Simple model for directed networks.
We study a model for directed networks based on the Watts-Stogatz model for small-world phenomena. We focus on some topological aspects of directed networks inspired in food web theory, namely, the fraction of basal and top nodes in the network and node level distributions. We argue that in directed networks basal nodes play an important role, collecting information or resources from the environment. We give analytical expressions for the fraction of basal and top nodes for the model, and study the node level distributions with numerical simulations.


Seroprevalence and incidence of hepatitis E virus infection in German blood donors.
Hepatitis E virus (HEV) is transmissible by transfusion. More data are needed about seroprevalence, incidence, and viremia in blood donors for the assessment of risk of transfusion-transmitted (TT)-HEV infections. Samples from 1019 whole blood donors were tested for anti-HEV immunoglobulin (Ig)G by enzyme-linked immunosorbent assay and Western blot. The incidence of HEV and presence of HEV RNA in donors who seroconverted were determined by testing archive samples and recipients of viremic donations were traced. Anti-HEV IgM and alanine transaminase (ALT) testing were also performed to assess the value of such measures in the prevention of TT-HEV infections. A total of 69 of 1019 donors tested positive for anti-HEV IgG (6.8% seroprevalence), and seroconversion for anti-HEV IgG occurred in seven of 69 donors within 2 years (incidence, 0.35%/year). Three of seven (42.8%) seroconverting donors provided an archive sample in which HEV RNA was detectable. One recipient of these donations was traceable; anti-HEV IgG, IgM, and HEV RNA testing were negative 41 days after transfusion. Neither ALT levels nor anti-HEV IgM detection correlated with the presence of HEV RNA. The seroprevalence of HEV was 6.8%, and the annual incidence 0.35%. HEV RNA was detectable in several seroconverting donors, without evidence for HEV transmission in the only traceable recipient. Since neither ALT nor anti-HEV IgM testing correlate with the presence of HEV RNA, HEV nucleic acid testing currently provides the only method for the prevention of TT-HEV infection. However, before implementation, more data about clinical relevance of TT-HEV infections and infectious dose of HEV are required.


Development of a Nursing Guideline for Improving Skin Integrity in High-Risk Infants.
High-risk infants are highly susceptible to skin impairment caused by invasive procedures, radiant warmers, and phototherapy, in addition to their intrinsic vulnerability. This leads to a vicious cycle that aggravates the risk of skin infections. Concerns have been raised that neonatal nurses may lack knowledge regarding feasible guidelines to improve skin integrity of high-risk newborns. A clinical guideline was developed for neonatal skin care practices based on skin physiology, and its educational effects on the knowledge and confidence of neonatal nurses was evaluated. A booklet was developed on skin care practice guidelines divided into topics determined through a nationwide survey. Using a quasi-experimental design with 46 neonatal nurses, education with this booklet improved nurses' knowledge of skin care practices but not their confidence. These findings highlight the importance of implementing a tailored systematic program rather than a single educational session on skin care in high-risk infants for neonatal nurses. [J Contin Educ Nurs. 2020;51(5):238-244.].


Vertical distributions and gamma dose rates of 40K, 232Th, 238U and 137Cs in the selected forest soils in Izmir, Turkey.
This paper presents the results obtained from a radioecological study carried out in the selected forest sites of Izmir, Turkey. The levels of gamma-emitting radionuclides, 40K, 232Th, 238U and 137Cs, in soils were determined using gamma spectroscopy. The activity profile for 40K, 232Th and 238U exhibits a uniform distribution with respect to depth. The depth distribution of 137Cs activity was established by fitting the experimental points to an exponential or a Gaussian function. About 42-97% of the 137Cs deposition was found in the first 10 cm of soil even after 18 y from Chernobyl accident. The dose-rate and annual-effective dose received from external irradiation were quantified. It is indicated that 137Cs from the fallout plays a less role in external radiation exposures in forest sites of Izmir than in potential exposures from naturally occurring radionuclides accounted for by soil.


Tuberculin sensitivity in a high-risk canine population.
An epidemiologic study of tuberculosis in dogs exposed to humans with recently reported tuberculosis was undertaken in Philadelphia between July 1966 and June 1968. A total of 29 dogs meeting the criteria for inclusion in the high-risk population were studied by history, physical examination, intradermal tuberculin tests, and radiographic and bacteriologic examination. Ten of the 29 dogs showed positive responses to US Department of Agriculture (USDA) standard mammalian tuberculin. Positive tuberculin tests to second strength PPD were demonstrated in five of the 10 responders to USDA mammalian tuberculin. No physical, radiographic or bacteriologic evidence of tuberculosis was found in any of the high-risk animals examined. In a comparison group of 70 dogs without knwon exposure to tuberculosis, two positive responses to USDA tuberculin were demonstrated and none to PPD.


COVID-19 associated EBV reactivation and effects of ganciclovir treatment.
Systemic reactivation of Epstein-Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the clinical consequences of EBV reactivation remain uncertain. In this retrospective study, we screened 1314 patients with confirmed COVID-19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)-immunoglobulin G (IgG), Epstein-Barr nuclear antigen-IgG, VCA-IgM, early antigen (EA)-IgG, CMV-IgG, and CMV-IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA-IgG levels were significantly higher in nonsurvivors than in survivors (median difference: -0.00005, 95% confidence interval, CI [-3.10, 0.00], p = .05). As compared to patients with COVID-19 who did not receive ganciclovir therapy, ganciclovir-treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir-treated patients. A high proportion of COVID-19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID-19 patients complicated with EBV reactivation warrants to be addressed in a placebo-controlled randomized trial in the future.


Measuring of IgG2c isotype instead of IgG2a in immunized C57BL/6 mice with Plasmodium vivax TRAP as a subunit vaccine candidate in order to correct interpretation of Th1 versus Th2 immune response.
Evaluation of the murine isotype antibodies is essential in subunit vaccine development because inbred mouse strains with diverse genetic backgrounds respond different to recombinant proteins. In this regard, the main goal of this study was to measuring and comparing the profile of IgG isotype responses in C57BL/6 mice. For this purpose, the extracellular region of plasmodium vivax thrombospondin-related adhesive protein (PvTRAP) gene was expressed in Escherichia coli Rosetta (DE3)-pET23a. Then, the recombinant PvTRAP alone or emulsified with Freund's complete adjuvant were applied for immunization of the C57BL/6 mice. The role of antibodies and cellular immune responses induced by recombinant PvTRAP were evaluated. The results showed the level of anti-rPvTRAP IgG2c was significantly higher than IgG2a in the groups that received rPvTRAP alone (mean OD490 = 0.798 ± 0.12 and 0.39 ± 0.1, respectively) and emulsified with CFA/IFA (mean OD490 = 1.48 ± 0.07 and 0.605 ± 0.13, respectively; P < 0.05, independent sample t-test). Additionally, the immunized mice with rPvTRAP and rPvTRAP + CFA/IFA had an intermediate-avidity IgG2a antibody but high-avidity IgG2c antibody as well as the mean of serum antibody titers results exhibited that in both rPvTRAP and rPvTRAP + CFA/IFA mouse groups, IgG2a end-point titer (1:3200 and 1:25,600, respectively) was noteworthy lower than IgG2c (1:25,600 and 1:102,400, respectively). Moreover, the results revealed the eliciting significant levels of IFN-γ (P < 0.05, independent sample t-test) and no detectable level of IL-4 in the mouse groups received rPvTRAP alone and emulsified with CFA/IFA as compared to the mouse control groups. In general, our results showed that for correctly interpreting of Th1 immune responses in C57BL/6 mouse strain it is critical to measure IgG2c instead of IgG2a along with IFN-γ.


Epidemiology of Chikungunya fever outbreak in Western Jamaica during July-December 2014.
Our study describes the 2014 Chikungunya outbreak in Western Jamaica in terms of geographic distribution and trend of the outbreak over time, and evaluates clinical symptoms of the disease based on pre-existing conditions. We conducted a retrospective, cross-sectional study of 609 clinically defined Chikungunya virus (CHIKV) fever cases that occurred in the four parishes of the Western Regional Health Authority of Jamaica from July 2014 to December 2014. Cases were not confirmed by laboratory tests but met clinical and epidemiological criteria of CHIKV fever. Our results show a propagated spread of CHIKV fever during the outbreak period with the peak at the end of October. Main urban cities, such as Montego Bay and Lucea, were identified as places that had high numbers of cases. Fever and arthralgia were the two most common clinical symptoms in CHIKV patients. Although a majority (80%) of infants aged <2 years had up to four symptoms (80%), the percentage of infants with higher numbers of symptoms (9-10) was higher than in older age groups. However, back pain was found to occur significantly more in older patients. Those with arthritis as a pre-existing condition were more likely to experience headache, asthenia, back pain, and periarticular edema. These findings can help public health officials develop more effective programs to prevent the spread of CHIKV outbreaks by focusing on crowded urban cities. The findings indicate that those who are likely to develop a higher number of symptoms, such as young infants and people with pre-existing conditions, such as arthritis, should be more closely monitored to better manage the disease outcome.


Polyelectrolyte Complex Based Interfacial Drug Delivery System with Controlled Loading and Improved Release Performance for Bone Therapeutics.
An improved interfacial drug delivery system (DDS) based on polyelectrolyte complex (PEC) coatings with controlled drug loading and improved release performance was elaborated. The cationic homopolypeptide poly(l-lysine) (PLL) was complexed with a mixture of two cellulose sulfates (CS) of low and high degree of substitution, so that the CS and PLL solution have around equal molar charged units. As drugs the antibiotic rifampicin (RIF) and the bisphosphonate risedronate (RIS) were integrated. As an important advantage over previous PEC systems this one can be centrifuged, the supernatant discarded, the dense pellet phase (coacervate) separated, and again redispersed in fresh water phase. This behavior has three benefits: (i) Access to the loading capacity of the drug, since the concentration of the free drug can be measured by spectroscopy; (ii) lower initial burst and higher residual amount of drug due to removal of unbound drug and (iii) complete adhesive stability due to the removal of polyelectrolytes (PEL) excess component. It was found that the pH value and ionic strength strongly affected drug content and release of RIS and RIF. At the clinically relevant implant material (Ti40Nb) similar PEC adhesive and drug release properties compared to the model substrate were found. Unloaded PEC coatings at Ti40Nb showed a similar number and morphology of above cultivated human mesenchymal stem cells (hMSC) compared to uncoated Ti40Nb and resulted in considerable production of bone mineral. RIS loaded PEC coatings showed similar effects after 24 h but resulted in reduced number and unhealthy appearance of hMSC after 48 h due to cell toxicity of RIS.


Psychiatric Case Review and Treatment Intensification in Collaborative Care Management for Depression in Primary Care.
This study examined whether psychiatric case review was associated with depression medication modification in a large implementation program of collaborative care for depression in safety-net primary care clinics. Registry data were examined from an implementation of the collaborative care model in Washington State. A total of 14,960 adults from 178 primary care clinics who initiated care between January 1, 2008, and September 30, 2014, and who had a baseline Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher were included. Rates of psychiatric case reviews and receipt of new depression medications were extracted from the registry for all patients and for a subset of patients who did not improve by eight weeks of treatment (did not achieve a PHQ-9 score of less than 10 or a reduction in PHQ-9 score of 50% or more, compared with baseline). One-half of patients received a new depression medication. Psychiatric case review in any given month was associated with a doubling of the probability of receiving a new medication in the following month. Among patients who did not improve by eight weeks of treatment, a psychiatric case review during weeks 8-12 was associated with a higher rate of receipt of new medications during weeks 8-16 or weeks 8-20. In a collaborative care program, psychiatric case review was associated with higher rates of subsequent receipt of a new depression medication. This finding supports the importance of psychiatric case review in reducing clinical inertia in collaborative care treatment of depression.


Changes in the community of ectomycorrhizal fungi and increased fine root number under adult beech trees chronically fumigated with double ambient ozone concentration.
Forest soils are an important but under-studied part of forest ecosystems. The effects of O(3) on below-ground processes in a mature forest have only received limited attention so far. In our study, we have analysed the community of ectomycorrhizal fungi and beech fine root dynamics over two growing seasons (2003 - 2004) in a 70-year old mixed spruce-beech forest stand, in which two groups of five adult beech trees were either fumigated by 2 x ambient ozone concentration or used as control. The main difference between previous studies and our approach was that previous studies were performed on seedlings in pot experiments or in closed or open top chambers, and not IN SITU, in a mature forest stand. Although beech is a relatively unresponsive species to tropospheric O(3), we found a pronounced effect of 2 x O(3) on the number of vital ectomycorrhizal root tips and non-turgescent fine roots. Both categories of roots were significantly increased when compared to controls in two consecutive years at each sampling event. The number of types of ectomycorrhizae and species richness increased in 2004, but not in the extremely dry year 2003. We hypothesised that the observed changes might be an expression of a transitional state in below-ground succession of niches caused by an O(3) induced effect on carbon allocation to roots and the rhizosphere. We have detected changes in ectomycorrhizal species level, however Shannon-Weavers species diversity index and percentage of types of ectomycorrhizae did not change significantly in any sampling year thus indicating our results cannot be unequivocally explained by summer drought in year 2003 or by O(3) exposure alone.


Path-integral simulations beyond the adiabatic approximation.
Within the adiabatic approximation, it is trivial to generalize existing imaginary time path-integral techniques to the case of multiple electronic surfaces. However, there are many times where nonadiabatic effects can play an important role. To this end, we reformulate the well-known path-integral expressions to incorporate multiple potential surfaces, without necessitating the adiabatic approximation. We show that the resulting expression, like its adiabatic counterpart, can be interpreted in terms of a simple classical isomorphic system and thus is amenable to simulation through Monte Carlo techniques. We derive simple expressions to compute expectation values of a general operator in both the nuclear coordinate and electronic state, and demonstrate the existence of a simple internal diagnostic that can be used to evaluate the magnitude of equilibrium nonadiabatic effects.


Induced photoemission from driven nonadiabatic dynamics in an avoided crossing system.
When vibrational dynamics on an ionic state (large dipole moment) is coupled to that on a neutral state (small dipole moment) such as at an avoided crossing in the alkali halide system, the population transfer between the states cause oscillation of the molecular dipole, leading to dipole emission. Such dynamics may be driven by an external field. We study how the coupled wavepacket dynamics is affected by the parameters (intensity, frequency) of the driving field with the aim of making use of the photoemission as an alternative detection scheme of femtosecond and subfemtosecond vibrational and electronic dynamics or as a characteristic optical source.


[Purification and characterization of insulin-like growth factor binding proteins (IGF-BP) in amniotic fluid--existence of a 160K IGF-BP].
Human amniotic fluid has been reported to contain 28-34K insulin-like growth factor (IGF) binding protein (32K-AFBP). The existence of 160K IGF-binding protein (160K-AFBP) in amniotic fluid was also demonstrated by affinity labeling studies. In this paper we describe procedures for purification of 160K-AFBP as well as 32K-AFBP from pre-term amniotic fluid and characterize these two binding proteins. IGF binding proteins were purified from batches of 500ml of pre-term amniotic fluid using ammonium sulphate precipitation, anion-exchange chromatography (Q-Sepharose) and Sephacryl S-200 HR chromatography. IGF binding activity during purification was quantitated by incubation with 125I-IGF-I and dextran-coated charcoal separation. The total recovery and purification of binding protein were 38% and 81.5-fold, respectively. The three major binding activities were eluted in fractions corresponding to a relative molecular mass of 160K, 60K and 30K when Q-Sepharose purified AFBPs were chromatographed on Sephacryl S-200 HR at neutral pH. HPLC of purified 160K binding activity on size exclusion column yielded a single peak of absorbance at 280nm, corresponding to an apparent molecular weight of 160K with three predominant peaks of binding to 125I-IGF-I, corresponding to molecular weights of 160K, 79K and 32K, respectively. On the other hand, purified 30K binding activity on HPLC yielded a single peak of absorbance at 280nm, corresponding to an apparent molecular weight of 32K coincident with a peak of binding to 125I-IGF-I. SDS-PAGE of HPLC purified 160K-AFBP in the presence of mercaptoethanol revealed eight bands by Coomassie Blue staining, five major bands corresponding to 160K, 78K, 69K, 54K, and 51K and three weaker bands corresponding to 45K, 36K, and 28K. The HPLC purified 32K-AFBP showed a single band of a molecular mass estimate of 32K on SDS-PAGE. These results indicate that human amniotic fluid contains at least two distinct IGF-binding proteins, and the structure of 160K-AFBP is similar to those of 150K binding protein in the circulation.


Aging metabolism: intervention strategies.
Human beings are subjected to aging and age-associated diseases. Life expectancy has improved impressively in the last century due to social and economic development, but despite increasing improvement is still more limited than average in those ones with chronic diseases such as treated HIV infection. There has been a substantial research on the underlying factors responsible for aging both in the general and the HIV-infected populations. Several specific targets for potential intervention have been identified but studies so far have been limited to small experiments in cultured cells or living beings other than humans such as mice or flies. Time has come for designing and developing human studies with those candidate therapies showing most promising benefits and least potential toxicities to treat age-related diseases.


G-Protein coupled receptors: answers from simulations.
Molecular-dynamics (MD) simulations are playing an increasingly important role in research into the modes of action of G-protein coupled receptors (GPCRs). In this field, MD simulations are unusually important as, because of the difficult experimental situation, they often offer the only opportunity to determine structural and mechanistic features in atomistic detail. Modern combinations of soft- and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research.


South American blastomycosis of the ureter.
A case of disseminated South American blastomycosis with unilateral involvement of the ureter and hydronephrosis is described; it is the third such case to be reported.


Congenital complete arhinia with alobar holoprosencephaly.
Congenital arhinia is a life-threatening, rare craniofacial disorder, which, when not identified and managed early can cause severe respiratory distress at birth due to upper airway obstruction. Since neonates are obligate nasal breathers, simultaneous sucking and breathing requirement in neonates with arhinia leads to respiratory distress. Inspiration and expiration through the oral passage alone may result in thoracic retraction, thereby further exacerbating respiratory distress. We report a rare case of congenital complete arhinia with alobar holoprosencephaly in a 9-month-old. With no family history of congenital malformations, maternal risk factors and uneventful pregnancy, a term female neonate was delivered vaginally without immediate post-delivery respiratory distress. Examination revealed microcephaly, absent fontanelles, fused cranial sutures and bilateral microphthalmia. Breathing was spontaneous, with no immediate signs of respiratory distress. An additional diagnosis of alobar holoprosencephaly was made after a head computed tomography (CT) scan was done. Management included the initial stabilisation phase of supplemental oxygen and an orogastric tube for feeding. The baby did not require both tracheostomy and gastrostomy tubes, as she was not in severe respiratory distress requiring a tracheostomy tube nor having difficulties feeding with the orogastric tube.


GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury.
This study investigated the effects of granulocyte macrophage-colony stimulating factor (GM-CSF) on the scar formation and repair of spinal cord tissues in rat spinal cord injury (SCI) model. Sprague-Dawley male rats (8 weeks old) were randomly divided into the sham-operated group, spinal cord injury group, and injury with GM-CSF treated group. A spinal cord injury was induced at T9/10 levels of rat spinal cord using a vascular clip. GM-CSF was administrated via intraperitoneal (IP) injection or on the dural surface using Gelfoam at the time of SCI. The morphological changes, tissue integrity, and scar formation were evaluated until 4 weeks after SCI using histological and immunohistochemical analyses. The administration of GM-CSF either via IP injection or local treatment significantly reduced the cavity size and glial scar formation at 3-4 weeks after SCI. GM-CSF also reduced the expression of core proteins of chondroitin sulfate proteoglycans (CSPGs) such as neurocan and NG2 but not phosphacan. In particular, an intensive expression of glial fibriallary acidic protein (GFAP) and neurocan found around the cavity at 4 weeks was obviously suppressed by GM-CSF. Immunostaining for neurofilament (NF) and Luxol fast blue (LFB) showed that GM-CSF preserved well the axonal arrangement and myelin structure after SCI. The expression of GAP-43, a marker of regenerating axons, also apparently increased in the rostral grey matter by GM-CSF. These results suggest that GM-CSF could enhance long-term recovery from SCI by suppressing the glial scar formation and enhancing the integrity of axonal structure.


Reward Accelerates the Preparation of Goal-directed Actions under Conflict.
Our goals sometimes conflict with our prepotent habitual responses, which often leads to impaired performance on a variety of tasks. People are better at exerting cognitive control to overcome prepotent and automatic responses when they are motivated by the prospect of reward. The standard experimental paradigms used to study this phenomenon examine free RTs that allow participants to select a variety of response strategies including delaying response initiation to avoid committing errors. However, this approach makes it difficult to determine which control processes are affected by reward. Does reward lead to improved performance via the inhibition of prepotent responses or the facilitation of goal-directed processing? Here, we use a forced-response paradigm to fix response initiation and systematically vary the time available for the cognitive processing necessary for response preparation. Using a probabilistic model that dissociates the preparation of habitual and goal-directed responses, we obtain evidence across multiple experiments (n = 87 people) that reward selectively accelerates the preparation of goal-directed actions in the context of conflict.


Analyses of antigenic and genetic diversities of Theileria sergenti piroplasm surface proteins.
Monoclonal antibodies (MoAbs) against Theileria sergenti Fukushima stock, an intraerythrocytic protozoan parasite of cattle, were produced. The MoAbs reacted with 32 kDa or 23 kDa piroplasm surface protein (p32 or p23) in Western blot analysis. Using a panel of the MoAbs, antigenic analysis of the stocks and field isolates distributed in Japan was carried out. The results revealed antigenic diversity of T. sergenti isolates, but diversity did not appear to be correlated with the geographical region of the isolates. N-terminal amino acids sequences analysis revealed substitutions of a few amino acids between the p23 of two T. sergenti stocks. The sequences couldn't be found in amino acid sequence of the p32 deduced from cDNA, which indicated that the p23 is not a proteolytic product of the p32. Genetic diversity of T. sergenti isolates was also observed by Southern blot analysis using a cDNA of the p32 as a probe.


Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts, misconceptions, and practical tips for pathologists.
Most pathologists are familiar with the microscopic features of tuberculosis and the need to examine special stains for acid-fast bacteria (AFB) in cases of granulomatous lung disease. However, misconceptions do exist, including the concept that finding AFB in "caseating granulomas" confirms the diagnosis of tuberculosis. This dogma is attributable to the high prevalence of tuberculosis in many countries, as well as unfamiliarity with the microscopic spectrum of non-tuberculous mycobacterial lung disease. This review aims to provide surgical pathologists with practical tips to identify AFB, illustrate the histologic overlap between pulmonary tuberculosis and non-tuberculous mycobacterial lung disease, and highlight the importance of cultures in this setting. M. tuberculosis and non-tuberculous mycobacteria cannot be reliably differentiated either on the basis of the tissue reaction or by bacterial morphology on acid-fast stains. Although a presumptive clinical diagnosis of tuberculosis can be made without culture-confirmation, the only definitive means to determine the true identity of AFB is by cultures or molecular methods. Making this distinction is most critical when AFB are found in incidentally detected lung nodules in geographic locations where the incidence of tuberculosis is low, because in such settings AFB in necrotizing granulomas of the lung are more likely to be non-tuberculous mycobacteria than M. tuberculosis.


Expanded Prenatal Genetic and Newborn Screening: One Family's Wild Ride.
The exponential rate at which genetic testing has been integrated into routine and high-risk obstetric care has been exciting to watch. With this technical explosion, however, the knowledge surrounding the benefits and limitations of prenatal genetic and newborn screening can be overlooked by both parents and providers. The following case exemplifies how a couple with infertility who underwent comprehensive prenatal expanded genetic carrier screening and parental karyotype experienced the benefits and limitations of such testing. It guides the reader through diagnostic testing for an infant, born to a father with a balanced translocation, who presented with an abnormal newborn screening result for an inherited metabolic disorder of fatty acid oxidation metabolism, very-long-chain acyl-coenzyme dehydrogenase deficiency, for which the prenatal expanded carrier screening result was negative.


Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review.
This study was aimed to analyze the commonalities and distinctions of voltage-gated sodium channels, Nav1.2, Nav1.6, in neurodevelopmental disorders. An observational study was performed including two patients with neurodevelopmental disorders. The demographic, electroclinical, genetic, and neuropsychological characteristics were analyzed and compared with each other and then with the subjects carrying the same genetic variants reported in the literature. The clinical features of one of them argued for autism spectrum disorder and developmental delay, the other for intellectual disability, diagnoses confirmed by the neuropsychological assessment. The first patient was a carrier of SCN2A (p.R379H) variant while the second was carrier of SCN8A (p.E936K) variant, both involving the pore loop of the two channels. The results of this study suggest that the neurodevelopmental disorders without overt epilepsy of both patients can be the consequences of loss of function of Nav1.2/Nav1.6 channels. Notably, the SCN2A variant, with an earlier expression timing in brain development, resulted in a more severe phenotype as autism spectrum disorder and developmental delay, while the SCN8A variant, with a later expression timing, resulted in a less severe phenotype as intellectual disability.


Platelet-Microcapsule Hybrids Leverage Contractile Force for Targeted Delivery of Hemostatic Agents.
We report a cell-mediated, targeted drug delivery system utilizing polyelectrolyte multilayer capsules that hybridize with the patient's own platelets upon intravenous administration. The hybridized platelets function as the sensor and actuator for targeted drug delivery and controlled release in our system. These capsules are biochemically and mechanically tuned to enable platelet adhesion and capsule rupture upon platelet activation and contraction, enabling the targeted and controlled "burst" release of an encapsulated biotherapeutic. As platelets are the "first responders" in the blood clot formation process, this platelet-hybridized system is ideal for the targeted delivery of clot-augmenting biotherapeutics wherein immediate therapeutic efficacy is required. As proof-of-concept, we tailored this system to deliver the pro-clotting biotherapeutic factor VIII for hemophilia A patients that have developed inhibitory antifactor VIII antibodies. The polyelectrolyte multilayer capsules physically shield the encapsulated factor VIII from the patient's inhibitors during circulation, preserving its bioactivity until it is delivered at the target site via platelet contractile force. Using an in vitro microfluidic vascular injury model with factor VIII-inhibited blood, we demonstrate a 3.8× increase in induced fibrin formation using capsules loaded with factor VIII at a concentration an order of magnitude lower than that used in systemic delivery. We further demonstrate that clot formation occurs 18 min faster when factor VIII loaded capsules are used compared to systemic delivery at the same concentration. Because platelets are integral in the pathophysiology of thrombotic disorders, cancer, and innate immunity, this paradigm-shifting smart drug delivery system can be similarly applied to these diseases.


Distinct mechanisms of phospholipase D activation and attenuation utilized by different mitogens in NIH-3T3 fibroblasts.
The activation of phospholipase D (PLD) by platelet-derived growth factor (PDGF), prostaglandin F2 alpha and 12-O-tetradecanoylphorbol 13-acetate (TPA) was studied in NIH-3T3 fibroblasts. PLD activation was determined by measuring the production of both [3H]phosphatidic acid and [3H]phosphatidylpropanol (products of the PLD-catalyzed hydrolysis and transphosphatidylation reactions, respectively), in cells that were metabolically pre-labeled with [3H]oleic acid. All mitogens caused a rapid (within 2 min) activation of PLD. Activation of PLD by prostaglandin F2 alpha and PDGF was transient and declined to near basal levels by 15 min and 55 min, respectively. In contrast, TPA-induced activation of PLD was sustained for at least 60 min of incubation. A combination of maximally effective concentrations of PDGF and TPA stimulated PLD activity in a non-additive manner, while the effect of prostaglandin F2 alpha was additional to that of either PDGF or TPA. The protein kinase inhibitor staurosporine inhibited PLD activation by PDGF or TPA with almost identical dose/response curves. In contrast, staurosporine potentiated prostaglandin-F2 alpha-induced PLD activation. The specific protein kinase C inhibitor GF109203X (a bisindolylmaleimide) inhibited PLD activation by prostaglandin F2 alpha and PDGF at concentrations higher than those required for inhibition of PLD activation induced by TPA. Depletion of cellular protein kinase C abolished PLD activation by all three mitogens without affecting in vitro activity of membrane-bound PLD. The distinct kinetics of PLD activation and its differential susceptibility to protein kinase inhibitors suggest the existence of agonist-specific activation and/or inactivation mechanisms. The results indicate also that protein kinase C participates in the mechanism of PLD activation via PDGF, while the effect of prostaglandin F2 alpha involves a pathway independent of protein kinase C.


Heathrow to ICU direct.
We present the case of a witnessed massive pulmonary embolism (PE) resulting in pulseless electrical activity (PEA) following a long-haul flight. Our patient was successfully treated with cardiopulmonary resuscitation (CPR) and thrombolysis in the Emergency Department at Christchurch Hospital and went on to complete her honeymoon in New Zealand.


Idiopathic Bilateral Suprachoroidal Haemorrhage: A Rare Case Presentation.
55-year-old male presented with sudden onset painful diminution of vision in both eyes. On local examination, his visual acuity was FC at 2 metres in right eye and FC at 1 m in left eye. The IOP in right eye was 46 mm Hg and 44 mm Hg in left eye. The patient was admitted and started on injection mannitol, oral syrup glycerol, and oral acetazolamide. Locally, timolol maleate and brimonidine were also started. The next day, his IOP was 17 mm Hg bilaterally but his visual acuity deteriorated to FC 1 m in right eye and hand movement in left eye with inaccurate projection of rays in both eyes. USG B-scan was performed which revealed bilateral choroidal detachment. The echotexture of fluid was suggestive of haemorrhage. As the IOP was controlled, systemic hyperosmotic/antiglaucoma agents were withdrawn in stepwise fashion over next two days. The patient was started on oral prednisolone. At 2 weeks, the visual acuity in both eyes was only perception of light, with inaccurate PR. IOP was 10 mm Hg in both eyes. USG B-scan revealed resorption of the hemorrhage, with partial resolution of the choroidal detachment. The final BCVA was 6/18 and 6/12 in right and left eye.


Room-temperature quantum bit memory exceeding one second.
Stable quantum bits, capable both of storing quantum information for macroscopic time scales and of integration inside small portable devices, are an essential building block for an array of potential applications. We demonstrate high-fidelity control of a solid-state qubit, which preserves its polarization for several minutes and features coherence lifetimes exceeding 1 second at room temperature. The qubit consists of a single (13)C nuclear spin in the vicinity of a nitrogen-vacancy color center within an isotopically purified diamond crystal. The long qubit memory time was achieved via a technique involving dissipative decoupling of the single nuclear spin from its local environment. The versatility, robustness, and potential scalability of this system may allow for new applications in quantum information science.


Development of an Optical Nanosensor Incorporating a pH-Sensitive Quencher Dye for Potassium Imaging.
One of the key challenges in the design of a sensor for measuring extracellular changes in potassium concentration is selectivity against the competing cation, sodium. Here, we present an optode-based nanosensor selective to potassium ions, owing to the addition of a pH-sensitive quencher molecule paired with a static fluorophore. The nanosensor was fabricated using emulsification and characterized in solution by absorbance and fluorescence spectroscopy. The resulting nanosensor detected potassium with nearly 1 order of magnitude higher selectivity compared to our chromoionophore-based optode nanosensors. In addition to the improved selectivity, the nanosensor has the following properties required for measurements in a biological environment: (1) a physiologically relevant dynamic range, (2) response to potassium ions at a physiological ionic strength, and (3) response to serum potassium in the presence of fouling biological components. The potassium nanosensor described in this study is envisioned to have application in cellular imaging and drug screening.


Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.
Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.


An Economic Evaluation of Food Safety Education Interventions: Estimates and Critical Data Gaps.
The economic evaluation of food safety interventions is an important tool that practitioners and policy makers use to assess the efficacy of their efforts. These evaluations are built on models that are dependent on accurate estimation of numerous input variables. In many cases, however, there is no data available to determine input values and expert opinion is used to generate estimates. This study uses a benefit-cost analysis of the food safety component of the adult Expanded Food and Nutrition Education Program (EFNEP) in Ohio as a vehicle for demonstrating how results based on variable values that are not objectively determined may be sensitive to alternative assumptions. In particular, the focus here is on how reported behavioral change is translated into economic benefits. Current gaps in the literature make it impossible to know with certainty how many people are protected by the education (what are the spillover effects?), the length of time education remains effective, and the level of risk reduction from change in behavior. Based on EFNEP survey data, food safety education led 37.4% of participants to improve their food safety behaviors. Under reasonable default assumptions, benefits from this improvement significantly outweigh costs, yielding a benefit-cost ratio of between 6.2 and 10.0. Incorporation of a sensitivity analysis using alternative estimates yields a greater range of estimates (0.2 to 56.3), which highlights the importance of future research aimed at filling these research gaps. Nevertheless, most reasonable assumptions lead to estimates of benefits that justify their costs.


Primary diffuse large B-cell lymphoma of the frontal sinus.
Primary frontal sinus lymphoma is a rare disease, with the presenting symptoms that are secondary to the tumor mass effect and often misleading. Here we describe the case of a 43-year-old male patient who presented with a 4-week history of a gradually enlarging painful diffuse swelling over the right frontal sinus region. We report the clinical presentation, differential diagnosis and treatment of the case. We also reviewed the available literature on the diffuse large B-cell lymphoma in the frontal sinus region. The article emphasizes the importance of early recognition of this rare disease.


[Neonatal respiratory morbidity after elective cesarean section at term].
Incidence of elective caesareans at term is increasing these last decades with an associated increase of neonatal respiratory morbidity. To analyse the influence of elective Caesarean delivery at term on the incidence of neonatal respiratory distress in order to propose an effective strategy of prevention. It is an analytical study compiling all births resulting from elective Caesarean at term (gestational age ranging between 37 and 41+6 GA), reported over two years period at the Charles Nicolle hospital (Tunis-Tunisia). We compared 250 live births, without maternal risk factors, delivered by elective Caesarean to 250 births delivered by vaginal way. Frequency of the elective Caesarean at term was of 3.6% live births; it was mainly indicated in the presence of a cicatricial uterus. The incidence of respiratory morbidity was 6% (15/250) in the group exposed to the elective caesarean versus 1.6% (4/250 cas) in the reference group, OR=3.9; 95%CI: [1, 28-11, 99] p<0.01. Before the term of 39 GA, OR=5.22; 95%CI: [1.14-23.87] p=0.01. After 39 GA, the risk of respiratory distress decreased: OR=1.86 95%CI: [0.30, 11.35] NS. The principal etiology of respiratory distress in the exposed group was the transitory tachypnea of the newborn. Incidence of respiratory distress was higher at newborn babies born from elective Caesarean with a significant reduction in this incidence after the term of 39 GA.


Cajal, Golgi, Nansen, Schäfer and the neuron doctrine.
The Nobel Prize for Physiology or Medicine of 1906 was shared by the Italian Camillo Golgi and the Spaniard Santiago Ramón y Cajal for their contributions to the knowledge of the micro-anatomy of the central nervous system. In his Nobel Lecture, Golgi defended the going-out-of-favour Reticular Theory, which stated that the nerve cells--or neurons--are fused together to form a diffuse network. Reticularists like Golgi insisted that the axons physically join one nerve cell to another. In contrast, Cajal in his lecture said that his own studies confirmed the observations of others that the neurons are independent of one another, a fact which is the anatomical basis of the now-accepted Neuron Doctrine (Theory). This much is well documented. Less well known, however, is the fact that evidence against the Reticular Theory had been mounting for some time prior to the Nobel Lecture. The Norwegian Fridtjof Nansen had reported in 1887 that, in his studies of the primitive creatures he studied in the sea near Bergen, he found no connections between the processes of the ganglion cells in their nervous systems. Nor is it adequately appreciated that ten years earlier, in 1877, the Englishman Edward Schäfer had similarly described seeing no connections between the nerve elements in the mantles of the jellyfish. This paper begins by charting the research that led directly to the awarding of the 1906 Nobel Prize. It then shows that long before the ultimate vindication of the Neuron Doctrine, researchers in several countries had been accumulating evidence that undermined or contradicted the Reticular Theory.


Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study.
Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (n=660), and b) OCs, PUFAs, and vitamins (n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and β-cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk. These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.


Progressive systemic sclerosis.
To date, largely because of convenience, therapeutic trials in progressive systemic sclerosis have been few and largely short-term retrospective single institution studies. For the future, there is a pressing need to expand efforts in this area to include: controlled, prospective studies with adequate numbers of patients employing, if necessary, a multicentre effort; careful classification of PSS patients into meaningful disease subsets and inclusion of this concept into experimental design; development and testing of criteria for disease staging and severity; refinement of current objective criteria for change (improvement or deterioration) and development of new, simple-to-perform, quantifiable descriptors for skin and internal organ involvement which are properly validated; studies of adequately long duration to avoid failing to detect significant differences between cases and controls; and attention to disease duration in study design, with special emphasis on choosing patients with early disease. A great deal of clinical epidemiological research will be required for progress in patient classification and improvement of methods of patient assessment. Careful planning of therapeutic trials and the inclusion of biostatistical expertise in the design phase of such studies is desirable if we are satisfactorily to answer the questions posed by each trial.


Participatory action research (PAR): an approach for improving black women's health in rural and remote communities.
Women are among the most disadvantaged members of any community, and they tend to be at greatest risk of illness. Black women are particularly vulnerable and more prone than White women to illnesses associated with social and economic deprivation, including heart disease and diabetes. They utilize preventive health services less often, and when they fall ill, the health of their families and communities typically suffers as well. This article discusses the process of doing innovative participatory action research (PAR) in southwest Nova Scotia Black communities. The effort resulted in the generation of a database, community action, and interdisciplinary analysis of the intersecting inequities that compromise the health and health care of African Canadian women, their families, and their communities. This particular research effort serves as a case study for explicating the key tenets of PAR and the barriers to and contradictions in implementing PAR in a community-academic collaborative research project.


Looking for heteroaromatic rings and related isomers as interstellar candidates.
Finding complex organic molecules in the interstellar medium (ISM) is a major concern for understanding the possible role of interstellar organic chemistry in the synthesis of prebiotic species. The present interdisciplinary report is a prospective study aimed at helping detection of heteroaromatic compounds or at least of some of their isomers in the ISM. The thermodynamic stabilities of the C(4)H(5)N, C(4)H(4)O, C(4)H(4)S families were calculated using density functional theory (DFT). It was found that pyrrole, furan and thiophene are unambiguously the most stable isomers at the 10-50 K temperatures of the ISM. Several of the less stable isomers were synthesized and flash vacuum thermolysis experiments were performed on these species. Although the detection of pyrrole in the pyrolysis of many compounds has been reported in the literature, we observed that none of its isomers led to pyrrole in these conditions, which suggests that other formation routes are to be considered. On the other hand, these three aromatic compounds present a very high stability, few % been decomposed at 1500 K by flash vacuum thermolysis; these experiments also show a great stability of crotonitrile that is the most stable compound that can be formed in these conditions. The rotational constants, dipole moments and IR frequencies of the low-lying isomers are given to encourage laboratory experiments on these prototype molecules.


Relationship between the Lower Limb Function and Shoulder and Elbow Injuries in Elementary School Baseball Pitchers.
We aimed to examine the relationship between the hip range of motion (ROM) and ankle ROM and throwing-related shoulder and elbow injuries in elementary school baseball pitchers. This retrospective comparative study (Level of evidence: Level III) included 195 baseball pitchers (mean age 10.8±1.0 years, range 8-12 years). All pitchers underwent physical function measurements, including height, weight, shoulder strength, and hip and ankle ROM. Shoulder and elbow injury was defined as shoulder and elbow pain that the pitchers had been aware of in the past or at the time of medical checkups. The results for the injured and non-injured groups were then compared. The shoulder ROM and strength in the injured and non-injured groups did not differ to a statistically significant extent. The hip external rotation on the dominant side (injured vs. non-injured: 48.9±11.1° vs. 53.3±9.7°, P<0.01), the hip internal rotation on the non-dominant side (injured vs. non-injured: 36.6±12.0° vs. 40.9±11.0°, P=0.01), and ankle plantar flexion on the non-dominant side (injured vs. non-injured: 52.0±6.8° vs. 54.3±6.7°, P=0.02) were significantly smaller in the injured group than in the non-injured group. The hip external rotation ROM on the dominant side and the hip internal rotation and ankle plantar flexion on the non-dominant side were significantly lower in the injured group than in the non-injured group. These results may suggest measures to reduce the incidence of elbow and shoulder injuries in elementary school baseball pitchers.


Long noncoding RNA SNHG16 induces sorafenib resistance in hepatocellular carcinoma cells through sponging miR-140-5p.
Sorafenib is widely used for treatment of hepatocellular carcinoma (HCC), but the acquired resistance remains a major obstacle for its application. Thus it is of critical importance to elucidate the molecular mechanisms underlying sorafenib resistance in HCC. This study aimed to determine the roles of long noncoding RNA SNHG16 in sorafenib-resistant HCC cells. HCC and matched adjacent normal liver tissue samples were obtained from 103 HCC patients. Sorafenib-resistant HepG2/SOR cell line was established from its parental HepG2 cells by exposure to increasing concentrations of sorafenib. SNHG16 and miR-140-5p expression levels in tissue samples and cells were detected by RT-qPCR analysis. The sensitivity of cells to sorafenib in vitro was evaluated by MTT assay, and the sensitivity of HepG2/SOR cells to sorafenib in vivo was estimated using the nude mouse-based xenograft model. The potential binding relation between SNHG16 and miR-140-5p was validated by dual luciferase reporter assay and biotinylated RNA pull-down assay. The results showed that SNHG16 expression was remarkably increased in HCC tissues and cell lines, and its high expression was closely associated with aggressive clinicopathological features and poor prognosis of HCC patients. Further experiments showed that SNHG16 is upregulated in HepG2/SOR cells, whereas knockdown of SNHG16 increases the sensitivity of HepG2/SOR cells to sorafenib in vitro and in vivo. Further mechanistic study identified that SNHG16 functions as an endogenous sponge for miR-140-5p in HepG2 cells, and in HCC tissues, the expression of miR-140-5p is negatively correlated with SNHG16 expression. Moreover, miR-140-5p overexpression also increases the sensitivity of HepG2/SOR cells to sorafenib, and the effects of SNHG16 knockdown on sorafenib resistance could be blocked by miR-140-5p inhibitor. Collectively, our findings demonstrated that knockdown of SNHG16 attenuated sorafenib resistance in HCC through sponging miR-140-5p, indicating that SNHG16 might be as a promising therapeutic target to boost the effectiveness of chemotherapy for HCC patients.


Gc serum groups and schizophrenia.
In an epidemiological study of schizophrenia in a North Swedish isolate, Böök et al. (1978) reported an association between schizophrenia and the genetic marker Gc2. In an attempt to confirm this observation, we examined a series of schizophrenic patients from Västerbotton County in Northern Sweden. In our material there was no difference between schizophrenic patients and controls with respect to the frequencies of Gc groups or genes. A reanalysis of the material by Böök et al. (1978) showed that schizophrenics compared to controls had a significant increase in the frequency of the Gc 2-1 group, but not of the Gc2 gene. The Gc distribution in the material by Böök et al. (1978) was similar to that previously reported by us in a series of patients with cycloid psychosis.


A clinical assessment of the Glidescope videolaryngoscope in nasotracheal intubation with general anesthesia.
To evaluate the efficacy and safety of the Glidescope videolaryngoscope as a device to aid nasotracheal intubation, and to determine whether the GSVL provides a better laryngeal view in patients with difficult laryngoscopy compared with the Macintosh laryngoscope. Prospective, clinical study. Two university hospitals. 156 healthy adult ASA physical status I and II undergoing elective plastic and intraoral surgery with general anesthesia. After anesthesia induction with intravenous injection of fentanyl 2 microg/kg, propofol 2 mg/kg, and vecuronium 0.1 mg/kg, nasotracheal intubation was performed using GSVL. Preoperative airway measurements were taken to predict potential difficult airways. During nasotracheal intubation using GSVL, laryngeal views, times required for full visualization of glottis and successful intubation, difficulty encountered and auxiliary maneuvers adopted, and upper airway trauma were recorded. The laryngeal views obtained by GSVL and by Macintosh laryngoscope were compared. The laryngeal views obtained by GSVL in all patients were Cormack and Lehane (C&L) grades I and II, and the success rate of intubation using GSVL at one attempt was 98.1%. The times required for visualization of the glottis and successful intubation were 40.2 +/- 11.5 s and 52.7 +/- 12.3 seconds, respectively. Patients with C&L grade II needed more auxiliary maneuvers to achieve successful intubation than did those with C&L grade I (P < 0.001). In 36 patients with potential difficult airways, the frequency of difficult laryngoscopy (C&L grades III and IV) with the Macintosh laryngoscope (58.3%) was significantly higher than with the GSVL (0%, P < 0.05). The frequency of minor upper airway trauma was 4.5%. The GSVL is an effective device for nasotracheal intubation and may be incorporated easily into routine clinical practice. Compared with the Macintosh laryngoscope, the GSVL can provide an improved laryngeal view in the patient with difficult airway.


The role of disulfide bonds in structure and activity of chlorotoxin.
Chlorotoxin is a small scorpion peptide that inhibits glioma cell migration. We investigated the importance of a major component of chlorotoxin's chemical structure - four disulfide bonds - to its tertiary structure and biological function. Five disulfide bond analogs of chlorotoxin were synthesized, with l-α-aminobutyric acid residues replacing each or all of the disulfide bonds. Chemical oxidation and circular dichroism experiments revealed that Cys III-VII and Cys V-VIII were essential for native structure formation. Cys I-IV and Cys II-VI were important for stability of enzymatic proteolysis but not for the inhibition of human umbilical vein endothelial cell migration. The disulfide bonds of chlorotoxin are important for its structure and stability and have a minor role in its activity against cell migration.


Comparison between the CEDIA and EMIT II immunoassays for the determination of benzodiazepines.
We evaluated a new, qualitative immunoassay for benzodiazepines in urine using CEDIA technology on the Hitachi 747 and compared its performance to an immunoassay using EMIT II methodology on the same instrument. A total of 500 urine samples received for routine drug screen analysis were prospectively examined for benzodiazepines by both methods. Samples producing positive results by either immunoassay method were analyzed by gas chromatography-mass spectrometry (GC-MS). Available medical records were reviewed for patients whose samples produced discrepant immunoassay results or that were positive in both immunoassays but negative by GC-MS. Samples that produced negative results in both immunoassays were not subjected to GC-MS analysis. Therefore, identification of an immunoassay result as a false negative only occurred when the sample produced a positive value in only one of the two immunoassays and was confirmed as positive by either GC-MS or medical record review. Following initial immunoassay screening and confirmation by GC-MS, a medical record review and reanalysis of GC-MS data was performed. After this in-depth analysis of the data, the CEDIA method produced 60 true-positives, 7 false positives and no false negatives. The EMIT II method produced 47 true positives, 1 fase positive and 13 false negatives. These differences appear to be due to the CEDIA assay being more sensitive for detection of lorazepam.


Activated platelets increase fibrinolysis of mesenchymal progenitor cells.
Bone regeneration is initiated by the formation of a blood clot. Activated platelets within this fibrin-rich matrix release signaling molecules that can attract mesenchymal progenitor cells. To gain insight into the cellular mechanism by which activated platelets can support the immigration of mesenchymal progenitors, we have tested the hypothesis that platelet-released signaling molecules increase the capacity of bone marrow stromal cells (BMSC) to activate plasminogen. We report herein that platelet-released supernatants (PRS) elevate total urokinase-type plasminogen activator (uPA) and total plasminogen activator inhibitor-1 (PAI-1) levels in BMSC, as assessed by immunoassay. Quantitative polymerase chain reaction showed an upregulation of uPA, uPA receptor, and PAI-1. Zymography and kinetic analysis based on casein hydrolysis revealed enhanced activity of cell-associated uPA upon exposure of BMSC to PRS. Inhibiting c-Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K) signaling reduced uPA production and decreased plasminogen activation. Corresponding Western blot analysis showed increased phosphorylation of JNK and AKT in BMSC treated with PRS. These results suggest that activated platelets can enhance the plasminogen activation capacity of mesenchymal progenitors through the stimulation of uPA production, requiring JNK and PI3K/AKT signaling. By this mechanism platelets may contribute to the organization of the blood clot during bone regeneration.


Global analysis of lysine succinylome in the periodontal pathogen Porphyromonas gingivalis.
The gram-negative anaerobe Porphyromonas gingivalis is not only a keystone periodontal pathogen but also an emerging systemic pathogen. Although the newly discovered protein post-translational modification (PTM), lysine succinylation (Ksuc), appears to play an important role in modulating metabolic processes in bacteria, this PTM has not been investigated in P gingivalis. In this study, we used a highly sensitive proteomics approach combining affinity enrichment with high-resolution liquid chromatography coupled with tandem mass spectrometry to examine Ksuc in P gingivalis. In total, 345 Ksuc sites in 233 proteins were identified and determined to be involved in a variety of cellular processes. In the region surrounding Ksuc sites, lysine residues were drastically overrepresented and sequence motifs with succinyl-lysine flanked by a lysine at the +3 or +6 positions appear to be unique to this pathogen. Additionally, our results suggest a crosstalk between Ksuc and glycosylation, but the overlap between Ksuc and acetylation in P gingivalis is quite different from that observed in other organisms. Notably, Ksuc was observed in proteins associated with established virulence factors, including gingipains, fimbriae, RagB, and PorR. Moreover, products of the factors necessary for P gingivalis in vitro survival (18.5%) were found to be succinylated at lysine sites and the same was observed in products of fitness factors for P gingivalis survival in both abscess and epithelial cell colonization environments (12%). Collectively, these results suggest that Ksuc may be a new mechanism in modulating the virulence, adaptation, and fitness of P gingivalis.


Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome.
Antibiotic use is associated with development of antimicrobial resistance and dysregulation of the microbiome (the overall host microbial community). These changes have in turn been associated with downstream adverse health outcomes. This review analyses recent important publications in a rapidly evolving field, contextualizing the available evidence to assist clinicians weighing the potential risks of antibiotics on a patient's microbiome. Although the majority of microbiome research is observational, we highlight recent interventional studies probing the associations between antibiotic use, microbiome disruption, and ill-health. These studies include germ-free mouse models, antibiotic challenge in healthy human volunteers, and a phase III study of the world's first approved microbiome-based medicine. The growing body of relevant clinical and experimental evidence for antibiotic-mediated microbiome perturbation is concerning, although further causal evidence is required. Within the limits of this evidence, we propose the novel term 'microbiotoxicity' to describe the unintended harms of antibiotics on a patient's microbiome. We suggest a framework for prescribers to weigh microbiotoxic effects against the intended benefits of antibiotic use.


CJ14939, a Novel JAK Inhibitor, Increases Oxaliplatin-induced Cell Death Through JAK/STAT Pathway in Colorectal Cancer.
Colorectal cancer is reported to have the highest mortality rate among human malignancies. Although many research results for the treatment of colorectal cancer have been reported, there is no suitable treatment when resistance has developed. Therefore, it is necessary to develop new therapeutic agents. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling plays an essential role in cell differentiation, proliferation, and survival. Abnormal activation of the JAK/STAT signaling pathway, by gene mutation or amplification, may induce cancer development, and sustained JAK/STAT activation is involved in chemoresistance. While many therapeutic agents have been developed to treat colon cancer, there remains no drug to overcome resistance to chemotherapies. The purpose of this study was to determine the potential of CJ14939 as a novel JAK inhibitor for the treatment of colorectal cancer. In this study, cell culture, cell death assay, 3- (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, colony formation assay, immunoblot analysis and tumor xenograft were applied. CJ14939 induced cell death, and inhibited phosphorylation of JAK1 and STAT3 in colorectal cancer cells. Furthermore, CJ14939 also promoted oxaliplatin-induced cell death, up-regulated expression of cleaved caspase-3, and down-regulated expression of phospho-JAK1 and phospho-STAT3. In vivo, co-treatment with CJ14939 and oxaliplatin notably reduced tumor growth when compared with CJ14939 or oxaliplatin treatment alone. This study identifies the important potential of CJ14939 in colorectal cancer treatment and suggests that combining CJ14939 with oxaliplatin might be a novel therapeutic strategy for patients with colorectal cancer.


Racial and ethnic distribution of faculty, students, and fellows in US epidemiology degree programs, 1992. Committee on Minority Affairs of the American College of Epidemiology.
The American College of Epidemiology Committee on Minority Affairs assessed the racial/ethnic distribution of faculty, students, and postdoctoral fellows in epidemiology degree programs in the United States in 1992. Fifty-six programs in schools of public health, medicine, or veterinary medicine completed a one-page anonymous questionnaire (85% response rate). Of 711 faculty members (median of 8 per program), 46 (6%) were minorities (US black, Hispanic, or Asian/Pacific Islander). Of 2142 students (1206 masters, 862 doctoral, 74 postdoctoral: median of 17 per program), 293 (14% of all students; 17% of US citizen students) were minorities. In the 46 doctoral programs, there were 36 black students (in 20 doctoral programs), 15 Hispanic students (in 9 programs), and no Native Americans. There were three minority postdoctoral fellows, all blacks (4% of all postdoctoral fellows). Determined, consistent, and sustained efforts will be required to boost the representation of blacks, Hispanics, and Native Americans in epidemiology.


Traditional healers as service providers in Ghana's National Health Insurance Scheme: the wrong way forward?
Concerned with the negative impacts of user fees on healthcare access and utilisation, following the enactment of a law in 2003, the Ghanaian government replaced the 'cash-and-carry' system with a National Health Insurance Scheme (NHIS). Even though many Ghanaians rely on traditional medicine (TRM) for reasons of culture, cost and personal preference, the incipient NHIS does not cover the services of TRM practitioners. Consultations with health policy-makers suggest that, in as much as the government recognises the invaluable contributions of TRM practitioners and would like to incorporate them in the incipient scheme, the provision of TRM in the country is still too disorganised, with few if any formal protocols and codes of conduct. Consequently, the inclusion of TRM practitioners in the NHIS is premature. This scholarly review seeks to bring TRM and its practitioners into the mainstream of healthcare provision in Ghana. Possibilities for medical pluralism in Ghana will be discussed with reference to best practices in countries such as China, India and Vietnam. This paper promotes medical pluralism in the form of Active Collaboration Between Fully Recognised Health Systems where there will be equity, mutual respect and understanding among traditional healers and physicians.


Effectiveness of perampanel in the treatment of pediatric patients with focal epilepsy and ESES: A single-center retrospective study.
Objective: To investigate the therapeutic effect and influencing factors of perampanel (PER) on electrical status epilepticus during sleep (ESES). Methods: We retrospectively analyzed the clinical data of pediatric patients with focal epilepsy and ESES who were treated at the Epilepsy Center of Shengjing Hospital of China Medical University between January 2016 and March 2022. Changes in the spike wave index (SWI) after 24 weeks of PER add-on treatment were compared. Kaplan‒Meier survival analysis, the log-rank test and multivariate Cox regression analysis were performed. Results: A total of 54 pediatric patients met the inclusion criteria, including 33 males and 21 females. The mean age at the diagnosis of epilepsy was 6.41 ± 2.14 years and at ESES diagnosis was 7.58 ± 2.40 years. The mean ESES duration before add-on PER was 25.31 ± 15.12 months. The mean age of the patients at add-on PER initiation was 9.69 ± 2.12 years. The ESES resolved in 29 children after 6 months of PER add-on treatment, and the response rate was 53.7%. Univariate analysis with the log-rank test showed that the therapeutic effect of PER differed according to the age at ESES diagnosis and ESES duration before add-on PER treatment. Multivariate Cox regression analysis showed that only ESES duration before PER administration was a risk factor for PER treatment failure, and the other factors had no effect on the therapeutic effect. Conclusion: PER add-on treatment has a good therapeutic effect on ESES and can be used as an alternative to corticosteroid and benzodiazepines. The therapeutic effect of PER add-on treatment was not related to the dose. A longer ESES duration results in a worse therapeutic effect. Therefore, more aggressive treatment measures should be implemented for ESES.


Astaxanthin ameliorates behavioral and biochemical alterations in in-vitro and in-vivo model of neuropathic pain.
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains limited. Astaxanthin, a marine natural drug, having potent anti-oxidant and anti-inflammatory activities is known to possess neuroprotective effects. However, effects of astaxanthin against nerve injury induce chronic pain remains unknown. Overactivity of glutamatergic NMDARs results in excitotoxicity which may participate in astrocytic and microglial activation during pathology which further contribute to the development of neuropathic pain. In this study, we investigate the effects of astaxanthin on oxido-inflammatory and NMDA receptor down-regulation pathway by using in-silico, in-vitro and in-vivo models of neuropathic pain. In-silico molecular docking study ascertained the binding affinity of astaxanthin to NMDA receptors and showed antagonistic effects. Data from in-vitro studies suggest that astaxanthin significantly reduces the oxidative stress induced by the lipopolysaccharides in C6 glial cells. In male Sprague dawley rats, a significant attenuation of neuropathic pain behavior was observed in Hargreaves test and von Frey hair test after astaxanthin treatment. Findings from the current study suggest that astaxanthin can be used as potential alternative in the treatment of chronic neuropathic pain. However, more detailed investigations are required to further probe the in-depth mechanism of action of astaxanthin.


Health services organizations computer innovation. Ready or not?
Health services organizations (HSOs) have expanded into increasingly integrated delivery systems requiring more sophisticated health information systems (HISs) to support decision making. Computer innovations are required in most HSOs to support these HISs. Health services organizations decision makers are faced with many complex decisions during the computer innovation process. One of their most important decisions is judging HSO innovation readiness. Accurate judgments about HSO innovation readiness will have a direct impact on how successful decision makers are as computer innovators.


Dengue Virus Coinfection in Human Immunodeficiency Virus-1-Infected Patients on the West Coast of Mexico.
Dengue virus infection in human immunodeficiency virus (HIV)-positive patients is not well studied. Previous reports suggest a transitory inhibition of the HIV-1 viral load, as well as a benign clinical progression of dengue. The follow-up of six HIV-1-infected patients, diagnosed and hospitalized with dengue virus infection in the State of Colima, Mexico, was carried out to analyze the progression of this viral coinfection. The presence of dengue virus serotype 1 was confirmed through molecular tests. No severe complications were observed in any of the patients during dengue virus infection. Significant alteration of the HIV-1 viral loads was not observed during dengue virus infection and 6 months after coinfection. Further studies are required to understand the pathology, as well as the clinical course, of these viral coinfections.


Pressure ulcer monitoring: a process of evidence-based practice, quality, and research.
A number of settings in eastern Ontario, Canada, have collaborated on establishing a common pressure ulcer monitoring system. This work was undertaken in a proactive effort to implement practice guideline recommendations related to pressure ulcer prevention. The monitoring system was developed at The Ottawa Hospital (Ottawa, Ontario, Canada), an acute care teaching hospital, and then shared with multiple settings, which adopted it. A work group was formed with clinical, quality, and research expertise. In a prospective (rather than retrospective) chart audit, 12-hour point prevalence surveys are conducted in which risk, occurrence, and interventions are tracked. Trained surveyors conduct a standard risk appraisal, head-to-toe skin assessment, and chart scan. Reporting mechanisms were developed at the organization, program, and unit levels. Between 2001 and 2007, despite an inpatient population of which usually more than 25% were at "high" risk, prevalence decreased from 18% to 14%. Fifteen years' experience in pressure ulcer monitoring suggests the following recommendations: (1) create and enable skin care champions to monitor and develop unit-based solutions in response to survey findings; (2) embed monitoring in the quality and professional practice infrastructure of the organization; (3) use existing structures and processes such as unit councils or quality committees; quality processes and practice panels are ideal venues to situate pressure ulcer monitoring at both organizational and unit levels; and (4) create a data collection process that is as clinically sensible and feasible as possible. Monitoring is the linchpin that formed the foundation for the long-term, systemwide undertaking of the prevention of pressure ulcers and that created the climate for change and continued momentum.


Electrochemical and spectroelectrochemical behavior of the main photodegradation product of nifedipine: the nitrosopyridine derivative.
To characterize the electrochemical behavior of the photodegradation product of nifedipine, i.e., 2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridine-carboxylic acid dimethyl ester (NPD) in different electrolytic media. We also evaluated the interaction between free radicals generated from NPD and xeno/endobiotics. Tast polarography, differential pulse polarography, and cyclic voltammetry were used for the characterization. Controlled potential electrolysis and ultraviolet-visible spectroscopy were used to generate and to detect the nitroso radical anion. In protic media, the NPD derivative gave a reversible well-defined peak either on Hg or glassy carbon electrodes in a reaction involving two electrons and two protons to give the hydroxylamine derivative. In mixed aqueous-organic media (pH 9) and in aprotic media, nitroso radical anion was isolated and characterized, exhibiting second-order dimerization rate constant (k2) values of 11,300 +/- 210 [Ms](-1) and 8,820 +/- 78 [Ms](-1), respectively. Reactivity of the nitroso radical anion with relevant pharmacologic targets revealed a significant interaction with the tested endo/xenobiotics (cysteamine, GSH, N-acetylcysteine, and adenine). Both in mixed and aprotic media, NPD generated free-radical species, the nitroso radical anion. Taking into account their respective interaction rate constants, the following tentative rank order of reactivity can be established as follows: cysteamine > N-acetylcysteine > GSH > adenine.


[AIDS epidemic and infection control in the United States].
AIDS is the second leading cause of death among persons 25-44 years of age. The risk to patients from physicians and other health care workers with HIV infection has also become a great public concern. There are no specific procedures for infection control in AIDS. Universal precautions are applied to AIDS as well as to any other infectious diseases. Recommended universal infection control in autopsy room is as follows: 1. Wear protective masks and eyewear (or face shields), laboratory coats, gloves, and waterproof aprons; 2. Develop and consistently practice the skills necessary to avoid penetrating injuries; 3. Decontaminate instruments and work areas contaminated during postmortem procedures with a 1:10 dilution of common household bleach, whose active ingredient is sodium hypochlorite; 4. Dispose of waste contaminated with body fluids into a red trash can indicated "BIOHAZARD". In case of accident such as needlestick or cut during autopsy of HIV infected corpe, the person should have the HIV antibody test and start taking azidothymidine (AZT) within 24 hours.


Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2.
Conserved DNA-damage responses (DDRs) sense genome damage and prevent mitosis of broken chromosomes. How cells lacking DDRs cope with broken chromosomes during mitosis is poorly understood. DDRs are frequently inactivated in cells with extra genomes (polyploidy), suggesting that study of polyploidy can reveal how cells with impaired DDRs/genome damage continue dividing. Here, we show that continued division and normal organ development occurs in polyploid, DDR-impaired Drosophila papillar cells. As papillar cells become polyploid, they naturally accumulate broken acentric chromosomes but do not apoptose/arrest the cell cycle. To survive mitosis with acentric chromosomes, papillar cells require Fanconi anemia proteins FANCD2 and FANCI, as well as Blm helicase, but not canonical DDR signaling. FANCD2 acts independently of previous S phases to promote alignment and segregation of acentric DNA produced by double-strand breaks, thus avoiding micronuclei and organ malformation. Because polyploidy and impaired DDRs can promote cancer, our findings provide insight into disease-relevant DNA-damage tolerance mechanisms.


Relationship between ultrasonographically determined renal dimensions and International Renal Interest Society stages in cats with chronic kidney disease.
The correlation between renal dimensions and renal function in cats with chronic kidney disease (CKD) is unclear. To investigate the relationship between renal dimensions and CKD severity in cats using ultrasound examination. Nineteen healthy cats and 30 cats with CKD. Renal ultrasound images obtained between 2012 and 2016 were reviewed. Severity of CKD was determined using the International Renal Interest Society CKD staging system. Renal length, cortical thickness, medullary thickness, and corticomedullary ratio were measured, and the relationship between these renal dimensions and serum creatinine concentrations as well as differences in dimensions between the control and disease groups was investigated. The sensitivity and specificity of the renal dimensions for differentiation of the CKD also were evaluated. The disease group was subdivided into stage I to II (15 cats) and stage III to IV (15 cats) groups. Cortical thickness was significantly decreased in both disease groups and negatively correlated with disease severity. Compared with other renal dimensions, cortical thickness had a stronger linear correlation with the reciprocal of the serum creatinine concentration and superior diagnostic performance (Youden index: left kidney, 90.0% sensitivity and 94.7% specificity for a cutoff of 4.7 mm; right kidney, 83.3% sensitivity and 94.7% specificity for a cutoff of 4.5 mm). Decreased renal cortical thickness is observed in cats with loss of renal function. Measurement of cortical thickness using ultrasonography could be a useful method to evaluate the progression of CKD in cats.


Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina.
The chick pineal gland and retina synthesize melatonin in a circadian rhythm with high levels during the night. The rhythmic changes in the hormone production result predominantly from the fluctuation in the activity of serotonin N-acetyltransferase (AA-NAT), a penultimate and key regulatory enzyme in melatonin biosynthesis. The aim of this study was to analyze the effects of an acute and prolonged in vivo treatment with a glucocorticoid dexamethasone (4 mg/kg, ip) on the nocturnal increase in AA-NAT activity in chick pineal gland and retina. In acute experiments, dexamethasone (single dose)-injected chicks were killed after 2 h, while in prolonged experiments the glucocorticoid was given once daily for 7 days and the animals were killed 26-32 h after the last injection. Acute administration of dexamethasone did not affect AA-NAT activity in the chick pineal gland and retina. In the pineal glands and retinas of chicks that were treated with dexamethasone for one week and then killed at the end of the light phase of the 12:12 h light-dark cycle, AA-NAT activity was significantly higher than the enzyme activity found in tissues isolated from the vehicle-treated (control) animals. In addition to that, the nocturnal increase in pineal and, to a lower extent, retinal AA-NAT activity was significantly lower in dexamethasone-treated birds when compared with the respective control groups. It is suggested that prolonged treatment of animals with dexamethasone reduces the amplitude of the rhythmic melatonin production, a phenomenon which may affect chronobiological processes being under control of this hormone.


Survey of sediment oxygenation in rhizospheres of the saltmarsh grass - Spartina anglica.
Although transport of oxygen via the aerenchyma tissue and subsequent oxygen loss across root surfaces is well-documented for salt marsh grasses, only few studies have measured the oxygenation of sediment surrounding roots and rhizomes. In this study, sediment oxygenation was assessed in situ in rhizospheres of the intertidal salt marsh grass, Spartina anglica - an invading species, vigorously spreading in many wetlands around the world. The rhizospheres of two populations of S. anglica with differing plant morphology growing in different sediment types were investigated in situ using a novel multifiber optode system with 100 oxygen probes. No oxygen was detected inside the rhizospheres at any depth in either location, indicating a limited impact of plant-mediated sediment oxygenation on the bulk anoxic sediment. Subsequent planar optode studies imaging the oxygen content around the roots substantiated these findings showing that sediment oxygenation was present in both locations, but it was confined only to the immediate vicinity of the root tips. The size of the oxic zones surrounding the root tips differed between sediment-types: in S. anglica growing in permeable sandy sediment, oxic root zones extended 1.5mm away from the roots surface compared to only 0.4mm in muddy tidal flat deposit, which had a substantially higher oxygen demand. The oxygen concentration inside the oxic root zones remained stable during continuous light and air-exposure of the aboveground biomass. In comparison, sediment oxygenation generated by burrowing infauna (Hediste diversicolor) showed to be markedly more temporally variability, reaching anoxic conditions multiple times during a 5-h period.


Pneumomediastinum: Radiological profile and associations of uncommon complication of COVID-19.
Spontaneous pneumomediastinum is an uncommon complication of Corona Virus Disease (COVID)-19 presenting mostly in moderate to severe cases. This is a retrospective observational imaging and hospital data-based study done on 15 confirmed patients of COVID-19 who underwent high resolution computed tomography (HRCT) thorax at the Department of Radio-Diagnosis of a tertiary medical center in the Himalayan foothills. The clinico-radiological profile of the study group was assessed and it was aimed at finding the association of pneumomediastinum with the severity of lung changes. A strong association of pneumomediastinum was observed with severe lung changes on HRCT thorax (n = 13, 87%, P < 0.00001). Dyspnea was the most common presenting factor. The mortality rate is high in mechanically intubated patients of pneumomediastinum with COVID-19 (75%). Pneumomediastinum is a complication of a severe COVID-19 disease spectrum. Along with severe lung parenchymal disease, systemic inflammation, systemic steroid therapy, comorbid state, and mechanical intubation, it is a part of the pool of poor prognostic factors. HRCT is essential for making a quick and comprehensive diagnosis, thereby, guiding the clinician for further management.


Occupational asthma diagnosis in workers exposed to organic dust.
The clinical evaluation of newly developed asthma in an adult should always include consideration of his occupational environment, since an abundance of different exposures, which are known causes of asthma, occur in workplaces. Two types of occupational asthma (OA) are distinguished, by whether they appear after a latency period: 1)Immunological OA, characterised by a latency period, caused by high and low-molecular-weight agents, with or without an IgE mechanism 2) Non-immunological, i.e. irritant induced asthma. The first step of the clinical evaluation is to confirm a diagnosis of asthma. Second step is to find out if there is a temporo-spatial distribution of symptoms and lung function that are indicative of OA. Third step is to determine if the disease at hand is an IgE or a non-IgE mediated disease. Last step is a challenge test that can be either unspecific, in order to assess the responsiveness of the lung, or specific challenge test, especially for the non-IgE mediated OA. The depth of clinical evaluation may vary from a situation in which a classical history confirms the clinical symptoms in e.g. a baker with confirmed allergy towards well-known allergens and a characteristic pattern in serial measurements of lung function, to more elaborate investigations in a situation with no or unknown allergen. In the latter situation, a specific challenge test might be necessary in order to find the offending agent. Finally, challenge tests are important in order to distinguish a causal relation from unspecific hyperresponsiveness in persons with pre-existing asthma. In these situations, extended sick leave and challenge tests can be the only way to find the answer.


Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot.
Dual antiplatelet therapy (DAPT) is recommended after elective percutaneous coronary intervention (PCI) in stable coronary artery disease (SCAD) patients; however, still one-third of patients do not obtain adequate platelet inhibition that may result in increased cardiovascular risk. The aim of the ONSIDE TEST study is to evaluate the clinical impact of point-of-care genotyping- and platelet function-based personalized dual antiplatelet strategies in SCAD individuals undergoing PCI. Fifty patients were randomized to one of the three study arms: 1) genotyping, 2) platelet function testing (PFT) and 3) control. Patients were tested with point-of-care Spartan RX CYP2C19 System (group 1) and VerifyNow P2Y12 assay (group 2). In cases of inadequate response to clopidogrel, a loading dose of prasugrel was administered before PCI. The main clinical endpoint is the incidence of periprocedural myocardial injury (PMI). Five (32%) patients in the genotyping arm and two (13%) in the in the PFT arm were identi-fied as poor clopidogrel metabolizers. The periprocedural platelet reactivity was significantly lower in the genotyping (80 ± 49.0 PRU) and PFT (36.5 ± 47 PRU) arms as compared to the control arm (176 ± 67.8 PRU), p = 0.01 and p = 0.03, respectively. PMI appeared in 17 (37%) patients of the entire study population. Personalized DAPT results in an improved platelet inhibition. Apart from genotyping and aggregometry, it is feasible to integrate into everyday clinical practice PMI rates which are relevant when comparing different strategies.


Acute diphenyl diselenide treatment reduces hyperglycemia but does not change delta-aminolevulinate dehydratase activity in alloxan-induced diabetes in rats.
This study was designed to evaluate the effect of diphenyl diselenide in a classical model of alloxan-induced diabetes in rats. Oxidative stress is involved in alloxan toxic effects and we have hypothesized that diphenyl diselenide via its antioxidant properties could confer protection against alloxan pancreatic toxicity. Diabetes was induced by administration of alloxan (150 mg/kg, intravenously). Diphenyl diselenide (10 mg/kg, subcutaneously) was administered for 6 d before (prevention group) or for 6 d after (remediation group) diabetes induction. Diphenyl diselenide treatment reduced the blood glucose and fructosamine levels, which were increased in alloxan-treated rats. However, the delta-aminolevulinate dehydratase (delta-ALA-D) activity inhibited by alloxan was not restored by diphenyl diselenide. Moreover, diphenyl diselenide caused by itself an inhibition in hepatic and renal delta-ALA-D activity. Our findings suggest that the acute treatment with diphenyl diselenide reduces the hyperglycemia but does not improve delta-ALA-D activity decreased by alloxan. Although the dose of diphenyl diselenide used here for treating diabetic animals has been relatively high and produced toxic effects, the compound or analogous molecules might not be rejected as a promising anti-hyperglycemic agent.


Creative Psychopharmacotherapy in Child and Adolescent Psychiatry and Experiences from Bosnia and Herzegovina.
Paediatric psychopharmacology involves the application of psychotropic agents to the treatment of children and adolescents with mental disorders and gathered knowledge from child and adolescent psychiatry (CAP), neurology, paediatrics and pharmacology. Defining elements of this discipline are: the metabolism of drugs is different in children than in adults (pharmacokinetics), the developing brain reacts specifically to the drug (pharmaco dynamics), and psychopathology itself is not differentiated yet. To make and overview of specifics in psychopharmacological use in CAP and emphasize some experiences from Bosnia and Herzegovina in that field. Through insight in current literature, we presented comprehensive findings and compare it with situation in Bosnia and Herzegovina. The most common conditions in which psycho pharmaceuticals are used in CAP were attention deficit hyperactivity disorders (ADHD), depressive and bipolar disorder, obsessive compulsive disorder and the treatment of early psychosis. Psycho pharmaceuticals were also used to treat agitated conditions in various causes. We made an overview of psycho pharmaceuticals use in Bosnia and Herzegovina CAP and emphasized the fact that psycho stimulants are not approved for the use yet, although they are mostly prescribed medicament in CAP over the world. That limits us in the effectiveness of the treatment in ADHD and put us in the situations to use other medicaments instead (anxiolytics, antipsychotics, mood stabilizers) which are not approved for that condition. The use of psycho pharmacotherapy in CAP is justified in cases where it is necessary to reduce the suffering of children and to improve their functionality at the time when cognitive, social and emotional advancement is most pronounced. Further research and clinical monitoring of efficacy and safety in the use of psycho pharmaceuticals in youngsters are necessary.


Power relations in the family health team: focus on nursing.
to analyze the power relations that permeate the work of the family health team, and to discuss perspectives of emancipation of these subjects, focusing on nursing and community health agents. a qualitative study with a family health team from a municipality in the countryside of the state of São Paulo. Data were collected through systematic observation and interview with workers. A thematic content analysis was performed. three categories were identified: the work of the family health team and power relations; power relations between the nurse and the healthcare team; and the relations among the nursing team and between community agents and the nurse. The team produces relations of power moved by hierarchical knowledge that move in the search for the reordering of powers. it is necessary to review the contradictions present in the performance scenario of the family health teams, with a view toward making power relations more flexible.


Development of a new type of high pressure calorimetric cell, mechanically agitated and equipped with a dynamic pressure control system: application to the characterization of gas hydrates.
A novel prototype of calorimetric cell has been developed allowing experiments under pressure with an in situ agitation system and a dynamic control of the pressure inside the cell. The use of such a system opens a wide range of potential practical applications for determining properties of complex fluids in both pressurized and agitated conditions. The technical details of this prototype and its calibration procedure are described, and an application devoted to the determination of phase equilibrium and phase change enthalpy of gas hydrates is presented. Our results, obtained with a good precision and reproducibility, were found in fairly good agreement with those found in literature, illustrate the various interests to use this novel apparatus.