Knowledge, Attitudes and Practices of Law Enforcement Officers on Rabies and Animal Control Issues in Kansas.
Rabies is a deadly zoonoses endemic in the United States, including Kansas. Animal control programmes that emphasize vaccination of dogs and cats, removal of stray animals and enforcement of licensure programmes have historically been essential in reducing the risk of rabies exposures to humans (Beran, 1991). Kansas does not mandate the use of animal control officers [ACOs] and in areas where there is no designated animal control officer, law enforcement officers [LEOs] are required to fill that role. Little is known about LEOs' knowledge of rabies, their current practices in responding to animal-related calls or if they receive any specialized training to perform the duties of an ACO. A web-based, voluntary and anonymous survey was sent to law enforcement officers in Kansas in January 2014. The survey included questions about animal control practices and a self-assessment of rabies knowledge. The response rate was 16.2%. All respondents indicated LEOs will respond to animal-related calls, even if there was an ACO available in their department or jurisdiction. A majority of respondents indicated they had not received training on safe animal handling (62.9%, 61/97) or zoonoses prevention (85.6%, 83/97), even though a strong majority considered such training important (89.7% and 79.4%, respectively). Most respondents (>80%) were able to correctly identify animals capable of transmitting rabies but were less aware of how rabies was transmitted or the severity of rabies in humans. Our results demonstrate that Kansas LEOs perform animal control duties, many without the proper training, even though most consider such training to be important to be able to perform their duties safely. Training on safe animal handling and zoonoses prevention should be provided to all LEOs in Kansas to enable them to safely execute their duties and provide timely and accurate information to citizens regarding rabies prevention.


How Serious Is Erectile Dysfunction in Men's Lives? Comparative Data From Korean Adults.
Whereas sexual function has long been assumed to be an important component of adult men's lives, the impact of sexual dysfunction has not been estimated in parallel to other modern disease entities. We compared the seriousness of erectile dysfunction (ED) with that of other diseases by use of self-administered questionnaires. Between January 2012 and July 2012, 434 healthy male volunteers (group 1) and 263 ED patients (group 2) were enrolled. The questionnaire consisted of the following: "If you must undergo only one disease in all your life, which disease could you select among these items or ED?" The comparative disease entities included hypertension, diabetes mellitus (oral hypoglycemic agent/insulin injection), hemodialysis, myocardial infarction, herpes zoster, chronic sinusitis, chronic otitis media, gastric cancer (early/late), lung cancer (early/late), liver cancer (early/late), and dementia. Group 1 recognized ED as being a more serious disease than hypertension, diabetes mellitus (oral hypoglycemic agent), herpes zoster, chronic sinusitis, and chronic otitis media. In comparison, group 2 recognized ED as being a more serious condition than diabetes mellitus (insulin injection) and dementia (p<0.001 and p<0.001, respectively). In particular, ED was deemed to be more serious than hemodialysis, gastric cancer (early), lung cancer (early), and liver cancer (early) by men in group 2 in their 30s to 40s, and these results were statistically significant compared with the same age subgroups in group 1 (p<0.001, p<0.007, p<0.02, and p<0.007, respectively). In contrast with their healthy counterparts, Korean men with ED recognized ED as being as serious as hemodialysis, dementia, and early stage cancer, which reflects the severe bother of ED in Korean patients.


Sleep apnea in early and advanced chronic kidney disease: Kaiser Permanente Southern California cohort.
Sleep apnea (SA) has been reported to be highly prevalent in the dialysis population. The reported rates of SA in dialysis are severalfold greater than the 2 to 4% estimated in the general population. This study sought to determine whether an association exists between SA and early stages of chronic kidney disease (CKD) where SA may represent an important comorbidity and potential risk factor in kidney disease. Cross-sectional study of adults from an integrated health plan with documented serum creatinine levels in the period January 1, 2002, through December 31, 2004. SA diagnosis determined by International Classification of Diseases, ninth revision, coding for SA and Current Procedural Terminology coding for positive airway pressure devices. Kidney function was determined by the estimated glomerular filtration rate (eGFR). Logistic was regression used to estimate the relative risk for SA. The overall prevalence of SA was 2.5% in the study population that included subjects with normal renal function and those with CKD. The odds ratios (ORs) for SA by eGFRs of 75 to 89, 60 to 74, 45 to 59, 30 to 44, and 15 to 29 mL/min per 1.73 m(2), respectively, compared to normal kidney function, after adjustment for age, sex, and number of visits, were as follows: 1.22 (95% confidence interval [CI], 1.18 to 1.25); 1.32 (95% CI, 1.27 to 1.37); 1.42 (95% CI, 1.35 to 1.50); 1.37 (95% CI, 1.25 to 1.50); and 1.32 (95% CI, 1.13 to 1.55). The increased ORs for eGFRs > 45 mL/min per 1.73 m(2) were sustained even after controlling for diabetes, heart failure, and hypertension. This study demonstrated an increased risk of SA in patients with early CKD. Further evidence of a causal relationship should be sought in the hope that the detection and management of SA may improve the course of CKD.


Disappearance of Seasonal Respiratory Viruses in Children Under Two Years Old During COVID-19 Pandemic: A Monocentric Retrospective Study in Milan, Italy.
Background: The containment measures adopted during COVID-19 pandemic have influenced the epidemiology of other respiratory viruses. Aim: We analyzed the modification of the incidence and etiology of lower respiratory tract infections (LRTIs) in young children during COVID-19 pandemic. Methods: Case series of all children under 2 years old hospitalized at a tertiary care Hospital in the Center of Milan, Italy diagnosed with LRTIs in three consecutive winter seasons (from the 1st of November to the last day of February in 2018/2019, 2019/2020 and 2020/2021). We compared the number of hospitalizations and viral detections in the 2020/2021 with the average of 2018/2019 and 2019/2020 (pre-COVID-19) using the Poisson distribution. Results: we enrolled 178 patients (66 from 2018/2019, 96 from 2019/2020, 16 from 2020/2021) 94 males (53%) and 84 females (47%), with a median (IQR) age of 5 (2-13) months. The number of hospitalizations during the 2020/2021 season was 80% lower than the average of the pre-COVID-19 seasons (16 vs. 81, p<0.001). Overall, 171 (96%) patient's nasopharyngeal aspirate (NPA) detected at least one virus (110, 64%, single-detection, 61, 36%, co-detections). In 2020/2021 we observed the disappearance of Respiratory Syncytial virus (0 vs. 54, p < 0.001), Influenza virus (0 vs. 6.5, p = 0.002), Metapneumovirus (0 vs. 8, p < 0.001), Parainfluenza viruses (0 vs. 3.5, p = 0.03) and a significant reduction of Adenovirus (2 vs. 7, p = 0.03), Bocavirus (2 vs. 7.5, p = 0.02) and Enterovirus (1 vs. 5, p = 0.04). No significant difference was found for Rhinoviruses (14 cases vs. 17, p = 0.2), other Coronaviruses (0 vs. 2, p = 0.1), and Cytomegalovirus (1 vs. 1, p = 0.7). Conclusions: We observed a striking reduction in hospitalizations due to LRTIs and a modification of the etiology, with enveloped viruses mainly affected.


Current standards in the treatment of chronic hepatitis C.
In Germany, 400 000 to 500 000 people are chronically infected with the hepatitis C virus (HCV), 70% to 80% of them with HCV genotype 1. Combined treatment with peginterferon-alfa and ribavirin leads to a sustained virologic response (SVR) in 40% to 50% of patients with genotype 1 and 70% to 80% of patients with genotypes 2 and 3. The HCV protease inhibitors boceprevir and telaprevir were approved for clinical use in Germany in 2011. Selective literature review. Treatment with peginterferon and ribavirin is recommended for a variable length of time depending on the HCV genotype (24 to 72 weeks for genotype 1, 16 to 48 weeks for genotypes 2 and 3), the baseline HCV-RNA concentration (greater or less than 600 000 to 800 000 IU/mL), and the decline in HCV-RNA concentration after 4 and 12 weeks of treatment. Either boceprevir or telaprevir is given in addition to peginterferon and ribavirin. In the approval studies, these triple combinations were shown to yield higher SVR rates than dual treatment for genotype 1 (66% to 75% versus 37% to 44%). If there is a favorable early decline in HCV-RNA, the treatment can be shortened to 24 to 28 weeks in 44% to 65% of patients with genotype 1. The SVR rates in genotype 1 patients who failed previous dual therapy were 69% to 88% for prior relapsers, 52% to 59% for partial responders, and 33% for null responders. Triple combination therapy is associated with new adverse events. Individualized treatment durations are recommended for the treatment of chronic hepatitis C with peginterferon and ribavirin. Triple therapy in combination with either boceprevir or telaprevir leads to a higher rate of SVR both in previously untreated genotype 1 patients and in those who have failed prior antiviral treatment.\


Religious Practices and Spiritual Well-Being of Schizophrenia: Muslim Perspective.
To explore religious activities and its functions on the spiritual wellbeing of Muslim patients with schizophrenia. Semi-structured in-depth interviews were conducted in six schizophrenia inpatients and two female nurses. Document analysis of the standard operating procedure related to patients' spiritual needs fulfilment and patients' medical records were also undertaken in order to triangulate data and to get insights about patient spiritual and religious activity. Thematic analysis was used to analyse data. Five themes and 12 sub themes were revealed from the study data. The five themes elicited from the study namely frequency, timing, barriers to perform religious activities, impact on health status and negative effects if not performing the religious activities. Religious activities such as salat and dhikr for schizophrenia inpatients are still performed five times a day and when they are not getting period. Feeling upset, restless, happy, grateful, and when they are missing their family was the common reason why patients perform the religious activities. The main barriers to performing salat and dhikr for example: insufficient prayer tools and Al-Qur'an, as well as patients' physical conditions. Religious activities such as salat and dhikr positively impact patients' physical and mental health status, mindfulness, and concentration. Negative impacts physical and emotional are released when patients did not perform salat and dhikr. The findings show that salat and dhikr which perform on time and regularly have a positive impact on the physical and mental health of schizophrenia inpatients. The author might recommend the mental health hospital provide adequate worship or prayer equipment (gown and Al-Qur`an) for patients.


Prediction of Antidepressant Treatment Outcome Using Event-Related Potential in Patients with Major Depressive Disorder.
(1) Background: Prediction of treatment outcome has been one of the core objectives in clinical research of patients with major depressive disorder (MDD). This study explored the possibility of event-related potential (ERP) markers to predict antidepressant treatment outcomes among MDD patients; (2) Methods: Fifty-two patients with MDD were recruited and evaluated through Hamilton depression (HAM-D), Hamilton anxiety rating scale (HAM-A), and CORE. Patients underwent a battery of ERP measures including frontal alpha symmetry (FAA) in the low alpha band (8-10 Hz), mismatch negativity (MMN), and loudness-dependent auditory evoked potentials (LDAEP); (3) Results: During the eight weeks of study, 61% of patients achieved remission, and 77% showed successful treatment responsiveness. Patients with low FAA in F5/F6 demonstrated a significantly higher remission/response ratio and better treatment responsiveness (F (2.560, 117.755) = 3.84, p = 0.016) compared to patients with high FAA. In addition, greater FAA in F7/F8 EEG channels was significantly associated with greater melancholia scores (r = 0.34, p = 0.018). Other ERP markers lacked any significant effect; (4) Conclusions: Our results suggested low FAA (i.e., greater left frontal activity) could reflect a good treatment response in MDD patients. These findings support that FAA could be a promising index in understanding both MDD and melancholic subtype.


Red blood cells derived from whole blood treated with riboflavin and ultraviolet light maintain adequate survival in vivo after 21 days of storage.
Pathogen reduction (PR) of whole blood (WB) may increase blood safety when applied before component separation. This study evaluates the in vivo performance of red blood cells (RBCs) derived from WB treated with the riboflavin and ultraviolet (UV) light PR (Mirasol) system. This was a prospective, two-center, single-blind, randomized, two-period, crossover clinical trial designed to evaluate autologous 51 Cr/99m Tc-radiolabeled recovery and survival of RBCs derived from Mirasol-treated WB compared to untreated WB. RBCs were stored in AS-3 for 21 days at 1 to 6°C. In vitro RBC variables were characterized. Frequency and severity of treatment-emergent adverse event (TEAE) and neoantigenicity were determined. Twenty-four healthy adult volunteers (n = 12 per site) were evaluated. The Mirasol 24-hr RBC recoveries were 82.5 ± 3.9% with one-sided 95% lower confidence limit of 80.9%, meeting US Food and Drug Administration acceptance criteria, albeit at lower level than controls (91.7 ± 6.8%, p < 0.001). Mean RBC survival and T50 were reduced in the Mirasol group (61 and 23 days, respectively) versus controls (82 and 36 days, respectively; p < 0.001) with a mean area under the curve survival of treated RBCs of 83% of untreated controls. End-of-storage hemolysis in the Mirasol group was 0.22 ± 0.1% (control, 0.15 ± 0.1%; p < 0.001). No neoantigenicity or differences in TEAEs were found. RBCs derived from Mirasol WB and stored for up to 21 days in AS-3 maintained acceptable cell quality and recovery, albeit modestly reduced compared with untreated RBCs. Mirasol WB may represent a valid single WB PR platform that allows manufacture of RBC for storage for up to 21 days.


Dual-Bioinspired Design for Constructing Membranes with Superhydrophobicity for Direct Contact Membrane Distillation.
Water flux and durability are the two critical parameters that are closely associated with the practical application of membrane distillation (MD). Herein, we report a facile approach to fabricate superhydrophobic polyimide nanofibrous membranes (PI NFMs) with hierarchical structures, interconnected pores, and high porosity, which was derived from the electrospinning, dual-bioinspired design, and fluorination processes. Bioinspired adhesive based on polydopamine /polyethylenimine (PDA/PEI) composite was first linked onto membrane substrates and then assembled lotus leaf hierarchical structure by binding the negatively charged silica nanoparticles (SiO2 NPs) via electrostatic attraction. The resultant superhydrophobic PI NFMs exhibit a water contact angle of 152°, robust hot water resistance of 85 °C, and high water entry pressure of 42 kPa. Moreover, the membrane with omniphobicity presents high water flux over 31 L m-2 h-1 and high salts rejection of ∼100% as well as robust durability for treating high salinity wastewater containing typical low surface tension and dissolved contaminants (Δ T = 40 °C). Significantly, the novel dual-bioinspired method can be used as a universal tool to modify various materials with hierarchical structures, which is expected to provide more effective alternative membranes for MD and even for other selective wetting separation fields.


Universal and nonuniversal properties of wave-chaotic scattering systems.
Prediction of the statistics of scattering in typical wave-chaotic systems requires combining system-specific information with universal aspects of chaotic scattering as described by random matrix theory. This Rapid Communication shows that the average impedance matrix, which characterizes such system-specific properties, can be semiclassically calculated in terms of ray trajectories between ports. Theoretical predictions are compared with experimental results for a microwave billiard, demonstrating that the theory successfully uncovered universal statistics of wave-chaotic scattering systems.


An Improved Total RNA Extraction Method for White Jelly Mushroom Tremella fuciformis Rich in Polysaccharides.
An improved method for extracting high quality and quantity RNA from a jelly mushroom and a dimorphic fungus-Tremella fuciformis which is especially rich in polysaccharides, is described. RNA was extracted from T. fuciformis mycelium M1332 and its parental monokaryotic yeast-like cells Y13 and Y32. The A260/280 and A260/230 ratios were both approximately 2, and the RNA integrity number was larger than 8.9. The yields of RNA were between 108 and 213 µg/g fresh wt. Downstream molecular applications including reverse transcriptional PCR and quantitative real-time PCR were also performed. This protocol is reliable and may be widely applicable for total RNA extraction from other jelly mushrooms or filamentous fungi rich in polysaccharides.


Hear them roar: A comparison of black-capped chickadee (Poecile atricapillus) and human (Homo sapiens) perception of arousal in vocalizations across all classes of terrestrial vertebrates.
Recently, evidence for acoustic universals in vocal communication was found by demonstrating that humans can identify levels of arousal in vocalizations produced by species across three biological classes (Filippi et al., 2017). Here, we extend this work by testing whether two vocal learning species, humans and chickadees, can discriminate vocalizations of high and low arousal using operant discrimination go/no-go tasks. Stimuli included vocalizations from nine species: giant panda, American alligator, common raven, hourglass treefrog, African elephant, Barbary macaque, domestic pig, black-capped chickadee, and human. Subjects were trained to respond to high or low arousal vocalizations, then tested with additional high and low arousal vocalizations produced by each species. Chickadees (Experiment 1) and humans (Experiment 2) learned to discriminate between high and low arousal stimuli and significantly transferred the discrimination to additional panda, human, and chickadee vocalizations. Finally, we conducted discriminant function analyses using four acoustic measures, finding evidence suggesting that fundamental frequency played a role in responding during the task. However, these analyses also suggest roles for other acoustic factors as well as familiarity. In sum, the results from these studies provide evidence that chickadees and humans are capable of perceiving arousal in vocalizations produced by multiple species. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[From CANUSA to ADEMEX: do we need a new paradigm for definition of peritoneal dialysis adequacy?].
Peritoneal dialysis doses were prescribed out of empirical criteria up to the mid-Ninety Then, the observational CANUSA study and the experimental ADEMEX study helped to define adequacy criteria according to urea kinetics model. This review analyzes the limits of a definition of adequacy grounded exclusively on urea kinetics, as well as the need for new parameters of adequacy. The evidence is presented fostering the hypothesis that the control of extra-cellular fluid excess and of other cardiovascular risk factors may now be considered a new target for adequacy.


Cystic papillary carcinoma of the thyroid gland. Diagnosis by needle aspiration with transmission electron microscopy.
A case of papillary carcinoma of the thyroid gland identified by needle aspiration cytology is presented, and correlation between the ultrastructure of the cytologic material and the neoplastic tissue is emphasized. Needle aspiration is recommended for diagnosis of thyroid gland lesions and may allow, without significant risk to the patient, establishment of a specific preoperative diagnosis.


Effect of brivaracetam on CYP3A activity, measured by oral midazolam.
Brivaracetam is a synaptic vesicle protein 2A ligand in phase III development for epilepsy. A phase I, open-label, randomized study was conducted in 42 healthy male participants to assess the effect of brivaracetam on CYP3A activity using midazolam as a probe. Participants were randomized to oral brivaracetam 5, 50, or 150 mg/day from Day 8 to Day 14. A single oral dose (7.5 mg) of midazolam was administered on Days 1, 13, and 20, and full pharmacokinetic profiles were obtained. For all brivaracetam doses, the areas under the plasma concentration-time curves from 0 to infinity (AUCinf ) for midazolam and 1'-hydroxymidazolam were similar on Days 13 and 20 compared with Day 1. Following brivaracetam 150 mg/day, the Day 13/Day 1 AUCinf ratio (90% confidence interval) was 1.09 (0.97, 1.21) and 1.04 (0.93, 1.17) for midazolam and 1'-hydroxymidazolam, respectively. For the Day 20/Day 1 comparison, the corresponding AUCinf ratios were 1.10 (0.98, 1.23) and 1.07 (0.97, 1.18). Maximum midazolam plasma concentration was increased on both Day 13 and Day 20 vs. Day 1 but the relevance of this finding was unclear. This study indicates that brivaracetam up to 150 mg/day has no significant inducing or inhibiting effect on CYP3A activity.


Estrogen-related receptor alpha 1 actively antagonizes estrogen receptor-regulated transcription in MCF-7 mammary cells.
The estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily. We show that the major isoform of the human ERRalpha gene, ERRalpha1, can sequence-specifically bind a consensus palindromic estrogen response element (ERE) and directly compete with estrogen receptor alpha (ERalpha) for binding. ERRalpha1 activates or represses ERE-regulated transcription in a cell type-dependent manner, repressing in ER-positive MCF-7 cells while activating in ER-negative HeLa cells. Thus, ERRalpha1 can function both as a modulator of estrogen responsiveness and as an estrogen-independent activator. Repression likely occurs in the absence of exogenous ligand since charcoal treatment of the serum had no effect on silencing activity. Mutational analysis revealed that repression is not simply the result of competition between ERalpha and ERRalpha1 for binding to the DNA. Rather, it also requires the presence of sequences within the carboxyl-terminal E/F domain of ERRalpha1. Thus, ERRalpha1 can function as either an active repressor or a constitutive activator of ERE-dependent transcription. We hypothesize that ERRalpha1 can play a critical role in the etiology of some breast cancers, thereby providing a novel therapeutic target in their treatment.


Highly efficient Blue-Emitting CdSe-derived Core/Shell Gradient Alloy Quantum Dots with Improved Photoluminescent Quantum Yield and Enhanced Photostability.
Highly efficient blue-emitting CdSe-derived core/shell gradient alloy quantum dots (CSGA QDs) with photoluminescence quantum yield (PL QY) of ca. 90% have been synthesized through a facile "one-pot" approach. CdSe nuclei are initially formed as core and gradient alloy shells such as CdSexS1-x/ZnSeyS1-y simultaneously encapsulate the preformed CdSe core in an energy-gradient fashion eventually followed by coating with ZnS shells due to the faster precursor reaction kinetics of Cd and Se compared to analog of Zn and S. During the formation of core/shell structure, red-shifting of absorption/emission peaks followed by blue-shifting of analogues were observed due to the intradiffusion of sulfur anion to CdSe luminescent center. In this gradient architecture, interfacial lattice strain can be effectively alleviated, and thus high PL QY (ca. 90%) and enhanced photochemical stability can be achieved. The synthesized blue-emitting gradient alloy QDs with superior optical properties tunable in the range of 450-490 nm can be used for highly efficient blue-emitters and potentially applicable for the fabrication of white-light LEDs.


Task dissociation in prospective memory performance in individuals with ADHD.
The present study investigated, for the first time, event- and time-based prospective memory (PM) in the same sample of adults with ADHD within one paradigm using parallel task constraints. A total of 25 individuals with ADHD and 25 matched neurotypical controls completed a computerized version of the Dresden Breakfast Task, which required participants to prepare breakfast following a set of rules and time restrictions. Although groups did not differ in event-based PM, results demonstrated a large-sized impairment in individuals with ADHD in time-based PM. Findings suggest a task-specific impairment in PM functioning and are discussed in an executive control framework of neurocognitive functioning in ADHD.


Competency milestones for medical students: Design, implementation, and analysis at one medical school.
Competency-based assessment seeks to align measures of performance directly with desired learning outcomes based upon the needs of patients and the healthcare system. Recognizing that assessment methods profoundly influence student motivation and effort, it is critical to measure all desired aspects of performance throughout an individual's medical training. The Accreditation Council for Graduate Medical Education (ACGME) defined domains of competency for residency; the subsequent Milestones Project seeks to describe each learner's progress toward competence within each domain. Because the various clinical disciplines defined unique competencies and milestones within each domain, it is difficult for undergraduate medical education to adopt existing GME milestones language. This paper outlines the process undertaken by one medical school to design, implement and improve competency milestones for medical students. A team of assessment experts developed milestones for a set of focus competencies; these have now been monitored in medical students over two years. A unique digital dashboard enables individual, aggregate and longitudinal views of student progress by domain. Validation and continuous quality improvement cycles are based upon expert review, user feedback, and analysis of variation between students and between assessors. Experience to date indicates that milestone-based assessment has significant potential to guide the development of medical students.


[Anatomic and radiologic studies of of ovarian arteries in women of various ages].
The main source of ovarian arterial blood supply is so called an ovarian arcade. It is an arterial system made of the uterine and ovarian artery junction. Depend on the source of information, there are different descriptions of ovarian arcade vessels, as well as there are different anatomical nomenclature. Anatomical material was taken from 63 women aged 15 to 85. Arterial vessels were appropriately prepared, filled with contrast medium and X-ray examined. An ovarian and uterine vessels junction into the ovarian arcade was observed in the all examined material. In order to be include into the arcade, an appropriate vessel diameter had to be stated at the level of uterine and tubal end. In multiparas in comparison with nulliparas, an average diameter was bigger about 17%. Number of vessels, the arcade gives to ovarian hilus is also of variable quantity. There are markedly less vessels in postmenopausal women.


Fundamental and Practical Insights on the Packing of Modern High-Efficiency Analytical and Capillary Columns.
New stationary phases are continuously developed for achieving higher efficiencies and unique selectivities. The performance of any new phase can only be assessed when the columns are effectively packed under high pressure to achieve a stable bed. The science of packing columns with stationary phases is one of the most crucial steps to achieve consistent and reproducible high-resolution separations. A poorly packed column can produce non-Gaussian peak shapes and lower detection sensitivities. Given the ever larger number of stationary phases, it is impossible to arrive at a single successful approach. The column packing process can be treated as science whose unified principles remain true regardless of the stationary phase chemistry. Phenomenologically, the column packing process can be considered as a constant pressure or constant flow high-pressure filtration of a suspension inside a column with a frit at the end. This process is dependent on the non-Newtonian suspension rheology of the slurry in which the particles are dispersed. This perspective lays out the basic principles and presents examples for researchers engaged in stationary phase development. This perspective provides an extensive set of slurry solvents, hardware designs, and a flowchart, a logical approach to optimal column packing, thus eliminating the trial and error approach commonly practiced today. In general, nonaggregating but high slurry concentrations of stationary phases tend to produce well packed analytical columns with small particles. Conversely, C18 packed capillary columns are best packed using agglomerating solvents.


Development of a conversion program to make SIMIND-generated SPECT data interfile acceptable to Xeleris.
The Monte Carlo code SIMIND is used in nuclear medicine for research purposes, and also for testing the validity of various applications. Conversion of a SIMIND-generated interfile (header and image data file) is required to process the simulated image data on a Xeleris workstation. Currently there is no conversion program provided with SIMIND to convert its interfile, which is acceptable in any nuclear medicine workstation. Manual editing of the header file is possible with any standard text editor but it is time-consuming (requiring ∼1 h) and stressful. To alleviate this, we have developed a conversion program using FreeMat V4.0 (an open source software similar to MATLAB from MathWorks). It takes an average of 0.04404 s to convert a SIMIND SPECT data interfile and make it acceptable to Xeleris.


[Cultivation of aerobic granular sludge for simultaneous nitrification and denitrification in SBR system].
The cultivation of aerobic granular sludge used for nitrogen removal in Sequencing Batch Reactor (SBR) fed with a synthetic municipal wastewater was investigated. The results showed that the aerobic granular sludge with the high activity of simultaneous nitrification and denitrification, could form in the reactor by controlling the addition of carbon source, and the removal rates of COD and NH3-N reached 74.0%-92.8% and 82.3%-98.5%, respectively, in the reactor. The granular formed was averagely 0.5-1.0 mm in diameter, and the Mixed Liquid Suspended Solids (MLSS) and the Sludge Volumetric Index (SVI) in the reactor were above 4.5 g/L and above 32.5, respectively. Compared with the normal aerobic activated sludge process, the system with aerobic granular sludge had a higher concentration of effective biomass and a much stronger ability of nitrogen removal.


Budesonide and formoterol in a single inhaler controls asthma in adolescents.
Despite the availability of effective treatments and national guidelines, morbidity from asthma remains high among adolescents. Adolescents need to be considered as a distinct group of individuals with different requirements to those of children and adults. In particular, their non-adherence to prescribed treatment regimens is of concern and is a significant factor contributing to the high rate of morbidity in adolescents. Studies in children aged 4 to 17 years suggest that the combination of an inhaled corticosteroid (ICS) and a long-acting beta2-agonist effectively controls asthma symptoms in patients who remain symptomatic on ICS alone. In order to improve adherence to therapy, the use of combined therapy with an ICS and a long-acting beta2-agonist in a single inhaler should be considered and the dosing frequency should be adjusted according to the severity of asthma symptoms. This should empower patients with a greater degree of self-management and may be important in helping adolescents feel responsible for the management of their asthma. Results from a recent subanalysis demonstrate that the combination of budesonide and formoterol administered twice daily via a single inhaler (Symbicort Turbuhaler) rapidly gains and maintains control of asthma in adolescents whose asthma is not controlled on ICS alone. It is anticipated that this will lead to improved adherence to therapy in this difficult-to-treat population.


Yeast phenotypic assays on translational control.
This chapter describes phenotypic assays on specific and general aspects of translation using yeast Saccharomyces cerevisiae as a model eukaryote. To study the effect on start codon selection stringency, a his4(-) or his4-lacZ allele altering the first AUG to AUU is employed. Mutations relaxing the stringent selection confer the His(+) phenotype in the his4(-) strain background or increase expression from his4-lacZ compared to that from wild-type HIS4-lacZ (Sui(-) phenotype). Translation of the Gcn4p transcription activator is strictly regulated by amino acid availability depending on upstream ORF (uORF) elements in the GCN4 mRNA leader. Mutations reducing the eIF2/GTP/Met-tRNA(i)(Met) complex level or the rate of its binding to the 40S subunit derepress GCN4 translation by allowing ribosomes to bypass inhibitory uORFs in the absence of the starvation signal (Gcd(-) phenotype). Mutations impairing scanning or AUG recognition generally impair translational GCN4 induction during amino acid starvation (Gcn(-) phenotype). Different amino acid analogs or amino acid enzyme inhibitors are used to study Gcd(-) or Gcn(-) phenotypes. The method of polysome profiling is also described to gain an ultimate "phenotypic" proof for translation defects.


Molecular characterization of an expressed sequence tag representing the cuticle-degrading serine protease gene (PII) from the nematophagous fungus Arthrobotrys oviformis by differential display technology.
The technology of mRNA-based differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) was used to detect a 246-bp differentially expressed fragment from the nematophagous fungus Arthrobotrys oviformis when young mycelia were induced with the round worm Haemonchus contortus. The fragment was converted into an expressed sequence tag (EST) through characterization at the molecular level. Homology search indicated that the differentially expressed fragment originated from the cuticle-degrading serine protease gene, which has been previously reported to play a role in nematophagous activity in A. oligospora, Dactylaria parvispora, A. musiformis, and other potential anti-fungal biological control agents. Several single nucleotide polymorphisms found to represent both synonymous as well as non-synonymous mutations within this short sequence stretch of 246 bp suggested genetic variability within the gene in this group of nematode-trapping fungi. The cloned EST fragment has potential for use as a hybridization probe for searching full-length gene from an appropriate cDNA library of this and related fungi. This is the first report of the identification of an EST representing the cuticle-degrading serine protease gene from A. oviformis using the technique of DDRT-PCR.


This Harlem life: black families and everyday life in the 1920s and 1930s.
This article uses Probation Department files to reconstruct the lives of five ordinary residents of Harlem. It highlights what that black metropolis offered those outside the political and cultural elite, who have dominated historical scholarship, showing how ordinary blacks negotiated the challenges of life in northern neighborhoods, and drew on institutions and organizations, to establish and sustain new lives. We offer the kind of individualized perspective on everyday life that other scholars have provided for high culture, but which does not exist for other realms of existence in Harlem, even in early twentieth century sociological studies of black life. Where scholars seeking to distinguish the neighborhood from a slum have pointed to the prevailing pride and self-confidence of its residents, this article directs attention to more immediate, concrete supports that sustained and enriched life in Harlem. Relationships with spouses, children, siblings and cousins sustained individuals faced with the social reality of living in overcrowded, deteriorating, disease infested housing, subject to the racism of white police, politicians and employers; so too did friendships made in nightclubs, speakeasies, dances and movie theatres, and membership of churches, fraternal organizations, social clubs, and sports clubs and teams.


Management of adrenal incidentaloma: size still matters.
A 56-year-old man was found to have an adrenal incidentaloma on a CT scan of the abdomen. Clinically and biochemically, the mass was not functional. MRI scan revealed a heterogeneously enhancing, T2-hyperintense, right-sided adrenal mass (4.5×6.5 cm). Meta-iodo-benzylguanidine scan was normal, making a diagnosis of pheochromocytoma unlikely. As the mass was larger that 4 cm, it was excised and histopathological examination revealed a rare, composite tumour: benign adrenal adenoma with haemangiomatous and myelolipomatous components. This case highlights the difficulties encountered by a clinician faced with investigating a potentially malignant adrenal mass (based on size) and correlates radiological findings with a rare histopathological specimen.


Chronic Mg2+ Deficiency Does Not Impair Insulin Secretion in Mice.
Magnesium is an essential mediator of a vast number of critical enzymatic cellular reactions in the human body. Some clinical epidemiological studies suggest that hypomagnesemia accounts for declines in insulin secretion in patients with type 2 diabetes (T2D); however, the results of various experimental studies do not support this notion. To address this discrepancy, we assessed the short- and long-term effects of hypomagnesemia on β-cell function and insulin secretion in primary mouse islets of Langerhans and in a mouse model of hypomagnesemia known as Trpm6Δ17 /fl;Villin1-Cre mice. We found that lowering the extracellular Mg2+ concentration from 1.2 mM to either 0.6 or 0.1 mM remarkably increased glucose-induced insulin secretion (GIIS) in primary islets isolated from C57BL/6 mice. Similarly, both the plasma insulin levels and GIIS rose in isolated islets of Trpm6Δ17 /fl;Villin1-Cre mice. We attribute these rises to augmented increases in intracellular Ca2+ oscillations in pancreatic β-cells. However, the glycemic metabolic profile was not impaired in Trpm6Δ17 /fl;Villin1-Cre mice, suggesting that chronic hypomagnesemia does not lead to insulin resistance. Collectively, the results of this study suggest that neither acute nor chronic Mg2+ deficiency suppresses glucose-induced rises in insulin secretion. Even though hypomagnesemia can be symptomatic of T2D, such deficiency may not account for declines in insulin release in this disease.


Update on vesicoureteral reflux: pathogenesis, nephropathy, and management.
Clinical reflux was first visualized over 100 years ago. In the 1950s and early 1960s, the assumption was that surgery to relieve bladder neck obstruction would have a positive effect on bladder function and reflux. By the early 1970s it was understood that the underlying structural problems leading to primary reflux were congenitally abnormal distal ureters and orifices. Researchers in the 1960s and 1970s demonstrated the connection between reflux and renal scarring. More recently, reflux nephropathy in the absence of urinary tract infections has been observed, leading researchers to investigate an association between bladder dysfunction and reflux with resulting nephropathy. The cornerstone of management of the child with vesicoureteral reflux is antibiotic prophylaxis; treatment regimens for various grades of reflux are reviewed. Indications for surgical treatment of reflux are also discussed. Controversies regarding vesicoureteral reflux, including duration of prophylactic treatment, remain to be resolved.


The Arabidopsis Lipid Transfer Protein 2 (AtLTP2) Is Involved in Cuticle-Cell Wall Interface Integrity and in Etiolated Hypocotyl Permeability.
Plant non-specific lipid transfer proteins (nsLTPs) belong to a complex multigenic family implicated in diverse physiological processes. However, their function and mode of action remain unclear probably because of functional redundancy. Among the different roles proposed for nsLTPs, it has long been suggested that they could transport cuticular precursor across the cell wall during the formation of the cuticle, which constitutes the first physical barrier for plant interactions with their aerial environment. Here, we took advantage of the Arabidopsis thaliana etiolated hypocotyl model in which AtLTP2 was previously identified as the unique and abundant nsLTP member in the cell wall proteome, to investigate its function. AtLTP2 expression was restricted to epidermal cells of aerial organs, in agreement with the place of cuticle deposition. Furthermore, transient AtLTP2-TagRFP over-expression in Nicotiana benthamiana leaf epidermal cells resulted in its localization to the cell wall, as expected, but surprisingly also to the plastids, indicating an original dual trafficking for a nsLTP. Remarkably, in etiolated hypocotyls, the atltp2-1 mutant displayed modifications in cuticle permeability together with a disorganized ultra-structure at the cuticle-cell wall interface completely recovered in complemented lines, whereas only slight differences in cuticular composition were observed. Thus, AtLTP2 may not play the historical purported nsLTP shuttling role across the cell wall, but we rather hypothesize that AtLTP2 could play a major structural role by maintaining the integrity of the adhesion between the mainly hydrophobic cuticle and the hydrophilic underlying cell wall. Altogether, these results gave new insights into nsLTP functions.


[Transforming growth factor-β1 induces differentiation of bone marrow-derived mesenchymal stem cells into myofibroblasts via production of reactive oxygen species].
The aim of this study was to investigate the mechanism underlying transforming growth factor-β1 (TGF-β1) induced differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into myofibroblasts. Primary mouse BMSCs were isolated from bone marrow by flushing the tibias and femurs of mice, and passage 3 to passage 5 of BMSCs were used in the experiments. BMSCs differentiation into myofibroblast was induced by different doses of TGF-β1. In addition, reactive oxygen species (ROS) inhibitor (N-acetylcysteine, NAC) was added to test its effect on the action of TGF-β1. Expressions of BMSCs differentiation parameters, α-smooth muscle actin (α-SMA), collagen α1(I) [Col α1(I)] and collagen α1(III) [Col α1(III)] were measured by real-time quantitative PCR (RT-qPCR) and Western blot analysis. BMSCs were preloaded for 15 min with 2', 7'-dichlorohydrofluorescein diacetate (DCFH-DA), then stimulated with TGF-β1 for different times, and fluorescence of ROS was measured using high content analysis. TGF-β1 stimulated differentiation of BMSCs into myofibroblasts and up-regulated expression of α-SMA, Col α1(I) and Col α1(III) in a dose-dependent manner, which blocked by ROS inhibitor NAC. In addition, TGF-β1 could induce a significant rapid and transient increase in ROS production in BMSCs, and the effect of TGF-β1 on ROS production was peaked at 30 min. TGF-β1 induced differentiation of BMSCs into myofibroblasts via production of ROS.


Earthworm species in various land use systems in the Campos Gerais region of Lapa, Paraná, Brazil.
The Campos Gerais region of Paraná are on an ancient plateau of sandstone origin and are covered with a diverse vegetation including mainly grasslands and various types of Atlantic Forest (particularly Araucaria forest). The region represents an important natural capital for biodiversity conservation as well as for agricultural and forestry production. However, little is known of the species richness and diversity of soil macroinvertebrates in this region. In the present study we evaluated earthworm species occurrence and richness in five land use systems (LUS) in the southern part of the Campos Gerais in Lapa county. Earthworms were handsorted from up to 18 soil monoliths on five occasions over three years (Feb. 2014, Feb., Mar., Nov. 2015, Jul. 2016) in the following LUS: old native forest, native grassland, young regenerating forest and grass lawn in the Uru Reserve and annual crop fields (soybean) in neighboring private farms (not all systems were sampled on all occasions). Nine earthworm species belonging to four families and five genera were found, of which six were native and three exotic species (Dichogaster gracilis, Amynthas gracilis, A. corticis). Of the native species, Urobenus brasiliensis and Andiorrhinus duseni (a large bodied-worm) are already well known from S and SE Brazil, while the remaining four were new species that require further description (Fimoscolex n.sp.1 and n.sp.2, Glossoscolex n.sp.1 and n.sp.2). In general, more species were found in February (summer) than March and November. The cropping system (soybean) had the lowest abundance and species richness in relation to other sites, although in the young and old forests no earthworms were found on some sample dates. Given the several new species found in this small reserve, and the relatively few sites studied thus far in the Campos Gerais, further efforts are needed to adequately characterize the earthworm fauna of the region, from which many other species are expected.


Marr's theory of the neocortex as a self-organizing neural network.
Marr's proposal for the functioning of the neocortex (Marr, 1970) is the least known of his various theories for specific neural circuitries. He suggested that the neocortex learns by self-organization to extract the structure from the patterns of activity incident upon it. He proposed a feedforward neural network in which the connections to the output cells (identified with the pyramidal cells of the neocortex) are modified by a mechanism of competitive learning. It was intended that each output cell comes to be selective for the input patterns from a different class and is able to respond to new patterns from the same class that have not been seen before. The learning rule that Marr proposed was underspecified, but a logical extension of the basic idea results in a synaptic learning rule in which the total amount of synaptic strength of the connections from each input ("presynaptic") cell is kept at a constant level. In contrast, conventional competitive learning involves rules of the "postsynaptic" type. The network learns by exploiting the structure that Marr assumed to exist within the ensemble of input patterns. For this case, analysis is possible that extends that carried out by Marr, which was restricted to the binary classification task. This analysis is presented here, together with results from computer simulations of different types of competitive learning mechanisms. The presynaptic mechanism is best known in the computational neuroscience literature. In neural network applications, it may be a more suitable mechanism of competitive learning than those normally considered.


Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial.
This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation.


Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes.
Mutations in T-cell antigen receptor (TCR) subunit genes cause rare immunodeficiency diseases characterized by impaired expression of the TCR at the cell surface and selective T lymphopenia. Here, detailed analyses of spontaneously arising somatic mutations that recover CD247, and thus TCR expression, in a newly identified CD247-deficient patient are described. The recovery of CD247 expression in some patient T cells was associated with both reversion of the inactivating mutation and a variant with a compensating mutation that could reconstitute TCR expression, but not as efficiently as wild-type CD247. Multiple mutations were found in CD247 complementary DNAs (cDNAs) cloned from the patient as well as in cDNA and genomic DNA from other individuals, suggesting that genetic variation in this gene is frequent. Analyses of other genes mutated in primary immunodeficiency diseases (PIDs) where reversions have been described also revealed a higher rate of mutation than that observed for genes mutated in PIDs where revertants have not been identified or control genes. These data support the hypothesis that the occurrence of somatic mutations that may reconstitute genetic defects in PID is related to an increased propensity of those genes to mutate.


ASSESSMENT OF RADON IN SOIL AND WATER IN DIFFERENT REGIONS OF KOLHAPUR DISTRICT, MAHARASHTRA, INDIA.
Researchers have already established that inhalation of high radon concentration is hazardous to human health. Radon concentration has been measured in water and soil, in various part of Kolhapur district has been carried out by the AQTEK Smart RnDuo which is an active device technique. The observed minimum value of the radon mass exhalation rate of the soil is 13.16 ± 0.83 mBq/kg/h and maximum is 35.11 ± 1.84 mBq/kg/h. The minimum value of the Radon concentration in water is 0.33 ± 0.052 Bq/L and maximum is 7.32 ± 0.078 Bq/L. These values of radon concentration are below the action of recommended level by the USEPA, which is set as the maximum contaminant level of 11.1-148 Bq/L of radon in drinking water. Total annual effective dose rate of water is 11 μSv/y. The purpose of present study is to assess radiological risk from consumption of water that provide in Kolhapur district and to evaluate the radon mass exhalation rate of soil in few places of Kolhapur district.


NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging.
Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, (19)F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a (19)F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180 nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2 mg/mL. The reported nanoemulsion's properties, including small particle size, visibility under (19)F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment.


Access to ambulatory care for poor persons.
Studies conducted during the 1970s have reported conflicting results concerning whether differences in use of physician services between poor and nonpoor persons have been eliminated. Using a sample of 92,737 persons from the 1982 National Health Interview Survey and a refined analytic method, this study reexamines utilization of ambulatory care services by persons above and below the poverty level. Before adjusting for health status, no differences were apparent in rates of physician contacts for persons above and below the poverty level. After adjusting for health status, persons below poverty were shown to have significantly fewer physician contacts than persons above poverty. Multivariate analysis revealed that Medicaid coverage can effectively counter the depressing effects of poverty on use of physician services. However, only 34 percent of the noninstitutionalized population below poverty level had Medicaid coverage in 1982. Public policy implications concerning Medicaid eligibility criteria are discussed.


A new instrument to aid the lateral tarsal sling procedure.
We describe a new surgical instrument and its use in the lateral tarsal sling procedure. We reviewed the charts of 23 cases of such surgery over 5 years and found its use to be an effective means of correcting horizontal eyelid laxity, with a low rate of complications. This approach provides a safe and effective alternative to the lateral tarsal strip procedure.


Identification of acyl donors and acceptor proteins for fatty acid acylation in BHK cells infected with Semliki Forest virus.
The modification of viral glycoproteins through the covalent attachment of fatty acids was studied in baby hamster kidney (BHK) cells infected with Semliki Forest virus (SFV). Comparative pulse-chase experiments with [3H]palmitic acid and [35S]methionine revealed that a precursor polypeptide, designated p62, of the structural SFV glycoprotein and E1 serve as the primary acceptors of acyl chains. Acylation of p62 occurs immediately prior to its proteolytical cleavage to E2 and E3 emphasizing the post-translational and specific nature of this hydrophobic modification. To trace the acyl donor(s) for protein acylation the covalent attachment of fatty acids to p62 was studied after extremely short labeling periods with [3H]palmitic acid and correlated to the metabolism of the exogenous tritiated fatty acid. The shortest possible labeling time, a 10 s pulse with [3H]palmitic acid, was sufficient to acylate SFV p62. Analysis of the labeled lipids extracted from the same cells revealed that palmitoyl-CoA and phosphatidic acid showed the highest specific radioactivity among the tritiated lipid species. Out of these lipid species palmitoyl-CoA was identified as the functional acyl donor lipid in a cell-free system for the acylation of polypeptides.


Effect of bacterial media on the evaluation of the antibacterial activity of a biomaterial containing inorganic antibacterial reagents or antibiotics.
Several studies have been performed to assess the effectivesness of the antibacterial coating of a biomaterial to reduce surgical site infection. However, evaluations of these materials are inconsistent, and therefore it is difficult to compare their antibacterial performance. In this study, we evaluated the influence of different media such as nutrient broth (NB), Mueller-Hinton broth (MHB) and fetal bovine serum (FBS) on the antibacterial activity of AgNO3- or gentamicin-added bone cement using a modified ISO 22196 standard to devise a method to evaluate the antibacterial activity of biomaterials in vitro. The antibacterial activity results against Staphylococcus aureus and Escherichia coil were different in each medium. The antibacterial activity of AgNO3 in FBS was lower than the other media, whereas the antibacterial activity of gentamicin in FBS was higher than in the other media. It was assumed that the fluctuating antibacterial activity was influenced by serum components. The results showed that the ISO 22196 antibacterial evaluation method is suitable to evaluate antibacterial biomaterials after modifying the medium to FBS.


[Clinical applications of G-CSF].
Granulocyte colony-stimulating factor is a 18 kD glycoprotein hormone which exhibits the following biological actions; (1) amplification and release into blood of bone marrow hematopoietic stem/progenitor cells, (2) enhancement of neutrophil production and stimulation of their release into blood and into tissues, (3) prolongation of neutrophil survival and activation of their various functions, (4) stimulation of myeloid leukemia cell growth. In patients with malignant neoplastic disorders, therefore, its recombinant human form (rhG-CSF) may be an effective strategy for various therapeutic purposes. These include reduction of the risk for infectious complications, more effective killing of malignant cells, and promotion of bone marrow transplantation. We have recently performed several clinical studies of rhG-CSF derived from Chinese hamster ovary cells. Results so far obtained from these studies strongly indicate that rhG-CSF can be safely and efficiently used for the above purposes.


The effect of BMI, serum leptin, and adiponectin levels on prognosis in patients with non-ischaemic dilated cardiomyopathy.
The recent studies demonstrated that obese heart failure patients have better prognosis - "obesity paradox". The aim of the study was to evaluate the relationship between body mass index (BMI), leptin and adiponectin concentrations and prognosis in patients with heart failure due to non ischeamic dilated cardiomyopathy (NIDCM). 128 patients with NIDCM were included and followed-up for three years. Leptin and adiponectin were measured at baseline using commercially available ELISA tests. Clinical data, routine laboratory parameters, NT-proBNP were assessed as risk factors for reaching the study endpoints: urgent heart transplantation (B), death (C), or combined endpoint death or urgent heart transplantation (D). Patient with adverse outcome had lower BMI and higher NT-proBNP concentration. Leptin was significantly elevated in group C and adiponectin was higher in groups B and D than in survived patients. Patients with leptin concentration below median or with adiponectin concentration above median were more often transplanted in three years follow-up (p = 0.029, p = 0.022, respectively). The cumulative probability of death was greater in patients with concentration of leptin above median (p = 0.024). In the multivariable Cox proportional hazards analyses, increasing leptin and lower BMI were predictors of death. Adiponectin was associated with higher risk of heart transplantation. Both an inverse association of BMI and positive association of leptin and adiponectin with combined endpoint were discovered. Further adjustment to established risk factors abolished association between combined endpoint and BMI, and modestly attenuate with adiponectin and leptin concentration. Evaluation of adiponectin and leptin concentrations was more useful than BMI in prediction of unfavourable outcome in patients with NIDCM. (Endokrynol Pol 2017; 68 (1): 26-34).


Synthesis of graft copolymers based on hyaluronan and poly(3-hydroxyalkanoates).
This work reports the synthesis and characterisation of new amphiphilic hyaluronan (HA) grafted with poly(3-hydroxyalkanoates) (PHAs) conjugates. Hydrolytic depolymerisation of PHAs was used for the synthesis of defined oligo(3-hydroxyalkanoates)-containing carboxylic terminal moieties. A kinetic study of the depolymerisation was followed to prepare oligomers of required molecular weight. PHAs were coupled with hydroxyl groups of HA mediated by N, N'-carbonyldiimidazole (CDI) or HSTU Tetramethyl-O-(N-succinimidyl) uronium hexafluorophosphate. For the first time, the covalent bonding of oligo derivatives of P(3-hydroxybutyrate), P(3-hydroxyoctanoate), P(3-hydroxyoctanoate-co-3-hydroxydecanoate) and P(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate) and HA was achieved by "grafting to" strategy. Achieved grafting degree was a function of hydrophobicity of PHA, Mw and polarity of the solvent. The most suitable reaction conditions were observed for oligo (3-hydroxybutyrate) grafted to HA (grafting degree of 14%). Graft copolymers were characterized by FT-IR, NMR, DSC and SEC-MALLS. Graft copolymers can be physically loaded with hydrophobic drugs and may serve as drug delivery system.


Effects of Music during Multiple Cesarean Section Delivery.
This experimental study was conducted to determine the level of anxiety in women undergoing multiple cesarean section. Sixty multiple cesarean section referrals were randomly assigned to either the experimental or control groups. Data was collected at the Karaman Public Health Hospital in Turkey, from June 2015 to June 2016. Songs chosen earlier by the patients were played during the cesarean section procedure for the experimental group. The control group was studied without music. Data was collected using a questionnaire form, and Visual Analogue Scale (VAS) was used to determine the anxiety levels. The t-test and chi-square test were used to analyse statistically significant differences between the groups. The VAS scores before and during the procedure showed significantly lower scores for the experimental group, compared to the control group (p<0.05). Music therapy reduces the physiological and cognitive responses of anxiety in patients undergoing multiple cesarean section, and can be used in the clinical practice.


LysM Proteins TaCEBiP and TaLYK5 are Involved in Immune Responses Mediated by Chitin Coreceptor TaCERK1 in Wheat.
Plant lysin motif (LysM) ectodomain receptors interact with pathogen-associated molecular patterns (PAMPs) and have critical functions in plant-microbe interactions. In this study, 65 LysM family genes were identified using the recent version of the reference sequence of bread wheat (Triticum aestivum), in which 23, 16, 20, and 6 members belonged to LysM-containing receptor-like kinases (LYKs), LysM-containing receptor-like proteins (LYPs), extracellular LysM proteins (LysMes), and intracellular nonsecretory LysM proteins (LysMns), respectively. The study found that TaCEBiP, TaLYK5, and TaCERK1 were highly responsive to PAMP elicitors and phytopathogens, with TaCEBiP and TaLYK5 binding directly to chitin. TaCERK1 acted as a coreceptor with TaCEBiP and TaLYK5 at the plasma membrane. Overexpression of TaCEBiP, TaLYK5, and TaCERK1 in Nicotiana benthamiana leaves exhibited enhanced resistance to Sclerotinia sclerotiorum. Subsequently, knocking down TaCEBiP, TaLYK5, and TaCERK1 genes with barley stripe mosaic virus-VIGS compromised the wheat defense response to an avirulent strain of Puccinia striiformis. The study concluded that wheat has two synergistic chitin perception systems for detecting pathogen elicitors, with the activated CERK1 intracellular kinase domain leading to signaling transduction. This research provides valuable insights into the functional roles and regulatory mechanisms of wheat LysM members under biotic stress.


The Role of Caveolin 1 in HIV Infection and Pathogenesis.
Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.


Unprecedented one-pot sequential thiolate substitutions under mild conditions leading to a red emissive BODIPY dye 3,5,8-tris(PhS)-BODIPY.
The simple reaction of phenylthiol with 8-MeS-BODIPY (1) in dichloromethane was readily accomplished to form 8-PhS-BODIPY (2). If the reaction is performed in THF 3,8-bis(phenylthio)-BODIPY (3) and 3,5,8-tris(phenylthio)-BODIPY (4) are sequentially formed in an unprecedented reaction. This provides a simple new methodology for the introduction of the phenylthio-moiety in the 3- and 5-positions. Alkyl thiols do not form multi-thiolated products under identical conditions, as exemplified using EtSH, where only 8-EtS-BODIPY (5) is formed.


Variable slice thickness (VAST) EPI for the reduction of susceptibility artifacts in whole-brain GE-EPI at 7 Tesla.
A new technique for 2D gradient-recalled echo echo-planar imaging (GE-EPI) termed 'variable slice thickness' (VAST) is proposed, which reduces signal losses caused by through-slice susceptibility artifacts, while keeping the volume repetition time (TR) manageable. The slice thickness is varied across the brain, with thinner slices being used in the inferior brain regions where signal voids are most severe. Various axial slice thickness schemes with identical whole-brain coverage were compared to regular EPI, which may either suffer from unfeasibly long TR if appropriately thin slices are used throughout, or signal loss if no counter-measures are taken. Evaluation is based on time-course signal-to-noise (tSNR) maps from resting state data and a statistical group-level region of interest (ROI) analysis on breath-hold fMRI measurements. The inferior brain region signal voids with static B0 inhomogeneities could be markedly reduced with VAST GE-EPI in contrast to regular GE-EPI. ROI-averaged event-related signal changes showed 48% increase in VAST compared to GE-EPI with regular "thick" slices. tSNR measurements proved the comparable signal robustness of VAST in comparison to regular GE-EPI with thin slices. A novel acquisition strategy for functional 2D GE-EPI at ultrahigh magnetic field is presented to reduce susceptibility-induced signal voids and keep TR sufficiently short for whole-brain coverage.


Change in the surface hydrophobicity of substrate cells during bdelloplast formation by Bdellovibrio bacteriovorus 109J.
During intraperiplasmic growth of Bdellovibrio bacteriovorus 109J, the substrate cell surface becomes more hydrophobic. This was shown (i) by comparing the sensitivity to hydrophobic antibiotics of wild-type and lipopolysaccharide mutant strains of Salmonella typhimurium to that of the bdellovibrio growing on these strains and (ii) by measuring the binding efficiency of these strains, Escherichia coli, and their derived bdelloplasts to octyl Sepharose. The kinetics of increase in surface hydrophobicity was similar to the kinetics of the conversion of the substrate cell peptidoglycan to a lysozyme-resistant form (M. Thomashow and S. Rittenberg, J. Bacteriol. 135:1008-1014, 1978), and hydrophobicity reached a maximum at about 60 min in a synchronous culture. The change in hydrophobicity was inhibited by chloramphenicol, suggesting that bdellovibrio protein synthesis was required. Control experiments revealed that the free-swimming bdellovibrio had a more hydrophobic surface than the deep rough mutants of S. typhimurium.


Comparison of oversized artery and vein grafts for interpositional pedicle lengthening in rat femoral artery.
Vessel grafting is commonly used for revascularization or pedicle lengthening. Although veins are more commonly used, they can form aneurysms when bridging an arterial gap. This can lead to thrombosis, and the risk is increased when there is a size discrepancy. This study reports the long-term results of arterial lengthening via size discrepant carotid artery and femoral vein grafts in a rat femoral artery model (1:1.5 ratio). A total of 28 rats were used in this study, divided into two groups of 14. By the 21st day, one anastomosis in each group has been found to be thrombosed. Long-term patency rates were the same for both groups (93.3%). Radiologic imaging showed that size match in the carotid artery grafts was excellent despite of slightly fusiform dilatation, but in the vein groups, pronounced aneurismal deformation and distortion in the anastomosis was seen. Histologic analysis revealed that in the arterial grafts, endothelial continuity was smooth and mural inflammation was less than that of the vein grafts. Organized or recanalized mural thrombi were seen in 38.5% in the vein grafts, whereas in arterial grafts there were none.


Expression of the HPV18/E6 oncoprotein induces DNA damage.
This study investigated possible variations in DNA damage in HeLa cells with silenced expression of the HPV/E6 oncogene compared with HeLa cells with normal expression of the E6 oncogene using the DNA breakage detection–fluorescence in situ hybridization (DBD–FISH) technique and a whole human genome DNA probe. The variable levels of DNA breaks present were measured quantitatively using image analysis after whole-genome DNA hybridization. HeLa cells with silenced expression of the HPV18/E6 oncogene showed a significant decrease in DNA damage compared with parental cells with normal expression of the E6 oncogene. These results were confirmed by alkaline comet assay. In conclusion, we demonstrated a decrease in DNA damage in HeLa clones associated with low expression of the HPV/E6 oncogene. The significance of this decrease regarding the HPV life cycle and carcinogenesis requires further exploration.


Why are children living in poverty getting fatter?
In recent decades, there has been a dramatic increase in unhealthy weight for both children and adults. The Canadian standard of living has changed in favour of more easily prepared, calorie-dense foods and sedentary practices. Many family characteristics have also changed over the past 50 years. More Canadian families are living in disadvantaged situations, forecasting a host of unhealthy behaviours and attitudes in adults. The poor are not only getting poorer, they are also becoming heavier. Children from disadvantaged families seem to be leading the trend in increasing prevalence of unhealthy weight. Because they live in neighbourhoods that are perceived as unsafe, these children are likely spending more time indoors. This is associated with watching more television, which not only displaces other forms of educational and active entertainment but also places them at risk of learning inaccurate information about proper eating. Social science research helps identify factors contributing most to the rise in excess weight within this population, thus providing essential clues for effective approaches to its eradication.


The effects of Ramadan fasting on activity and energy expenditure.
Fasting during the month of Ramadan entails abstinence from eating and drinking between dawn and sunset and a major shift in meal times and patterns with associated changes in several hormones and circadian rhythms; whether there are accompanying changes in energy metabolism is unclear. We have investigated the impact of Ramadan fasting on resting metabolic rate (RMR), activity, and total energy expenditure (TEE). Healthy nonobese volunteers (n = 29; 16 women) fasting during Ramadan were recruited. RMR was measured with the use of indirect calorimetry. In subgroups of participants, activity (n = 11; 5 women) and TEE (n = 10; 5 women) in free-living conditions were measured with the use of accelerometers and the doubly labeled water technique, respectively. Body composition was measured with the use of bioelectrical impedance. Measurements were repeated after a wash-out period of between 1 and 2 mo after Ramadan. Nonparametric tests were used for comparative statistics. Ramadan fasting did not result in any change in RMR (mean ± SD: 1365.7 ± 230.2 compared with 1362.9 ± 273.6 kcal/d for Ramadan and post-Ramadan respectively, P = 0.713, n = 29). However, controlling for the effects of age, sex, and body weight, RMR was higher in the first week of Ramadan than in subsequent weeks. During Ramadan, the total number of steps walked were significantly lower (n = 11, P = 0.001), while overall sleeping time was reduced and different sleeping patterns were seen. TEE did not differ significantly between Ramadan and post-Ramadan (mean ± SD: 2224.1 ± 433.7 compared with 2121.0 ± 718.5 kcal/d for Ramadan and post-Ramadan, P = 0.7695, n = 10). Ramadan fasting is associated with reduced activity and sleeping time, but no significant change in RMR or TEE. Reported weight changes with Ramadan in other studies are more likely to be due to differences in food intake. This trial is registered at clinicaltrials.gov as NCT02696421.


Effects of Inter-electrode Distance on Delayed Onset Muscle Soreness in Microcurrent Therapy.
[Purpose] This study examined the effect of the distance between the two electrodes on delayed onset muscle soreness during microcurrent therapy. [Methods] In this study 24 healthy women who hadn't exercised regularly for six months were selected and randomly divided into two groups. Delayed onset muscle soreness (DOMS) was induced and experimental Group 1 were given microcurrent treatment with the electrodes attached at a close distance evaluated. Experimental Group 2 received the same treatment with the electrodes attached at a greater distance apart. Visual analogue scale pain and the RIII reflex were evaluated after inducing DOMS and after one day, two days, three days and four days of microcurrent treatment. [Results] The visual analogue scale and amplitude of RIII amplitude only showed significant differences with the length of time of the treatment. [Conclusion] This study found that difference of interelectrode distance has no influence on VAS pain and the RIII reflex of DOMS. Although there were no significant differences in RIII amplitude, we suspect that it may be influenced by current parameters such as frequency and intensity.


Analysis of HTT CAG repeat expansion in Italian patients with amyotrophic lateral sclerosis.
HTT full-penetrance pathogenic repeat expansions, the genetic cause of Huntington's disease (HD), have been recently reported in a minority of frontotemporal dementia/amyotrophic lateral sclerosis (ALS) patients (0.13%). We analyzed HTT CAG repeats in an Italian cohort of ALS patients (n = 467) by repeat-primed polymerase chain reaction. One patient harbored two expanded alleles in the HTT gene (42 and 37 CAG repeats). The absence of HD typical symptoms and the clinical picture consistent with ALS, corroborated by the diagnostic assessment, apparently excluded a misdiagnosis of HD.


[52-year-old patient with subcutaneous space-occupying lesion in immunosuppression].
We report the case of a 52-years-old male patient, who was diagnosed with subcutaneous alveolar echinococcosis 6 months after liver transplantation for HCV-related cirrhosis. Nether the explanted nor the transplantated liver revealed an echinococcus focus. Therefore a rare primary extrahepatic manifestation was likely. Interestingly, the echinococcal larvae had developed protoscolices. The development of mature tapeworms in human is a rarity, which could be related to the immunosuppressive therapy after liver transplantation. The patient was curatively treated by surgical removal of the subcutaneous tumor and a postoperative therapy with albendazole. Furthermore, HCV reinfection (genotype 2b) was successfully treated with interferone alpha 2b and ribavirine for 6 months.


Intraoperative frozen section assessment of sentinel lymph nodes in the operative management of women with symptomatic breast cancer.
Maximisation of the potential of sentinel lymph node biopsy as a minimally invasive method of axillary staging requires sensitive intraoperative pathological analysis so that rates of re-operation for lymphatic metastases are minimised. The aim of this study was to describe the test parameters of the frozen section evaluation of sentinel node biopsy for breast cancer compared to the gold standard of standard permanent pathological evaluation at our institution. The accuracy of intraoperative frozen section (FS) of sentinel nodes was determined in 94 consecutive women undergoing surgery for clinically node negative, invasive breast cancer (37:T1 disease; 43:T2; 14:T3). Definitive evidence of lymphatic spread on FS indicated immediate level II axillary clearance while sentinel node "negativity" on intraoperative testing led to the operation being curtailed to allow formal H&E analysis of the remaining sentinel nodal tissue. Intraoperative FS correctly predicted axillary involvement in 23/30 patients with lymphatic metastases (76% sensitivity rate) permitting definitive surgery to be completed at the index operation in 87 women (93%) overall. All SN found involved on FS were confirmed as harbouring tumour cells on subsequent formal specimen examination (100% specificity and positive predictive value) with 16 patients having additional non-sentinel nodes found also to contain tumour. Negative Predictive Values were highest in women with T1 tumours (97%) and lessened with more local advancement of disease (T2 rates: 86%; T3: 75%). Of those with falsely negative FS, three had only micrometastatic disease. Intraoperative FS reliably evaluates the status of the sentinel node allowing most women complete their surgery in a single stage. Thus SN can be offered with increased confidence to those less likely to have negative axillae hence expanding the population of potential beneficiaries.


Spectrum of artificial light at night drives impact of a diurnal species in insect food web.
Artificial light at night (ALAN) has become a profound form of global anthropogenic environmental change differing in from natural light regimes in intensity, duration, distribution and spectra. It is clear that ALAN impacts individual organisms, however, population level effects, particularly of spectral changes, remain poorly understood. Here we exposed experimental multigenerational aphid-parasitoid communities in the field to seven different light spectra at night ranging from 385 to 630 nm and compared responses to a natural day-night light regime. We found that while aphid population growth was initially unaffected by ALAN, parasitoid efficiency declined under most ALAN spectra, leading to reduced top-down control and higher aphid densities. These results differ from those previously found for white light, showing a strong impact on species' daytime performance. This highlights the importance of ALAN spectra when considering their environmental impact. ALAN can have large impacts on the wider ecological community by influencing diurnal species.


Poor perinatal outcome associated with retained cerclage in patients with premature rupture of membranes.
To evaluate the role of immediate cerclage removal versus retention in patients experiencing premature rupture of the membranes remote from term (PROM). Thirty patients with prophylactic cerclage experiencing PROM at 24-32 weeks were managed expectantly after either immediate removal in 20 (67%) or retention of the cerclage in ten (33%). Thirty-three patients without cerclage and with PROM at the same gestational age were used as controls. More patients with retained cerclage (nine of ten, 90%) had delivery delayed for at least 48 hours after PROM compared to patients with immediate cerclage removal (ten of 20, 50%) (P < .05). Perinatal mortality was significantly higher for those with retained cerclage (seven of ten, 70%) than with immediate removal (two of 20, 10%) or in the control group (six of 33, 18%) (P < .001). Sepsis was responsible for most of the poor outcomes in the retained-cerclage group (71%). Although retaining the cerclage prolonged the latency period between PROM and delivery, that benefit was more than offset by a greatly increased perinatal mortality rate. Our study supports immediate cerclage removal regardless of gestational age in cases of PROM.


Particulate air pollution and susceptibility to the development of pulmonary tuberculosis disease in North Carolina: an ecological study.
Although Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (PTB), environmental factors may influence disease progression. Ecologic studies conducted in countries outside the USA with high levels of air pollution and PTB have suggested a link between active disease and ambient air pollution. The present investigation is the first to examine the ambient air pollution-PTB association in a country, where air pollution levels are comparatively lower. We used Poisson regression models to examine the association of outdoor air pollutants, PM10 and PM2.5 with rates of PTB in North Carolina residents during 1993-2007. Results suggest a potential association between long-term exposure to particulate matter (PM) and PTB disease. In view of the high levels of air pollution and high rates of PTB worldwide, a potential association between ambient air pollution and tuberculosis warrants further study.


Optimizing therapy of seizures in patients with endocrine disorders.
Endocrinologic disorders, such as thyroid dysfunction or diabetes, may be comorbidities in patients with epilepsy. The choice of medication should address such comorbidities wherever possible. Enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine, phenytoin, barbiturates, and oxcarbazepine among the new AEDs, may reduce the levels of free and total thyroxin. However, clinically relevant thyroid dysfunction owing to AED treatment is rare. Nevertheless, there are now better alternative AEDs with similar efficacy to the classic first-line drugs but without their enzyme-inducing properties. Such drugs should be considered in cases of thyroid dysfunction to reduce the likelihood of iatrogenic adverse effects. Sufficient data on some of the new AEDs to support this hypothesis are, however, still lacking and urgently needed. Several reports have pointed out the possible negative impact of valproate on glucose and insulin metabolism and particularly on body weight. The increased risk for development of polycystic ovarian syndrome remains a matter of debate but is certainly another argument for the development of alternative agents. The group of new AEDs offers some potential candidates. Topiramate is the AED that is most likely to lead to weight loss; this may be perceived as a positive side effect in some patients. This review summarizes the data on the possible impact of AEDs in endocrinological disorders, concentrating on thyroid dysfunction, insulin/glucose metabolism, and body weight.


Novel solid-phase membrane tip extraction and gas chromatography with mass spectrometry methods for the rapid analysis of triazine herbicides in real waters.
Novel, fast, selective, eco-friendly and reproducible solid-phase membrane tip extraction and gas chromatography with mass spectrometry methods were developed and validated for the analysis of triazine herbicides (atrazine and secbumeton) in stream and lake waters. The retention times of atrazine and secbumeton were 7.48 and 8.51 min. The solid-phase membrane tip extraction was carried out in semiautomated dynamic mode on multiwall carbon nanotubes enclosed in a cone-shaped polypropylene membrane cartridge. Acetone and methanol were found as the best preconditioning and desorption solvents, respectively. The extraction and desorption times for these herbicides were 15.0 and 10.0 min, respectively. The percentage recoveries of atrazine and secbumeton were 88.0 and 99.0%. The linearity range was 0.50-80.0 μg/L (r(2) > 0.994), with detection limits (<0.47 μg/L, S/N = 3) and good reproducibility (<8.0%). The ease of operation, eco-friendly nature, and low cost of solid-phase membrane tip extraction made these methods novel. The Solid-phase membrane tip extraction method was optimized by considering the effect of extraction time, desorbing solvents and time.


Steroid secretion by follicles and cysts from the hypothyroid, hCG-treated rat.
Hypothyroid rats develop cystic follicles after daily administration of human chorionic gonadotropin (hCG). This study was undertaken to compare progesterone, testosterone, and estradiol secretion by antral follicles (0.9-1.0 mm) and cysts (small; 1.2-2.0 mm; large: > 2.0 mm) from hypothyroid, hCG-treated rats with that of antral follicles from euthyroid, saline-treated animals. After 3, 5, or 10 days of hCG injections, follicles and cysts were dissected from the ovaries, diameter determined, and incubated in minimum essential medium (MEM) for 2 hr at 37 degrees C. Media were assayed for progesterone, testosterone, and estradiol by RIA. Progesterone secretion by antral follicles removed after 3, 5, or 10 days was similar but small cysts secreted significantly more of this steroid than did antral follicles. Large cysts secreted significantly more progesterone than all other follicles and cysts. After 10 days of treatment with hCG, antral follicles from hypothyroid, hCG-treated rats secreted two to three times more testosterone than similar follicles from euthyroid, saline-treated animals. Changes in estradiol secretion were not apparent until after 10 days of hCG treatment. Both small and large cysts from those animals secreted significantly more estradiol than all other follicle and cyst groups. These results suggest that steroid secretion by follicles and cysts could be contributing to elevated serum levels of progesterone and testosterone during the first 10 days of cyst induction. However, cysts may be contributing estradiol only during the later stages of cyst induction.


Studies on the hormonal regulation of plasminogen activator production in the rat ovary.
When granulosa cells are prepared from rats primed with PMSG, it is possible to induce plasminogen activator (PA) production in vitro with a variety of hormones. We have compared the effects of the gonadotropins FSH and LH on granulosa cells in culture. Although both hormones can induce enzyme secretion, the time courses of their effects are different. Whereas FSH yields a linear increase in PA production starting 2 h after the time of hormone addition, the effect of LH shows a longer lag phase, but it eventually reaches the same degree of stimulation as FSH. Experiments with an inhibitor of prostaglandin (PG) synthesis, indomethacin, and with PGs suggest the following interpretation. Granulosa cells that can produce PA can be directly stimulated by FSH, but only a small fraction of these cells can be induced by LH. However, the population that is responsive to LH begins to produce PGs after hormone treatment, and the PGs can then stimulate the entire population. Cumulus cells, which have few LH receptors, can be induced by FSH and PGs, but not LH. Experiments involving treatment of rats with indomethacin in vivo or treatment of follicles in vitro demonstrate that this compound can suppress PA secretion in the ovary, which may partially explain its ability to inhibit ovulation.


Proliferative nodules in congenital melanocytic nevi: a clinicopathologic and immunohistochemical analysis.
Congenital melanocytic nevi (CMN) occur in 1% to 2% of newborns, and the risk of malignant melanoma is increased in patients with large CMN. Appearance at birth or later of a nodular or hyperpigmented area within a CMN simulates malignant melanoma and prompts biopsy. Although their clinical and pathologic features seem ominous, proliferative nodules (PNs) typically are benign and may regress, although atypical features cause greater concern. Here we report clinical and pathologic findings with outcome in 10 children who had multiple biopsies of large CMN with PNs. We reviewed 78 separate samples from the 10 patients and classified the 60 PNs according to published criteria. A subset of 30 samples containing both the CMN and a PNs was analyzed for immunohistochemical reactivity for melanocytic (S-100 protein, HMB45, melan-A), lymphocytic (CD45), cell-cycle/proliferative (Mib-1, p16, p21, p27, c-Myc), apoptotic (p53, Bax, c-kit, CD95), and anti-apoptotic (bcl-2) markers. Both CMN and PNs had similar expression of melanocytic, lymphocytic, and most cell-cycle/proliferative and apoptotic markers, including Mib-1, p16, p21, p27, c-Myc, Bax, CD95, and bcl-2. A greater proportion of PNs than CMN were reactive for p53 (67% vs. 30%, P < 0.0098) and c-kit (97% vs. 3%, P < 0.0001). p53 and p21 expression in CMN and all types of PNs were inversely correlated. When ordinary and atypical PNs were compared, the atypical PNs more frequently expressed p53, Mib-1, Bax, and bcl-2, but less frequently expressed p21. The c-kit expression in nearly all PNs and its absence in nearly all CMN is potentially useful for recognition of PN, suggests a delayed melanocytic maturation process in proliferative nodules, and may be likely indicative of their benign nature. p53 reactivity in concert with a lack of p21 up-regulation by immunohistochemistry suggests that a p53 mutation may be present in PN, although the immunohistochemical findings alone cannot exclude possible overexpression of wild-type p53. Regressive, involutional, or maturational changes were observed in sequential samples from 4 patients. No patient developed malignant melanoma or another melanocytic nevus-associated malignancy during the follow-up period. These findings underscore the similarities between PNs and the underlying CMN and suggest that maturational, proliferative, and apoptotic processes are involved in their clinical evolution.


An HMM model for coiled-coil domains and a comparison with PSSM-based predictions.
Large-scale sequence data require methods for the automated annotation of protein domains. Many of the predictive methods are based either on a Position Specific Scoring Matrix (PSSM) of fixed length or on a window-less Hidden Markov Model (HMM). The performance of the two approaches is tested for Coiled-Coil Domains (CCDs). The prediction of CCDs is used frequently, and its optimization seems worthwhile. We have conceived MARCOIL, an HMM for the recognition of proteins with a CCD on a genomic scale. A cross-validated study suggests that MARCOIL improves predictions compared to the traditional PSSM algorithm, especially for some protein families and for short CCDs. The study was designed to reveal differences inherent in the two methods. Potential confounding factors such as differences in the dimension of parameter space and in the parameter values were avoided by using the same amino acid propensities and by keeping the transition probabilities of the HMM constant during cross-validation. The prediction program and the databases are available at http://www.wehi.edu.au/bioweb/Mauro/Marcoil


Seroclassification of hitherto nontypeable Actinobacillus actinomycetemcomitans strains: evidence for a new serotype e.
Serotyping of 89 Actinobacillus actinomycetemcomitans isolates by indirect immunofluorescence with serotype-specific monoclonal antibodies yielded 10 nontypeable strains. The aim of the present study was to re-evaluate the seroclassification of these strains with a different assay. Electroblotted antigens of nontypeable isolates and selected reference strains were immunostained with 37 human sera containing high antibody titers to A. actinomycetemcomitans. Such immunoblots typically showed an immunodominant, serotype-specific antigen smear. Twelve human sera were found to recognize specifically serotype a, 10 serotype b and 9 serotype c. Three sera contained antibodies to 2 or all 3 serotype antigens; 3 sera had no activity to any reference strain smear antigen. There was complete agreement between the seroclassification of the reference strains with the monoclonal and the polyclonal reagents. Seven of the 10 strains, nontypeable with monoclonal antibodies, could also not be typed by the human sera. Of the remaining 3 strains, one belonged to a previously unrecognized serovar of serotype a, and 2 isolates expressed a novel smear antigen detected by the 3 human sera containing no antibodies to the serotype a, b, or c antigens. We propose that these 2 strains be assigned to a new A. actinomycetemcomitans serotype, designated serotype e.


Using large-scale molecular data sets to improve breast cancer treatment.
The treatment of breast cancer patients could potentially be advanced by having a more complete understanding of breast cancer biology, including a catalog of recurrently altered genes. Over the last decade, thousands of human breast tumors have been profiled for gene expression and DNA copy number alterations, and ongoing efforts in DNA sequencing are establishing the set of somatically mutated genes. Much of the molecular data being generated resides in the public domain, available as a resource for further research. The challenge then becomes how to best utilize all these data, to mine them for candidate biomarkers and targets, which is the subject of this review. Some examples of integrative analysis and combining results from diverse data sets are also presented.


Diagnosis and management of ileocolic pseudoaneurysms.
Ileocolic pseudoaneurysmal disease is a rare splanchnic aneurysm that affects 3 out of 100 000 patients, and only 7 cases have been described in the past 40 years in patients without preexisting connective tissue disorders. Abdominal pain is the most common presenting symptom and nearly 30% of patients present with hemorrhage. Ileocolic pseudoaneurysms are diagnosed by contrasted computed tomography scans and verified by arteriography. We present a case report and review of the literature in which a patient was initially managed by coil embolization, followed by laparotomy and suture ligation due to pseudoaneurysm rupture.


A Bibliometric Analysis of Neurosurgical Practice Guidelines.
In the last 20 yr, the rate of neurosurgical guideline publication has increased. However, despite the higher volume and increasing emphasis on quality there remains no reliable means of measuring the overall impact of clinical practice guidelines (CPGs). To utilize citation analysis to evaluate the dispersion of neurosurgical CPGs. A list of neurosurgical guidelines was compiled by performing electronic searches using the Scopus (Elsevier, Amsterdam, Netherlands) and National Guideline Clearinghouse databases. The Scopus database was queried to obtain current publication and citation data for all included documents and categorized based upon recognized neurosurgical specialties. The h-index, R-index, h2-index, i10-index, and dissemination index (D-Index) were manually calculated for each subspecialty. After applying screening criteria the search yielded 372 neurosurgical CPGs, which were included for bibliometric analysis. The overall calculated h-index for neurosurgery was 56. When broken down by subspecialty trauma/critical care had the highest value at 35, followed by spine and peripheral nerve at 30, cerebrovascular at 28, tumor at 16, pediatrics at 14, miscellaneous at 11, and functional/stereotactic/pain at 6. Cerebrovascular neurosurgery was noted to have the highest D-Index at 3.4. A comprehensive framework is useful for guideline impact analysis. Bibliometric data provides a novel and adequate means of evaluating the successful dissemination of neurosurgical guidelines. There remains a paucity of data regarding implementation and clinical outcomes of individual guidelines.


Penetration and distribution of thiocolchicoside through human skin: comparison between a commercial foam (Miotens) and a drug solution.
Penetration and distribution of thiocolchicoside from a commercially available foam (Miotens 0.25%, w/v) through human excised full-thickness skin were evaluated using two different in vitro apparatus: a Franz diffusion cell and a Saarbruecken penetration model-based cell. In order to evaluate the intrinsic capability of the drug to penetrate into the skin, a simple drug aqueous solution prepared at the same drug concentration as Miotens was also tested. Results showed that both apparatus were suitable to study thiocolchicoside penetration into human skin. Penetrated drug amounts were comparable using the two apparatus, probably because skin acts as "sink" for the drug. Miotens was found to significantly promote thiocolchicoside accumulation into full human skin thickness in comparison with the simple drug solution. The mixture of propylene glycol and propylene glycol diperlargonate contained into Miotens foam has been proven to be effective to promote penetration of thiocolchicoside into human skin.