Chronic pancreatitis: functional testing.
This article reviews the evolution of functional testing of the pancreas in Japan for the diagnosis and treatment of chronic pancreatitis (CP), contrasting the pre- with the postsecretin test (S test) era. In the pre-S test era, the diagnosis was based on symptoms, clinical findings, fasting serum diastase levels, and the vagostigmin- and ether-stimulation test unless morphologic evidence was available. The S test and CCK-pancreozymin (PZ) test (PS test) were introduced into Japan around 1963 and have been used as the gold standard of the exocrine pancreatic-function test. Through a series of attempts at standardization in 1971, 1985, and 1987, the method was standardized to collect duodenal juice for 60 min through a double- or triple-lumen tube after a bolus or during a continuous i.v. injection of secretin (100 U). The S test, however, is an invasive and cumbersome procedure. As a result, N-benzoyl-L-tyrosal-p-aminobenzoic acid (BT-PABA) testing and fecal chymotrypsin testing were introduced into Japan in the middle and late 1970s, respectively. Although simple and noninvasive, these two methods were found have lower sensitivity and specificity than the conventional S test. These two methods, therefore, are presently used more often for monitoring the course of disease and therapeutic effects. Additionally, the glucose tolerance test can be performed to detect endocrine pancreatic insufficiency.


The Underreporting of Vision Problems in Statutory Documents of Children with Williams Syndrome and Down Syndrome.
Vision problems can lead to negative developmental outcomes. Children with Williams syndrome and Down syndrome are at higher risk of vision problems, and these are less likely to be detected due to diagnostic overshadowing and difficulty accessing eye-care. Education, Health and Care (EHC) plans are statutory documents, introduced by the Children and Families Act 2014 in England, with the intention of integrating provision across these domains. Vision issues should be reported in these plans, and recommendations made about appropriate adjustments for them. We analysed the EHC plans from 53 children with Down or Williams syndrome. Our results showed significant underreporting, especially for children with Williams syndrome, and little explanation of what adjustments should be made. We also report pockets of good practice.


Ordered arrays of magnetic metal nanotubes and nanowires encapsulated with carbon tubes.
The ordered arrays of magnetic metal (including Fe, Co and Ni) nanotubes and nanowires encapsulated with carbon tubes are controllably synthesized by employing the array of C tubes as second-order template and combining with electrodeposition technique. The wall thickness and diameter of carbon nanotubes are uniform along the whole tubes; also the wall thickness of inner metal nanotubes is adjustable from 25 nm to solid nanowires. These composite structures are characterized by X-ray diffractometer (XRD), energy-dispersive spectrometry (EDS), Raman scattering spectrum, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The magnetic properties show that coaxial nanotubes and nanocables composite arrays all exhibit magnetic anisotropy with the easy direction perpendicular to axis of the metal nanotubes or nanowires except the Ni at C coaxial nanotubes array that has no preferable magnetization axis.


A method to quantify the uptake rate of 2-[18F]fluoro-2-deoxy-D-glucose in tissues.
A two-compartment model is used to derive the tissue time-activity curve of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG). At the later phase of the 18F-FDG activity in the tissue, the model leads to a method which allows the assessment of the 18F-FDG uptake rate constant. The proposed method is both compared with the standard uptake value (SUV) method and with Patlak's graphical analysis.


Cullin 3 regulates ADAMs-mediated ectodomain shedding of amphiregulin.
A disintegrin and metalloproteinase (ADAM) family are crucial enzymes for ectodomain shedding of multiple substrates and are involved in diverse biologic and pathologic processes. However, the molecular mechanism underlying substrate selectivity of ADAMs is poorly understood. In this study, we observed that disruption of actin polymerization by pharmacological inhibitors, latrunculin A (LatA) and cytochalasin D (CyD), induced ectodomain shedding of epidermal growth factor (EGF) family ligands. Induced shedding activity by LatA or CyD was suppressed by a metalloprotease inhibitor KB-R7785, indicating that ADAMs-mediated shedding is tightly controlled by actin cytoskeleton. We also investigated roles of cullin family, a component of cullin-RING based E3 ubiquitin ligases, in ectodomain shedding, since cullin family is implicated in the regulation of cytoskeletal dynamics. Knockdown of cullin 3 (Cul3) by a specific siRNA inhibited ectodomain shedding of amphiregulin (AREG), a member of EGF family, and responses were associated with activation of RhoA GTPase and induction of stress fiber formation. On the other hand, the RhoA inhibitor C3 transferase rescued AREG shedding reduced by Cul3 knockdown. These results describe a novel molecular mechanism of Cul3 to regulate AREG shedding by modulating cytoskeletal dynamics in a RhoA dependent manner.


Imprinting of BALB/c mice with low Leishmania infantum parasite dose markedly protects spleen against high-dose challenge.
In this study, we investigated in the BALB/c model, the dose-dependent protective potential of previous infection with Leishmania infantum parasites, against a high-dose challenge and showed for the first time that low-dose imprinting conferred substantial spleen resistance. Mice were immunized for 1 month or 5 months by IV route with parasite inocula ranging from 10(4) to 10(7) and from 10(3) to 10(5), respectively, and challenged for 1 month with 3 x 10(7) parasites. Liver protection was directly proportional to the parasite dose used for infection and reached 90-95% whereas, only low doses (< or =10(5)) protected spleen. Maximal spleen resistance (80%) was reached in mice infected for 5 months with 10(5) parasites. In most cases, protection was accompanied in spleen, by restored in vitro responses to Leishmania antigens. Analysis of anti L. infantum isotype responses and in vitro antigen-induced cytokine production, indicated that the acquired protection was irrespective of a Th1/Th2 imbalance.


Nitric oxide attenuates cardiac myocyte contraction.
Cardiac muscle fibers have microvessels in close proximity, the distance from the nearest capillary being no greater than 8 microns. We performed experiments on isolated, electrically stimulated, contracting guinea pig cardiac myocytes to test whether NO from endothelium or nitrovasodilators or directly superfused in solution might affect myocyte contractility. In endothelium-myocyte coculture experiments, 10(-7) M bradykinin reduced myocyte shortening by 11 +/- 3.5%. This effect was abolished in the presence of NG-nitro-L-arginine methyl ester and was unaffected by indomethacin. Sodium nitroprusside, but not organic nitrovasodilators, reduced myocyte contraction amplitude by 23% at 3 x 10(-5) M. This effect was reversed by methylene blue. Superfusion with NO solution had an effect similar to sodium nitroprusside, as did exposure to 8-bromoguanosine 3',5'-cyclic monophosphate. Thus the present study shows that cardiac myocyte contraction is attenuated by NO, which appears to act via production of guanosine 3',5'-cyclic monophosphate within the myocytes. Because cardiac myocytes in vivo are in such close proximity to endothelium, the effects of endothelial products on cardiac myocyte contractility may be important in myocardial function.


Can we differentiate minimally invasive adenocarcinoma and non-invasive neoplasms based on high-resolution computed tomography features of pure ground glass nodules?
The purpose of our study was to assess the differentially diagnostic value of radiographic characteristics of pure ground glass nodules (GGNs) between minimally invasive adenocarcinoma and non-invasive neoplasm. Sixty-seven pure GGNs (28 minimally invasive adenocarcinomas (MIA) and 39 pre-invasive lesions) were analyzed from June 2012 to June 2015. Pre-invasive lesions consisted of 15 atypical adenomatous hyperplasia (AAH) and 24 adenocarcinomas in situ (AIS). High-resolution computed tomography (HRCT) features and volume of MIA and pre-invasive lesions were assessed. Fisher exact test, independent sample t test, Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were performed. Inter-observer agreement indexes for the diameter, mean HRCT attenuations and volume of pure GGNs were all high (ICC>0.75). Univariate analyses showed that lesion diameter, mean HRCT attenuation, and volume value differed significantly between two groups. Among HRCT findings, GGN shape as round or oval (F = 13.456, P = 0.002) and lesion borders as smooth or notched (F = 15.742, P = 0.001) frequently appeared in pre-invasive lesions in comparison with MIA. Type II and type III of the relationship between blood vessels and pure GGNs suggested higher possibility of malignancy than type I. HRCT features of pure GGNs can help to differentiate MIA from non-invasive neoplasms.


The effect of nanoparticle size and NLS density on nuclear targeting in cancer and normal cells; impaired nuclear import and aberrant nanoparticle intracellular trafficking in glioma.
The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer. For such reason, here, the nuclear delivery efficiency of S-NPs and L-NPs was assessed as a function of their NLS density in cancer and non-cancer cells. For S-NPs, in all cells tested, NLS was unnecessary for nuclear delivery; unmodified S-NPs showed higher nuclear delivery than NLS-S-NPs due to their ability to gain nuclear entry in a passive manner. For L-NPs, L-NLS-L-NPs showed ≈ 8.5, 33, 1.8 and 7.2 fold higher nuclear deliveries than H-NLS-L-NPs in L929 fibroblasts, primary human fibroblasts, HEK 293 and lung cancer cells, respectively. In glioma however, unmodified L-NPs showed highest nuclear delivery, whereas NLS-L-NPs were retained in the cytoplasm. Experiments conducted in the presence of inhibitors of the classical nuclear import pathway indicated that due to overexpression of importin α, classical nuclear import in glioma is impaired leading to aberrant NP intracellular trafficking and nuclear import.


Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial.
This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia. This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death. The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes. Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia. (NCT0172946).


Blood cultures.
Bacteremia and fungemia are encountered commonly and are associated with significant morbidity and mortality. Laboratory detection is therefore of paramount importance. Principles of successful blood culturing, clinically important technical issues, manual and automated detection systems, and interpretation of culture results are reviewed in this article.


[Monthly cycles of 1-week therapy with itraconazole for patients with Tinea pedis].
Monthly cycles of 1-week therapy with oral itraconazole at 200 mg daily for tinea pedis was assessed to determine its acceptability to patients. Thirty-four patients (17 men and 17 women) with intractable tinea pedis, with informed consent, took 200 mg of itraconazole once daily for one week over a month period until mycological studies showed negative results for up to 4 months. The overall mycological effectiveness was about 80% after this therapy. Information was also gathered on the influence of this therapy on the patients quality of life by questionnaires. Nineteen (70%) among the 27 patients who answered the questionnaire preferred this 1-week administration of itraconazole over a month-long period compared with continuous daily therapy. Twenty-two (81%) preferred this therapy over topical treatment. We recommend to this therapy be added for the treatment of intractable tinea pedis.


Reasons for the invasive success of a guppy (Poecilia reticulata) population in Trinidad.
The introduction of non-native species into new habitats poses a major threat to native populations. Of particular interest, though often overlooked, are introductions of populations that are not fully reproductively isolated from native individuals and can hybridize with them. To address this important topic we used different approaches in a multi-pronged study, combining the effects of mate choice, shoaling behaviour and genetics. Here we present evidence that behavioural traits such as shoaling and mate choice can promote population mixing if individuals do not distinguish between native and foreign conspecifics. We examined this in the context of two guppy (Poecilia reticulata) populations that have been subject to an introduction and subsequent population mixing event in Trinidad. The introduction of Guanapo River guppies into the Turure River more than 50 years ago led to a marked reduction of the original genotype. In our experiments, female guppies did not distinguish between shoaling partners when given the choice between native and foreign individuals. Introduced fish are therefore likely to benefit from the protection of a shoal and will improve their survival chances as a result. The additional finding that male guppies do not discriminate between females on the basis of origin will further increase the process of population mixing, especially if males encounter mixed shoals. In a mesocosm experiment, in which the native and foreign populations were allowed to mate freely, we found, as expected on the basis of these behavioural interactions, that the distribution of offspring genotypes could be predicted from the proportions of the two types of founding fish. This result suggests that stochastic and environmental processes have reinforced the biological ones to bring about the genetic dominance of the invading population in the Turure River. Re-sampling the Turure for genetic analysis using SNP markers confirmed the population mixing process and showed that it is an on-going process in this river and has led to the nearly complete disappearance of the original genotype.


Clinics in diagnostic imaging (71). Left iliopsoas abscess secondary to vertebral osteomyelitis.
A 26-year-old woman presented with a progressively painful lump at her left groin and upper thigh for five months. She also had intermittent back pain for three years. Radiographs and CT showed osteolytic destruction of the several contiguous thoracolumbar vertebrae with a large left iliopsoas abscess that extended to involve the left gluteus maximus and adductor magnus muscles. She responded well to a course of antibiotics. The role of imaging and imaging features of iliopsoas abscesses are discussed, together


Gambler clusters and problem gambling severity: A cluster analysis of Swedish gamblers accessing an online problem gambling screener.
It has been proposed that overall gambling involvement has a stronger association with problem gambling (PG) than any specific game type. However, few studies have used multiple analytic approaches on the same data set to assess these relationships. The aims of the current study were to identify patterns of gambling activity (PGAs) and to assess the relationships between different game types, PGAs, gambling involvement, and PG as measured by the Problem Gambling Severity Index (PGSI), using two different approaches. In a sample of Swedish gamblers who screened their gambling habits at the Swedish national gambling helpline website (N = 7,463, 79% males), seven different PGAs were identified. Increased gambling involvement was associated with PG severity, and the strength of the association varied by game type. Online casino games and electronic gambling machines had the weakest involvement effect and lotteries the strongest. Almost 50% of the gamblers belonged to the online casino PGA, characterized by online casino gambling. Gamblers in this PGA showed higher PGSI scores compared to three PGAs: online sports/online casino, horse/lottery, and online sports, and they had lower PGSI scores compared to the diverse PGA, characterized by engagement in all game types. No differences in PGSI scores were found between gamblers in three PGAs with high probability of online casino gambling but with varying engagement levels in other game types. In a Swedish context, the results from this study indicate that the focus of prevention and regulation should be on game types with the strongest associations with PG, namely, online casino games. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Phosphorylation of ERK and dystrophin S3059 protects against inflammation-associated C2C12 myotube atrophy.
The dystrophin-glycoprotein complex (DGC) is a multiprotein structure required to maintain muscle fiber membrane integrity, transmit force by linking the actin cytoskeleton with the extracellular matrix, and maintain muscle homeostasis. Membrane localization of dystrophin is perturbed in muscles wasting as a consequence of cancer cachexia, tenotomy, and advanced aging, which are all associated with low level, chronic inflammation. Strategies to preserve dystrophin expression at the sarcolemma might therefore combat muscle wasting. Phosphorylation of dystrophin serine 3059 (S3059) enhances the interaction between dystrophin and β-dystroglycan. To test the contribution of amino acid phosphorylation to muscle fiber size changes, dystrophin constructs with phospho-null and phosphomimetic mutations were transfected into C2C12 muscle cells or AAV-293 cells in the presence or absence of kinase inhibitors/activators to assess effects on myotube diameter and protein function. Overexpression of a dystrophin construct with a phospho-null mutation at S3059 in vitro reduced myotube size in healthy C2C12 cells. Conversely overexpression of a phosphomimetic mutation at S3059 attenuated inflammation-induced myotube atrophy. Increased ERK activation by addition of phorbol myristate acetate (PMA) also reduced inflammation-associated myotube atrophy and increased the interaction between dystrophin and β-dystroglycan. These findings demonstrate a link between increased ERK activation, dystrophin S3059 phosphorylation, stabilization of the DGC, and the regulation of muscle fiber size. Interventions that increase dystrophin S3059 phosphorylation to promote stronger binding of dystrophin to β-dystroglycan may have therapeutic potential for attenuation of inflammation-associated muscle wasting.


Novel derivatives of benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, and antitumor evaluation.
Novel derivatives of benzo[b]thieno[2,3-c]quinolones 3a-j were synthesized in a multistep synthesis starting from substituted benzo[b]thiophene-2-carbonyl chlorides, to their corresponding benzo[b]thiophene-2-carboxamides, which were photochemically dehydrohalogenated to their corresponding substituted benzo[b]thieno[2,3-c]quinolones. Compound 4 was prepared from 3i by alkylation with 3-dimethylaminopropyl chloride in the presence of NaH. Compounds 7a,b were prepared from 3g in the multistep synthesis from compounds 5 and 6. Compounds 3b, 3c-f, 3h, 7a, and 7b were found to exert cytostatic activity against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), human fibroblast cell lines (WI-38). The compounds that bear a 3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma cells (HBL, ME 67.3, and ME 67.1), a potential mechanism of action was examined. Analysis of DNA and Annexin-V-FLUOS staining indicated that compound 4 causes cell death by apoptosis.


Continuous renal replacement therapy for non-renal indications: experience in children.
The role of continuous renal replacement therapy in patients with acute renal failure is well recognized. CRRT has also become an important modality of treatment in various acute situations without renal failure. To describe our experience with CRRT in acutely ill infants and children without renal failure. We analyzed all infants and children who underwent CRRT during the years 1998-2000 in the pediatric intensive care unit and we focus our report on those who were treated for non-renal indications. Fourteen children underwent 16 sessions of CRRT. The indications for CRRT were non-renal in 7 patients (age range 8 days to 16 years, median = 6.5). Three children were comatose from maple syrup urine disease, three were in intractable circulatory failure secondary to septic shock or systemic inflammatory response, and one had sepsis with persistent lactic acidosis and hypernatremia. Three children underwent continuous hemodiafiltration and four had continuous hemofiltration. The mean length of the procedure was 35 +/- 24 hours. All patients responded to treatment within a short period (2-4 hours). No significant complications were observed. Two patients experienced mild hypothermia (34 degrees C), one had transient hypotension and one had an occlusion of the cannula requiring replacement. Our findings suggest that CRRT is a safe and simple procedure with a potential major therapeutic value for treating acute non-renal diseases in the intensive care setting.


Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment.
Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.


A defect in the blood-retina barrier in the optic nerve head region in the rabbit and the monkey.
The permeability properties of the tissues in the optic nerve head region have been investigated in monkey and rabbit using horseradish peroxidase as an histochemical tracer. Following intravenous administration, the tracer diffused from the peripapillary choroid into the different parts of the optic nerve head region, and also into the receptor layer of the sensory retina adjacent of Kuhnt intermediary tissue. This observation demonstrates a defect in the blood-retina barrier in this region. The defect in the permeability barrier is most likely located either to the retinal pigment epithelium near the optic nerve head, to the Kuhnt intermediary tissue, or to the junction between these tissues.


[A Single Preventive Counseling in the Hospital Does Not Improve the Prognosis of Patients After Percutaneous Coronary Intervention].
The purpose of the study "Invasive Techniques for the treatment of atherosclerosis: the effectiveness of secondary preventive intervention" (IMLA-TRAC) - long-term efficacy of single preventive counseling of patients with coronary heart disease (CHD) in a stationary treatment for percutaneous coronary intervention (PCI). In a prospective, randomized, controlled trial included 160 patients with coronary artery disease who underwent PCI between the ages of 38 to 87 years (mean age 59,43+/-8,94 years, 81.9% male). Included in the study, patients were randomized in a ratio of 1: 1 into 2 groups - the primary (n=80) and control (n=80). Patients in both groups received standard hospital treatment and hospital doctors recommendations. In addition to these patients of the main group carried out a preventive educational program After being discharged from hospital patients in both groups were followed for 12 months. The study showed that a single prevention counseling, conducted in patients with coronary heart disease at the stage of hospital treatment over a planned or emergency PCI, does not provide a stable positive dynamics of the main risk factors and has no effect on mortality and combined end point. There is only a small positive dynamics of individual indicators, for example, significantly lower intake of saturated fats, an increase in adherence to treatment, in particular, receive aspirin. Further studies are needed to determine the most effective models for preventive intervention in patients with coronary artery disease, which can start in a hospital, but should continue on an outpatient or remote formats.


Remarkable Reactivity of Boron-Substituted Furans in the Diels-Alder Reactions with Maleic Anhydride.
The reactivity of boron-substituted furans as dienes in the Diels-Alder reaction with maleic anhydride has been investigated. Gratifyingly, the furans with boryl substituents at C-3 gave the exo cycloadduct exclusively with excellent yields. In particular, the potassium trifluoroborate exhibited outstanding reactivity at room temperature. Theoretical calculations suggested that the trifluoroborate group is highly activating and also that the thermodynamics is the main factor that determines whether the products can be obtained efficiently or not.


Colonoscopy Comfort: An Evidence-Based Practice Project.
Decreased discomfort after colonoscopy is a high priority for patients. Typically, air is used to insufflate the bowel during colonoscopy, but emerging literature shows that carbon dioxide insufflation decreases postoperative discomfort and flatus. An evidence-based practice project was developed and implemented by a surgical department at a community hospital. The Director of Surgical Services brought the evidence to the staff, secured agreement from a physician champion, and the new process was quickly adopted. Patients experienced less discomfort and flatus postprocedure with carbon dioxide insufflation, and were able to be discharged expediently. These patient outcomes validated the literature and confirmed the success of the practice change.


Clinical utility of a functional lumen imaging probe in management of dysphagia following head and neck cancer therapies.
Background and aims Chemoradiotherapy for head and neck cancer (HNC) with/without laryngectomy commonly causes dysphagia. Pharyngoesophageal junction (PEJ) stricturing is an important contributor. We aimed to validate a functional lumen imaging probe (the EndoFLIP system) as a tool for quantitating pretreatment PEJ distensibility and treatment-related changes in HNC survivors with dysphagia and to evaluate the diagnostic accuracy of EndoFLIP-derived distensibility in detecting PEJ strictures. Methods We studied 34 consecutive HNC survivors with long-term (> 12 months) dysphagia who underwent endoscopic dilation for suspected strictures. Twenty non-dysphagic patients undergoing routine endoscopy served as controls. PEJ distensibility was measured at endoscopy with the EndoFLIP system pre- and post-dilation. PEJ stricture was defined as the presence of a mucosal tear post-dilation. Results PEJ stricture was confirmed in 22/34 HNC patients (65 %). During distension up to 60 mmHg, the mean EndoFLIP-derived narrowest cross-sectional area (nCSA) in HNC patients with strictures, without strictures, and in controls were 58 mm2 (95 % confidence interval [CI] 22 to 118), 195 mm2 (95 %CI 129 to 334), and 227 mm2 (95 %CI 168 to 316), respectively. A cutoff of 114 mm2 for the nCSA at the PEJ had perfect diagnostic accuracy in detecting strictures (area under the receiver operating characteristic curve = 1). In patients with strictures, a single session of dilation increased the nCSA by 29 mm2 (95 %CI 20 to 37; P < 0.001). In patients with no strictures, dilation caused no change in the nCSA (mean difference 13 mm2 [95 %CI -4 to 30]; P = 0.13). Conclusions EndoFLIP is a highly accurate technique for the detection of PEJ strictures. EndoFLIP may complement conventional diagnostic tools in the detection of pharyngeal outflow obstruction.


M3-muscarinic receptor subtype predominates in the bovine iris sphincter smooth muscle and ciliary processes.
The distribution of mRNAs encoding muscarinic acetylcholine receptor (mAChR) subtypes (M1, M2, M3, and M4) was investigated in the bovine iris-ciliary body by Northern blot hybridization with subtype-specific oligonucleotide probes that were complementary to unique regions of the M1, M2, M3, and M4 mAChRs. Whole rat brain RNA, which contains all four subtypes, was employed as a positive control. Both the iris sphincter and the ciliary processes were found to contain predominantly the M3 mAChR subtype and minor amounts of the M2 subtype. Traces of the M4 subtype were detected also in the ciliary processes.


An Unusual Presentation of Cardiofaciocutaneous Syndrome Diagnosed Through Whole Genome Sequencing: A Case Report.
Cardiofaciocutaneous syndrome is a rare, sporadic disease caused by germline mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway. Patients usually present with craniofacial anomalies, cardiac defects, and neurocutaneous abnormalities. The features of cardiofaciocutaneous syndrome overlap with two other syndromes known as Noonan's syndrome and Costello's syndrome. Similarly, those two syndromes are caused by mutations in the Ras/MAPK pathway. The diagnosis of cardiofaciocutaneous syndrome is suspected based on the clinical presentation and confirmed by genetic analysis. We report a case of a seven-month-old boy who presented with complaints of developmental delay, poor weight gain, and seizures. Physical examination revealed several dysmorphic features, including coarse facies, long philtrum, thin upper lip, a broad forehead, and long toes. Neurological examination showed hypotonia in all four limbs, with normal power and reflexes. However, the infant did not have any remarkable cutaneous abnormalities. Whole-exome sequencing picked up a BRAF gene mutation, and the patient was diagnosed with cardiofaciocutaneous syndrome. On follow-up, the patient developed findings suggestive of autoimmune hepatitis. Cardiofaciocutaneous syndrome remains a challenging diagnosis that requires a detailed assessment of the patient, as well as qualified centers with genetic analysis for diagnosis confirmation. Management of cardiofaciocutaneous patients requires a multidisciplinary team approach in order to improve the outcomes. Further exploration is required into atypical presentations of the disease as well as autoimmune disease associated with RASopathies.


Evolutionary Origins of Drought Tolerance in Spermatophytes.
It is commonly known that drought stress is a major constraint limiting crop production. Drought stress and associated drought tolerance mechanisms are therefore under intense investigation with the view to future production of drought tolerant crops. With an ever-growing population and variable climate, novel approaches need to be considered to sustainably feed future generations. In this context, definitions of drought tolerance are highly variable, which poses a major challenge for the systematic assessment of this trait across the plant kingdom. Furthermore, drought tolerance is a polygenic trait and understanding the evolution of this complex trait may inform us about patterns of gene gain and loss in relation to diverse drought adaptations. We look at the transition of plants from water to land, and the role of drought tolerance in enabling this transition, before discussing the first drought tolerant plant and common drought responses amongst vascular plants. We reviewed the distribution of a combined "drought tolerance" trait in very broad terms to encompass different experimental systems and definitions used in the current literature and assigned a binary trait "tolerance vs. sensitivity" in 178 extant plant species. By simplifying drought responses of plants into this "binary" trait we were able to explore the evolution of drought tolerance across the wider plant kingdom, compared to previous studies. We show how this binary "drought tolerance/sensitivity" trait has evolved and discuss how incorporating this information into an evolutionary genomics framework could provide insights into the molecular mechanisms underlying extreme drought adaptations.


Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?: Alternating Chromatin States Provide a Basis for Domain Architecture in Drosophila.
The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC-binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in Drosophila appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered.


A retrospective study of treatment persistence and adherence to α-blocker plus antimuscarinic combination therapies, in men with LUTS/BPH in the Netherlands.
To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics. Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.


Molecular characterization of methicillin-resistant Staphylococcus aureus with emergence of epidemic clones of sequence type (ST) 22 and ST 772 in Mumbai, India.
A total of 412 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated between October 2006 and June 2009, representing a mixed hospital- and community-associated patient population from Mumbai, India, were evaluated. MRSA was characterized by multiplex PCR amplification of the Panton-Valentine leukocidin (PVL) gene and the mecA gene, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing (MLST). PCR results were compared with patient risk factors (CDC guidelines) and antimicrobial susceptibility profiles. A total of 395 MRSA strains were mecA positive, and 224 were PVL gene positive. A total of 97 mecA-positive strains were SCCmec III (25%), 136 were SCCmec IV (34%), and 162 were SCCmec V (41%). All SCCmec III strains were multidrug resistant, and all patients had risk factors. Of the SCCmec IV and V strains, 73% were multidrug susceptible and 72% of the associated patients had no risk factors. The multidrug susceptibility and absence of patient risk factors in 72% of cases with SCCmec IV and SCCmec V MRSA demonstrate the presence of community-associated MRSA (CA-MRSA) in Mumbai. Twenty-one percent of these patients had risk factors, signifying CA-MRSA infiltration into hospitals. MLST showed clonal expansion of multidrug-susceptible sequence type (ST) 22 (SCCmec IV) and ST 772 (SCCmec V), both of which feature in Asian studies and may be slowly replacing the multidrug-resistant ST 239 (SCCmec III) in hospitals. The PVL gene-positive methicillin-sensitive S. aureus (MSSA) strains were ST 30 and were postulated to be related to the penicillin-resistant S. aureus phage type 80/81, notorious for its virulence in the 1950s.


Patients' perceptions of the impact of treatments and products on their experience of leg ulcer pain.
Very little research has explored patients' experience of pain with different cleansing agents and dressings. We therefore undertook a longitudinal study of their impact on leg ulcer pain. Patients with leg ulcers referred to community nurses were eligible to participate. They were followed up for six months, completing questionnaires about the impact on pain of each wound treatment used. A treatment episode was defined as the use of a wound cleansing agent, primary dressing and bandages. When one aspect of treatment changed, a new treatment episode began. There were 210 treatment episodes for 96 leg ulcer patients. In 206 episodes cleansing agents were used. Cleansing caused pain in 22% of episodes and relieved pain in 27%. Of the five most commonly used dressing types, low-adherent dressings were the least likely to cause pain. Only 56% of patients were able to tolerate full compression bandaging and pain was the most common reason for non-compliance. A substantial proportion of patients felt that leg ulcer treatments caused pain. A greater emphasis on the impact of treatment on pain and healing is warranted both clinically and in research.


[The cardiac situation of newborn children after long-term tocolysis with fenoterol (author's transl)].
516 newborn children were subject to a thorough cardiac and neurological test program after a long-term tocolysis with Fenoterol with and without a supplementary medication of Verapamil. No symptoms of a myocardial damage caused by the drug appeared neither in the electrocardiogram nor by means of lab-chemical parameters such as CK-MB, Serum-Myoglobin and CK-B. Except for premature children, no significant neurological characteristics were found either. Due to the low quantity of Fenoterol passing through the placenta and based on the minimum cumulation of Fenoterol in the fetal tissue, especially in the fetal myocardium, a tocolysis does not seem to have any significantly dangerous fetal effects, if control parameters are strictly adhered to. The endeavoured therapeutical objective, namely the prevention of premature labour, thus justifies the application of the betasympathomimetic Fenoterol.


The sperm epigenome does not display recurrent epimutations in patients with severely impaired spermatogenesis.
In the past 15 years, numerous studies have described aberrant DNA methylation of imprinted genes (e.g. MEST and H19) in sperm of oligozoospermic men, but the prevalence and genomic extent of abnormal methylation patterns have remained unknown. Using deep bisulfite sequencing (DBS), we screened swim-up sperm samples from 40 normozoospermic and 93 patients diagnosed as oligoasthenoteratozoospermic, oligoteratozoospermic or oligozoospermic, which are termed OATs throughout the manuscript, for H19 and MEST methylation. Based on this screening, we defined three patient groups: normal controls (NC), abnormally methylated oligozoospermic (AMO; n = 7) and normally methylated oligozoospermic (NMO; n = 86). Whole-genome bisulfite sequencing (WGBS) of five NC and five AMO samples revealed abnormal methylation levels of all 50 imprinting control regions in each AMO sample. To investigate whether this finding reflected epigenetic germline mosaicism or the presence of residual somatic DNA, we made a genome-wide inventory of soma-germ cell-specific DNA methylation. We found that > 2000 germ cell-specific genes are promoter-methylated in blood and that AMO samples had abnormal methylation levels at these genes, consistent with the presence of somatic cell DNA. The comparison between the five NC and six NMO samples revealed 19 differentially methylated regions (DMRs), none of which could be validated in an independent cohort of 40 men. Previous studies reported a higher incidence of epimutations at single CpG sites in the CTCF-binding region 6 of H19 in infertile patients. DBS analysis of this locus, however, revealed an association between DNA methylation levels and genotype (rs2071094), but not fertility phenotype. Our results suggest that somatic DNA contamination and genetic variation confound methylation studies in sperm of infertile men. While we cannot exclude the existence of rare patients with slightly abnormal sperm methylation at non-recurrent CpG sites, the prevalence of aberrant methylation in swim-up purified sperm of infertile men has likely been overestimated, which is reassuring for patients undergoing assisted reproduction.


The Use of Trace and Essential Elements in Common Clinical Disorders: Roles in Assessment of Health and Oxidative Stress Status.
During the early life, the diet of infants is mainly dominated by milk. Milk is a natural food rich in trace elements focus on essential elements. These elements are very necessary for human metabolism and since they cannot be synthesized by the body, the only source available for the humans to obtain them is by ingestion of natural food. This mini-review aims at updating the knowledge on trace elements, outlining their natural food sources, and their possible implications in common clinical disorders in early and adult life. However, it was found that consumption of food with micronutrients and trace elements may release intracellular compounds and offer oxidative protection or exacerbate oxidative damage to metabolically compromised cells.


Structural and sociocultural factors associated with cervical cancer screening among HIV-infected African American women in Alabama.
African American women have disproportionately high prevalence rates of HIV and cervical cancer. HIV-infected women are significantly less likely to obtain recommended cervical cancer screenings than HIV-uninfected women. The purpose of this study was to examine sociocultural and structural factors associated with cervical cancer screening among HIV-infected African American in Alabama. The PEN-3 Model and the Health Belief Model were used as theoretical frameworks. In-depth interviews were conducted with twenty HIV-infected African American women to identify perceptions, enablers, and nurturers, perceived susceptibility, perceived severity, and perceived benefits related to cervical cancer and screening. The most common positive perceptions, enablers, and nurturers that contributed to cervical cancer screening included internal motivation and awareness of the importance of HIV-infected women getting Pap tests due to their weakened immune system. Negative perceptions, enablers, and nurturers included lack of knowledge about cervical cancer and screening, and lack of perceived susceptibility to cervical cancer. The results of this study can be used to guide the development of culturally relevant cervical cancer and screening education interventions aimed at increasing cervical cancer screening adherence among HIV-infected African American women.


Potent inhibitory activity of HSR-6071, a new antiallergic agent, on passive cutaneous anaphylaxis (PCA).
Antiallergic effects of 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (HSR-6071), a newly synthesized agent, were investigated. The 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats was inhibited in a dose-dependent manner by i.v. and p.o. administration of the agent (ED50 = 0.0096 mg/kg and 0.18 mg/kg, respectively). The IgE-mediated histamine release from rat peritoneal exudate cells was inhibited by HSR-6071, with an IC50 of 4.6 x 10(-10) M. Regarding the non-immunological histamine release, HSR-6071 inhibited compound 48/80-induced, but not A23187-induced and spontaneous histamine release. On the other hand, an increase in vascular permeability induced by histamine, serotonin and bradykinin was unaffected by HSR-6071 in doses sufficient to inhibit PCA. In addition, the contractile responses of isolated guinea pig ileum to histamine, acetylcholine and serotonin were also unaffected by the agent even in a high concentration of 10(-4) M. These results indicate that HSR-6071 possesses a potent antiallergic activity and that the inhibition of PCA by HSR-6071 may be due to the suppression of chemical mediators release from mast cells.


Hedgehog signaling pathway: Epigenetic regulation and role in disease and cancer development.
The evolutionarily conserved Hedgehog (Hh) signaling pathway have critical roles in development and homeostasis of tissues. Under physiological conditions, Hh is controlled at different levels via stem cell maintenance and tissue regeneration. Aberrant activation of this signaling pathway may occur in a wide range of human diseases including different types of cancer. In this review we present a concise overview on the key genes composing Hh signaling pathway and provide recent advances on the molecular mechanisms that regulate Hh signaling pathway from extracellular and receptors to the cytoplasmic and nuclear machinery with a highlight on the role of microRNAs. Furthermore, we focus on critical studies demonstrating dysregulation of the Hh pathway in human disease development, and potential therapeutic implications. Finally, we introduce recent therapeutic drugs acting as Shh signaling pathway inhibitors, including those in clinical trials and preclinical studies.


Is it appropriate for Korean women to adopt the 2009 Institute of Medicine recommendations for gestational weight gain?
The 2009 Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) are intended for use among women in the United States. Little data are available on whether the 2009 IOM recommendations can be applied to Asian women. This study aimed to evaluate whether the recommendations are related to adverse pregnancy outcomes in Korean pregnant women. A retrospective cohort study was conducted for all singleton-pregnant women at a university hospital in Korea. After classifying the enrolled women into four Korean pre-pregnancy body mass index (BMI) categories, the risk of adverse pregnancy outcomes were analyzed for women who gained inadequate or excessive GWG based on 2009 IOM recommendations. Of 7,843 pregnancies, 64.0% of women had normal pre-pregnancy BMI and 42.7% achieved optimal GWG. Across all BMI categories, adverse pregnancies outcomes such as small for gestational age (SGA), large for gestational age (LGA), preterm birth, preeclampsia, and cesarean due to dystocia were significantly associated with GWG (all P ≤ 0.001).Women with normal BMI who gained inadequate weight were more likely to develop SGA and preterm birth and less likely to develop LGA (adjusted odds ratio (aOR) 2.21, 1.33, and 0.54, respectively). Whereas, women with normal BMI who gained excessive weight were more likely to develop LGA, preterm birth, preeclampsia, and cesarean section due to dystocia (aOR 2.10, 1.33, 1.37, and 1.37, respectively) and less likely to develop SGA (aOR 0.60). It is tolerable for Korean women to follow recommended GWG from the 2009 IOM guidelines to decrease adverse pregnancy outcomes. This will be helpful for antenatal care on GWG not only for Korean pregnant women, but also other Asian women who have lower BMI criteria than Caucasian women.


Long-term use of benzodiazepines in older patients in Germany: a retrospective analysis.
The purpose of this study was to analyze the prevalence of long-term benzodiazepine use in older adults treated in general and neuropsychiatric practices in Germany. This study included 32,182 patients over the age of 65 years who received benzodiazepine prescriptions for the first time between January 2010 and December 2014 in general and neuropsychiatric practices in Germany. Follow up lasted until July 2016. The main outcome measure was the proportion of patients treated with benzodiazepines for >6 months. The proportion of patients with benzodiazepine therapy for >6 months increased with age (65-70 years: 12.3%; 71-80 years: 15.5%; 81-90 years: 23.7%; >90 years: 31.6%) but did not differ significantly between men (15.5%) and women (17.1%). The proportion of patients who received benzodiazepines for >6 months was higher among those with sleep disorders (21.1%), depression (20.8%) and dementia (32.1%) than among those with anxiety (15.5%). By contrast, this proportion was lower among people diagnosed with adjustment disorders (7.7%) and back pain (3.8%). Overall, long-term use of benzodiazepines is common in older people, particularly in patients over the age of 80 and in those diagnosed with dementia, sleep disorders, or depression.


Lactate/pyruvate monitoring during carotid endarterectomy under general anaesthesia versus cervical plexus block: A randomised controlled study.
Carotid endarterectomy (CEA) reduces the risk of stroke in patients with significant carotid stenosis and may be performed under general anaesthesia (GA) or regional anaesthesia (RA). This study aimed to compare RA and GA with regard the jugular venous bulb blood lactate and pyruvate levels. This randomised-controlled trial was done between October-2013 and September-2015. Thirty-six patients were randomised into either GA or RA groups, with six excluded after randomisation. In the RA group, combined deep and superficial cervical plexus blocks were performed. In the GA group, anaesthesia was induced with propofol and fentanyl. In both groups, monitoring of neurological function was done. Sampling of the contralateral jugular bulb blood was done. The main outcome measures were lactate and pyruvate in the jugular venous blood. For comparing categorical data, Chi-square test was used, and for the numerical variables, t-test was used. Demographics were comparable in the two Groups. Serum lactate and pyruvate levels were higher in the GA group than RA group. At 120 min under anaesthesia, lactate and pyruvate levels under RA vs. GA, respectively were 0.76±0.03 mEq/L vs. 1.14±0.06, p-0.001 mEq/L, and 0.08± 0.00 mEq/L vs. 0.10±0.01 mEq/L, p=0.006. Lactate/ pyruvate ratios were normal in both groups. The mean blood pressure was significantly lower in the GA group during anaesthesia. In patients undergoing Carotid endarterectomy, serum levels of both lactate and pyruvate were higher under general versus regional anaesthesia.


Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors.
We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.


[Role of serotonin receptors in vascular tone in the pithed rat].
Serotonin (5-hydroxytryptamine; 5-HT) has been shown to produce vascular sympatho-inhibition in a wide variety of isolated blood vessels by activation of prejunctional 5-HT1 receptors. After considering the mechanisms involved in modulating neuroeffector transmission, the present review analyzes the experimental findings identifying the pharmacological profile of the 5-HT receptors that inhibit the sympathetically-induced vasopressor responses in pithed rats. Thus, 5-HT-induced sympatho-inhibition has been shown to be: (i) unaffected by physiological saline or by the selective antagonists ritanserin (5-HT2), MDL72222 (5-HT3) or tropisetron (5-HT3/4); (ii) blocked by methysergide, a non-selective 5-HT1/2 receptor antagonist; and (iii) potently mimicked by 5-carboxamidotryptamine (5-CT), a non-selective 5-HT1 receptor agonist, as well as by the selective agonists 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP93,129 (5-HT1B), and sumatriptan (5-HT1B/1D). These findings show the involvement of prejunctional 5-HT1 receptors. With the use of selective antagonists, it has been shown subsequently that the sympatho-inhibition induced by indorenate, CP93, 129, and sumatriptan was selectively antagonized by WAY100635 (5-HT1A), cyanopindolol (5-HT1A/1B), and GR127935 (5-HT1B/1D), respectively. These results demonstrate that the 5-HT1 receptors mediating sympatho-inhibition on the systemic vasculature of pithed rats resemble the pharmacological profile of the 5-HT1A, 5-HT1B, and 5-HT1D subtypes.


An implantable left atrial pressure sensor lead designed for percutaneous extraction using standard techniques.
An implantable left atrial pressure (LAP) monitoring system for guiding the management of patients with advanced heart failure has the potential to require extraction, particularly in the setting of infection. The LAP sensor lead was designed to be suitable for ease of percutaneous extraction using standard techniques for extracting pacemaker and defibrillator leads. The clinical experience, to date, with percutaneous extraction of the LAP sensor lead is presented. A total of 82 patients underwent successful implantation of the LAP sensor lead using transseptal catheterization. Five patients of the 82 patients during a cumulative follow-up period of 267 patient-years (median of 2.9 years/patient) underwent percutaneous extraction using manual traction with a locking stylet and/or an excimer laser sheath to bore through adhesions. The distal fixation anchors of the LAP sensor lead are designed to fold forward during extraction so that the sensor module can easily separate from the interatrial septum. Percutaneous extraction of the LAP sensor lead was accomplished successfully in all five patients with no embolic events, vascular tears, perforations, or other complications requiring surgical intervention. Manual traction alone was sufficient to detach the LAP sensor lead from the interatrial septum in all cases. Use of the excimer laser sheath was needed in selected cases to bore through scar tissue within the venous insertion site, but not within the heart. The extraction of the LAP sensor lead was accomplished safely using standard techniques and equipment for percutaneously extracting pacemaker and defibrillator leads.


A suite of microsatellite markers for genetic management of captive cracids (Aves, Galliformes).
Cracids are medium to large frugivorous birds that are endemic to the Neotropics. Because of deforestation and overhunting, many species are threatened. The conservation of several species has relied on captive breeding and reintroduction in the wild, but captive populations may be inbred. Microsatellite tools can permit the construction of genetic pedigrees to reduce inbreeding, but only a few loci are available for this group of birds. Here, we present 10 novel polymorphic microsatellite loci and the cross-amplification of these and of 10 additional loci available in the literature in a panel of 5 cracid species, including 3 species with high conservation concern. We provide the first polymorphic loci for the jacutinga, Aburria jacutinga (N = 8), and red-billed curassow, Crax blumenbachii (N = 9), and additional loci for bare-faced curassow, C. fasciolata (N = 8), Alagoas curassow, Pauxi mitu (N = 5), and razor-billed curassow, P. tuberosa (N = 5). The average number of alleles was 2.9 for A. jacutinga, 2.7 for C. blumenbachii, 3.5 for C. fasciolata, 2.6 for P. mitu, and 5.7 for P. tuberosa. The mean expected heterozygosities were 0.42, 0.40, 0.48, 0.37, and 0.59, respectively. The average probabilities that the set of loci would not exclude a pair of parents of an arbitrary offspring were 2.9% in A. jacutinga, 1% in C. blumenbachii, 0.5% in C. fasciolata, 0.4% in P. mitu, and 0.002% in P. tuberosa suggesting that these loci may be adequate for parentage analysis and to implement ex situ genetic management plans.


Bioelectrical impedance may predict cell viability during ischemia and reperfusion in rat liver.
Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia.


Increased physical activity decreases periodontitis risk in men.
Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40-75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents--METs); the first report of professionally diagnosed periodontitis was considered a case. Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95-0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76-1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (beta = -0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health.


Role of ERK1/2 MAPK signaling in the maintenance of myelin and axonal integrity in the adult CNS.
Oligodendrocytes form myelin during postnatal development and then maintain a functional myelin sheath throughout adult life. While many regulators of developmental myelination have been identified, the signal transduction mechanisms that regulate oligodendrocyte functions in adulthood are not well understood. The extracellular signal-regulated kinases-1 and -2 (ERK1/2), downstream mediators of mitogen-activated protein kinases (MAPKs), have emerged as prominent regulators of myelin formation. Here, we investigated whether these signaling molecules are also required for myelin maintenance in the adult CNS. Inducible conditional ablation of Erk1/2 in oligodendrocytes of the adult CNS resulted in a downregulation of myelin gene expression. Although myelin thickness was reduced and some axons were demyelinated, the majority of axons were wrapped by intact myelin sheaths that appeared structurally normal. However, late onset of progressive axonal degeneration, accompanied by astrogliosis, microglial activation, partial loss of oligodendrocytes, and functional impairment, occurred in the adult mice lacking ERK1/2 activity. Conditional ablation of Fibroblast Growth Factor receptors-1 and -2 (FGFR1/2) in oligodendrocytes also resulted in downregulation of myelin gene expression and development of axonal degeneration as the mice aged. Further, the level of the key transcription factor myelin gene regulatory factor (Myrf) was downregulated or upregulated in mice with genetic loss or gain of ERK1/2 function, respectively. Together, our studies demonstrate that ERK1/2-MAPK signaling is required for the long-term maintenance of myelin and axonal integrity in the adult CNS and suggest that FGFR1/2 and Myrf may, in part, contribute to signaling upstream and downstream of ERK1/2 in maintaining these oligodendrocyte functions during adulthood.


Predicting genetic regulatory response using classification.
Studying gene regulatory mechanisms in simple model organisms through analysis of high-throughput genomic data has emerged as a central problem in computational biology. Most approaches in the literature have focused either on finding a few strong regulatory patterns or on learning descriptive models from training data. However, these approaches are not yet adequate for making accurate predictions about which genes will be up- or down-regulated in new or held-out experiments. By introducing a predictive methodology for this problem, we can use powerful tools from machine learning and assess the statistical significance of our predictions. We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences ('motifs') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment ('parents'). Thus, our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurements to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S.cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. We also show how to extract significant regulators, motifs and motif-regulator pairs from the learned models for various stress responses. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks. The MLJava package is available upon request to the authors. Supplementary: Additional results are available from http://www.cs.columbia.edu/compbio/geneclass


Coronary artery spasm in a transplant patient.
The mechanism of coronary spasm is poorly understood. We report a case of coronary artery spasm in a cardiac transplant patient. Pharmacologic testing indicated denervation of the patient's heart. Therefore coronary artery spasm may occur despite cardiac denervation. This case demonstrates that intact autonomic nervous system and cardiac innervation are not essential for coronary artery spasm.


The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer.
Men with prostate specific antigen (PSA) only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. These patients are often treated with androgen suppression. We evaluate the effects of androgen suppression on cognitive function. Hormone naïve patients without evidence of metastases with an increasing PSA were treated with intermittent androgen suppression consisting of 9 months of leuprolide and flutamide followed by an off treatment period determined by the increase in PSA. Cognitive function tests were administered at baseline, after 9 months of androgen suppression and after 3 months off treatment. Cognitive tests measured spatial abilities, spatial memory, verbal fluency, verbal memory and selective attention. A total of 19 patients 52 to 76 years old completed the intermittent androgen suppression study along with 15 healthy community dwelling control participants. Combined androgen blockade reduced PSA and testosterone in all patients compared to baseline. Patients did not significantly change on measures of verbal and spatial memory, executive functions or language. Patients declined on a measure of spatial rotation and improved on a measure of verbal memory during treatment which continued during the off treatment period. Although preliminary, these findings demonstrate that 9 months of combined androgen blockade resulted in a beneficial effect on verbal memory but adversely affected a measure of spatial ability. Intermittent androgen suppression for a period of 9 months in otherwise healthy men with prostate cancer may have beneficial and adverse effects on cognition that are selective.


Quit Smoking Experts' Opinions toward Quality and Results of Quit Smoking Methods Provided in Tobacco Cessation Services Centers in Iran.
One of the core responsibilities of health system is to treat tobacco dependence. This treatment includes different methods such as simple medical consultation, medication, and telephone counseling. To assess physicians' opinions towards quality and result of different quit smoking methods provided in tobacco cessation services centers in Iran. In this cross-sectional and descriptive study, random sampling of all quit centers at country level was used to obtain a representative sample size of 100 physicians. Physicians completed a self-administered questionnaire which contained 10 questions regarding the quality, cost, effect, side effects, and the results of quitting methods using a 5-point Likert-type scale. Percentages, frequencies, mean, T-test, and variance analyses were computed for all study variables. Most experts preferred to use combination quit smoking methods and then Nicotine Replacement Therapy (NRT) with 26 and 23, respectively. The least used methods were quit line and some methods without medication with 3 cases. The method which gained the maximum scores were telephone consultation, acupuncture, Willpower, Champix, combined method, and Interactive Voice Response (IVR) with the mean of 23.3, 23, 22.5, 22, 21.7 and 21.3, respectively. The minimum scores were related to e-cigarette, some methods without medication, and non-NRT medication with the mean of 12.3, 15.8 and 16.2, respectively. There were no significant differences in the mean of scores based on different cities (P = 0.256). Analysis of variance in mean scores showed significant differences in the means scores of different methods (P < 0.000). According to physicians acupuncture, personal methods and Champix are the most effective methods and these methods could be much more feasible and cost effective than other methods.


Egg white protein hydrolysate decreased blood pressure via the competing endogenous RNA regulatory networks in female spontaneously hypertensive rats.
Despite numerous studies having reported the effects and mechanisms of antihypertensive peptides including peptides derived from egg white proteins, the role of peptides in a female hypertensive animal model is unknown. On the other hand, the role of epigenetic modulation by peptide treatment has rarely been investigated. This study sought to investigate the effect of egg white protein hydrolysate (EWH) in female spontaneously hypertensive rats (SHRs) as well as to explore the underlying mechanisms from the perspectives of the transcriptome and the profiles of non-coding RNAs. Young (12-14-week-old) female SHRs were orally administered 250 mg per kg body weight (low-dose) or 1000 mg per kg body weight (high-dose) EWH daily for 10 weeks. The blood pressure of the rats was monitored weekly. The mRNA and non-coding RNAs (miRNA, lncRNA, and circRNA) in the aorta were profiled by the high-throughput RNA-seq technique. Differentially expressed (DE) RNAs in the aorta were identified for the construction of the competing endogenous RNA (ceRNA) networks and key molecules were validated by qRT-PCR. The treatment of the high-dose EWH showed a significant effect on reducing blood pressure in female SHRs. Bioinformatic analyses revealed 813, 90, 347 and 869 DE-mRNAs, DE-miRNAs, DE-lncRNAs and DE-circRNAs, respectively. The CNTN5-LncRNA-XR_001835895.1-miR-384-5p was identified as the central network which was validated in the aorta and circulation of female SHRs. The results from this study demonstrated that the treatment with EWH reduced blood pressure via regulating the ceRNA networks in female SHRs, which provided novel insights into the mechanisms of food protein-derived antihypertensive peptides.


Surveying the damage: a review of research on consequences of alcohol misuse in college populations.
This article provides a review and synthesis of professional research literature on the types, extent and patterns of negative consequences produced by students' misuse of alcohol in college populations based on survey research conducted during the last two decades. Considerable evidence is available documenting a wide range of damage by some students' drinking done to themselves as well as to other individuals, although some types of consequences remain speculative. Damage and costs to institutions are likely to be substantial, but this claim remains largely an inference based on current studies. Drinking by males compared with that of females produces more consequences for self and others that involve public deviance, whereas females' drinking contributes equally with males to consequences that are personal and relatively private. Research on racial/ethnic background, time trends and developmental stages reveals patterns in student data on consequences of drinking, but these data are very limited in the literature. Evidence suggests there is only a modest correlation between students' self-perception of having a drinking problem and the many negative consequences of drinking that are reported.


Incidence of breakthrough infections after COVID-19 vaccination among the COVID-19 vaccine recipients at a Tertiary Care Hospital in Srinagar.
COVID-19 infections despite complete vaccination are called breakthrough infections. Breakthrough infections may decrease the vaccination confidence among people. This study was conducted soon after the Covishield vaccine was approved for use in J and K to find out the incidence of breakthrough infections among the recipients of the Covishield vaccine at SKIMS and to find out the associated factors. List of beneficiaries (between February 14, and May 15, 2021) was obtained from the records. Information was gathered telephonically. Incidence of breakthrough infections 6-month postvaccination was determined. Among 919 participants, the incidence of breakthrough infections was 2.7% (25 cases). The medical profession was associated with a higher frequency of breakthrough infections. Most infections were mild to moderate (96%). One (4%) person required hospitalization. Thus, COVID-19 infections can occur despite complete vaccination. Increased exposure places an individual at higher risk of breakthrough infections. Therefore, where exposure is high, COVID-appropriate behavior should be followed despite being vaccinated.


Ischiofemoral impingement in an 11-year-old girl.
Ischiofemoral impingement (IFI) is the entrapment of the quadratus femoris muscle (QFM) between the trochanter minor of the femur and the ischium-hamstring tendon. Patients with IFI generally present with hip pain, which may radiate toward the knee. Although there is no specific diagnostic clinical test for this disorder, the presence of QFM edema/fatty replacement and narrowing of the ischiofemoral space and the quadratus femoris space on magnetic resonance imaging (MRI) are suggestive of IFI. The optimal treatment strategy of this syndrome remains obscure. Patients may benefit from a conservative treatment regimen that includes rest, activity restriction, nonsteroidal anti-inflammatory drugs, and rehabilitation procedures, just as with other impingement syndromes. Herein we report an 11-year-old girl with IFI who was successfully treated conservatively. To our knowledge, our case is the youngest patient reported in the English literature. MRI remains an important tool in the diagnosis of IFI, and radiologists should be aware of the specific features of this entity.


Independent lung ventilation in a patient with complex congenital heart disease.
Independent lung ventilation (ILV) is recognized as a method of treating unilateral lung disease. We report the use of ILV in a 22-year-old woman with acute respiratory failure and complex congenital heart disease with different sources of left and right pulmonary blood flow. She had a palliated single-ventricle circulation with pulsatile pulmonary blood flow from an aorto-pulmonary central shunt to her left lung and nonpulsatile pulmonary blood flow via a classic Glenn shunt (superior vena cava to right pulmonary artery). On admission she was hypoxemic and hypotensive. Her chest radiograph revealed opacification of the left lung and hyperinflation of the right lung, which was more compliant than the left lung. Following placement of a double-lumen endotracheal tube, synchronized ILV was instituted. ILV allowed us to deliver lower ventilator pressure to the right lung, which alleviated the over-distention of the right lung (to which pulmonary blood flow was supplied by the nonpulsatile Glenn shunt) while higher airway pressures were delivered to the diseased left lung, to facilitate re-expansion. There was immediate improvement in gas exchange and blood pressure. After 3 days the double-lumen endotracheal tube was changed to a single-lumen tube. She was extubated on day 6 and discharged on day 13. This case demonstrates the advantage of ILV in a patient with abnormal pulmonary blood flow and different lung mechanics in the left and right lungs.


Flux conversion and evidence of relaxation in a high-beta plasma formed by high-speed injection into a mirror confinement structure.
High-beta plasmoids can survive the violent dynamics of supersonic reflection off mirror structures, producing a stable high-beta field-reversed configuration (FRC). This shows both the robustness of FRCs and their tendency to assume a preferred plasma state, possibly conforming to a relaxation principle. The key observations are (1) approximate preservation of the magnetic helicity, (2) substantial conversion from toroidal to poloidal magnetic flux, (3) substantial toroidal flow, and (4) a high-beta quiescent final state. These results are from the Translation, Confinement, and Sustainment experiment where a disorganized plasmoid is injected at super-Alfvenic speed into a confinement chamber. After successive reflections from end mirrors, the plasmoid settled into a near-FRC state with high beta and low toroidal magnetic field. The flux conversion and helicity preservation are inferred by an interpretive model.


Hourglass-shaped nitinol prostatic stent in treatment of patients with lower urinary tract symptoms due to bladder outlet obstruction.
To assess the efficacy and safety of the thermoexpandable hourglass-shaped nitinol prostatic stent in the treatment of patients with lower urinary tract symptoms due to bladder outlet obstruction. The stents were inserted in an outpatient setting under local anesthesia and direct vision. Five different stent lengths (2.0 to 4.0 cm) were used, depending on the length of the prostatic urethra. Assessment of voiding function and symptom scores was performed at baseline, directly after stent insertion, at 14 days, and 1, 3, 6, and 12 months after stent placement. We enrolled 35 men in the trial. In 5 patients, insertion of the stent failed, mainly because of anatomical limitations. After all placement procedures, minimal temporary hematuria was observed. Spontaneous voiding was achieved in all patients, with immediate significant improvements in voiding parameters and symptom scores. The median indwelling time of the stent was 70 days. Kaplan-Meier survival analysis showed that at 14 days and at 3, 6, and 12 months, the stent was still in situ in 73%, 40%, 33%, and 23% of the patients, respectively. The main reason for removal of the stent was migration (93%), in most cases toward the bladder. Removal was uneventful in all but 1 case. The placement of the thermoexpandable hourglass-shaped nitinol stent results in relief of outflow obstruction and improvement of symptom scores. Because of the high migration rate, however, this stent design needs further improvement to be suitable for clinical practice.


Teatime Threats. Choking Incidents at the Evening Meal.
To explore caregiver perceptions of the socio-environmental issues around evening meal ('teatime') which influence choking. Mealtime difficulties for people with intellectual disabilities and/or mental illness may be underdiagnosed. Difficulties affect quality of life with social aspects impacting on service-users and caregivers. Reporting of choking incidents has increased locally following widespread training. Analysis of reports showed most incidents were occurring around evening meal. A qualitative study of caregivers witnessing a choking incident was undertaken. Semi-structured interviews explored perceptions of the causes. Data were analysed using thematic analysis. Thematic analysis elicited individual service user characteristics, and social and contextual factors implicated in choking. The findings will facilitate risk assessment for service-users and inform mealtime practice. Staff familiarity is a key factor. Further research involving service-users is indicated to complement these findings. This study widens the focus of recent studies which have considered physical more than socio-environmental aspects of mealtime difficulties.


Substrate doping: A strategy for enhancing reactivity on gold nanocatalysts by tuning sp bands.
We suggest that the reactivity of Au nanocatalysts can be greatly increased by doping the oxide substrate on which they are placed with an electron donor. To demonstrate this, we perform density functional theory calculations on a model system consisting of a 20-atom gold cluster placed on a MgO substrate doped with Al atoms. We show that not only does such substrate doping switch the morphology of the nanoparticles from the three-dimensional tetrahedral form to the two-dimensional planar form, but it also significantly lowers the barrier for oxygen dissociation by an amount proportional to the dopant concentration. At a doping level of 2.78%, the dissociation barrier is reduced by more than half, which corresponds to a speeding up of the oxygen dissociation rate by five orders of magnitude at room temperature. This arises from a lowering in energy of the s and p states of Au. The d states are also lowered in energy, however, this by itself would have tended to reduce reactivity. We propose that a suitable measure of the reactivity of Au nanoparticles is the difference in energy of sp and d states.


Mechanistic Computational Models of MicroRNA-Mediated Signaling Networks in Human Diseases.
MicroRNAs (miRs) are endogenous non-coding RNA molecules that play important roles in human health and disease by regulating gene expression and cellular processes. In recent years, with the increasing scientific knowledge and new discovery of miRs and their gene targets, as well as the plentiful experimental evidence that shows dysregulation of miRs in a wide variety of human diseases, the computational modeling approach has emerged as an effective tool to help researchers identify novel functional associations between differential miR expression and diseases, dissect the phenotypic expression patterns of miRs in gene regulatory networks, and elucidate the critical roles of miRs in the modulation of disease pathways from mechanistic and quantitative perspectives. Here we will review the recent systems biology studies that employed different kinetic modeling techniques to provide mechanistic insights relating to the regulatory function and therapeutic potential of miRs in human diseases. Some of the key computational aspects to be discussed in detail in this review include (i) models of miR-mediated network motifs in the regulation of gene expression, (ii) models of miR biogenesis and miR⁻target interactions, and (iii) the incorporation of such models into complex disease pathways in order to generate mechanistic, molecular- and systems-level understanding of pathophysiology. Other related bioinformatics tools such as computational platforms that predict miR-disease associations will also be discussed, and we will provide perspectives on the challenges and opportunities in the future development and translational application of data-driven systems biology models that involve miRs and their regulatory pathways in human diseases.


X(3915) and X(4350) as new members in the P-wave charmonium family.
The analysis of the mass spectrum and the calculation of the strong decay of P-wave charmonium states strongly purport to explain the newly observed X(3915) and X(4350) as new members in the P-wave charmonium family, i.e., chi{c0}{'} for X(3915) and chi{c2}{''} for X(4350). Under the P-wave charmonium assignment to X(3915) and X(4350), the J{PC} quantum numbers of X(3915) and X(4350) must be 0{++} and 2{++} respectively, which provide important criteria to test the P-wave charmonium explanation for X(3915) and X(4350) proposed by this Letter. The decay behavior of the remaining two P-wave charmonium states with the second radial excitation is predicted, and an experimental search for them is suggested.


Halothane, enflurane and isoflurane anaesthesia for adenoidectomy in children, using two different premedications.
In 48 children subjected to adenoidectomy, comparisons of airway problems, heart rates, cardiac arrhythmias, ventilation and stress hormone reactions were studied during halothane, enflurane and isoflurane anaesthesia. Sixteen children were anaesthetized with either of the three agents and eight patients in each group received diazepam 0.25 mg kg-1 and atropine 0.015 mg kg-1 rectally (DA) as premedication and the remainder diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and scopolamine 0.01 mg kg-1 (DMS) rectally. All children were intubated and breathing spontaneously. Equianaesthetic inspired concentrations of halothane, enflurane and isoflurane were used. Airway problems were of the same magnitude during halothane and isoflurane anaesthesia but were less frequent with both agents compared with enflurane anaesthesia. DMS reduced the number of airway reactions in all groups. Respiratory rates were uninfluenced by anaesthesia, intubation and surgery during enflurane anaesthesia. Cardiac arrhythmias were less frequent with enflurane and isoflurane than with halothane. Plasma ACTH and cortisol were similar with all three agents. During induction of anaesthesia in the DA-premedicated halothane group, however, plasma catecholamines were higher than in the group which received DMS, in contrast to the findings during enflurane and isoflurane anaesthesia. The DMS premedication decreased the response of plasma ACTH, cortisol and plasma catecholamines to surgery.


Characterization of Naegleria species by restriction endonuclease digestion of whole-cell DNA.
Whole-cell DNA in Naegleria spp. and two related genera was examined by restriction endonuclease digestion and fractionation of the fragments by agarose gel electrophoresis. Visual inspection of ethidium bromide-stained gels shows differences in banding pattern between N. fowleri, N. lovaniensis, N. gruberi, N. jadini, N. australiensis, Didasculus thorntoni and Willaertia magna, and between the two subspecies of N. australiensis. Even between strains belonging to the same species differences could be observed. Significant differences were seen between strains of N. fowleri according to the continent of origin, and a hypothesis on the ancestry and the dispersal of N. fowleri was deduced from it. A N. fowleri strain isolated from one of the very few cured human infections showed the most distinct pattern within the species. The considerable variation detected with serological and biochemical techniques between strains of N. australiensis as well as between strains of N. gruberi, was confirmed in the analysis of their whole-cell DNA. With this technique the existence of N. jadini, D. thorntoni, W. magna and two Naegleria strains as separate systematic entities is substantiated.


Prevalence and correlates of cervical squamous intraepithelial lesions among HIV-infected and uninfected women in Central Kenya.
cervical intraepithelial neoplasia the precursor of cervical cancer occurs with increased frequency in women infected with human immunodeficiency virus (HIV). This study aimed at determining the prevalence and correlates of abnormal cervical cytology among HIV-infected women and compare to the uninfected women. a cross-sectional study conducted among HIV-infected and uninfected women enrolled in a HIV study in Central Kenya. All women had baseline Pap smear examination assessed using Bethesda system. Bivariate and multivariate logistic regression methods were employed to assess the correlates of cervical squamous epithelial lesions (CSIL). a total 480 women had an acceptable baseline smear, 373 (78%) were HIV-infected. Median age was 30.2 years [IQR 25.4-35.5]. Overall prevalence of CSIL was 37% (176/480) with the prevalence of low grade squamous intraepithelial lesion (LSIL), atypical squamous cells undetermined significance (ASCUS), high grade squamous intraepithelial lesions (HSIL) and atypical glandular cells (AGC) were 17%, 14%, 4% and 2% respectively. HIV-infected women had a higher prevalence of CSIL at 42% as compared to HIV-uninfected women at 19%. HIV infection was the predictor associated with development of CSIL at multivariate analysis and specifically, HIV-infected women were 3 times (AOR 3.1, 95% CI: 1.8 - 5.4, p<0.005) more likely to have CSIL than HIV-uninfected women. The age 35 - 44 years was protective to developing CSIL (AOR 0.45, 95% CI: 0.24 - 0.87, p=0.018). cervical squamous epithelial lesions is a major problem among Kenyan women. HIV infection confers a higher risk to development of CSIL. Cervical cancer screening should be an established practice in HIV programs.


[Recalled parental rearing and the wish to have a child - are there associations?].
The present study concerns the impact of recalled parental rearing behaviour on both the intensity of the wish to have a child and on different motives to have a child. Until now there are no empirical studies as to this objective. Our study is based on a representative sample of 1509 persons aged 18 to 50 years. The statistical analyses were restricted to those subjects who lived in partnership and reported an actual wish to have a child (n = 331). The data were assessed by self-reporting scales: The Questionnaire of Recalled Parental Rearing Behaviour "Fragebogen zum erinnerten elterlichen Erziehungsverhalten, FEE", the Partnership Questionnaire "Partnerschaftsfragebogen, PFB", and the Leipzig Questionnaire of Motives to Have a Child "Leipziger Fragebogen zu Kinderwunschmotiven, LKM". A recalled parental rearing behaviour, which was characterized as having been rejective, overprotective and less emotionally warm was associated with such motives which do not promote the wish to have own children (fear of personal restrictions and a low degree of social support). Simultaneously, a negative parental rearing behaviour was correlated with a stronger desire for social recognition by an own child. The recalled maternal rearing behaviour was altogether stronger associated with motives to have a child than the paternal. On the other hand, no relevant associations could be found between the recalled parental rearing behaviour and the intensity of the wish to have a child.


[Acute respiratory failure in a medical intensive care unit. Incidence and prognosis].
Acute respiratory failure had occurred in 89 of 1594 patients in a medical intensive care unit (5.6%), 26.8% of all patients (332) on long-term mechanical ventilation. Compared with the other chronically ventilated patients those with acute respiratory failure averaged a lower age, the proportion of women was higher and the duration of ventilation longer. The death rate was significantly higher (78.7% compared with 58.3%). The important prognostic factors included the underlying disease, additional abnormal organ function, severity of pulmonary gas exchange abnormality, and advanced age. If there was septicaemia, peritonitis, liver cirrhosis with bleeding oesophageal varices or polytrauma with acute renal failure the death rate was over 80%; after hypovolaemic shock, pancreatitis or postoperative pulmonary failure it was less than 65%. Patients who had abnormal function of at most one other organ in addition and an inspiratory arterial pO2 difference below 250 mm Hg, measured 12 hours after onset of mechanical ventilation, had a relatively favourable prognosis with a death rate of 33%, while in the other groups of patients it was 86-100%.


Trust your Endocrinologist - Report and Recommendations on the Ordering of Reverse T3 Testing.
Laboratory testing for markers of thyroid function is essential for the diagnosis of thyroid disease, yet, the landscape of thyroid function testing is complex and inappropriate test orders are common. Reverse T3 (rT3) is frequently seen on thyroid function testing menus as a marker of nonthyroidal illness. However, the diagnostic utility of rT3 for this indication is questionable, and testing of rT3 is not recommended by any professional practice guidelines. We reviewed a set of rT3 orders at our institution, and identified that 11 of 20 orders appeared inappropriate with respect to clinical context. These orders were less likely to have been placed at the recommendation of an endocrinologist relative to appropriate orders. We recommend that all providers refer to professional guidelines for thyroid function testing, and consult with an endocrinologist for appropriate usage of esoteric or non-standard thyroid function tests.


Role of HER receptors family in development and differentiation.
Members of the epidermal growth factor receptor family of receptor tyrosine kinases play a critical role in both development and oncogenesis. The latter is suggested by the frequent overexpression of HER-2, EGFR, and HER-3 in some human carcinomas, primarily breast and squamous cancer. The biological activities of the EGFR family are exerted through various ligand-receptor and receptor-receptor interactions. One receptor that plays a central role in this signaling network is HER-2/Neu, which is considered the preferred heterodimerization partner for other members of the EGFR family. The role of these receptors and their ligands in development is discussed, with particular emphasis on their ability to mediate a variety of pathways and cellular responses, including proliferation, differentiation, and apoptosis.


Expanding the physician's role in addressing the oral health of adults.
Many disadvantaged adults visit physicians or hospital emergency departments to receive relief from dental pain. Physicians also see patients with general questions or concerns about their oral health. Unfortunately, because physicians generally have received little oral health training, patients often do not receive comprehensive emergency services or appropriate counseling. This situation has begun to change, as there has been a growing sentiment among the dental and medical communities that better integration and coordination between medicine and dentistry would be beneficial. Reports from the Institute of Medicine and professional associations and foundations reflect the need for better integration. I have outlined the rationale for and progress toward expanding the physician's role in addressing the oral health of adults.


Spotlight On Early-career Researchers: an interview with Verena Ruprecht.
Verena Ruprecht is a group Leader in the Cell & Developmental Biology program at the Centre for Genomic Regulation (CRG) in Barcelona. She studies organismal development using zebrafish as a system, taking an interdisciplinary approach involving cell and molecular biology, imaging and mathematical tools to obtain information on the scale of molecules, cells, and tissues. We have asked Dr. Ruprecht about her research and thoughts about the future of her field as part our series on early-career researchers.