrelevant processes.


Urgent pedal bypass grafting for salvage of a critically ischaemic limb with a thrombosed popliteal aneurysm.
The absence of infra-popliteal runoff in patients with acute limb-threatening ischaemia due to thrombosed popliteal aneurysm entails a high risk of amputation. If sufficient runoff cannot be restored by thrombolysis of crural arteries or by thrombectomy, the only chance to salvage the limb is pedal bypass grafting. The authors present a clinical case of acute lower limb ischaemia in a patient with popliteal aneurysm thrombosis and occlusion of the crural arteries treated successfully with urgent pedal bypass grafting with distal anastomosis to the dorsal pedal artery.


Fetal echocardiography. VII. Doppler color flow mapping: a new technique for the diagnosis of congenital heart disease.
One of the difficulties for the fetal sonographer is the complete elucidation of structural defects of the cardiovascular system that are associated with intracardiac or great vessel flow disturbances. With the recent introduction of Doppler color flow mapping, in which blood flow is displayed in color superimposed on a real-time image, it has been impossible to identify flow disturbances in the pediatric and adult patient. This study was undertaken to determine whether Doppler color flow mapping could be used in the fetus to identify normal and abnormal cardiovascular anatomy. Thirty-five normal and high-risk fetuses were examined between 16 and 40 weeks of gestation. Doppler color flow mapping identified normal and abnormal anatomy (ventricular septal defect, atrial septal defect, endocardial fibroelastosis, dysplastic pulmonary valve, and tricuspid regurgitation). It appears that Doppler color flow mapping will add a new dimension to fetal cardiovascular imaging.


Early complications in delayed breast reconstruction: A prospective, randomized study comparing different reconstructive methods in radiated and non-radiated patients.
There is little high-quality scientific evidence identifying the best and safest methods for delayed breast reconstruction, with most previous studies retrospective in nature. The primary aim was to compare early complication rates for two different breast-reconstructive methods in radiated and non-radiated patients, using a validated scale. The secondary aim was to identify predictors for complications. This study represents a clinical, randomized, prospective trial (ClinicalTrials.Gov identifier: NCT03963427), where the patients were divided into two study arms: non-radiated and radiated. In the non-radiated arm, patients were randomized to a one-stage lateral thoracodorsal flap with an implant or two-stage expander reconstruction. In the radiated arm, patients were randomized to a latissimus dorsi reconstruction combined with an implant or deep inferior epigastric artery perforator (DIEP) reconstruction. All adverse events were classified according to Clavien-Dindo and summarization of overall morbidity was performed by calculating the Comprehensive Complication Index score. The study was conducted from 2008 to 2020. The complication frequencies were similar for the two surgical methods within each arm. In the non-radiated arm, risk factors for any complication were any comorbidities, and in the radiated arm, factors were a high body mass index and a contralateral operation. The usage of the Clavien-Dindo scale in reconstructive surgery is feasible, but further validation is needed. In non-radiated patients, the frequencies of short-term complications were similar for lateral thoracodorsal flap and expander reconstruction, whereas in radiated patients, they were similar for DIEP and latissimus dorsi. The complication profile of the methods varied.


[Pyogenic granuloma of the oral mucosa].
Pyogenic granuloma is regarded as a vascular proliferation that may result from trauma or local irritation. The most common intraoral site is the gingiva, affected in 75 % of cases. Therapy of pyogenic granuloma consists of surgical excision. Recurrence after excision may occur. In our patient, there were no post-operative complications.


Decentralized energy in flexible energy system: Life cycle environmental impacts in Belgium.
Decentralized energy systems enable a higher integration of electricity generation by renewable energy sources supported by electric storage and may significantly reduce greenhouse gas emissions for electricity generation. While the environmental impact of single technologies has received great attention in recent years, the environmental impacts of decentralized energy generation and storage technologies remain unaddressed. This study presents a cradle-to-grave life cycle assessment of those technologies in Belgium for 2030 and 2050. The system technologies comprise single-Si photovoltaic installations combined with lithium-ion and second-life batteries. To compile the life cycle inventory (LCI), energy balances are built based on a Belgian impact energy model. The flexibility of the energy system is introduced by different EV charging strategies and distinct modes of stationary battery storage with the Belgium electricity grid, represented by four different scenarios: i) low flexibility, ii) medium flexibility, iii) high flexibility, and iv) high flexibility with high prosumer potential (PPH). The midpoint impact categories climate change, land use, mineral resource scarcity and terrestrial ecotoxicity of ReCiPe life cycle impact assessment method are analyzed. The decentralized energy generation and storage technologies in Belgium in 2050 result in 64.51 gCO2eq/kWh of consumed electricity for the medium flexibility scenario, representing a 72 % decrease compared to 2014. However, these reductions are driven by changes in the national electricity mix. Land use impacts are also reduced, up to 72 % for the high flexibility PPH scenario. In contrast, mineral resource scarcity and terrestrial ecotoxicity rise over time in the high flexibility PPH scenario in 2050 to 46 % and 66 %, respectively. A perturbation analysis is conducted to assess the sensitivity of the results, showing solar irradiation as the most sensitive parameter. One way to further reduce the environmental impacts of decentralized energy systems could be to investigate new strategies for the end-of-life of photovoltaic installations and batteries.


The state-of-the-science: access to postacute care rehabilitation services. A review.
To identify and summarize potential factors that influence access to postacute care (PAC) rehabilitation services. Ovid Medline and agency-specific (eg, RAND Corp, Research Triangle Institute, U.S. Department of Health and Human Services) searches, using combinations of the terms health services accessibility, delivery of healthcare, access to care, post-acute, postacute, and access. Names of prominent authors were also searched to retrieve their relevant articles. The initial search resulted in 823 articles published between 1980 and 2006. After we reviewed titles and abstracts, we obtained and examined 49 potential sources. Our final sample of 35 studies had descriptions and/or analyses of measures that might serve as indictors of access to PAC settings. Key information abstracted from each article and document included author(s), year of publication, patient groups, sample size, health care setting, and a brief summary of the access-related issues in PAC. Studies varied by patient group, care setting, and access categories. Indicators of access to PAC rehabilitation services were classified into 4 categories: financial (46%), personal (31%), structural (26%), and attitudinal (23%). Many studies assessed more than 1 category. We identified categories of information that can be used to develop a monitoring system for PAC services. The inclusion of access indicators in existing health report cards and quality indicator systems should be further explored.


Brain perfusion abnormalities in a sibship with parkin-linked parkinsonism.
We demonstrated brain perfusion abnormalities in a sibship with parkin-linked parkinsonism. The sibship consisted of a 64-year-old man and a 62-year-old woman. Both patients had homozygous deletions of exon 4 in the parkin gene. Hypoperfusion in the superior and middle frontal gyrus, and head of caudate nucleus was seen by SPECT with easy Z score imaging system in both patients. These findings may reflect their executive dysfunction demonstrated by neuropsychological tests.


[A case of ear miasis in a 2-month-old child].
A clinical case is presented - a rare observation of ear myasis in a 2-month-old child.


Outcome of obstetric fistula repair after 10-day versus 14-day Foley catheterization.
To compare outcome between 10-day and 14-day bladder drainage after obstetric fistula repair. In a randomized prospective study at Hamlin Fistula Center, Bahir Dar, Ethiopia, patients presenting with obstetric vesicovaginal fistula between 2007 and 2010 were randomized to undergo 10-day (group 1) or 14-day (group 2) postoperative catheterization. Fistulas were categorized via Goh classification. The inclusion criteria were any type of vesicovaginal fistula except circumferential or recurrent. In total, 189 women were enrolled: 107 in group 1, and 82 in group 2. The groups were similar in age, parity, duration of labor, and time from injury to surgical repair. There was no significant difference in fistula stage according to the Goh classification (urethral length, P=0.3; fistula size, P=0.9; and vaginal scarring, P=0.3). There were 3 fistula breakdowns in group 1, and 6 in group 2. The difference in cure was not significant (P=0.15, confidence interval -0.009 to 0.1). There was no significant difference in non-fistula-related incontinence or urinary retention after repair. The outcome of postoperative catheterization for 10 days was not inferior to that for 14 days. A similar treatment outcome with a shorter duration of catheterization will have a significant impact on reducing infection and cost.


Improved distributed Δ -coloring.
We present a randomized distributed algorithm that computes a Δ -coloring in any non-complete graph with maximum degree Δ ≥ 4 in O ( log Δ ) + 2 O ( log log n ) rounds, as well as a randomized algorithm that computes a Δ -coloring in O ( ( log log n ) 2 ) rounds when Δ ∈ [ 3 , O ( 1 ) ] . Both these algorithms improve on an O ( log 3 n / log Δ ) -round algorithm of Panconesi and Srinivasan (STOC'93), which has remained the state of the art for the past 25 years. Moreover, the latter algorithm gets (exponentially) closer to an Ω ( log log n ) round lower bound of Brandt et al. (STOC'16).


Serum gold concentrations during treatment with auranofin.
Serum gold concentrations were measured in rheumatoid arthritis patients during chronic treatment with the orally adsorbable gold compound auranofin. In agreement with data in the literature, the highest serum gold concentration was reached after 16 weeks of treatment with 6 mg auranofin daily. A striking finding in this study was that thereafter the serum gold concentrations did not appear to plateau but declined gradually. Statistically this resulted in a significantly lower concentration after one year as compared with week 16 (p less than 0.05, paired t-test). It is suggested that a shift from protein bound gold to cell-bound gold might be the explanation.


Factors associated with HPV vaccine acceptability and hesitancy among Black mothers with young daughters in the United States.
Compared to other-race peers, Black women are disproportionately impacted by human papillomavirus [HPV] infection, related health outcomes, and cervical cancer mortality as a result of suboptimal HPV vaccine uptake during adolescence. Few studies in the United States have examined psychosocial determinants of HPV vaccine acceptability and hesitancy among Black parents. The current study integrated the health belief model and the theory of planned behavior to evaluate the extent to which psychosocial factors are associated with pediatric HPV vaccination intentions among this population. Black mothers (N = 402; age range = 25 to 69 years, M = 37.45, SD = 7.88) of daughters ages 9 to 15 years completed an online survey assessing HPV infection and vaccine beliefs and attitudes across four domains: Mother's HPV Perceptions, Mother's Vaccine Attitudes, Cues to Action, and Perceived Barriers to HPV Vaccination. Participants indicated their willingness to vaccinate their daughter on a 5-level ordinal scale ("I will definitely not have my daughter get the vaccine" to "I will definitely have my daughter get the vaccine") which was dichotomously recoded for binomial logistic regressions. Half of the sample (48%) intended to vaccinate their daughter. Number of daughters, mother's HPV vaccine status, perceived HPV vaccine benefits, HPV vaccine safety concerns, pediatric HPV vaccine peer norms, and doctor recommendations emerged as independent factors of Black mothers' intentions to vaccinate their daughters against HPV when controlling for all other factors. In addition to medical training to increase doctor recommendation of the HPV vaccine for Black girls, population-tailored public health messaging aimed at promoting HPV vaccine acceptance among Black mothers is urgently needed. This messaging should engage community support and emphasize the benefits of vaccination for adolescent Black girls while also addressing parental concerns regarding the safety of pediatric HPV vaccination.


Glomus tumours of the knee: a case series.
To review clinical and magnetic resonance imaging (MRI) features of patients with glomus tumour of the knee, and compare the present findings with cases from the English literature. The orthopaedic oncology and pathology databases at The University of Chicago were reviewed for cases of glomus tumour and small subcutaneous anterior knee masses. For all glomus tumours, the site of the tumour and age and sex of the patient were recorded. For those tumours arising in the knee, the symptom profile and MRI characteristics were recorded. The English literature was reviewed for cases describing glomus tumours in the knee. Thirty-four patients with glomus tumour were recorded. Five glomus tumours occurred in the anterior knee, all in men aged ≥30 years, four of whom had a several-year history of pain prior to diagnosis. MRI showed small (<2 cm) nodular enhancing masses. Review of the English literature supports the anterior knee as a common location for lower-extremity glomus tumours, with a male predominance and several years of pain preceding diagnosis. Although rare, glomus tumours occur in the knee. Unlike the classic description of glomus tumours occurring in the fingers most typically in women <30 years of age, those that occur in the knee tend to do so in men >30 years, and many years of pain can precede diagnosis. The astute radiologist may be the first to suggest this diagnosis if a small, painful, enhancing, nodular subcutaneous mass is noted on knee MRI examinations.


Effects of the renin inhibitor A-64662 in monkeys and rats with varying baseline plasma renin activity.
The efficacy of the potent, primate selective renin inhibitor A-64662 was studied in monkeys and rats with varying baseline plasma renin activity (PRA) to elucidate the relationship between PRA and the hypotensive response induced by this compound. The effect of a single bolus of vehicle or A-64662 at 0.001, 0.01, 0.1, 1.0, and 10.0 mg/kg i.v. was compared in 30 normal and 30 salt-depleted, anesthetized monkeys (n = 5/dose). Baseline mean arterial pressure (MAP) was similar among all groups, but baseline PRA was elevated in salt-depleted monkeys. A-64662 induced a comparable dose-related fall in MAP, affecting the magnitude and duration of action, accompanied by inhibition of PRA, the duration of which was dose-related in both the normal and salt-depleted groups. However, the minimum effective doses required to reduce MAP by approximately 10% were 0.01 mg/kg for the salt-depleted monkeys and 0.1 mg/kg for the normal monkeys. In a second study, three consecutive boluses of vehicle or A-64662 at 0.1, 1.0, and 10.0 mg/kg were administered to anephric monkeys, human renin-infused anephric monkeys, and normal monkeys (n = 4/group). A dose of 0.1 mg/kg was ineffective, but the 1.0 mg/kg dose lowered MAP by 11 +/- 3% (mean +/- SE) in the anephric monkeys. The infusion of renin into anephric monkeys restored the efficacy of A-64662 at the 0.1 and 1.0 mg/kg doses to responses comparable to those of the normal monkeys. A-64662 at 10.0 mg/kg caused a similar fall in MAP of 50 to 60% in anephric, renin-infused anephric, and normal monkeys in the absence of detectable PRA.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro and in vivo activities of posaconazole against Coccidioides immitis.
Posaconazole (SCH 56592) was tested against 25 strains of Coccidioides immitis to determine their in vitro susceptibilities. The geometric mean 48-h MIC of posaconazole (POSA) was 0.5 microg/ml, the MIC range was 0.25 to 1 microg/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC50) and the MIC90 were 0.5 and 1 microg/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 microg/ml, the MIC range was 0.125 to 0.5 microg/ml, and the MIC50 and MIC90 were both 0.25 microg/ml. Two strains of C. immitis were selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates. POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day was compared with ITRA administered at 10 and 30 mg/kg three times a day. The spleens and livers of mice that died or survived to day 50 were removed to measure the fungal burdens. Mice had >or=90% survival when they were treated with >or=0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and livers from mice treated with 10 mg of POSA per kg showed >or=70% sterilization. No sterilization of whole spleens and livers from mice treated with ITRA was seen. POSA displayed potent in vivo activity against the two strains of C. immitis tested.


Management of Post-Traumatic Subglottic Stenosis and Pharyngosubglottic Fistula.
Injury to the aerodigestive tract following external laryngeal trauma is rare. Reports of acquired laryngopharyngeal fistula are very few. We report a very rare presentation of penetrating neck trauma presenting with fracture of the cricoid cartilage, subglottic stenosis and pharyngosubglottic fistula. The term 'pharyngosubglottic fistula' is used here for the first time to describe a communication tract between hypopharynx and subglottis. The successful surgical management of this case is discussed.


Lymphomatous meningitis presenting as atypical cluster headache.
We report a woman who developed atypical cluster headache as the first manifestation of trigeminal dysfunction from leptomeningeal lymphoma. Progression to a complete trigeminal neuropathy led to resolution of her pain. The role of the trigeminal nerve in the expression of the signs and symptoms of cluster headache is discussed.


Restoration of CPEB4 prevents muscle stem cell senescence during aging.
Age-associated impairments in adult stem cell functions correlate with a decline in somatic tissue regeneration capacity. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we provide a proteomic analysis of physiologically aged murine muscle stem cells (MuSCs), illustrating a pre-senescent proteomic signature. During aging, the mitochondrial proteome and activity are impaired in MuSCs. In addition, the inhibition of mitochondrial function results in cellular senescence. We identified an RNA-binding protein, CPEB4, downregulated in various aged tissues, which is required for MuSC functions. CPEB4 regulates the mitochondrial proteome and activity through mitochondrial translational control. MuSCs devoid of CPEB4 induced cellular senescence. Importantly, restoring CPEB4 expression rescued impaired mitochondrial metabolism, improved geriatric MuSC functions, and prevented cellular senescence in various human cell lines. Our findings provide the basis for the possibility that CPEB4 regulates mitochondrial metabolism to govern cellular senescence, with an implication of therapeutic intervention for age-related senescence.


Comparison of sexual function of people with colorectal cancer with and without colostomy bag in Iran: a comparative cross-sectional study.
The aim of this study was to investigate and compare sexual function in individuals with colorectal cancer, with and without a colostomy bag. A quantitative, descriptive-comparative design was employed, and a cluster random sampling method was used to recruit 252 patients with colorectal cancer. Data collection tools included a participants characteristics form, the International Index of Erectile Function (IIEF) for men, and the Female Sexual Function Index (FSFI) for women. The mean IIEF total score for men with a colostomy was 26.17 ± 15.30, and for men without a colostomy, it was 29.05 ± 17.14. The mean FSFI total score for women with a colostomy was 6.40 ± 7.21, and for women without a colostomy, it was 9.10 ± 14.67. There was no statistically difference in IIEF scores between men with and without colostomy bags (p > 0.05). However, women with colostomy bags had significantly lower FSFI scores compared to women without colostomy bags (p < 0.05). Addressing sexual concerns in individuals with colorectal cancer is crucial for enhancing their sexual well-being and overall quality of life. Comprehensive support, timely interventions, and targeted services are essential to help patients navigate the challenges and improve their overall well-being.


Summation of excitation with a single conditioning stimulus in the canine heart.
A subthreshold stimulus was reported to become effective in producing a propagated ventricular response when preceded by another subthreshold stimulus or stimuli, a phenomenon that is known as summation of excitation but has not been studied systematically. Effect on summation of current intensity and coupling interval of a conditioning stimulus (Sc, protocol #1) and that of stimulation site of Sc (protocol #2) were determined in anesthetized, open-chest dogs. Effective refractory period (ERP) was determined with an extrastimulus (S2) at a ventricular pacing cycle length (S1S1) of 500 msec. Pulse width of S1, S2 and Sc was 2 msec. For pacing protocol #1 (12 dogs), current intensity of S1 and S2 was equal (twice diastolic threshold, 2, 5, or 15 mA), and that of Sc was equal to or lower than that of S1. S1S2 interval was fixed 1 msec shorter than ERP, and Sc was delivered 5 msec prior to S2. The S1Sc interval was shortened in 2 msec steps. Summation was present if Sc plus S2 evoked a propagated response. Prevalence of summation increased along with an increase in current intensity of Sc (P less than 0.01). For pacing protocol #2 (7 dogs), current intensity of S1, S2 and Sc was equal (twice diastolic threshold, 5 or 10 mA). As the distance between site of Sc and that of S2 increased, prevalence of summation decreased (P less than 0.01). Summation did not occur when Sc was delivered at a site only 5 mm away from the site of S2. In conclusion, summation of excitation with a single conditioning stimulus was both time and strength dependent, and limited in development spatially.


Molecular mechanism of ion channel protein TMEM16A regulated by natural product of narirutin for lung cancer adjuvant treatment.
Cancer chemotherapy drugs are widely criticized for their serious side effects and low cure rate. Therefore, adjuvant therapy as a combination with chemotherapy administration is being accepted by many patients. However, unclear drug targets and mechanisms limit the application of adjuvant treatment. In this study, we confirmed TMEM16A is a key drug target for lung adenocarcinoma, and narirutin is an effective anti-lung adenocarcinoma natural product. Virtual screening and fluorescence experiments confirmed that narirutin inhibits the molecular target TMEM16A, which is specific high-expression in lung adenocarcinoma. Molecular dynamics simulations and electrophysiological experiments revealed the precise molecular mechanism of narirutin regulating TMEM16A. The anticancer effect of narirutin and its synergistic effect on cisplatin were explored by cell proliferation, migration, and apoptosis assays. The signaling pathways regulated by narirutin were analyzed by western blot. Tumor xenograft mice experiments demonstrated the synergistic anticancer effect of narirutin and cisplatin, and the side effects of high concentrations of cisplatin were almost eliminated. Pharmacokinetic experiments showed the biological safety of narirutin is satisfactory in vivo. Based on the significant anticancer effect and high biosafety, naringin has great potential as a functional food in the adjuvant treatment of lung cancer.


Nursing students' perceptions toward the nursing profession from clinical practicum in a baccalaureate nursing program-a qualitative study.
The purpose of this study was to explore senior nursing students' perceptions toward the nursing profession and their experiences in clinical practicum in Taiwan. This study used semistructured interview guides and unstructured face-to-face dialogue with the participants based on a qualitative method. A purposive sample with a snowball method from a baccalaureate nursing program in Southern Taiwan was used to recruit participants. A total of 30 senior nursing students participated in this study. Data were collected from February to May 2011. The interviews were transcribed verbatim, and data were analyzed based on the phenomenological approach of qualitative methodology. Data were categorized into three major themes: in-depth recognition of nursing, recognition of the meaning and value of life, and decision conflicts for being a nurse. The findings of the study not only help nursing educators further understand the educational effects of clinical practicum, but also provide information for managers of medical organizations to recruit and train newly graduated nurses.


Studies of resistance to chloroquine, quinine, amodiaquine and mefloquine among Philippine strains of Plasmodium falciparum.
One hundred cases of slide-confirmed Plasmodium falciparum malaria admitted to the San Lazaro Hospital, Manila, Philippines were screened for in vitro resistance to chloroquine, quinine, amodiaquine and mefloquine using the microtechnique. 59 of the 100 primary parasite isolates produced schizonts, whereas the remaining 41 isolates did not. 51 of the 59 isolates tested were resistant in vitro to chloroquine and eight were sensitive. In contrast, three of the primary isolates were resistant to quinine, three showed resistance to amodiaquine and four were mefloquine-resistant. 43 of the strains judged chloroquine-resistant in vitro were fully in vitro sensitive to amodiaquine, quinine and mefloquine. One chloroquine-resistant isolate was also resistant to quinine alone. Three isolates that were resistant to chloroquine were also resistant to amodiaquine. An additional three were cross-resistant to chloroquine and mefloquine. A single isolate was found to be resistant to chloroquine, quinine and mefloquine and another was cross-resistant to chloroquine, quinine and amodiaquine. All strains demonstrating in vitro resistance to amodiaquine, quinine or mefloquine also showed in vitro resistance to chloroquine. The parasites in 22 patients showed in vivo resistance to chloroquine therapy. 86% were of the R1 type, 9% were R2 and 5% R3. All 22 patients demonstrating in vivo resistance to chloroquine showed in vitro resistance.


Isolation, structure and reactivity of a scandium boryl oxycarbene complex.
The reaction of a half-sandwich scandium boryl complex 1 with CO (1 atm) afforded a novel boryl oxycarbene complex 2. The structure of 2 was characterized by 1H, 13C and 11B NMR, X-ray diffraction, and DFT analysis. Further reaction of 2 with CO (1 atm) yielded a phenylamido- and boryl-substituted enediolate complex 3 through C-C bond formation between CO and the carbene unit in 2 and cleavage and rearrangement of the Si-N bond in the silylene-linked Cp-amido ligand. Upon heating, insertion of the carbene atom into a methine C-H bond in the boryl ligand of 2 took place to give an alkoxide complex 4. The reactions of 2 with pyridine and 2-methylpyridine led to insertion of the carbene atom into an ortho-C-H bond of pyridine and into a methyl C-H bond of 2-methylpyridine, respectively. The reaction of 2 with ethylene yielded a borylcyclopropyloxy complex 7 through cycloaddition of the carbene atom to ethylene.


Gold-thickness-dependent Schottky barrier height for charge transfer in metal-assisted chemical etching of silicon.
Large-area, vertically aligned silicon nanowires with a uniform diameter along the height direction were fabricated by combining in situ-formed anodic aluminum oxide template and metal-assisted chemical etching. The etching rate of the Si catalyzed using a thick Au mesh is much faster than that catalyzed using a thin one, which is suggested to be induced by the charge transport process. The thick Au mesh in contact with the Si produces a low Au/Si Schottky barrier height, facilitating the injection of electronic holes from the Au to the Si, thus resulting in a high etching rate.


The use of herbs and complementary and alternative medicine in pediatric preoperative patients.
To determine the use of herbs and complementary and alternative medicine among a pediatric preoperative population. Prospective, consecutive clinical study and survey questionnaire. Children's Hospital pediatric preoperative clinic. A total of 1,100 surveys were distributed to pediatric patients under the age of 18 years during their preoperative visit over an 8-month period. The survey consisted of a questionnaire about the use of herbs and complementary and alternative therapies within 1 year before the anticipated surgery. The patient or legal guardian was asked whether the patient had tried any of the complementary and alternative medical therapies within 1 year before the scheduled surgical procedure. Of 1,021 completed surveys received, 29.5% of these patients indicated they had tried one or more complementary and alternative therapies in the past year before the surgery, and 12.8% of the pediatric patients used herbal remedies before the surgery. Herbs and complementary and alternative medical therapies are frequently used in pediatric populations. Anesthesiologists need to be aware the usage of various herbal supplements in pediatric patients. It is important then to determine the potential of drug and anesthetic interactions in the perioperative period.


Substitution saturation and nuclear paralogs of commonly employed phylogenetic markers in the Caryophyllidea, an unusual group of non-segmented tapeworms (Platyhelminthes).
Caryophyllidean cestodes (Platyhelminthes) represent an unusual group of tapeworms lacking serially repeated body parts that potentially diverged from the common ancestor of the Eucestoda prior to the evolution of segmentation. Here we evaluate the utility of two nuclear and two mitochondrial molecular markers (ssrDNA and lsrDNA, nad3 and cox1) for use in circumscribing generic boundaries and estimating interrelationships in the group. We show that these commonly employed markers do not contain sufficient signal to infer well-supported phylogenetic estimates due to substitution saturation. Moreover, we detected multiple trnK+nad3+trnS+trnW+cox1 haplotypes within individuals, indicating a history of gene exchange between the mitochondrial and nuclear genomes. The presence of such nuclear paralogs (i.e. numts), to our knowledge described here in cestodes for the first time, together with the results of phylogenetic, saturation and split-decomposition analyses all suggest that finding informative markers for estimating caryophyllidean evolution is unusually problematic in comparison to other major lineages of tapeworms.


Oxygen boundary crossing probabilities.
The probability that an oxygen particle will reach a time dependent boundary is required in oxygen transport studies involving solution methods based on probability considerations. A Volterra integral equation is presented, the solution of which gives directly the boundary crossing probability density function. The boundary crossing probability is the probability that the oxygen particle will reach a boundary within a specified time interval. When the motion of the oxygen particle may be described as strongly Markovian, then the Volterra integral equation can be rewritten as a generalized Abel equation, the solution of which has been widely studied.


Expanding the spectrum of congenital anomalies of the diencephalic-mesencephalic junction.
We aimed to describe the clinico-radiological findings of patients with disorders of diencephalic-mesencephalic junction (DMJ) formation and midbrain anteroposterior patterning. We reviewed the DMJ anatomy of 445 patients with brain malformations. Associated supra/infratentorial abnormalities and clinical findings were noted. Craniocaudal and anteroposterior diameters of midbrain, pons, medulla, vermis, and transverse cerebellar diameter were compared with age-matched controls. Post hoc tests were corrected according to Bonferroni (p(B)). Two patterns of DMJ anomaly were identified in 12 patients (7 females, mean age 41 months). Type A was characterized by hypothalamic-mesencephalic fusion on axial plane, with possible midbrain ventral cleft (7 patients). Anteroposterior (p(B) = .006) and craniocaudal (p(B) = .027) diameters of the pons, craniocaudal diameter of the vermis (p(B) = .015), and transverse cerebellar diameter (p(B) = .011) were smaller than the controls. Corticospinal tract, basal ganglia, and commissural anomalies were also associated. Clinical findings included spastic-dystonic tetraparesis, hypothalamic dysfunction, epilepsy, and severe developmental delay. Type B was characterized by incomplete thalamic-mesencephalic cleavage on sagittal plane, with parenchymal bands connecting the interthalamic adhesion with the midbrain (five patients). Anteroposterior diameters of midbrain (p(B) = .002), pons (p(B) = .0004), and medulla (p(B) = .002) as well as the vermian anteroposterior (p(B) = .040) and craniocaudal diameters (p(B) = .014) were smaller than the controls. These patients were less neurologically impaired, most presenting mild developmental delay. The spectrum of DMJ patterning defects is wide and may be associated with several brain malformations. Infratentorial brain structures should be carefully evaluated to better define the type of associated midbrain-hindbrain anomalies.


Immunology and immunotherapy in gastric cancer.
Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. As the diagnosis of early gastric cancer is difficult, most patients are at a late stage of cancer progression when diagnosed. The current therapeutic approaches based on surgical or endoscopic resection and chemotherapy indeed improve patients' outcomes. Immunotherapy based on immune checkpoint inhibitors has opened a new era for cancer treatment, and the immune system of the host is reshaped to combat tumor cells and the strategy differs according to the patient's immune system. Thus, an in-depth understanding of the roles of various immune cells in the progression of gastric cancer is beneficial to application for immunotherapy and the discovery of new therapeutic targets. This review describes the functions of different immune cells in gastric cancer development, mainly focusing on T cells, B cells, macrophages, natural killer cells, dendritic cells, neutrophils as well as chemokines or cytokines secreted by tumor cells. And this review also discusses the latest advances in immune-related therapeutic approaches such as immune checkpoint inhibitors, CAR-T or vaccine, to reveal potential and promising strategies for gastric cancer treatment.


Contrast reaction training in US radiology residencies: a COARDRI study.
To perform a survey-based assessment of current contrast reaction training in US diagnostic radiology residency programs. An electronic survey was distributed to radiology residency program directors from 9/2015-11/2015. 25.7% of programs responded. 95.7% of those who responded provide contrast reaction management training. 89.4% provide didactic lectures (occurring yearly in 71.4%). 37.8% provide hands-on simulation training (occurring yearly in 82.3%; attended by both faculty and trainees in 52.9%). Wide variability in contrast reaction education in US diagnostic radiology residency programs reveals an opportunity to develop and implement a national curriculum.


The population-specific distribution and frequencies of genomic variants in the SLC3A1 and SLC7A9 genes and their application in molecular genetic testing of cystinuria.
Cystinuria is a common inherited aminoaciduria resulting in nephrolithiasis. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. Considering the population-specific distribution of genetic variants in the SLC3A1 gene, we focused our study on mutations in SLC3A1 and SLC7A9 described more than once in the literature. We evaluated the usefulness of this restricted analysis as a diagnostic approach. Furthermore, the data obtained were used to estimate the frequency of heterozygote carriers of SLC3A1 mutations in the general European population. A total of 22 unclassified cystinuric patients were screened for genetic variants in four exons of both SLC3A1 and SLC7A9 in which the most common mutations have been identified. For screening, we used single strand conformation polymorphism analysis (SSCP), restriction assays, real-time PCR and direct sequencing. In total, we identified mutations in 17 of our 22 patients, including a new mutation (R365Q) as well as a novel polymorphism (c.1035G/A) within the SLC3A1 gene. An ethnic influence on the distribution of mutations was confirmed: T216M in SLC3A1 is the major mutation in south-eastern Europe, whereas M467T in SLC3A1 is mainly found in western Europe. A complex duplication in SLC3A1 is restricted to German patients. Generally, we could show that a stepwise analysis directed to the most common mutations in the two cystinuria genes is sufficient to detect variants in more than 75% of patients of European origin. The test consists of nine different PCR-based approaches and therefore represents a low-cost, reliable and timesaving diagnostic tool.


T-cell subsets regulating anti-acetylcholine-receptor-antibody formation in myasthenia gravis and characterization of suppressor T-cell factors involved.
The in vitro generation of anti-acetylcholine-receptor (AChR)-antibody-forming cells from B cells of myasthenia gravis (MG) patients occurred only in the presence of OKT4+ cells. Anti-AChR-antibody formation by lymphocytes from MG patients was suppressed by normal T cells, and the requirement of both OKT4+ and OKT8+ cells was suggested for this suppression. Culture supernatant from normal T cells stimulated with excess doses of AChR antigen, but not T cells from patients, suppressed anti-AChR-antibody formation by lymphocytes from patients. The fraction of the culture supernatant with molecular weight of 45,000 to 67,000 seemed to contain an AChR-antigen-specific and antigen-binding suppressor factor with some allogeneic barrier, while the fraction with a molecular weight of 10,000 to 28,000 contained the antigen-nonspecific factor.


Copper interference in the determination of iron in serum using ferrozine.
Random samples of sera were analysed for copper and iron. Based on the data presented in this paper and substantiated by other workers, the ferrozine method for the determination of serum iron is the most sensitive method currently available, provided the interference due to copper is effectively eliminated.


Neuropsychiatric aspects of concussion: acute and chronic sequelae.
Concussion - also known as mild traumatic brain injury - is a transient disturbance of neurological function resulting from traumatic forces imparted to the brain that often produce cognitive, behavioral and systemic symptoms. In this review of the literature, we discuss the pathophysiology of both acute and chronic neuropsychiatric sequelae of concussions, followed by a brief overview of evaluation and management of these sequelae.


Does L to D-amino acid substitution trigger helix→sheet conformations in collagen like peptides adsorbed to surfaces?
The present work reports on the structural order, self assembling behaviour and the role in adsorption to hydrophilic or hydrophobic solid surfaces of modified sequence from the triple helical peptide model of the collagenase cleavage site in type I collagen (Uniprot accession number P02452 residues from 935 to 970) using (D)Ala and (D)Ile substitutions as given in the models below: Model-1: GSOGADGPAGAOGTOGPQGIAGQRGVV GLOGQRGER. Model-2: GSOGADGP(D)AGAOGTOGPQGIAGQRGVVGLOGQRGER. Model-3: GSOGADGPAGAOGTOGPQG(D)IAGQRGVVGLOGQRGER. Collagenase is an important enzyme that plays an important role in degrading collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism by which this degradation occurs is not completely understood. Our results show that adsorption of the peptides to the solid surfaces, specifically hydrophobic triggers a helix to beta transition with order increasing in peptide models 2 and 3. This restricts the collagenolytic behaviour of collagenase and may find application in design of peptides and peptidomimetics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.


Ring-Closing Metathesis with Vicinal Dibromoalkenes as Protected Alkynes: A Synthetic Approach to Macrocyclic Enynes.
A new strategy to access macrocyclic enynes was developed. To block undesired ene-yne cyclization pathways, alkynes were protected via bromination and the resultant acyclic vic-(E)-dibromotrienes participated in selective ene-ene ring closing metathesis reactions. Zinc-promoted deprotection of (E)-dibromodienes provided macrocyclic enynes in high yields.


The formation of mutagenic derivatives of benzo[a]pyrene by peroxidising fatty acids.
Benzo[a]pyrene (B[a]P) when incubated in the presence of peroxidising polyunsaturated fatty acids such as linoleic acid (C18:2), arachidonic acid (C20:4), eicosapentaenoic acid (C20:5) or docosahexaenoic acid (C22:6) was converted to oxidised products. Between 7% and 9% of the B[a]P was oxidised in one hour when incubated with arachidonic acid and docosahexaenoic acid. 1,6- 3,6- and 6,12-Quinone derivatives of B[a]P were identified by HPLC. The products of B[a]P oxidation were shown to be mutagenic when tested using Sister chromatid exchange (SCE) technique and the occurrence of SCEs in CHV79 cells was increased significantly. Lipid peroxides also induced SCEs in the absence of B[a]P and there was a positive correlation between the frequency of SCEs and the extent of lipid peroxidation. The results indicate that the oxidation of B[a]P mediated by the non-enzymic peroxidation of polyunsaturated fatty acids is likely to play a role in mutagenesis and, possibly, also in carcinogenesis.


Platelet aggregation in six families with Bartter's syndrome.
Bartter's syndrome has so far been considered to be an autosomal recessive inherited disease, because of the occurrence of the syndrome in siblings. Both sexes are equally involved. Until now no family has been described in which parents as well as children suffered from the disease. It has recently been found that 'obligatory carriers', i.e. parents of affected children, showed the same pattern of platelet aggregation inhibition as their affected children. We investigated eight patients as well as their parents and siblings, and found that all persons included in the study showed impaired thrombocyte aggregation, especially after low salt intake. We conclude that the restriction of dietary sodium facilitates the measurement of the platelet abnormality.


Effect of gold nanoparticles on glutathione and malondialdehyde levels in liver, lung and heart of rats.
We studied the effect of gold nanoparticles (NPs) on oxidative stress markers including reduced glutathione (GSH) and malondialdehyde (MDA) in different organs of rats. Adult male Wistar-Kyoto rats were randomly divided into 3 groups of 5 animals each. One group served as control and received vehicle only. The remaining two groups were treated with 50 μl of 10 nm sized gold NPs, daily for 3 and 7 days, respectively. The rats were sacrificed 24 h after the last injection of NPs. Administration of gold NPs did not cause any significant change in GSH levels in liver, lung and heart on day 3 or day 7. There was no significant effect of gold NPs on MDA levels in lung and heart whereas significant increases in MDA levels were found in the liver of rats treated with gold nanoparticles on both 3 and 7 days post-dosing (ANOVA F = 7.113, P = 0.010). In conclusion, the findings of this preliminary study suggest that gold NPs of 10 nm diameter produce significant lipid peroxidation in rat liver however lungs and heart do not show any oxidative stress. Further studies are warranted to examine the effects of a broader dose range of gold NPs on the levels of free radical indices in different organs of rats.


Lysosomal enzyme activities in sheep plasma and lymph.
The activities of acid phosphatase, beta-glucuronidase and N-acetyl-beta-glucosaminidase were measured in blood plasma, afferent and efferent popliteal lymph, intestinal lymph and in four different organs of the sheep. Acid phosphatase had an optimum activity at pH 4-5 while beta-glucuronidase and N-acetyl-beta-glucosaminidase had optimal activities at pH 5-0 and pH 4-5-5-0, respectively. Comparative studies showed that the sheep had very low activities of acid phosphatase and relatively low activities of N-acetyl-beta-glucosaminidase in the blood plasma compartment in relation to the activities of these enzymes in the plasma of the rabbit and the rat. The tissue activities of all three enzymes were relatively high when compared with those in the two non-ruminant species. It is considered that the low plasma activities of acid phosphatase in the sheep reflect a rapid turnover of this enzyme in the plasma compartment. The activities of the three enzymes in regional lymph indicated that acid phosphatase was being added to the capillary filtrate at a regional tissue level, whereas beta-glucuronidase and N-acetyl-beta-glucosaminidase in lymph were derived from filtration from the blood plasma compartment on a molecular weight basis. The high lymph: plasma ratios observed for acid phosphatase activity in intestinal lymph may indicate a function of this enzyme in lipid absorption in the sheep.


Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.
Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.


Adenosine receptor agonists attenuate the development of diazepam withdrawal-induced sensitization in mice.
In the present study, the effects of adenosine agonists on the development of sensitization to withdrawal signs precipitated after sporadic treatment with diazepam, in mice, were investigated. To obtain the sensitization, the animals were divided into groups: continuously and sporadically treated with diazepam (15.0 mg/kg, s.c.). The adenosine receptor agonists (CPA, CGS 21,680 and NECA) were administered in sporadically diazepam treated mice during two diazepam-free periods. Concomitant administration of pentetrazole (55.0 mg/kg, s.c.) with flumazenil (5.0 mg/kg, i.p.) after the last injection of diazepam or vehicle, induced the withdrawal signs, such as clonic seizures, tonic convulsion and death episodes. The major finding of our experiments is attenuation of withdrawal signs in sensitized mice, inducing by all adenosine agonists. Only higher dose of CPA produced significantly decreased the number of withdrawal incidents, while both used doses of CGS 21,680 and NECA produced more clear effects. These results support the hypothesis that adenosinergic system is involved in the mechanisms of sensitization to the benzodiazepine withdrawal signs, and adenosine A(2A) receptors play more important role in that process.


Development and application of biotechnologies in the metal mining industry.
Metal mining faces a number of significant economic and environmental challenges in the twenty-first century for which established and emerging biotechnologies may, at least in part, provide the answers. Bioprocessing of mineral ores and concentrates is already used in variously engineered formats to extract base (e.g., copper, cobalt, and nickel) and precious (gold and silver) metals in mines throughout the world, though it remains a niche technology. However, current projections of an increasing future need to use low-grade primary metal ores, to reprocess mine wastes, and to develop in situ leaching technologies to extract metals from deep-buried ore bodies, all of which are economically more amenable to bioprocessing than conventional approaches (e.g., pyrometallurgy), would suggest that biomining will become more extensively utilized in the future. Recent research has also shown that bioleaching could be used to process a far wider range of metal ores (e.g., oxidized ores) than has previously been the case. Biotechnologies are also being developed to control mine-related pollution, including securing mine wastes (rocks and tailings) by using "ecological engineering" approaches, and also to remediate and recover metals from waste waters, such as acid mine drainage. This article reviews the current status of biotechnologies within the mining sector and considers how these may be developed and applied in future years.


Asymmetric inferior oblique anterior transposition for incomitant asymmetric dissociated vertical deviation.
Inferior oblique anterior transposition (IOAT) is indicated in patients with incomitant dissociated vertical deviation (DVD) larger in adduction. In general, bilateral surgery is recommended in patients with DVD unless there is deep monocular amblyopia. The purpose of this study is to evaluate the results of asymmetric IOAT in patients with asymmetric incomitant DVD larger in adduction. Retrospective chart review of the records of all patients with incomitant asymmetric DVD associated with inferior oblique (IO) overaction who underwent asymmetric IO weakening procedure. In all patients, the eye with more DVD in adduction underwent IOAT to the temporal corner of the insertion of the inferior rectus (IR) muscle, and the eye with less DVD underwent IOAT to a position 3-4 mm posterior to the insertion of the IR. No other muscles were operated simultaneously. No patient had previous surgery on any cyclovertical extracular muscle. Fourteen patients were included. Mean age at surgery was 10.3 ± 8.8 years (range 4-33). Primary position DVD preoperatively was 18 ± 2 PD in the eye with the larger DVD compared to 1.1 ± 1.0 PD postoperatively (p < 0.0001). DVD asymmetry between the lateral gaze with the largest DVD and the lateral gaze with the smallest DVD was 9.8 ± 3.1 PD (range 5-14 PD) preoperatively vs 1.1 ± 1.0 PD (range 0-2 PD), (p < 0.0001). Ten patients had preoperative V-pattern >10 PD (24.7 ± 8.7 PD, range 12-50 PD) preoperatively vs no patients postoperatively (mean V-pattern 4.4 ± 2.0 PD), (p < 0.0001). Postoperative follow up was 1.6 ± 0.7 years (range 1-3 years). In patients with asymmetric incomitant DVD, asymmetric IOAT improves lateral incomitance without increasing the risk of antielevation, limitation in upgaze rotation, or hypertropia, or worsening the DVD in the eye with less deviation preoperatively.


Genome mapping statistics and bioinformatics.
The unprecedented availability of genome sequences, coupled with user-friendly, web-enabled search and analysis tools allows practitioners to locate interesting genome features or sequence tracts with relative ease. Although many public model organism- and genome-mapping resources offer pre-mapped genome browsing, biologists also still need to perform de novo mapping analyses. Correct interpretation of the results in genome annotation databases or the results of one's individual analyses requires at least a conceptual understanding of the statistics and mechanics of genome searches, the expected results from statistical considerations, as well as the algorithms used by different search tools. This chapter introduces the basic statistical results that underlie mapping of nucleotide sequences to genomes and briefly surveys the common programs and algorithms that are used to perform genome mapping, all available via public hosted web sites. Selection of the appropriate sequence search and mapping tool will often demand tradeoffs in sensitivity and specificity relating to the statistics of the search.


Multiplexed cytokine sandwich immunoassays: clinical applications.
Flow cytometric, microsphere-based immunoassays have been developed for the simultaneous detection of soluble analytes in a variety of sample types. The ability to discriminate between individual microspheres on the basis of size, fluorescent intensity, and/or wavelength has allowed the simultaneous analysis of multiple analytes from the same sample. Cytokines are particularly good candidates for multiplexed analysis. Through intricate networks and complex feedback mechanisms, cytokines modulate each other as well as a multitude of cellular events and play an important role in health and disease. The simultaneous measurement of multiple cytokines in a single biological sample has tremendous potential value to further our understanding of the role of these immunomodulators in health and disease. This chapter describes a multiplexed, microsphere-based flow cytometric method to quantitate and compare multiple cytokines simultaneously in human serum. Serum poses a challenge for multiplexed cytokine analysis owing to the presence of numerous proteins and other potentially interfering factors. Assessment of the "real world" performance of the multiplexed, microsphere-based flow cytometry assay with clinically relevant sample types is critical for determining the proper application of these methods in deciphering the role of cytokines in disease pathogenesis and for evaluating drug action.


A mathematical model of the process of ligament repair: effect of cold therapy and mechanical stress.
This article proposes a mathematical model that predicts the wound healing process of the ligament after a sprain, grade II. The model describes the swelling, expression of the platelet-derived growth factor (PDGF), formation and migration of fibroblasts into the injury area and the expression of collagen fibers. Additionally, the model can predict the effect of ice treatment in reducing inflammation and the action of mechanical stress in the process of remodeling of collagen fibers. The results obtained from computer simulation show a high concordance with the clinical data previously reported by other authors.


The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients.
Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84-1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.


Comparative sensitivity of field and laboratory populations of Hyalella azteca to the pyrethroid insecticides bifenthrin and cypermethrin.
Hyalella azteca are epibenthic invertebrates that are widely used for toxicity studies. They are reported to be more sensitive to pyrethroid insecticides than most other test species, which has prompted considerable use of this species in toxicity testing of ambient surface waters where the presence of pyrethroids is suspected. However, resident H. azteca have been found in some ambient water bodies reported to contain surface water and/or sediment pyrethroid concentrations that are toxic to laboratory reared H. azteca. This observation suggests differences in the sensitivities of laboratory reared and field populations of H. azteca to pyrethroids. The goal of the present study was to determine the sensitivities of laboratory reared and field populations of H. azteca to the pyrethroids bifenthrin and cypermethrin. Specimens of H. azteca were collected from resident populations at field sites that are subject to varied land-use activities as well as from laboratory populations. These organisms were exposed to bifenthrin- or cypermethrin-spiked water in 96-h water-only toxicity tests. The resulting data demonstrated that: 1) field-collected populations in urban and agricultural settings can be >2 orders of magnitude less sensitive to the pyrethroids than laboratory reared organisms; 2) field-collected organisms varied in their sensitivity (possibly based on land-use activities), with organisms collected from undeveloped sites exhibiting sensitivities similar to laboratory reared organisms; and 3) the sensitivity of field-collected "tolerant" organisms increased in subsequent generations reared under laboratory conditions. Potential mechanisms for these differences are discussed.


[Multiparametric MRI of the prostate].
Multiparametric magnetic resonance imaging (mpMRI) is an integral component of prostate cancer diagnostics. According to the S3 guidelines on prostate cancer, mpMRI should be used for the primary diagnostics of prostate cancer as well as in active surveillance (AS). Basically, mpMRI consists of high-resolution T2-weighted (T2w) sequences, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences, which in turn are the basis for structured reporting according to the prostate imaging reporting and data system (PI-RADS) classification.


A methodology to evaluate differential costs of full field digital as compared to conventional screen film mammography in a clinical setting.
The use of full field digital mammography (FFDM) in alternative to conventional screen film mammography (SFM) in the current practice is delayed by the high costs of FFDM. The present study, performed at the Centro per lo Studio e la Prevenzione Oncologica of Florence, using both FFDM and SFM, was aimed at estimating the impact of introducing the new FFDM technique on overall mammography costs. We estimated the differential costs of both methods, based on real expenditures, as provided by the administrative department, and on radiologists, radiographers and other staff's working time. Two different workload scenarios (5000 and 10,000 tests/year per mammography equipment) were considered. Common costs of both techniques were censored for study purpose. Beside a higher cost due to purchase and hire/leasing costs of equipment, FFDM implies a greater workload for radiologists (reading time almost doubled). SFM implies a greater workload for the administrative staff to run the archive and for loading/unloading films of the roller viewer, whereas no different workload has been observed for radiographers. Overall FFDM costs 24.22-26.46 for examination more than SFM for the 5000 tests scenario and 9.91-12.15 more for the 10,000 tests scenario. Although present study estimates cannot easily be generalised to any local setting, the model for cost calculation is easy to be exported to another scenario by applying different local parameters. The advantages made available by FFDM (computerised data recording, tele-transmission, tele-reporting, tele-consulting, automatic display on monitor of previous exams and use of CAD) may justify the higher cost, but a limited reduction in purchase and assistance costs could easily allow a turnover, with FFDM being more convenient than SFM even on the cost side.


A method for structuring complex clinical knowledge and its representational formalisms to support composite knowledge interoperability in healthcare.
The use and interoperability of clinical knowledge starts with the quality of the formalism utilized to express medical expertise. However, a crucial challenge is that existing formalisms are often suboptimal, lacking the fidelity to represent complex knowledge thoroughly and concisely. Often this leads to difficulties when seeking to unambiguously capture, share, and implement the knowledge for care improvement in clinical information systems used by providers and patients. To provide a systematic method to address some of the complexities of knowledge composition and interoperability related to standards-based representational formalisms of medical knowledge. Several cross-industry (Healthcare, Linguistics, System Engineering, Standards Development, and Knowledge Engineering) frameworks were synthesized into a proposed reference knowledge framework. The framework utilizes IEEE 42010, the MetaObject Facility, the Semantic Triangle, an Ontology Framework, and the Domain and Comprehensibility Appropriateness criteria. The steps taken were: 1) identify foundational cross-industry frameworks, 2) select architecture description method, 3) define life cycle viewpoints, 4) define representation and knowledge viewpoints, 5) define relationships between neighboring viewpoints, and 6) establish characteristic definitions of the relationships between components. System engineering principles applied included separation of concerns, cohesion, and loose coupling. A "Multilayer Metamodel for Representation and Knowledge" (M*R/K) reference framework was defined. It provides a standard vocabulary for organizing and articulating medical knowledge curation perspectives, concepts, and relationships across the artifacts created during the life cycle of language creation, authoring medical knowledge, and knowledge implementation in clinical information systems such as electronic health records (EHR). M*R/K provides a systematic means to address some of the complexities of knowledge composition and interoperability related to medical knowledge representations used in diverse standards. The framework may be used to guide the development, assessment, and coordinated use of knowledge representation formalisms. M*R/K could promote the alignment and aggregated use of distinct domain-specific languages in composite knowledge artifacts such as clinical practice guidelines (CPGs).


[Cell cultures of the epithelium of the bile ducts: a possible model for the study of atresia of the bile ducts].
The pathogenic mechanism of biliary atresia is still unknown. Assuming that primary lesion is localized at the epithelial layer of the biliary ducts, authors describe a technique of culturing biliary duct cells in monolayer fashion. Light and electron microscopy demonstrate the epithelial origin of the cultured cells. These cells can be used to test some of the pathogenic theories in vitro hitherto proposed.


Bisphosphonate related osteonecrosis of the jaws: clinico-pathological investigation and histomorphometric analysis.
Clinico-pathological evaluation of bisphosphonate (BP)-related osteonecrosis of jaws, comparison between oral (PO) and intravenous (IV) BPs and histomorphometric analysis of associated actinomyces. Retrospective clinical and histomorphometric analysis. Data on background, clinical, treatment and follow-up were analyzed. Actinomyces colonies were identified by typical filamentous colony morphology, Gram, and PAS stains. Colony density and relative colony surface area were measured. Fifty-two patients were included, 37 (71.2%) IV, 15 (28.8%) PO BPs. with a mean duration of 2.33 and, 4.33 years respectively. One hundred percent of cases exhibited actinomyces colonization. The relative colony surface area was significantly higher in PO treatment (P = .024), with no differences in density, healing time or antibiotic treatment periods. High frequency of diabetes mellitus (60% PO cases) and corticosteroid treatment (25% of cases) were recorded. Infection with actinomyces is a common denominator in BP-related osteonecrosis of the jaws (BRONJ), regardless of administration route. Diabetes and corticosteroid treatment seem to be important contributing factors for BRONJ.


Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.


The Role of Vitamin D in Health and Disease: A Narrative Review on the Mechanisms Linking Vitamin D with Disease and the Effects of Supplementation.
Vitamin D insufficiency or deficiency (VDD) is a very prevalent condition in the general population. Vitamin D is necessary for optimal bone mineralization, but apart from the bone effects, preclinical and observational studies have suggested that vitamin D may have pleiotropic actions, whereas VDD has been linked to several diseases and higher all-cause mortality. Thus, supplementing vitamin D has been considered a safe and inexpensive approach to generate better health outcomes-and especially so in frail populations. Whereas it is generally accepted that prescribing of vitamin D in VDD subjects has demonstrable health benefits, most randomized clinical trials, although with design constraints, assessing the effects of vitamin D supplementation on a variety of diseases have failed to demonstrate any positive effects of vitamin D supplementation. In this narrative review, we first describe mechanisms through which vitamin D may exert an important role in the pathophysiology of the discussed disorder, and then provide studies that have addressed the impact of VDD and of vitamin D supplementation on each disorder, focusing especially on randomized clinical trials and meta-analyses. Despite there already being vast literature on the pleiotropic actions of vitamin D, future research approaches that consider and circumvent the inherent difficulties in studying the effects of vitamin D supplementation on health outcomes are needed to assess the potential beneficial effects of vitamin D. The evaluation of the whole vitamin D endocrine system, rather than only of 25-hydroxyvitamin D levels before and after treatment, use of adequate and physiologic vitamin D dosing, grouping based on the achieved vitamin D levels rather than the amount of vitamin D supplementation subjects may receive, and sufficiently long follow-up are some of the aspects that need to be carefully considered in future studies.


CHIR-258: a potent inhibitor of FLT3 kinase in experimental tumor xenograft models of human acute myelogenous leukemia.
Fms-like tyrosine kinase 3 (FLT3) encodes a receptor tyrosine kinase (RTK) for which activating mutations have been identified in a proportion of acute myelogenous leukemia (AML) patients and associated with poor clinical prognosis. Given the relevance of FLT3 mutations in AML, we investigated the activity of CHIR-258, an orally active, multitargeted small molecule, with potent activity against FLT3 kinase and class III, IV, and V RTKs involved in endothelial and tumor cell proliferation in AML models. CHIR-258 was tested on two human leukemic cell lines in vitro and in vivo with differing FLT3 mutational status [MV4;11 cells express FLT3 internal tandem duplications (ITD) versus RS4;11 cells with wild-type (WT) FLT3]. Antiproliferative activity of CHIR-258 against MV4;11 was approximately 24-fold greater compared with RS4;11, indicating more potent inhibition against cells with constitutively activated FLT3 ITD. Dose-dependent down modulation of receptor phosphorylation and downstream signaling [signal transducer and activator of transcription 5 (STAT5) and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase] in MV4;11 cells with CHIR-258 confirmed the molecular mechanism of action. Target modulation of phospho-FLT3, phospho-STAT5, and phospho-ERK in MV4;11 tumors was achieved at biologically active doses of CHIR-258. Tumor regressions and eradication of AML cells from the bone marrow were shown in s.c. and bone marrow engraftment leukemic xenograft models. Tumor responses were characterized by decreased cellular proliferation and positive immunohistochemical staining for active caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting cell death was mediated in part via apoptosis. Our data indicate that CHIR-258 may be an effective therapy in FLT3-associated AML and warrants clinical trials.


Esophagoscopy for removal of foreign bodies in the pediatric population.
A retrospective chart review of children who had rigid esophagoscopy for potential foreign body ingestion from 1998 to 2001 was conducted at Children's Hospital of Michigan Detroit. All pediatric patients less than 11 years of age who presented with suspected foreign body ingestion in a hospital setting over a 4-year period were retrospectively studied. Patient characteristics noted included age, sex and clinical presentation. Pre-operative radiographic findings, esophagoscopy findings, clinical presentations and types of foreign bodies were recorded. A history compatible with foreign body ingestion dictates diagnostic endoscopy with or without radiographic confirmation, and an acceptable rate of performing esophagoscopy without finding a foreign body was found to be 6.2%.


Cholinergic responses in cloned human TE671/RD tumour cells.
The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca2+ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca2+ ([Ca2+]i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca2+]i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca2+ channels. The stimulation of the nAChR induced transient whole-cell currents (IACh). Little or no current was detected in isotonic extracellular Ca2+, with Cs+ in the patch pipette. Cell pretreatment with muscarine reduced IACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/RD cells, muscarinic stimulation increases [Ca2+]i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides.


3-D numerical evaluation of density effects on tracer tests.
In this paper we present numerical simulations carried out to assess the importance of density-dependent flow on tracer plume development. The scenario considered in the study is characterized by a short-term tracer injection phase into a fully penetrating well and a natural hydraulic gradient. The scenario is thought to be typical for tracer tests conducted in the field. Using a reference case as a starting point, different model parameters were changed in order to determine their importance to density effects. The study is based on a three-dimensional model domain. Results were interpreted using concentration contours and a first moment analysis. Tracer injections of 0.036 kg per meter of saturated aquifer thickness do not cause significant density effects assuming hydraulic gradients of at least 0.1%. Higher tracer input masses, as used for geoelectrical investigations, may lead to buoyancy-induced flow in the early phase of a tracer test which in turn impacts further plume development. This also holds true for shallow aquifers. Results of simulations with different tracer injection rates and durations imply that the tracer input scenario has a negligible effect on density flow. Employing model cases with different realizations of a log conductivity random field, it could be shown that small variations of hydraulic conductivity in the vicinity of the tracer injection well have a major control on the local tracer distribution but do not mask effects of buoyancy-induced flow.


Insulin versus glipizide treatment in patients with non-insulin-dependent diabetes mellitus. Effects on blood pressure and glucose tolerance.
Insulin resistance that exists in patients with essential hypertension and in those with non-insulin-dependent diabetes mellitus (NIDDM) may be the common denominator for the impaired glucose homeostasis and elevated blood pressure (BP) levels in patients with NIDDM. Therefore, treatment that improves insulin action may also improve BP levels. Consequently, a four-phase (glipizide v insulin) cross-over design study was conducted to determine a better effect of glipizide treatment on insulin sensitivity and the effect this has on BP in 19 NIDDM patients. Patients were subjected to 1 month of diet only (phase I) followed by 3 months of glipizide treatment (phase II), then an additional 1 month of diet only (phase III), and finally 3 months of insulin treatment (phase IV). At the end of phases I, II, and IV oral glucose tolerance tests (OGTT) were performed and plasma glucose, insulin, and C-peptide levels were analyzed. Fasting plasma glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides, glycated hemoglobin, fructosamine, and 2-h postprandial plasma glucose were also analyzed at each phase. Supine and sitting BP levels and body weights were determined biweekly during the study. With the exception of higher plasma insulin and C-peptide levels during the OGTT (area under the curve) in phase IV (insulin) v phase II (glipizide) (both P < .05), and higher fasting plasma insulin levels (P < .06), there were no consistently significant metabolic differences between phases IV and II.(ABSTRACT TRUNCATED AT 250 WORDS)


Convolutamydine A and synthetic analogues have antinociceptive properties in mice.
Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects.


Pelvic lymphocele after pediatric renal transplantation: a successful technique for prevention.
Pelvic lymph accumulation (lymphocele) is a recognized complication of renal transplantation. During a 12-year period 166 renal transplants were performed in 143 children at our institution. From 1973 to 1979, 5 lymphoceles were treated in 64 children. From 1979 until the present a technique of peritoneal fenestration has been performed in 69 children, in whom 1 lymphocele developed. Lymphoceles required surgical treatment in 5 of the remaining 10 cases that were not fenestrated. Our experience with peritoneal fenestration as a method of lymphocele prevention has been excellent, and we recommend it as a prophylactic addition to renal transplant surgery.


Evaluating Dengue Virus Pathogenesis in Mice and Humans by Histological and Immunohistochemistry Approaches.
The analysis of dengue virus (DENV) infected tissues in mice experimental model and in human biopsies/autopsies may support the pathogenesis studies. Through such models, it is possible to investigate possible histopathological changes caused by the infection and detections of different targets of interest, such as viral antigens, immune cells, and cytokines. In this chapter, we showed a brief review of how histological and immunohistochemistry approaches may improve the knowledge in this field.


Suppression of tumor growth and invasion in 9,10 dimethyl benz(a) anthracene induced mammary carcinoma by the plant bioflavonoid quercetin.
Administration of quercetin, a common polyphenolic component of many vascular and edible plants including vegetables, fruits and tea significantly reduced the tumor volume in rats induced for mammary carcinoma using dimethyl benz (a) anthracene (DMBA). Dose response was assessed, by treating the animals with different doses (15-45 mg/kgbw) of quercetin and 25 mg/kgbw was taken as effective dose. Quercetin was administered as an intra tumoral injection once a week for 4 weeks. Serum levels of carcino embryonic antigen (CEA), a potent marker for tumor growth and invasion was significantly decreased on quercetin treatment. Quercetin caused a significant decrease in the activities of acid phosphatase and Cathepsin D in serum of experimental animals. Activities of lysosomal enzymes- (beta-D galactosidase, beta-D glucuronidase, beta-D glucosidase and sialidase), in serum and tissue were significantly altered in DMBA animals compared to control animals. However, quercetin treatment caused no significant change in lysosomal enzyme activities in tissues, whereas the activities were significantly lowered in serum. Partial purification of tissue type plasminogen activator (t-PA) from the tumor and kidney showed increased activity in the DMBA induced animals. Serum urokinase, -like plasminogen activator (u-PA) was also increased in animals with tumor, indicating tumor invasion. Administration of quercetin caused a significant decrease of both t-PA and u-PA. In conclusion, the present study suggests the possible role of quercetin in primary and invasive mammary tumor treatment. The above observations in vivo warrant further studies, due to the easy availability, common occurrence and low toxicity of this dietary bioflavonoid.


Rescue extracorporeal circulation as bridge to recovery in fulminant cocaine-induced heart failure.
Cocaine is an increasing cause of admission in the emergency room. The widespread abuse of this drug during the last decade in the USA is now widely emerging in Europe. Because of its various cardio-vascular complications, cocaine is one of the most death-related drugs known at this time. The following report describes the dramatic case of a young man polydrug addict presenting at our institution with life-threatening acute heart failure that developed shortly after his very first cocaine intake. Because of the lack of response to intensive medical treatment, we decided to perform a percutaneous extracorporeal circulation membranous oxygenation (ECMO) that allowed survival and rapid left ventricular function recovery. This report highlights cocaine as a rising trigger of acute heart failure in young people and is, to the best of our knowledge, the first report that illustrates ECMO as an effective hemodynamic support in the course of fulminant cocaine-induced cardiomyopathy.


Association between IFNA genotype and the risk of sarcoidosis.
Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process ( IFNA17, IFNB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, ETA-1, and NRAMP1) in an association-based study of 102 Japanese patients with sarcoidosis, 114 with tuberculosis, and 110 control subjects. After correction for multiple testing, an IFNA17 polymorphism (551T-->G) was found to be associated with susceptibility to sarcoidosis (odds ratio 3.27 [95% CI: 1.44-7.46], P=0.004, P(c)=0.04), but not to tuberculosis. We observed no significant associations with the other polymorphisms of the Th1-related genes. We further typed another IFNA polymorphism ( IFNA10 60T-->A) and confirmed two major haplotypes of the IFNA gene, viz., allele 1: IFNA10 [60T]- IFNA17 [551T] and allele 2: IFNA10 [60A]- IFNA17 [551G], in the Japanese population. In healthy subjects, IFNA allele 2, which is over-represented in patients with sarcoidosis, was significantly associated with increased IFN-alpha and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN-alpha significantly increases the risk of sarcoidosis.


Impaired flow-mediated endothelium-dependent and endothelium-independent vasodilation of the brachial artery in patients with atherosclerotic peripheral vascular disease.
A flow-mediated endothelium-dependent vasodilation and endothelium-independent nitroglycerin-induced vasodilation were carried out in 70 patients and 15 age-matched adults without any atherosclerotic risk factors to clarify vascular responsiveness in patients with atherosclerotic peripheral vascular disease. The percent change in flow-mediated vasodilation was significantly lower in patients than in controls (5.4 +/- 0.7% vs 12.8 +/- 2.2%, P < .001). Moreover, the percent change in nitroglycerin-induced vasodilation measured after sublingual administration of nitroglycerin was lower in patients than in controls (5.8 +/- 0.6% vs 10.2 +/- 1.5%, P < .01). On multiple regression analysis, none of the determinant factors showed a significant correlation with flow-mediated vasodilation. In contrast, Fontaine classification was found to be a significant predictor for nitroglycerin-induced vasodilation (r = -0.307, P < .05). There is a significant positive correlation between nitroglycerin-induced vasodilation and ankle-brachial pressure index in the patients. The data showed that vasoditation function were markedly impaired in end-stage patients with peripheral vascular disease.