Effect of varicocelectomy on testis volume and semen parameters in adolescents: a meta-analysis.
Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials (RCTs) and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml (95% confidence interval [CI]: 0.6, 5.2; P< 0.05) for the varicocele side and 1.5 ml (95% CI: 0.3, 2.7; P< 0.05) for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 × 10 6 ml-1 (95% CI: -1.4, 28.8; P = 0.075), 2.5% (95% CI: -3.6, 8.6; P= 0.424), and 2.9% (95% CI: -3.0, 8.7; P= 0.336) respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates.


Epidemiology of Streptococcus uberis intramammary infections in a dairy herd.
From 1987 to 1991, almost 36,000 quarter samples of mammary secretion representing 1790 lactations of 510 dairy cows from a research herd were collected for bacteriological examination. The percentage of cows infected with Streptococcus uberis ranged from 12 to 16% of cows/year. S. uberis was isolated from 14.2% of lactations over the 5-year period. The prevalence of S. uberis intramammary infection (IMI) was significantly higher in cows with > or = 4 lactations than in cows with 3 or fewer lactations. Regardless of lactation number, the prevalence of S. uberis was highest before parturition, during early lactation and near drying off. The prevalence of S. uberis infected quarters ranged from 1.3 to 2.3% of quarters/year; the prevalence rate for the 5-year period was 2% of quarters. The quarter prevalence of S. uberis was lowest in cows with < or = 3 lactations, increased significantly with lactation number and was highest in cows with > or = 6 lactations. The percentage of quarters infected with S. uberis varied significantly by year. The majority (95%) of S. uberis IMI were subclinical. The ratio of subclinical IMI to clinical IMI was lowest during early lactation, and increased with days in milk, and with lactation age except for cows in their 5th and 6th lactations. Results of this epidemiological investigation suggest that opportunities exist where suitable control measures could be applied to reduce the impact of S. uberis infections in the dairy herd.


Real-time, evidence-based medicine instruction: a randomized controlled trial in a neonatal intensive care unit.
The study assesses potential for improving residents' evidence-based medicine searching skills in MEDLINE through real-time librarian instruction. Ten residents on a rotation in a neonatal intensive care unit participated. Residents were randomized into an instruction and a non-instruction group. Residents generated questions from rounds and searched MEDLINE for answers. Data were collected through observation, search strategy analysis, and surveys. Librarians observed searches and collected data on questions, searching skills, search problems, and the test group's instruction topics. Participants performed standardized searches before, after, and six-months after intervention and were scored using a search strategy analysis tool (1 representing highest score and 5 representing lowest score). Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction. Post-intervention, the test group formulated better questions, used limits more effectively, and reported greater confidence in using MEDLINE. The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting. The test and control groups had the following average search scores respectively: 3.0 and 3.5 (pre-intervention), 3.3 and 3.4 (post-intervention), and 2.0 and 3.8 (six-month post-intervention). Data suggest that measurable learning outcomes were achieved. Residents receiving instruction improved and retained searching skills six-months after intervention.


Review of neurophysiological findings in patients with schizophrenia.
Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry have been proposed as a basis for this disorder. In this article, we focus on electroencephalography and magnetoencephalography findings in patients with schizophrenia. Auditory-P50, -N100, and -P300 findings, visual-P100, -N170, and -N400 findings, and neural oscillations in patients with schizophrenia are overviewed. Published results suggest that patients with schizophrenia have neurophysiological deficits from the very early phase of sensory processing (i.e., P50, P100, N100) to the relatively late phase (i.e., P300, N400) in both auditory and visual perception. Exploring the associations between neural substrates, including neurotransmitter systems, and neurophysiological findings, will lead to a more comprehensive understanding of the pathophysiology of schizophrenia.


[Preparation of the 5-Fu floating sustained release tablet for gastric retention].
To develop a pH independent floating sustained release tablet for gastric retention using 5-Fluorouracil (5-Fu) as a model drug. According to the theory of the Hydro-dynamically Balanced System, the granules for the floating and drug loading layer were prepared separately and pressed together to make two-layer floating tablets for gastric retention. The floating kinetics indexes were measured and the data about drug release studied with media of different pH values. An excellent floating ability was observed in the media of different acidity for the gastric retentive tablet prepared according to the optimum formulation. The in vitro drug release can be modified by the regulation of the formulation ingredients. At the rotating speed of 100 r/min and in 0.1 mol/L HCl, the drug release was found to conform to first-class dynamics rule. The two-layer floating tablet made in this experiment,whose floating ability is independent of the gastric acidity variation, is of the possibility to be used for the auxiliary treatment of gastric carcinoma because of its prolonged gastric retention.


Compact region extraction using weighted pixel linking in a pyramid.
This correspondence describes a method of image segmentation based on a ``pyramid'' of reduced-resolution versions of the image. It defines link strengths between pixels at adjacent levels of the pyramid, based on proximity and similarity, and iteratively recomputes the pixel values and adjusts the link strengths. After a few iterations, the strengths stabilize, and the links that remain strong define subtrees of the pyramid; the leaves of each tree are the pixels belonging to a compact (piece of a) homogeneous region in the image.


Arterial aneurysms associated with arteriovenous malformations of the brain: classification, incidence, risk of hemorrhage, and treatment-a systematic review.
Aneurysms associated with brain arteriovenous malformations (bAVMs) influence the natural history of these lesions and pose important therapeutic challenges. However, the epidemiology, natural history, and appropriate management of the aneurysms associated with bAVMs are not completely understood due to the paucity of large and uniform studies. We performed a systematic review of published series examining the association between aneurysms and bAVMs with the purpose of clarifying the prevalence, risk of hemorrhage, and appropriate management of these lesions. PRISMA/MOOSE guidelines were followed. We conducted a comprehensive literature search of three databases (PubMed, Ovid MEDLINE, and Ovid EMBASE) on aneurysms associated with bAVMs. Only studies examining consecutive case series of aneurysms associated with bAVMs were included. From the collected studies, we extracted data regarding prevalence of bAVM-associated aneurysms, risk of aneurysm rupture in relation to bAVM location and aneurysm characteristics, and treatment-related outcomes. Our systematic review included 44 articles with a total of 10,093 bAVMs. The proportion of bAVMs with an associated aneurysm was 20.2 % (95 % CI = 19.4-20.9 %). Among ruptured bAVMs with associated aneurysms, the aneurysm was the source of hemorrhage in 49.2 % (95 % CI = 43.7-54.7 %) of cases. Flow-related aneurysms were the most common source of aneurysm rupture (78.5 %, 95 % CI = 70.6-84.9 %). Infratentorial bAVM-associated aneurysms presented a higher risk of rupture (60 %, 95 % CI = 47.4-71.9 %) when compared with supratentorial lesions (29 %, 95 % CI = 21.4-38.5 %). Endovascular treatment of aneurysms associated with bAVMs had a cure rate of 80.0 % (95 % CI = 73.3-85.3 %), complication rate of 8.7 % (95 % CI = 5.5-13.1 %), and a good neurological outcome rate of 78.8 % (95 % CI = 72.5-83.9 %). Twenty percent of bAVMs harbored arterial aneurysms. The presence of aneurysm increases the risk of bleeding of the bAVM, especially when flow-related or infratentorially located. Aneurysms associated with bAVMs should be treated promptly. Selective endovascular treatment of bAVM-associated aneurysms appears safe and effective.


Wave energy level and geographic setting correlate with Florida beach water quality.
Many recreational beaches suffer from elevated levels of microorganisms, resulting in beach advisories and closures due to lack of compliance with Environmental Protection Agency guidelines. We conducted the first statewide beach water quality assessment by analyzing decadal records of fecal indicator bacteria (enterococci and fecal coliform) levels at 262 Florida beaches. The objectives were to depict synoptic patterns of beach water quality exceedance along the entire Florida shoreline and to evaluate their relationships with wave condition and geographic location. Percent exceedances based on enterococci and fecal coliform were negatively correlated with both long-term mean wave energy and beach slope. Also, Gulf of Mexico beaches exceeded the thresholds significantly more than Atlantic Ocean ones, perhaps partially due to the lower wave energy. A possible linkage between wave energy level and water quality is beach sand, a pervasive nonpoint source that tends to harbor more bacteria in the low-wave-energy environment.


An Education and Field Experience Program to Increase Detection of Human Immunodeficiency Virus and Hepatitis C Virus.
Baltimore is an urban center that has been highly impacted by human immunodeficiency virus (HIV) and hepatitis C virus (HCV); however, many individuals are unaware of their HIV and/or HCV status. In 2013, the Johns Hopkins Center for AIDS Research (CFAR) developed Generation Tomorrow, an HIV and HCV education, testing, and counseling program with community input and collaboration. The aims of Generation Tomorrow are to increase HIV and HCV awareness and detection in Baltimore and engage the next generation of health professionals (students) and community members (peers) in HIV and HCV outreach services. The Generation Tomorrow educational component includes formal HIV and HCV testing and counselling training, and a lecture series for students and peers. The participants then engage in field assignments and outreach events with Johns Hopkins associated programs or community-based organizations. Generation Tomorrow trained 71 students and peers in three cohorts, 70% of whom reported that they planned to stay in HIV- and/or HCV-related work. From October 2014 to May 2015, which represents the first year that Generation Tomorrow ran with the full academic calendar, Generation Tomorrow students and peers worked with partner organizations to conduct 1,104 HIV rapid antibody tests and found 19 individuals (1.72%) to be HIV positive. Additionally, 778 HCV rapid antibody tests were conducted and 175 individuals (22.5%) were HCV antibody positive. Generation Tomorrow has been successful in engaging students and community peers in HIV and HCV education, testing, and counseling, and has documented HIV and HCV positivity rates well above general community prevalence.


Occurrence and stability of hetero-hexamer associations formed by β-carboxysome CcmK shell components.
The carboxysome is a bacterial micro-compartment (BMC) subtype that encapsulates enzymatic activities necessary for carbon fixation. Carboxysome shells are composed of a relatively complex cocktail of proteins, their precise number and identity being species dependent. Shell components can be classified in two structural families, the most abundant class associating as hexamers (BMC-H) that are supposed to be major players for regulating shell permeability. Up to recently, these proteins were proposed to associate as homo-oligomers. Genomic data, however, demonstrated the existence of paralogs coding for multiple shell subunits. Here, we studied cross-association compatibilities among BMC-H CcmK proteins of Synechocystis sp. PCC6803. Co-expression in Escherichia coli proved a consistent formation of hetero-hexamers combining CcmK1 and CcmK2 or, remarkably, CcmK3 and CcmK4 subunits. Unlike CcmK1/K2 hetero-hexamers, the stoichiometry of incorporation of CcmK3 in associations with CcmK4 was low. Cross-interactions implicating other combinations were weak, highlighting a structural segregation of the two groups that could relate to gene organization. Sequence analysis and structural models permitted the localization of interactions that would favor formation of CcmK3/K4 hetero-hexamers. The crystallization of these CcmK3/K4 associations conducted to the elucidation of a structure corresponding to the CcmK4 homo-hexamer. Yet, subunit exchange could not be demonstrated in vitro. Biophysical measurements showed that hetero-hexamers are thermally less stable than homo-hexamers, and impeded in forming larger assemblies. These novel findings are discussed within the context of reported data to propose a functional scenario in which minor CcmK3/K4 incorporation in shells would introduce sufficient local disorder as to allow shell remodeling necessary to adapt rapidly to environmental changes.


Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions.
A 24 hour gastric aspiration study was carried out on nine Polya gastrectomy, eight pernicious anaemia, and nine matched control subjects. Intragastric pH, bacteria, nitrite, and N-nitroso compounds were assessed half hourly whilst ambulant and hourly when in bed. Both total and nitrate reducing bacterial counts were positively related to pH (chi 2 = 279.3; p less than 0.001), as was nitrite concentration (F = 19.1; p less than 0.0001). By contrast, total (F = 40.6; p less than 0.0001) and stable (F = 257.4; p less than 0.0001) N-nitroso compound concentrations were negatively related to pH. Clear differences in these gastric juice factors were not apparent between matched control and either pernicious anaemia, or Polya gastrectomy because the Polya gastrectomy and matched control groups were heterogeneous for gastric acidity. Thus, although eight of eight pernicious anaemia subjects were hypoacidic (defined as intragastric pH greater than 4 for greater than 50% of both daytime and night time periods), only five of nine Polya gastrectomy and two of nine matched control subjects were hypoacidic. When subjects were rearranged into hypoacidic (n = 15) and acidic (n = 11) groups, bacterial counts (p less than 0.01) and nitrite concentrations (p less than 0.01) were higher, whereas N-nitroso compounds tended to be lower (NS) in the hypoacidic group. These data suggest that, although hypoacidity predisposes to bacterial overgrowth and nitrite generation, it does not enhance nitrosation. Instead, this is maximal at low pH, suggesting chemical rather than bacterial nitrosation, contrary to the nitrosamine hypothesis of gastric carcinogenesis.


Gene conversion tracts stimulated by HOT1-promoted transcription are long and continuous.
The recombination-stimulating sequence, HOT1, corresponds to the promoter of transcription by yeast RNA polymerase I. The effect of HOT1 on mitotic interchromosomal recombination was examined in diploid strains carrying a heterozygous URA3 gene on chromosome III. The frequency of Ura- recombinants was increased 20-fold when HOT1 was inserted into the chromosome III copy marked with URA3, at a location 48 kbp centromere-proximal to URA3. Ura- recombinants were increased only 2-fold when HOT1 and URA3 were on opposite homologues. These results suggest that most HOT1-promoted Ura- recombinants result from gene conversion and that sequences on the HOT1-containing chromosome are preferentially converted. Characterization of Ura- recombinants isolated from strains carrying multiple markers on chromosome III indicates that HOT1-promoted gene conversion tracts are unusually long (often greater than 75 kbp) and almost always continuous. Furthermore, conversion tracts frequently extend to both sides of HOT1. We suggest that HOT1 promotes the formation of a double-strand break which is often followed by exonucleolytic digestion. Repair of the broken chromosome could then result from gap repair or from replicative repair primed only by the centromere-containing chromosomal fragment.


Household transmission of COVID-19 in 2020 in New South Wales, Australia.
Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study examines factors associated with transmission among cases diagnosed with coronavirus disease 2019 (COVID-19) and their household contacts, in New South Wales (NSW), Australia, during July-October 2020. A register of all laboratory-confirmed COVID-19 cases was used to extract demographic and clinical information for cases and household contacts. Secondary attack rates (SARs) among household members were calculated and generalised estimating equations were used to estimate risks of transmission in relation to various characteristics of the primary case and the household contacts. In total, 229 households were included; they consisted of 229 primary cases and 659 close contacts. The overall household SAR was 22.5% (148/659). After adjusting for symptoms, age and sex of primary case, spouse status of household contacts and household size, the odds of secondary transmission were lower in primary cases who were asymptomatic at diagnosis than in symptomatic cases (odds ratio, OR: 0.13; 95% confidence interval (95% CI): 0.04-0.48); and higher in primary cases aged 60 years and over than in those aged 19-39 years (OR: 3.45; 95% CI: 1.53- 7.75). Being a spouse of the primary case was also associated with increased transmission compared to non-spouses (OR: 1.93; 95% CI: 1.24-3.02). After adjustments, there was no significant effect on transmission of the primary case's sex, or of the number of people in the household. This study documents demographic and clinical characteristics that increase transmission rates in households in the period prior to the introduction of SARS-CoV-2 variants. These data can be used as a baseline from which to compare household transmission in outbreaks dominated by new variants.


The changing view of neural specificity.
The generation of specific patterns of neuronal connections has usually been regarded as a central problem in neurobiology. The prevailing view for many years has been that these connections are established by complementary recognition molecules on the pre- and postsynaptic cells (the chemoaffinity theory). Experimental results obtained in the past decade, however, indicate that the view that axon guidance and synaptogenesis proceed according to restrictive chemical markers is too narrow. Although a more rigid plan may prevail in some invertebrates, the formation of specific connections in vertebrates also involves competition between axon terminals, trophic feedback between pre- and postsynaptic cells, and modification of connections by functional activity.


Do faxed quitline referrals add value to dental office-based tobacco-use cessation interventions?
The Ask, Advise, Refer (AAR) model of intervening with patients who use tobacco promotes a brief office-based intervention plus referral to a tobacco quitline. However, there is little evidence that this model is effective. The primary aim of this study was to evaluate the effects on patients' tobacco use of two levels of a dental office-based intervention compared with usual care. The authors randomly assigned 68 private dental clinics to one of three conditions: 5 As (Ask, Advise, Assess, Assist, Arrange); 3 As (AAR model); or usual care, and they enrolled 2,160 participants. At the 12-month assessment, compared with those in usual care, participants in the two intervention conditions combined were more likely to report cessation of tobacco use, as measured by nine-month prolonged abstinence (3 percent versus 2 percent; F(1,66) = 3.97, P < .10) and 12-month point prevalence (12 percent versus 8 percent; F(1,66) = 7.32, P < .01). There were no significant differences between participants in the clinics using the 5 As and 3 As strategies. The results of this study are inconclusive as to whether referrals to a quitline add value to brief dental office-based interventions. Patients receiving telephone counseling quit tobacco use at higher rates, but only a small percentage of those proactively referred actually received counseling. The results confirm those of previous research: that training dental practitioners to provide brief tobacco-use cessation advice and assistance results in a change in their behavior, and that these practitioners are effective in helping their patients to quit using tobacco.


Is There A Difference Between Disease-Free Survival Of Oral Squamous Cell Carcinoma Referred By Dentists Versus Other Physicians? A Systematic Review.
To compare disease-free survival rates in oral squamous cell carcinoma patients initially attended and referred by dentists versus other physicians. The systematic review was conducted after registration with the International prospective register of systematic reviews at the University of York, the United Kingdom, and comprised search on Medline, PubMed, Cochrane and CINAHAL Plus databases for studies published up to December 2021. The Population-Intervention-Comparison- Outcomes-Study criteria was used to search for studies involving patients diagnosed with oral squamous cell carcinoma receiving referrals by dentist or by other healthcare providers. Disease-free survival of patients was taken as the main outcome. Customized data collection proforma was used to record data in line with the Preferred Reporting Items in Systematic Reviews and Meta- Analysis guidelines. Data was subjected to systematic, qualitative review. Of the 344 studies found, 8(2.3%) were analysed in detail. Patients referred by dentists ranged from 22.6% to 54%. Males comprised 53% to 70.3% of the sample. The highest number of referrals was made by primary physicians, ranging from 27.4% to 71.6%. Upto 67.6% cases were diagnosed with stage 1 and 2 oral cancer. The highest 5-year survival rate was 75% in a study where 59% patients were diagnosed at an early stage of disease. The relative scarcity of studies makes it impossible to draw an association between oral cancer survival rate and type of referral.


[The assessment of the role of different drug classes in the therapy of opioid dependence].
Based on clinical observation and the results of the treatment of 377 patients with opioid dependence, overall efficacy of 10 main classes of standard pharmaceuticals has been evaluated. The advantages and disadvantages of certain groups of drugs are discussed. The drugs of the first line proved to be alpha 2-adrenergic agents, neuroleptics and opioid receptors antagonists. An expressed specificity of neuroleptic and other medical responses of opioid addicts was detected. It is suggested that high tolerability to opioids results in the cerebral reactivity changes. A problem of resistance of many psychopathological phenomena, specific for opioid dependence, to drug therapy is discussed.


Variability in the size, composition, and function of insect flight muscles.
In order to fly, insects require flight muscles that constitute at least 12 to 16% of their total mass, and flight performance increases as this percentage increases. However, flight muscles are energetically and materially expensive to build and maintain, and investment in flight muscles constrains other aspects of function, particularly female fecundity. This review examines ways in which insects vary the size of their flight muscles, and how variation in the relative size and composition of flight muscles affects flight performance. Sources of variability in flight muscle size and composition include genetic differences within and between species, individual phenotypic responses to environmental stimuli, and maturational changes that occur before and during the adult stage. Insects have evolved a wide variety of ways to adjust flight muscle size and contractile performance in order to meet demands imposed by variation in life history and ecology.


Individual and population sex allocation patterns.
A variety of sex allocation models is considered in which the reproductive returns on investment in males differ from the returns on investment in females, the amounts of resources available for reproduction vary in the population, the costs of making male and female reproductive structures differ, and the conception sex ratio may be fixed and there may be an initial minimum investment per offspring. Results of these models include quantitative predictions for both individual- and population-level sex allocation, an opportunity to study the magnitude of changes in predicted patterns as key variables change, and therefore an analysis of the robustness of Fisher's equal investment theory. One example is that Fisher's argument is extremely robust for high fecundity organisms, but, in low fecundity organisms, is sensitive to differences between the sexes in reproductive returns on investment per offspring, a situation that occurs in many vertebrates to which Fisher's theory is often applied. A second example is that individual- and population-level patterns often depend strongly on the distribution of resources available for reproduction among individuals in the population.


Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. extracts.
The present study aims to clarify the inhibitive effect of the compounds from Rheum palmatum L. on the SARS-3CL protease. The SARS-CoV 3CL gene was amplified from RNA of the SARS virus by PCR. The SARS-CoV 3CL protease was purified from a colon bacillus recombinant. Drugs and 3CL protease were incubated together. The inhibition rate and IC(50) were calculated based on absorbance. Components from the Rheum palmatum L. had a high level of anti-SARS-CoV 3CL protease activity. The IC(50) was 13.76 +/- 0.03 microg/mL and the inhibition rate was up to 96%. In conclusion, extracts from Rheum palmatum L. have a high level of inhibitory activity against 3CL protease, suggesting that extracts from Rheum palmatum L. may represent a potential therapeutic for SARS.


Absence of Whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling.
Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+ block might play a special role. In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NMDAR subunits and other important neurotransmitter receptors. Our results show that coincidence detection by, and/or Ca2+ permeability of, NMDARs is necessary for the development of somatotopic maps in the brainstem and suggest that highly specific signaling underlies synaptic refinement.


Colorectal cancer with indeterminate pulmonary nodules.
Colorectal cancer (CRC) is one of the most common malignancies with a dismal prognosis. Indeterminate pulmonary nodules (IPNs) are lung nodules with uncertain nature, generally defined as a noncalcified nodule smaller than 10 mm in diameter or solid nodule no greater than 20 mm at maximum diameter without malignant character. With the widespread use of preoperative staging computed tomography (CT) of the chest and follow-up CT, IPNs are frequently detected in patients with CRC, which makes diagnosis more controversial. Generally, progression to pulmonary metastasis from IPNs is rare. Thus, no further interventions were needed for IPNs in CRC patients. A second reviewing of scans with IPNs by both clinicians and experienced thoracic radiologists may help to obtain a more accurate diagnosis.


Numerical simulation of self-sustained oscillation of a voice-producing element based on Navier-Stokes equations and the finite element method.
Surgical removal of the larynx results in radically reduced production of voice and speech. To improve voice quality a voice-producing element (VPE) is developed, based on the lip principle, called after the lips of a musician while playing a brass instrument. To optimize the VPE, a numerical model is developed. In this model, the finite element method is used to describe the mechanical behavior of the VPE. The flow is described by two-dimensional incompressible Navier-Stokes equations. The interaction between VPE and airflow is modeled by placing the grid of the VPE model in the grid of the aerodynamical model, and requiring continuity of forces and velocities. By applying and increasing pressure to the numerical model, pulses comparable to glottal volume velocity waveforms are obtained. By variation of geometric parameters their influence can be determined. To validate this numerical model, an in vitro test with a prototype of the VPE is performed. Experimental and numerical results show an acceptable agreement.


Preparation and characterisation of fluconazole vaginal films for the treatment of vaginal candidiasis.
Objective of the present study was to develop and evaluate vaginal films with essential in vitro studies. Films were developed using hydroxypropyl methylcellulose as a polymer and formulations were coded. The developed films were evaluated with Fourier transform infrared spectroscopy, drug content, viscosity, surface pH, thickness, mechanical characterisation and in vitro drug release study. Fourier transform infrared spectroscopy results confirmed that there is no chemical interaction between drug and stabilisers/excipients. The batch variation was not more than 5% for average thickness and weight of the films. The drug content for the prepared formulation was in the range of 72.32±0.18% to 94.48±0.54%. Viscosity of the formulations increased with the increase in concentration of polymer. Mechanical characterisation revealed that tensile strength and percentage elongation of the films improved as there is increase in degree of substitution of the polymer, but the values of modulus decreased which confirmed that all the prepared films are soft in nature. The in vitro study indicated that 1 and 2% concentrations of polymer are the least concentrations to control the release of drug whereas the 4% concentration of polymer is a good and more effective concentration to control the release. Only one prepared formulation released the drug by following anomalous transport whereas other film formulations released the fluconazole by following Fickian diffusion mechanism. Prepared vaginal films may be an important alternative for the treatment of vaginal candidiasis, because these prepared films suggest the benefits of controlled release of fluconazole at the site of absorption.


Role of recently evolved miRNA regulation of sunflower HaWRKY6 in response to temperature damage.
MicroRNAs (miRNAs) are small 21-nucleotide RNAs that post-transcriptionally regulate gene expression. MiR396 controls leaf development by targeting GRF and bHLH transcription factors in Arabidopsis. WRKY transcription factors, unique to plants, have been identified as mediating varied stress responses. The sunflower (Helianthus annuus) HaWRKY6 is a particularly divergent WRKY gene exhibiting a putative target site for the miR396. A possible post-transcriptional regulation of HaWRKY6 by miR396 was investigated. Here, we used expression analyses, performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and northern blots together with computational approaches to establish the regulatory interaction between HaWRKY6 and the identified sunflower miR396. Arabidopsis plants expressing a mi396-resistant version of HaWRKY6 confirmed the miRNA-dependency of the HaWRKY6 silencing. Sunflower plants exposed to high temperatures or salicylic acid presented opposite expression of HaWRKY6 and miR396. Experiments using the wildtype and miRNA-resistant versions of HaWRKY6 showed altered stress responses. Our results showed a role of the recently evolved miR396 regulation of HaWRKY6 during early responses to high temperature. Our study reveals how a miRNA that normally regulates development has been recruited for high-temperature protection in sunflower, a plant particularly well adapted to this type of stress.


Runoff losses of suspended sediment, nitrogen, and phosphorus from a small watershed in Korea.
Nutrients and sediments in runoff lead to the degradation of water quality of lakes and streams. The development of schemes to mitigate such degradation requires a characterization of the underlying transport processes. The objectives of this study were to develop annual and seasonal load-discharge relationships for suspended sediment (SS), total nitrogen (TN), and total phosphorus (TP) losses from a small mixed land use watershed and to use these relationships to explicate the annual and monthly patterns of losses of these species. Data from 1996 to 2004 were used to develop load-discharge relationships for SS, TN, and TP at the HP#6 watershed, a subwatershed of the Balhan reservoir watershed located in Bongdam-myun and Paltan-myun, Gyeonggi-do, Korea. Standard least squares curve fitting and S-estimation procedures were used to fit power functions to the data collected over this time period. The fitted load-discharge relationships are indicative of seasonal variations in SS and TN and of TP losses from HP#6. The exponents of the fitted power functions for TN and TP in the fall, for TP in summer season, and for SS in all seasons are >1, indicating that the concentrations of these species increase as flow rate increases. Most of the SS, TN, and TP transported in runoff left the watershed between April and September; thus, cost-efficient strategies can be established by focusing on this period. Further study of the seasonal variations is required for a better characterization of seasonal losses of SS, TN, and TP in runoff from the HP#6 watershed.


A Monte Carlo method for locally multivariate brain mapping.
Locally multivariate approaches to functional brain mapping offer a highly appealing complement to conventional statistics, but require restrictive region-of-interest hypotheses, or, in exhaustive search forms (such as the "searchlight" algorithm; Kriegeskorte et al., 2006), are excessively computer intensive. We therefore propose a non-restrictive, comparatively fast yet highly sensitive method based on Monte Carlo approximation principles where locally multivariate maps are computed by averaging across voxelwise condition-discriminative information obtained from repeated stochastic sampling of fixed-size search volumes. On simulated data containing discriminative regions of varying size and contrast-to-noise ratio (CNR), the Monte Carlo method reduced the required computer resources by as much as 75% compared to the searchlight with no reduction in mapping performance. Notably, the Monte Carlo mapping approach not only outperformed the general linear method (GLM), but also produced higher discriminative voxel detection scores than the searchlight irrespective of classifier (linear or nonlinear support vector machine), discriminative region size or CNR. The improved performance was explained by the information-average procedure, and the Monte Carlo approach yielded mapping sensitivities of a few percent lower than an information-average exhaustive search. Finally, we demonstrate the utility of the algorithm on whole-brain, multi-subject functional magnetic resonance imaging (fMRI) data from a tactile study, revealing that the central representation of gentle touch is spatially distributed in somatosensory, insular and visual regions.


The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market.
Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by double-stranded RNA, a remarkable progress was achieved in RNA interference (RNAi). Changes in the chemical structure of synthetic oligonucleotides make them more stable and specific, and new delivery strategies became progressively available. The attention of pharmaceutical industry rapidly turned to RNAi, as an opportunity to explore new drug targets. This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). Regarding miRNAs, their content can be down- or up-regulated, by using miRNA inhibitors (AntimiRs) or miRNA mimics. Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of RNAi technology is easily understood taking into account: (i) the different drug targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of administration (ocular, intravenous, subcutaneous, intratumoral). Although some issues are still matters of concern (delivery, toxicity, cost, and biological barriers), RNAi definitively opens a wide avenue for drug development.


Fast Convolution with Laplacian-of-Gaussian Masks.
We present a technique for computing the convolution of an image with LoG (Laplacian-of-Gaussian) masks. It is well known that a LoG of variance a can be decomposed as a Gaussian mask and a LoG of variance a1 < a. We take advantage of the specific spectral characteristics of these filters in our computation: the LoG is a bandpass filter; we can therefore fold the spectrum of the image (after low pass filtering) without loss of information, which is equivalent to reducing the resolution. We present a complete evaluation of the parameters involved, together with a complexity analysis that leads to the paradoxical result that the computation time decreases when a increases. We illustrate the method on two images.


Colo-renal fistula: An unusual cause of hematochezia.
A 76 year old woman with bloody stools and symptomatic anemia presented to the Emergency Department approximately 2 wk after computed tomography (CT)-guided cryoablation to a 4.5 cm renal cell carcinoma on her left posterior kidney. The patient was initially prepped for a colonoscopy to view possible causes of lower gastrointestinal bleeding. However, the patient had a CT with PO contrast that revealed a variation of a renoalimentary fistula. The patient was subsequently brought to the operating room, and it was discovered that a colo-renal fistula had formed, with transmural perforation of the posterior descending colon. A left nephrectomy, left colectomy with colostomy and Hartmann's pouch was performed.


Enzymatically prepared n-alkyl esters of glucuronic acid: the effect of freeze-drying conditions and hydrophobic chain length on thermal behavior.
In this work, some of the physicochemical properties of enzymatically prepared n-alkyl esters of glucuronic acid are presented. Two questions are addressed. The first concerns the influence of post-purification freeze-drying conditions on octyl glucuronate thermotropic behavior. Depending on the amount of water added before freeze-drying, the alpha/beta anomeric ratio determined by (1)H NMR is affected and differences are observed in DSC thermograms probably due to polymorphism. The second question concerns the effect of hydrophobic chain length on the thermal behavior. An increase of both transition temperature and transition enthalpy is observed by increasing the number of carbon atoms in the alkyl chain (C8<C10<C12<C14). This kind of results can provide relevant information for the processing and the practical use of these nonionic surfactants.


Correlation between apparent diffusion coefficients on diffusion-weighted MRI and standardized uptake value on FDG-PET/CT in pancreatic adenocarcinoma.
Diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (PET/CT) is increasingly recognized as important for assessing tumor malignancy in oncology. Apparent diffusion coefficient (ADC) and standardized uptake value (SUV) are negatively correlated in some types of cancer based on tumor aggressiveness. To evaluate relationships between ADC of magnetic resonance imaging and SUV of PET/CT in pancreatic adenocarcinomas. Twenty-nine patients histopathologically diagnosed with pancreatic adenocarcinomas were evaluated. ADC maps were generated from 3 T-MRI using b values (b = 0, 800 s/mm(2)). PET/CT was performed 60 min after intravenous injection of FDG (3.7 MBq/kg). The margins of tumors on DW-MRI and PET/CT were assessed to measure ADC and SUV of tumor appropriately. For tumors considered well-marginated, minimal and mean ADC as well as maximal and mean SUV were measured. The correlation of ADC and SUV were statistically evaluated and survival period stratified on ADC and SUV also evaluated. Twenty-two tumors on DW-MRI and 25 on PET/CT were deemed well-marginated. Minimal ADC was significantly and negatively correlated with maximal and mean SUV (r = -0.61, P = 0.0040; r = -0.66, P = 0.0015), and mean ADC also showed significantly and negatively correlation with maximal and mean SUV (r = -0.50, P = 0.024; r = -0.54, P = 0.012). There was no significant difference on overall survival stratified on ADC and SUV. ADC and SUV were significantly correlated in pancreatic adenocarcinomas, although no significant findings were observed in overall survival.


A survey of community exercise programmes for stroke survivors in Scotland.
Stroke is the most common cause of complex disability in the community. Physical fitness is often reduced after stroke, but training can improve fitness and function. UK and international stroke clinical guidelines recommend long-term exercise participation for stroke survivors. However, there has been no previous research into what services are available to support this. In 2009, we conducted the first European survey of community Exercise after Stroke services. A link to our web-based survey was emailed to health, leisure service and stroke charity contacts in Scotland with email and telephone follow-up to non-respondents. The overall response rate was 64% (230/361). A total of 14 Exercise after Stroke services were identified, the majority of which were run by charity collaborations (7/14), followed by leisure centre services (4/14) and health services (3/14). We sought information on session content, referral and assessment processes, and the qualifications of exercise instructors. This information was cross-referenced with current clinical and exercise guidelines to determine whether existing resources were sufficient to meet stroke survivors' needs for safe, effective and sustainable access to exercise. The results indicated a shortage of stroke-specific community exercise programmes. Further service development is required to ensure appropriate instructor training and referral pathways are in place to enable stroke survivors to access exercise services in accordance with current guidelines.


Nuclear and cytoplasmic genes controlling synthesis of variant mitochondrial polypeptides in male-sterile maize.
The polypeptides synthesized in vitro by mitochondria isolated from etiolated maize shoots of a number of different nuclear and cytoplasmic genotypes have been compared by using polyacrylamide gel electrophoresis. We have previously shown that mitochondria from maize plants carrying the T or C forms of cytoplasmically inherited male sterility (cms-T and cms-C mitochondria) can be distinguished from each other and from the mitochondria of normal (N) plants by the synthesis of a single additional or variant polypeptide species. Using lines that carry the T cytoplasm, and that differ principally in the presence or absence of nuclear "restorer" alleles that suppress the male-sterile phenotype, we find that these nuclear genes specifically suppress synthesis of the 13,000 M(r) variant polypeptide. A 21,000 M(r) polypeptide that is synthesized by N mitochondria is not detectable among the translation products of cms-T mitochondria from either restored or nonrestored lines. Results obtained with a number of lines possessing dominant restorer alleles from different sources indicate that it is the restorer gene at the Rf(1) locus that is primarily responsible for regulating synthesis of the 13,000 M(r) polypeptide. Mitochondria from lines with the S form of cytoplasmic male sterility (cms-S) were found to synthesize a group of minor polypeptides, ranging in molecular weight from 42,000 to 88,000, which were not detected in N, cms-T, or cms-C mitochondria. In the case of the S and C forms of male sterility no differences were found between the translation products of mitochondria from restored and nonrestored lines.


Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats.
1,2-Diacylglycerol has been proposed to be a secondary messenger; therefore, in this study we evaluated the amount of 1,2-diacylglycerol in heart tissue from streptozocin-induced diabetic rats and examined the effect of insulin treatment on 1,2-diacylglycerol content. Diabetic rats had lower body and ventricular weights and higher ratios of ventricular to body weight, all of which shifted toward normal values after 4 wk of untreated diabetes followed by 4 wk of insulin treatment. The contents of major phospholipids were significantly depressed in the diabetic rat hearts. In contrast, the triglyceride and cholesterol contents in the myocardium were increased by streptozocin injection and completely normalized by insulin treatment, and glucose levels returned to normal. The 1,2-diacylglycerol content in the myocardium was also significantly elevated in the diabetic rats compared with age-matched controls. Moreover, the 1,2-diacylglycerol content was significantly higher in rats with 4 wk of diabetes than in those with 8 wk of diabetes. Insulin treatment in the diabetic rats, however, did not produce any decrease in 1,2-diacylglycerol content. The results of this study suggest that the development of cardiomyopathy induced by streptozocin injection is associated with a high 1,2-diacylglycerol level, which may result in the activation of protein kinase C. Insulin is one of the agonists that generates 1,2-diacylglycerol in myocytes; however, the relationship between the sustained 1,2-diacylglycerol level and the normalization of diabetes by insulin administration is unclear.


Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials.
A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS) showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset. Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables. The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found. Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment.


[Indications and techniques for removal of subluxated lenses (author's transl)].
Extraction only appears indicated in cases of anteriour luxation and phakolytic glaucoma. Visual disturbances due to a dislocated lens should be considered relative indications for removal, since functional improvement cannot be expected as a rule. Expression of the lens through a corneoscleral incision is the method of choice in cases of anterior luxation (Fig. 1) as well as in subluxations without vitreous prolapse (Fig. 2) Open-sky vitrectomy allows for clearing of the route of extraction in cases of subluxation with vitreous in the anterior chamber (Fig. 3). A pars plana approach may be chosen in cases with a soft nucleus (Fig. 4) whereas luxated lenses with a hard nucleus are first aspirated (soft capsule and cortex), then the hard nucleus is luxated into the anterior chamber and finally extracted through a small corneoscleral incision, thus avoiding prolonged perfusion of the anterior chamber necessary for stripper techniques.


Multivariate meta-analysis.
Meta-analysis is now a standard statistical tool for assessing the overall strength and interesting features of a relationship, on the basis of multiple independent studies. There is, however, recent acknowledgement of the fact that in many applications responses are rarely uniquely determined. Hence there has been some change of focus from a single response to the analysis of multiple outcomes. In this paper we propose and evaluate three Bayesian multivariate meta-analysis models: two multivariate analogues of the traditional univariate random effects models which make different assumptions about the relationships between studies and estimates, and a multivariate random effects model which is a Bayesian adaptation of the mixed model approach. Our preferred method is then illustrated through an analysis of a new data set on parental smoking and two health outcomes (asthma and lower respiratory disease) in children.


Modulated Rashba-Dresselhaus Spin-Orbit Coupling for Topology Control and Analog Simulations.
We show theoretically that Rashba-Dresselhaus spin-orbit coupling (RDSOC) in lattices acts as a synthetic gauge field. This allows us to control both the phase and the magnitude of tunneling coefficients between sites, which is the key ingredient to implement topological Hamitonians and spin lattices useful for simulation perpectives. We use liquid crystal based microcavities in which RDSOC can be switched on and off as a model platform. We propose a realistic scheme for implementation of a Su-Schrieffer-Heeger chain in which the edge states existence can be tuned, and a Harper-Hofstadter model with a tunable contrasted flux for each (pseudo)spin component. We further show that a transverse-field Ising model and classical XY Hamiltonian with tunable parameters can be implemented, opening up prospects for analog physics, simulations, and optimization.


Current status of the treatment of acute colonic diverticulitis: a systematic review.
This paper addresses the current status of the treatment of acute colonic diverticulitis by an evidence-based review. A systematic search in PUBMED, MEDLINE, EMBASE and Google scholar on colonic diverticulitis was performed. Diagnostic tools, randomized controlled trials, non-randomized comparative studies, observational epidemiological studies, national and international guidelines, reviews of observational studies on elective and emergency surgical treatment of diverticulitis, and studies of prognostic significance were reviewed. Criteria for eligibility of the studies were diagnosis and classification, medical treatment, inpatients and outpatients, diverticulitis in young patients, immunosuppression, recurrence, elective resection, emergency surgery, and predictive factors. Some 92 publications were selected for comprehensive review. The review highlighted that computed tomography is the most effective test in the diagnosis and staging of acute diverticulitis; outpatient treatment can be performed for uncomplicated diverticulitis in patients without associated comorbidities; conservative treatment is aimed at those patients with uncomplicated acute diverticulitis; elective surgery must be done on an individual basis; laparoscopic approach for elective treatment of diverticulitis is appropriate but may be technically complex; in perforated diverticulitis, resection with primary anastomosis is a safe procedure that requires experience and should take into account strict exclusion criteria. The heterogeneity of patients with colonic diverticular disease means that both elective and urgent treatment should be tailored on an individual basis.


Olfactory ability in the healthy population: reassessing presbyosmia.
Age-associated loss of olfactory function, or presbyosmia, has been described in many studies of olfactory ability. Presbyosmia has been ascribed to idiopathic causes despite recognition that many neurodegenerative diseases also induce loss of olfactory function and increase in incidence in the aged population. Often this olfactory loss is unnoticed or unreported by affected individuals. More effective olfactory function in women compared with men is another common feature of many studies of olfactory function. Here we report on normative data from an Australian population study (n = 942) that has been divided into 2 subpopulations and reassessed as (included) a population of healthy, nonmedicated, nonsmokers with no history of nasal problems (n = 485) and (excluded) a population of participants who were either medicated, smokers or had a history of nasal problems (n = 457). The "included" data set shows a strong relationship between self-reporting of olfactory sensitivity and olfactory function score. The included data set shows a small but significant decline in olfactory ability after 65 years of age and better olfactory function in females compared with males. Data from the excluded population show a marked decline in olfactory ability after 65 years of age, no difference between males and females, and a weak relationship between self-reporting of olfactory function and actual olfactory function. The power of this approach is that it provides a normative data set against which many factors such as medication schedules and pathological conditions can be compared.


Sensitization processes in drug addiction.
In 1993, Robinson and Berridge published their first review that laid out the incentive sensitization theory of addiction (Robinson and Berridge 1993 Brain Res Rev 18:247). Its basic point is that repeated exposure to drugs of abuse causes hypersensitivity to drugs and drug-associated stimuli of the neural circuits mediating incentive salience, an important way in which motivational stimuli influence behavior. In laymen's terms, it states that this drug-induced hypersensitivity of motivational circuitry would mediate an increase in drug "wanting," thus being responsible for the dramatically exaggerated motivation for drugs displayed by addicts. This theory has been exceptionally influential, as evidenced by the fact that the original review paper about this theory (Robinson and Berridge 1993 Brain Res Rev 18:247) has been cited 2,277 times so far, and subsequent updates of this view (Robinson and Berridge 2000 Addiction 95(Suppl 2):S91; Robinson and Berridge 2001 Addiction 96:103; Robinson and Berridge 2003 Ann Rev Psychol 54:25) have been cited 274, 297, and 365 times, respectively, adding up to more than 3,200 citations within 15 years. The present chapter aims to delineate the merits and limitations of the incentive sensitization view of addiction, and whether incentive sensitization occurs in humans. We conclude that since incentive sensitization most prominently occurs after the first few drug exposures, it may represent an important initial step in the addiction process. During the expression of full-blown addiction, characterized by loss of control over drug intake and use of large quantities of drugs, the expression of incentive sensitization may be transiently suppressed. However, detoxification and the gradual disappearance of tolerance and withdrawal symptoms may unmask sensitization, which could then play an important role in the high risk of relapse.


Complete genome sequences of human respiratory syncytial virus genotype a and B isolates from South Korea.
There is a paucity of complete genome sequence information for human respiratory syncytial virus (HRSV). To this end, we sequenced the complete genome sequences of HRSV genotype A (HRSV-A/IC688/12) and genotype B (HRSV-B/GW0047/14 and HRSV-B/IC0027/14). This information will increase the understanding of HRSV genetic diversity, evolution, pathogenicity, antigenicity, and transmissibility.


Meat consumption, ornithine decarboxylase gene polymorphism, and outcomes after colorectal cancer diagnosis.
Dietary arginine and meat consumption are implicated in colorectal cancer (CRC) progression via polyamine-dependent processes. Polymorphism in the polyamine-regulatory gene, ornithine decarboxylase 1 (Odc1, rs2302615) is prognostic for CRC-specific mortality. Here, we examined joint effects of meat consumption and Odc1 polymorphism on CRC-specific mortality. The analytic cohort was comprised of 329 incident stage I-III CRC cases diagnosed 1994-1996 with follow- up through March 2008. Odc1 genotyping was conducted using primers that amplify a 172-bp fragment containing the polymorphic base at +316. Dietary questionnaires were administered at cohort entry. Multivariate Cox proportional hazards regression analysis for CRC-specific mortality was stratified by tumor, node, metastasis (TNM) stage, and adjusted for clinically relevant variables, plus meat consumption (as a continuous variable, i.e., the number of medium-sized servings/week), Odc1 genotype, and a term representing the meat consumption and Odc1 genotype interaction. The primary outcome was the interaction of Odc1 and meat intake on CRC-specific mortality, as assessed by departures from multiplicative joint effects. Odc1 genotype distribution was 51% GG, 49% GA/AA. In the multivariate model, there was a significant interaction between meat consumption and Odc1 genotype, P-int = 0.01. Among Odc1 GA/AA CRC cases in meat consumption Quartiles 1-3, increased mortality risk was observed when compared to GG cases (adjusted hazards ratio (HR) = 7.06 [95% CI 2.34-21.28]) - a difference not found among cases in the highest dietary meat consumption Quartile 4. Effects of meat consumption on CRC-specific mortality risk differ based on genetic polymorphism at Odc1. These results provide further evidence that polyamine metabolism and its modulation by dietary factors such as meat may have relevance to CRC outcomes.


Calculations of actual corneal astigmatism using total corneal refractive power before and after myopic keratorefractive surgery.
To calculate actual corneal astigmatism using the total corneal refractive astigmatism for the 4-mm apex zone of the Pentacam (TCRP4astig) and keratometric astigmatism (Kastig) before and after photorefractive keratectomy or laser in situ keratomileusis. Uncomplicated 56 eyes after more than 6 months from the surgery were recruited by chart review. Various corneal astigmatisms were measured using the Pentacam and autokeratometer before and after surgery. Three eyes were excluded and 53 eyes of 38 subjects with with-the-rule astigmatism (WTR) were finally included. The astigmatisms were investigated using polar value analysis. When TCRP4astig was set as an actual astigmatism, the efficacy of arithmetic or coefficient adjustment of Kastig was evaluated using bivariate analysis. The difference between the simulated keratometer astigmatism of the Pentacam (SimKastig) and Kastig was strongly correlated with the difference between TCRP4astig and Kastig. TCRP4astig was different from Kastig in magnitude rather than meridian before and after surgery; the preoperative difference was due to the posterior cornea only; however, the postoperative difference was observed in both anterior and posterior parts. For arithmetic adjustment, 0.28 D and 0.27 D were subtracted from the preoperative and postoperative magnitudes of Kastig, respectively. For coefficient adjustment, the preoperative and postoperative magnitudes of Kastig were multiplied by 0.80 and 0.66, respectively. By arithmetic or coefficient adjustment, the difference between TCRP4astig and adjusted Kastig would be less than 0.75 D in magnitude for 95% of cases. Kastig was successfully adjusted to TCPR4astig before and after myopic keratorefractive surgery in cases of WTR. For use of TCRP4astig directly, SimKastig and Kastig should be matched.


Epsilon-aminocaproic acid in coronary artery bypass graft surgery: preincision or postheparin?
Epsilon-aminocaproic acid (epsilon-ACA), an antifibrinolytic agent, is used in cardiac surgery to decrease postoperative bleeding. Theoretical concerns exist about the potential for epsilon-ACA to contribute to thrombotic complications. For this reason epsilon-ACA administration is sometimes delayed until after heparinization. This study investigated the impact of the timing of epsilon-ACA administration on its efficacy. In this double-blind study, 90 patients undergoing primary coronary artery bypass graft surgery were prospectively randomized to receive either epsilon-ACA commencing prior to skin incision (bolus 150 mg/kg, followed by an infusion at 15 mg x kg(-1) x hr(-1), epsilon-ACA commencing after heparin (same doses), or placebo. All infusions were terminated at the end of cardiopulmonary bypass. Criteria for the transfusion of blood products were standardized. Postoperative chest tube drainage (at 6 h, 12 h, and at chest tube removal) and blood transfusion requirements of the three groups were compared. At all time intervals, the placebo group had significantly greater chest tube drainage than either of the two epsilon-ACA groups (P < 0.005). At no time did a significant difference exist between the two epsilon-ACA groups. A trend existed for the placebo group to require more blood products than either epsilon-ACA group. Epsilon-ACA produces a reduction in chest tube drainage in patients undergoing primary coronary artery bypass graft surgery. This effect is similar whether the drug is given prior to incision or following anticoagulation. Given the similar hemostatic efficacy and the theoretical potential for thrombotic complications, it may be prudent to administer epsilon-ACA following anticoagulation.


[Surgical wound infections--have we achieved all that is possible?].
There is still a solid foundation for a further reduction of surgical wound infections. Every twentieth surgical bed is occupied by a patient with this complication. Though three out of four wards register the infections, serious problems with the methods have been established. Thus, it would not be justifiable to use the current registrations for monitoring for clinical and administrative purposes. Death or serious health consequences are to many patients the reality after a wound infection; the social and economical costs are also important. Better systems for surveillance of infections or complications must be developed specifically for the Danish hospitals. The hygienic expertise must be strengthened. Increased resources based on long-term planning are required to prevent more wound infections. Hospital hygiene will be a suitable subject for quality improvement. The surgical specialties should be encouraged to settle standards for specific procedures as to acceptable levels of infection.


Utilization of energy-providing substrates in the isolated working rat heart.
1. An improved perfusion system for the isolated rat heart is described. It is based on the isolated working heart of Neely, Liebermeister, Battersby & Morgan (1967) (Am. J. Physiol. 212, 804-814) and allows the measurement of metabolic rates and cardiac performance at a near-physiological workload. The main improvements concern better oxygenation of the perfusion medium and greater versatility of the apparatus. Near-physiological performance (cardiac output and aortic pressure) was maintained for nearly 2 h as compared with 30 min or less in the preparations of earlier work. 2. The rates of energy release (O2 uptake and substrate utilization) were 40-100% higher than those obtained by previous investigators, who used hearts at subphysiological workloads. 3. Values are given for the rates of utilization of glucose, lactate, oleate, acetate and ketone bodies, for O2 consumption and for the relative contributions of various fuels to the energy supply of the heart. Glucose can be replaced to a large extent by lactate, oleate or acetate, but not by ketone bodies. 4. Apart from quantitative differences there were also major qualitative differences between the present and previous preparations. Thus insulin was not required for maximal rates of glucose consumption at near-physiological, in contrast with subphysiological, workloads when glucose was the sole added substrate. When glucose oxidation was suppressed by the addition of other oxidizable substrates (lactate, acetate or acetoacetate), insulin increased the contribution of glucose as fuel for cardiac energy production at high workload. 5. In view of the major effects of workload on cardiac metabolism, experimentation on hearts performing subphysiologically or unphysiologically is of limited value to the situation in vivo.


Will more organs save more lives? Cost-effectiveness and the ethics of expanding organ procurement.
The assumption that procuring more organs will save more lives has inspired increasingly forceful calls to increase organ procurement. This project, in contrast, directly questions the premise that more organ transplantation means more lives saved. Its argument begins with the fact that resources are limited and medical procedures have opportunity costs. Because many other lifesaving interventions are more cost-effective than transplantation and compete with transplantation for a limited budget, spending on organ transplantation consumes resources that could have been used to save a greater number of other lives. This argument has not yet been advanced in debates over expanded procurement and could buttress existing concerns about expanded procurement. To support this argument, I review existing empirical data on the cost-effectiveness of transplantation and compare them to data on interventions for other illnesses. These data should motivate utilitarians and others whose primary goal is maximizing population-wide health benefits to doubt the merits of expanding organ procurement. I then consider two major objections: one makes the case that transplant candidates have a special claim to medical resources, and the other challenges the use of cost-effectiveness to set priorities. I argue that there is no reason to conclude that transplant candidates' medical interests should receive special priority, and that giving some consideration to cost-effectiveness in priority setting requires neither sweeping changes to overall health priorities nor the adoption of any specific, controversial metric for assessing cost-effectiveness. Before searching for more organs, we should first ensure the provision of cost-effective care.


Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene.
Infrequent and rare genetic variants in the human population vastly outnumber common ones. Although they may contribute significantly to the genetic basis of a disease, these seldom-encountered variants may also be miss-identified as pathogenic if no correct references are available. Somatic and germline TP53 variants are associated with multiple neoplastic diseases, and thus have come to serve as a paradigm for genetic analyses in this setting. We searched 14 independent, globally distributed datasets and recovered TP53 SNPs from 202,767 cancer-free individuals. In our analyses, 19 new missense TP53 SNPs, including five novel variants specific to the Asian population, were recurrently identified in multiple datasets. Using a combination of in silico, functional, structural, and genetic approaches, we showed that none of these variants displayed loss of function compared to the normal TP53 gene. In addition, classification using ACMG criteria suggested that they are all benign. Considered together, our data reveal that the TP53 coding region shows far more polymorphism than previously thought and present high ethnic diversity. They furthermore underline the importance of correctly assessing novel variants in all variant-calling pipelines associated with genetic diagnoses for cancer.


Determinants of exposure to fragranced product chemical mixtures in a sample of twins.
Fragranced product chemical mixtures may be relevant for environmental health, but little is known about exposure. We analyzed results from an olfactory challenge with the synthetic musk fragrance 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopento-γ-2-benzopyran (HHCB), and a questionnaire about attitudes toward chemical safety and use of fragranced products, in a sample of 140 white and 17 black twin pairs attending a festival in Ohio. Data for each product were analyzed using robust ordered logistic regressions with random intercepts for "twin pair" and "sharing address with twin", and fixed effects for sex, age, education, and "ever being bothered by fragrances". Due to the small number of black participants, models were restricted to white participants except when examining racial differences. Overall patterns of association were summarized across product-types through random-effects meta-analysis. Principal components analysis was used to summarize clustering of product use. The dominant axis of variability in fragranced product use was "more vs. less", followed by a distinction between household cleaning products and personal care products. Overall, males used fragranced products less frequently than females (adjusted proportionate odds ratio 0.55, 95% confidence interval 0.33, 0.93). This disparity was driven by personal care products (0.42, 95% CI: 0.19, 0.96), rather than household cleaning products (0.79, 95% CI: 0.49, 1.25) and was particularly evident for body lotion (0.12, 95% CI: 0.05, 0.27). Overall usage differed by age (0.64, 95% CI: 0.43, 0.95) but only hand soap and shampoo products differed significantly. "Ever being bothered by fragrance" had no overall association (0.92, 95% CI: 0.65, 1.30) but was associated with laundry detergent use (0.46, 95% CI: 0.23, 0.93). Similarly, black vs. white differences on average were not significant (1.34, 95% CI: 0.55, 3.28) but there were apparent differences in use of shampoo (0.01, 95% CI: 0.00, 0.69), body lotion (4.67, 95% CI: 1.18, 18.47), and perfume (6.22, 95% CI:1.08, 35.89). There was no overall association with thinking about product risks (0.90, 95% CI: 0.79, 1.02), nor with inability to smell HHCB (0.84, 95% CI: 0.63, 1.12). Exposure to fragranced products may differ demographically. The relevance for health disparities should be studied.


Deletion of the middle region of the transcription factor ClrB in Penicillium oxalicum enables cellulase production in the presence of glucose.
Enzymes that degrade lignocellulose to simple sugars are of great interest in research and for biotechnology because of their role in converting plant biomass to fuels and chemicals. The synthesis of cellulolytic enzymes in filamentous fungi is tightly regulated at the transcriptional level, with the transcriptional activator ClrB/CLR-2 playing a critical role in many species. In Penicillium oxalicum, clrB overexpression could not relieve the dependence of cellulase expression on cellulose as an inducer, suggesting that clrB is controlled post-transcriptionally. In this study, using a reporter gene system in yeast, we identified the C-terminal region of ClrB/CLR-2 as a transcriptional activation domain. Expression of clrBID , encoding a ClrB derivative in which the DNA-binding and transcriptional activation domains are fused together to remove the middle region, led to cellulase production in the absence of cellulose in P. oxalicum Strikingly, the clrBID -expressing strain produced cellulase on carbon sources that normally repress cellulase expression, including glucose and glycerol. Results from deletion of the carbon catabolite repressor gene creA in the clrBID -expressing strain suggested that the effect of clrBID is independent of CreA's repressive function. A similar modification of clrB in Aspergillus niger resulted in the production of a mannanase in glucose medium. Taken together, these results indicate that ClrB suppression under noninducing conditions involves its middle region, suggesting a potential strategy to engineer fungal strains for improved cellulase production on commonly used carbon sources.


Review article: therapeutic roles of acupuncture in functional gastrointestinal disorders.
Acupuncture has been practiced empirically in China for several millennia, and is being increasingly accepted by practitioners and patients worldwide. Functional gastrointestinal disorders are common in clinical gastroenterology. The prevalence of one or more functional gastrointestinal disorders is estimated to be as high as 70% in general population using Rome diagnostic criteria. Since functional gastrointestinal disorders are diagnosed based on symptoms and the exact aetiologies for most of functional gastrointestinal disorders are not completely known, it is not unusual that the treatment for these disorders is unsatisfactory and alternative therapies are attractive to both patients and practitioners. During the latest decades, a considerable number of studies have been performed on acupuncture for the treatment of functional gastrointestinal disorders and underlying mechanisms. In this article, we reviewed available data in the literature on the applications and mechanisms of acupuncture for the treatment of functional gastrointestinal disorders, including functional oesophageal disorders, nausea and vomiting, functional dyspepsia, irritable bowel syndrome, constipation, etc. A summary is provided based on the quality and quantity of published studies regarding the efficacy of acupuncture in treating these various disorders. In addition, the methodology of acupuncture is also introduced.


Clinical manifestations of the anti-IgLON5 disease.
To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.


Once- Versus Twice-daily Mesalazine to Induce Remission in Paediatric Ulcerative Colitis: A Randomised Controlled Trial.
Trials in adults suggested that, in ulcerative colitis [UC], once-daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective than twice-daily [BD] dosing. In this induction of remission, investigator-blinded, randomised controlled-trial, we aimed to compare effectiveness and safety of once- versus twice-daily mesalazine in paediatric UC. Children, aged 4-18 years with a PUCAI [Paediatric Ulcerative Colitis Activity Index] of 10-55 points at inclusion, were randomised in blocks of six with blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The primary outcome was mean PUCAI score at Week 6. A total of 83/86 randomised children were eligible and analysed: 43 in the OD group and 40 in the BD group (mean age 14 ± 2.7 years, 43 [52%] males, 51 [62%] extensive colitis). The groups did not differ with regard to disease activity or any other parameter at baseline. There was no difference in median PUCAI score between the OD group and BD group at Week 6: 15 ( interquartile range [IQR] 5-40) versus 10 [0-40]; p = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78]. Proportion of children in remission [PUCAI < 10] at Week 6 was 13 [30%] OD versus 16 [40%] BD; p = 0.35]. Most adverse events were related to disease aggravation; the rates of serious adverse events were similar [p > 0.2]. In this first randomised controlled trial in children, no differences were found between OD and BD dosing for any clinical outcome. Remission was achieved in 35% of children treated with mesalazine for active UC.


Inpatient diagnoses during Adolf Meyer's tenure as director of the Henry Phipps Psychiatric Clinic, 1913-1940.
Between 1936 and 1950, detailed abstracts were prepared on all patients admitted to The Phipps Psychiatric Clinic from its opening in 1913 through 1950. Of these abstracts, 74% contained follow-up reports. Except for four papers on schizophrenia and affective disorders published between 1939 and 1943, none of this material has ever been analyzed. The present paper, the first of a series, examines the 8172 first admissions from 1913 through 1940, the period of Adolf Meyer's tenure as Clinic Director. Based on discharge diagnoses, we have sorted the patients into eight diagnostic groups with the following frequencies; schizophrenia, 17%; paranoid state, 3%; manic-depressive, 7%; depression, 27%; organic, 20%; neuroses, 15%; substance abuse, 6%; psychopath, 5%. Our manic-depressive group contains cases discharged primarily as hyperthymergasia, mania, or manic depressive insanity (MDI). Of the 349 cases diagnosed MDI at discharge, 10 had neither a history of nor present symptoms of mania, and these were put in the depression group. Frequencies for most of the diagnoses remained remarkably stable over the 28-year period. Only 9% were discharged recovered, whereas 43% were rated unimproved. Mean length of hospitalization was 76 days, with 10% of the patients readmitted. The mean length of follow-up was 9 years. Correlations of diagnoses, year of admission, length of stay, condition at discharge, age, sex, readmissions, change of diagnoses, somatic treatment, length of follow-up, and deaths in the clinic are presented. Meyer's influence on diagnostic practice is discussed.


[Extramedullary plasmocytoma of the nasopharynx].
A case of extramedullary plasmacytoma sited in the nasopharynx in a 25 years old women is presented. The first symptomatology was otology; no evidence of plasmocytoma after clinical study were found in another site. We also do a revision of diagnostic and therapeutic management. We ind this case interesting because his site of origin and the patient's sex.


Interpolation processes in the perception of real and illusory contours.
The spatial and temporal characteristics of mechanisms that bridge gaps between line segments were determined. The presentation time that was necessary for localisation and identification of a triangular shape made up of pacmen, pacmen with lines, lines, line segments (corners), or pacmen with circles (amodal completion) was measured. The triangle was embedded in a field of distractors made up of the same components but at random orientations. Subjects had to indicate whether the triangle was on the left or on the right of the display (localisation) and whether it was pointing upward or downward (identification). Poststimulus masks consisted of pinwheels for the pacmen stimuli or wheels defined by lines. Stimuli were presented on a grey background and defined by luminance or isoluminant contrast. Thresholds were fastest when the triangle was defined by real contours, as for the pacmen with lines (105 ms) and the lines only (92 ms), slightly slower for corners (118 ms) and pacmen (136 ms), and much slower for the amodally completed pacmen (285 ms). For all inducer types localisation was about 20 ms faster than identification. In a second experiment the relative length of the gap between inducers was varied. Thresholds increased as a function of gap length, indicating that the gaps between the inducers need to be interpolated. There was no significant difference in the speed of this interpolation process between the pacman stimuli and the line-segment stimuli. About 40 ms were required to interpolate 1 deg of visual angle, corresponding to about one third of the distance between inducers. In a third experiment, it was found that processing of isoluminant stimuli was as fast as for low-contrast luminance stimuli, when targets were defined by real contours (lines), but much slower for illusory contours (pacmen). The conclusion is that the time necessary to interpolate a contour depends greatly on the spatial configuration of the stimulus. Since interpolation is faster for the line-segment stimuli, which do not elicit the percept of an illusory contour, the interpolation process seems to be independent of the formation of illusory contours.


The mode of action of tricyclic antidepressants: a brief review of recent progress.
Until recently the tricyclic antidepressants were thought to act by inhibiting uptake of the biogenic amines noradrenaline and 5-hydroxytryptamine (serotonin). But this did not explain why the depressed mood takes several weeks to respond, whereas biogenic amine uptake is inhibited soon after treatment begins. Nor did it explain why some clinically effective antidepressants have little effect if any on biogenic amine uptake. Recent work suggests that changes in receptor sensitivity may be responsible. By the use of radiolabelled, high-affinity, high-specificity drugs and receptor-binding assays it is now proving possible to characterize neurotransmitter receptors in greater detail, and this is expected to throw further light on the mechanisms underlying changes in receptor sensitivity.


[The multidisciplinary practice guideline "The responsible use of biologicals"].
A multidisciplinary working group has developed a practice guideline containing various recommendations on the responsible and efficient use of biologicals. These biologicals include both soluble immune-receptor proteins and monoclonal antibodies that are aimed at immune mediators, receptors or cells. They are produced by biotechnology. Biologicals are used to treat patients with immune-mediated inflammatory disorders (IMIDs) such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, juvenile idiopathic arthritis (JIA), psoriasis, ulcerative colitis, Crohn's disease, uveitis and sarcoidosis. This article summarises the most important recommendations contained in the practice guideline. The practice guideline is intended for members of the medical profession in addition to patients, who are considering, or are already, using biologicals.


Neurons in paradoxical sleep and motivated behavior.
Single-cell recordings were taken with electrodes permanently implanted in unrestrained rats during normal sleep, paradoxical sleep, quiet awake, and highly motivated awake periods. In most areas, neuronal activity increased when normal sleep changed to paradoxical sleep. The hypothalamus showed a significantly greater increase than most other areas. The hippocampus differed strikingly from all other areas by showing a decrement in all cases. The average firing rates in paradoxical sleep exceeded those of the quiet awake state as well as those of normal sleep. Comparison of paradoxical sleep with motivated behavior illustrated that changes in brain activity during paradoxical sleep were related to anatomically specifiable groupings, but no such differentiation appeared in motivated behavior.


Evaluation of an automated method for leukocyte differential counts based on electronic volume analysis.
An electronic blood cell counter (Coulter S-plus IV) classifies leukocytes as lymphocytes, large mononuclear cells, or granulocytes based on volume after treatment with a reagent. Correlation coefficients as compared with stained film microscopy are .94 for lymphocytes, .91 for granulocytes, and .49 for mononuclear cells. As a screening tool, it could reduce the number of traditional manual differential cell counts. We devised criteria for identifying those specimens requiring additional visual examination, giving particular attention to "low-density" abnormalities. Over 2,200 specimens were studied. Among 791 specimens obtained primarily from inpatients, the screening procedure yielded 267 true-positive, 298 false-positive, 213 true-negative, and 13 false-negative specimens. The 1,216 specimens obtained primarily from outpatients included 54 true-positive, 234 false-positive, 912 true-negative, and 16 false-negative specimens. All false-negative specimens represented low-density abnormalities. The usefulness of this approach is partially dependent on patient population.


RESCUE-AF in Patients Undergoing Atrial Fibrillation Ablation: The RESCUE-AF Trial
Although contact force (CF)–sensing catheters improve procedural effectiveness and safety of atrial fibrillation ablation, recent reports documented a higher incidence of atrioesophageal fistula formation relative to ablation with non–CF-sensing catheters.The present study was to assess whether restricting CF to <20 g reduced risk for esophageal injury (EI) in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. This prospective, single-center, randomized study enrolled 89 consecutive patients (mean age, 57.2±11.3 years; 57.3% men) with atrial fibrillation (68.5% paroxysmal and 31.5% persistent). Computed tomography angiography, transesophageal echocardiography, and esophageal endoscopy were conducted before the procedure, and a repeat esophageal endoscopy was performed after the procedure. Patients were randomized to restricted-CF group (n=44) or non-CF group (n=45), with circumferential pulmonary vein isolation using a CF-sensing (CF restricted to <20 g) or non–CF-sensing catheter, respectively. The primary end point was rate of EI post ablation. Baseline characteristics were evenly distributed between groups, without a case of preprocedural EI. With the same power setting, similar ablation time and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus in all patients in the restricted-CF group versus non-CF groups, there were no cases versus 9 (20%) cases of EI post ablation, respectively, with similar rate of freedom from atrial tachyarrhythmias at mean 31.3±6.5 months follow-up (68.2% versus 64.4%; P=0.3798). Risk for EI was minimized when CF was restricted to <20 g at the posterior left atrial wall, where the circumferential pulmonary vein isolation lesion set and the course of the esophagus overlapped in all subjects.


Posterior Iliac Crest Bone Graft: How Much Is Enough?
Autogenous bone grafting is the gold standard for reconstructing craniofacial defects. Mandibular defects are reliably reconstructed with free nonvascularized bone, such as from the posterior iliac crest (PIC). In light of improved imaging, including 3-dimensional computed tomography scanning, a more accurate defect estimation is possible. A strong understanding of bone graft available is necessary. The purpose of this study was an updated review of the dissection and quantification of the amount of bone that can be safely harvested. Bilateral bicortical osteotomy was performed on 55 cadavers to obtain 110 PIC bone grafts. Demographic factors and bicortical osteotomy measurements were recorded. Average osteotomy lengths, widths, and depths were 7.4, 5.5, and 1 cm, respectively. The average bicortical osteotomy volume was 40.6 cm. During the dissection, the authors identified 2 anatomical variants with respect to muscle insertion into the PIC. In variation 1, which occurred in 62% of dissections, the latissimus dorsi and thoracolumbar fascia did not originate from the PIC. When this occurred, the quadratus lumborum attached to the PIC. In variation 2, which occurred in 38% of dissections, the latissimus dorsi and thoracolumbar fascia originate from the PIC. By identifying the maximal bone volume obtainable from a PIC graft and noting 2 anatomical variants, this study allows for more accurate surgical planning and management.


Predictors of self-reported academic performance among undergraduate medical students of Hawassa University, Ethiopia.
This study was conducted to identify predictors of self-reported academic performance in undergraduate medical students at Hawassa University. An analytical cross-sectional study involving 592 undergraduate medical students was conducted in November 2012. The academic performance of the study subjects was measured by self-reported cumulative grade point average (GPA) using a self-administered questionnaire. Data were entered and analyzed using Statistical Package for the Social Sciences version 16 software. Pearson's bivariate correlations, multiple linear regression, and multiple logistic regression were used to identify predictors of academic performance. The self-reported academic performance of students had been decreasing as the academic years progressed, with the highest and lowest performance being in the premedicine (mean GPA 3.47) and clinical I (mean GPA 2.71) years, respectively. One hundred and fifty-eight (26.7%) of the participants had ever been delayed, 37 (6.2%) had ever re-sat for examination, and two (0.3%) had ever been warned due to academic failure. The overall variation in self-reported academic performance of the students was 32.8%. Participant age alone explained 21.9% of the variation. On the other hand, university entrance examination results, substance use at university, and medicine as first choice by students were identified as predictors of variation in self-reported academic performance, accounting for 6.9%, 2.7%, and <1% of the variation, respectively. Students who had never used tobacco, alcohol, or khat after starting university were twice as likely to score a self-reported cumulative GPA above 3.0 (adjusted odds ratio 1.95, 95% confidence interval 1.25-3.02) and less likely to be delayed, have to re-sit an examination, or be warned (adjusted odds ratio 0.47, 95% confidence interval 0.29-0.77). Only 32.8% of the variation in self-reported academic performance was explained by the studied variables. Hence, efficacious mechanisms should be designed to combat the intervenable determinants of self-reported academic performance, like substance use and a low medical school entrance examination result. Further studies should also be undertaken to gain a better understanding of other unstudied determinants, like personality, learning style, cognitive ability, and the system used for academic evaluation.


Communication Experiences in Primary Healthcare with Refugees and Asylum Seekers: A Literature Review and Narrative Synthesis.
Refugee and asylum seeker population numbers are rising in Western countries. Understanding the communication experiences, within healthcare encounters, for this population is important for providing better care and health outcomes. This review summarizes the literature on health consultation communication experiences of refugees and asylum seekers living in Western countries. Seven electronic databases were searched from inception to 31 March 2019. Studies were included if they aimed to improve, assess or report on communication/interaction in the primary health care consultation setting with refugees or asylum seekers, and were conducted in Western countries. A narrative synthesis of the literature was undertaken. Thematic analysis of the 21 included articles, showed that refugees and asylum seekers experience a range of communication challenges and obstacles in primary care consultations. This included practical and relational challenges of organizing and using informal and formal interpreters and cultural understanding of illness and healthcare. Non-verbal and compassionate care aspects of communication emerged as an important factor in helping improve comfort and trust between healthcare providers (HCP) and refugees and asylum seekers during a healthcare encounter. Improvements at the systems level are needed to provide better access to professional interpreters, but also support compassionate and humanistic care by creating time for HCPs to build relationships and trust with patients.


Site-directed deletion mutagenesis within the T4 endonuclease V gene: dispensable sequences within putative loop regions.
Endonuclease V from bacteriophage T4 may be one of the first DNA-repair enzymes to have its three-dimensional structure determined by X-ray crystallography (Morikawa et al., 1988). However, since this structure is not yet available, analyses of the sequence of the protein were performed in order to guide site-directed mutational studies of enzyme structure-function relationships. The enzyme is predominantly alpha-helical, so that an algorithm which finds the locations of turns or loops in the structure would be expected to approximately locate the helices along the sequence. Two loop sites were identified which might be adjacent in the tertiary structure according to a model developed from the loop predictions and the derived secondary structure. Deletion of three residues at each loop site produced protein molecules which retained considerable in vitro enzyme activity and in vivo repair function. However, the mutant proteins did not accumulate as well within the cell as the wild-type enzyme, suggesting that the nascent molecules folded inefficiently. Combination of the two deletions yielded a molecule with activity enhanced over one of the individual mutants, a result which can be interpreted as a classic second-site mutational reversion. This result supports the hypothesis that these regions are adjacent in the enzyme tertiary structure.