New paradigm for understanding in-flight decision making errors: a neurophysiological model leveraging human factors.
Human factors centered aviation accident analyses report that skill based errors are known to be cause of 80% of all accidents, decision making related errors 30% and perceptual errors 6%1. In-flight decision making error is a long time recognized major avenue leading to incidents and accidents. Through the past three decades, tremendous and costly efforts have been developed to attempt to clarify causation, roles and responsibility as well as to elaborate various preventative and curative countermeasures blending state of the art biomedical, technological advances and psychophysiological training strategies. In-flight related statistics have not been shown significantly changed and a significant number of issues remain not yet resolved. Fine Postural System and its corollary, Postural Deficiency Syndrome (PDS), both defined in the 1980's, are respectively neurophysiological and medical diagnostic models that reflect central neural sensory-motor and cognitive controls regulatory status. They are successfully used in complex neurotraumatology and related rehabilitation for over two decades. Analysis of clinical data taken over a ten-year period from acute and chronic post-traumatic PDS patients shows a strong correlation between symptoms commonly exhibited before, along side, or even after error, and sensory-motor or PDS related symptoms. Examples are given on how PDS related central sensory-motor control dysfunction can be correctly identified and monitored via a neurophysiological ocular-vestibular-postural monitoring system. The data presented provides strong evidence that a specific biomedical assessment methodology can lead to a better understanding of in-flight adaptive neurophysiological, cognitive and perceptual dysfunctional status that could induce in flight-errors. How relevant human factors can be identified and leveraged to maintain optimal performance will be addressed.


Serial CT for Nonoperatively Managed Splenic Injuries.
The role of serial computed tomography (CT) in the nonoperative management of blunt splenic injuries (NOMSIs) remains unclear. The purpose of the study was to determine the utility of serial CT of Grade 2-5 NOMSI in the modern era. Blunt splenic injuries were identified over a 3.5-year period, ending in 6/2020. Our institutional protocol for NOMSI mandates a repeat 24-hour CT for Grade 2-5 injuries. Patients age<18, Grade 1 injuries and patients that underwent intervention prior to repeat scan were excluded. Demographics, comorbidities, timing of events (admission, CTs, splenectomy, and angiography), injury details, procedural details, total transfusion requirements, complications, length of stay, mortality, and discharge disposition were recorded. Descriptive statistics were performed. 219 patients with Grade 2-5 NOMSI had both an initial and 24-hour CT after exclusions. 24-hour CT identified 14 patients with new PSA(s) and 11 (5%) went to angiography within 24 hours with 9 (4%) undergoing angioembolization and 4 (2%) had splenectomy. Two hundred and four (93%) had no intervention though eventually 12 went on to angiography and 6 went for splenectomy. The 24-hour CT rarely altered management in the absence of clinical indication or prior PSA on initial CT with 5 (2%) receiving a therapeutic embolization and 2 (1%) had a nontherapeutic angiogram. No deaths were attributable to splenic injury. Routine 24-hour CT for NOMSI did not impact management. Clinical status and change in exam may warrant repeat CT in select cases in the setting of a plausible alternate explanation. Prompt angioembolization or splenectomy is more appropriate in clear-cut cases of failed NOMSI.


Application of cucumber mosaic virus to efficient induction and long-term maintenance of virus-induced gene silencing in spinach.
Virus-induced gene silencing (VIGS) is a useful tool for functional genomics in plants. In this study, we tried to apply cucumber mosaic virus (CMV) to efficient induction of VIGS in spinach. Although VIGS for spinach had been previously developed based on two viruses (beet curly top virus and tobacco rattle virus), they still have some problems with systemic movement and long-term maintenance of VIGS in spinach. Although ordinary CMV strains infect spinach inducing distinct mosaic symptoms, using a CMV pseudorecombinant, we can modify the viral pathogenicity to attenuate viral symptoms that may mask the silencing phenotype. We here successfully demonstrated the viral ability to silence the phytoene desaturase (PDS) and the dihydroflavonol 4-reductase (DFR) genes in spinach. Because CMV could quickly induce VIGS even at 7-10 days postinoculation and the virus did not disappear even at the flowering stage, this CMV-based VIGS system would contribute to functional genomics in spinach and especially to the elucidation of molecular mechanisms for some properties unique to spinach such as plasticity of sex expression; the CMV-induced VIGS can last until the flowering stage after the virus was inoculated onto the seedling.


An Organic Hybrid Indium-Telluride Incorporating Binuclear Complexes [In2(ea)4]2+ with a Bridging Oxygen Donor.
The new organic hybrid indium-telluride [In2(ea)2Te2]n (1; Hea = ethanolamine) exhibits a new type of one-dimensional polymeric chain based on the linkages of dinuclear [In2(ea)4]2+ and [In2Te4]2- units, which offers the first example of an indium-telluride framework incorporating binuclear complexes [In2(ea)4]2+ with a bridging O donor. 1 shows a distinctive photocurrent response and photocatalytic properties under visible-light illumination.


Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumors.
The bradykinin analog, RMP-7, was investigated for its ability to selectively increase uptake of molecular tracers in RG2 glial tumors. When infused in low doses (0.1 microgram/kg/min) through the intracarotid artery ipsilateral to RG2 gliomas in rats, RMP-7 significantly increased the permeability of tumor capillaries to methotrexate and to four other tracers of varying molecular weights, compared to intracarotid infusion of vehicle alone. Tracers used to examine permeability included radiolabeled alpha-aminoisobutyric acid (M(r) 103 D), sucrose (M(r) 342 D), methotrexate (M(r) 454.5 D), inulin (M(r) 5000 D), and dextran (M(r) 70,000 D). Permeability was expressed as the unidirectional transfer constant, Ki (microliters/gm/min). The permeability (Ki) of tumors in the RMP-7 group compared to the vehicle control group was as follows: alpha-aminoisobutyric acid, 35.3 +/- 9.11 versus 12.7 +/- 4.56 (p < 0.001); sucrose, 16.5 +/- 3.83 versus 9.28 +/- 3.12 (p < 0.05); methotrexate, 26.3 +/- 10.3 versus 8.98 +/- 6.78 (p < 0.005); inulin, 13.5 +/- 3.23 versus 6.55 +/- 4.32 (p < 0.005); dextran, 15.2 +/- 3.42 versus 1.47 +/- 1.24 (p < 0.001). The permeability of RG2 gliomas to high-molecular-weight dextran (70,000 D) was 10.3-fold higher in the RMP-7 group than in the vehicle control group. Intracarotid infusion of RMP-7 did not significantly increase the blood volume in tumor or brain tissue. The permeability of normal brain capillaries was unaffected by intracarotid infusion of 0.1 microgram/kg/min RMP-7 relative to that achieved in tumor. These data support the idea that intracarotid infusion of RMP-7 will be a useful technique for selective delivery of antitumor compounds to brain tumors.


THE EFFECTS OF BODY MASS, PHYLOGENY, HABITAT, AND TROPHIC LEVEL ON MAMMALIAN AGE AT FIRST REPRODUCTION.
I examined age at first reproduction of 547 mammalian species to determine the influence of diet and habitat on the evolution of life-history traits. Body mass correlated positively with age at first reproduction, explaining 56% of the variance. Habitat and trophic groups deviated significantly from the allometric curve in a pattern generally consistent with predictions from r/K selection theory and its modifications. However, mammalian orders also deviated significantly from the allometric curve, and different habitat and diet groups contained different ratios of mammalian orders. When the effects of orders were removed, residual deviations did not differ among ecological groups. Adjusting for ecological differences did not eliminate the differences between orders. These results suggest that body mass (or some correlated factor) and phylogeny strongly constrain age at first reproduction. Ecological factors appear to have little effect on the evolution of age at first reproduction. Apparent differences in weight-specific ages at first reproduction within habitats and trophic groups may be the result of ecological selection of order composition in the present, rather than ecologically driven evolution of life history in the past.


Understanding end-user support for health information technology: a theoretical framework.
Support is often considered an important factor for successful implementation and realising the benefits of health information technology (HIT); however, there is a dearth of research on support and theoretical frameworks to characterise it. To develop and present a comprehensive, holistic, framework for characterising enduser support that can be applied to various settings and types of information systems. Scoping review of the medical informatics and information systems literature. A theoretical framework of end-user support is presented. It includes the following facets: support source, location of support, support activities, and perceived characteristics of support and support personnel. The proposed framework may be a useful tool for describing and characterising enduser support for HIT. it may also be used by decision makers and implementation leaders for planning purposes.


Blood-brain barrier permeability of normal appearing white matter in relapsing-remitting multiple sclerosis.
Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before and after injection of Gd-DTPA. The pre-injection baseline T1 of NAWM (945±55 [SD] ms) was prolonged in RR-MS relative to healthy controls (903±23 ms, p = 0.028). Gd-DTPA injection shortened T1 to a similar extent in both groups. Mean T1 of NAWM was 866±47 ms in the NAWM of RR-MS patients and 824±13 ms in the white matter of healthy controls. The regional variability of T1 values expressed as the coefficient of variation (CV) was comparable between the two groups at baseline, but not after injection of the contrast agent. After intravenous Gd-DTPA injection, T1 values in NAWM were more variable in RR-MS patients (CV = 0.198±0.046) compared to cerebral white matter of healthy controls (CV = 0.166±0.018, p = 0.046). We found no evidence of a global BBB disruption within the NAWM of RR-MS patients undergoing immunomodulatory treatment. However, the increased variation of T1 values in NAWM after intravenous Gd-DTPA injection points to an increased regional inhomogeneity of BBB function in NAWM in relapsing-remitting MS.


Initial fetal platelet counts predict the response to intravenous gammaglobulin therapy in fetuses that are affected by PLA1 incompatibility.
Fetal alloimmune thrombocytopenia is the result of maternal fetal platelet antigen incompatibility; intracranial hemorrhage is its most serious complication. Our previous studies have demonstrated an inability to accurately predict fetal platelet counts in this disorder. The goal of the present investigation was to identify factors that would predict the response of the fetal platelet count to therapy so that use of fetal blood sampling could be minimized. Patients who were eligible for the study were all those who (1) had alloimmune thrombocytopenia secondary to Pl(A1) (HPA-1a, Zw(A)) platelet antigen incompatibility, (2) were treated with maternally administered intravenous immunoglobulin at 1 g/kg of body weight per week, with or without low dose steroids, and (3) had percutaneous fetal blood sampling before the initiation of therapy (first fetal blood sampling) and again 3 to 7 weeks afterwards (second fetal blood sampling). In this retrospective review, 74 patients who were affected by alloimmune thrombocytopenia had a median platelet count of 21,000 per microliter at the first fetal blood sampling and 47,000 per microliter at the second fetal blood sampling, with a median increase in platelet count of 24,000 per microliter. Response to treatment was defined as either (1) an improvement in platelet count (the second fetal blood sampling greater than the first fetal blood sampling, and second fetal blood sampling > 20,000 per microliter) or (2) a minimal decline in platelet count (the first fetal blood sampling > or = 40,000 per microliter and the difference between the first and second fetal blood sampling < or = 10,000 per microliter). The first fetal blood sampling had prognostic value for the second fetal blood sampling (P = .0001), although the previous sibling birth platelet count and history of sibling intracranial hemorrhage did not predict the platelet count at the first or second fetal blood sampling or the change in platelet count between the samplings. When the patients were segregated to first fetal blood sampling of > 20,000 per microliter versus < or = 20,000 per microliter, the response rates for the 2 groups were 89% (33/37 patients) versus 51% (19/37 patients; P = .001). In fetal alloimmune thrombocytopenia secondary to Pl(A1) platelet antigen incompatibility, fetuses with platelet counts > 20,000 per microliter at the initiation of therapy were predicted to maintain their platelet count at the second fetal blood sampling at > 20,000 per microliter. The characteristics of the previous sibling, as previously reported, did not predict the initial fetal blood sampling, the second fetal blood sampling, or the response to treatment.


[Evaluate the effectiveness of laser therapy in the treatment of diabetic maculopathy].
Diabetes mellitus concerns a growing number of people in the world. Its complications are an important social problem. Diabetic macular edema (DME) is one of the leading causes of visual loss in the course of the disease. Deterioration of vision is typically the patients with long-standing, poorly controlled diabetes, both type 1 and 2. DME can occur at any stage of the disease. Because structural changes in the macula are reversible in the initial period, it is important to start treatment early. In the treatment of diabetic uses three techniques retinal laser--direct photocoagulation, photocoagulation a "grid" and the panphotocoagulation. The aim of this study was to evaluate the effectiveness of laser therapy in the treatment of diabetic macular edema. The study included 90 patients (180 eyes) with DME, 50 women and 40 men aged from 18 to 80 years with a visual acuity of 0.08 to 0.7 with the best corrected on the Snellen chart. 9 people were with type 1 diabetes, 81 with type 2. 86 patients applied insulin, 4 people took drugs. Eye with poor visual acuity was qualified for the treatment. In all patients enrolled in the study visual acuity, anterior segment of the eye in the slit lamp and fundus by indirect ophthalmoscopy with Volk 78D lens were evaluated. DME was diagnosed on the basis of the results of fluorescein angiography and optical coherence tomography. In the patients laser therapy was performed twice: on day 1 after qualification and four months later. Performed two types of laser: the focal photocoagulation and the type of "grid" depending on the severity of DME. Retinal photocoagulation was performed using a diode laser 810 nm Diode Laser Systems OcuLight SL and SLx Iris Medical Models. Patients were monitored at 4 and 8 months after the laser therapy. The results were statistically analyzed. Duration of diabetes less than 10 years was in 67 patients, over 10 years in 23. In patients with diabetes under 10 years predominated limited type of macular edema (92.65%), in patients over 10--diffuse (72.73%). As a result of the treatment in 34 patients (37.8%) visual acuity was improved. 91.18% of them had limited macular edema. In 47 patients (52.2%) showed the stabilization of vision. These patients had also more limited type of edema (74.47%). In 9 patients (10%) visual impairment were observed and they were mostly patients with diffuse macular edema (66.67%). Average visual acuity in patients with limited macular edema before laser therapy was 0.37 +/- 0.18. In the four months after the laser treatment improved slightly (0.38 +/- .18). After 8 months of treatment the average visual acuity in this group remained at a level of 0.44 +/- 0.16. In patients with diffuse macular edema output type visual acuity was significantly lower and averaged only 0.16 +/- 0.1. In 4 months after the laser was found in this group decreased vision (Vo = 0.13 +/- 0.08). In 8 months after surgery visual acuity averaged 0.15 +/- 0.09. Average visual acuity before laser therapy in this group was 0.36 +/- 0.17, and 8 months after was at the level of 0.43 +/- 0.16. In patients with diabetes more than 10 years laser therapy has not brought the desired effect, and visual acuity were as follows: before treatment--0.18 +/- 0.16 and 8 months after--0.17 +/- 0.14 (p < 0.0001). Average macular thickness before laser therapy in patients with limited edema was 348.14 +/- 33.47 microns. In 4 months after the laser has been observed decreased to 340.29 +/- 31.2 microns, and after 8 months of further withdrawal of edema to an average of 337.88 +/- 32.95 microns. In patients with diffuse type average macular thickness was 394.38 +/- 38.18. After 4 months of laser treatment exacerbation of edema (mean 399 +/- 38.08). After 8 months, the thickness of macula in this group was average 388.95 +/- 32.85. Laser therapy is an effective type of treatment for DME. Better results after laser therapy are obtained in patients with a short-term macular edema and good visual acuity. In order to maintain useful visual acuity, patients with DME should undergo laser treatment in the early stages of the disease.


Combating the COVID-19 Epidemic: Experiences from Vietnam.
The COVID-19 pandemic is spreading fast globally. Vietnam's strict containment measures have significantly reduced the spread of the epidemic in the country. This was achieved through the use of emergency control measures in the epidemic areas and integration of resources from multiple sectors including health, mass media, transportation, education, public affairs, and defense. This paper reviews and shares specific measures for successful prevention and control of COVID-19 in Vietnam, which could provide useful learning for other countries.


Role of the cAMP signaling pathway in the dissemination and development on pepper fruit anthracnose disease caused by Colletotrichum scovillei.
The ascomycete fungus Colletotrichum scovillei causes severe anthracnose disease on the fruit of sweet pepper and chili pepper (Capsicum annuum L.) worldwide. Understanding the biology of C. scovillei would improve the management of fruit anthracnose diseases. The cyclic adenosine monophosphate (cAMP) signaling pathway regulates diverse cellular and physiological processes in several foliar fungal pathogens. We investigated the roles of the cAMP signaling pathway in C. scovillei using pharmaceutical and genetic approaches. Exogenous cAMP was found to increase conidiation, appressorium formation, and anthracnose disease development in C. scovillei. CsAc1, CsCap1, and CsPdeH, which regulate the intracellular cAMP level, were deleted by homology-dependent gene replacement. Expectedly, the intracellular cAMP level was significantly decreased in ΔCsac1 and ΔCscap1 but increased in ΔCspdeh. All three deletion mutants exhibited serious defects in multiple fungal developments and pathogenicity, suggesting regulation of the intracellular cAMP level is important for C. scovillei. Notably, exogenous cAMP recovered the defect of ΔCsac1 in appressorium development, but not penetration, which was further recovered by adding CaCl2. This result suggests that CsAc1 is associated with both the cAMP and Ca2+ signaling pathways in C. scovillei. ΔCscap1 produced morphologically abnormal conidia with reduced tolerance to thermal stress. ΔCspdeh was completely defective in conidiation in C. scovillei, unlike other foliar pathogens. Taken together, these results demonstrate the importance of cAMP signaling in anthracnose disease caused by C. scovillei.


Transforming growth factor beta 1 is a novel susceptibility gene for adolescent idiopathic scoliosis.
A genetic association study of the transforming growth factor beta 1 (TGFB1) gene with adolescent idiopathic scoliosis (AIS) in Russian population. To determine whether common genetic polymorphisms C-509T (rs1800469) and Arg25Pro (rs1800471) of the TGFB1 gene are associated with susceptibility to AIS. An importance of growth factors for the pathogenesis of AIS has been demonstrated by the findings of abnormal expression of these proteins in the spine and surrounding tissues in patients with AIS. However, no studies have been performed to investigate the relationship between genetic polymorphisms of the TGFB1 gene and susceptibility to AIS. A total of 600 unrelated adolescents from Central Russia (Moscow) were recruited in this study, including 300 patients with AIS and 300 age- and sex-matched healthy adolescents. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The allele -509T and genotype -509TT of the TGFB1 gene were significantly associated with the increased risk of idiopathic scoliosis in both females and males (P < 0.01). Logistic regression analysis has revealed a recessive model of the genetic association between polymorphism C-509T of the TGFB1 gene and AIS. Moreover, we found sexual dimorphisms in the relationships of SNP C-509T of the TGFB1 gene with both the age of disease onset and curve severity: the polymorphism was found to determine both an early onset of scoliosis and the severity of curvature in females but not in males (P < 0.05). This study, for the first time, highlights the importance of TGFB1 gene for the development and progress of AIS. We hypothesize several mechanisms by which the TGFB1 gene may contribute to spinal deformity in patients with AIS.


The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer.
It is unclear whether a subunit of glutamate cysteine ligase [a modifier subunit (GCLM) and a catalytic subunit (GCLC)] is an effective target for ameliorating cisplatin (CDDP)-resistance. We inhibited each subunit of GCL mRNA using a specific ribozyme (M-Rz and C-Rz) in the pulmonary adenocarcinoma cell line A549. GCL activity was suppressed by the ribozyme. CDDP-resistance was more effectively ameliorated when GCLM rather than GCLC was inhibited. GCLM is a potentially more effective pharmacologic target for ameliorating CDDP-resistance in non-small cell lung cancer than GCLC.


Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis.
To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies. Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively. Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc. In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.


Alterations of circadian rhythmicity and sleep in aging: endocrine consequences.
All 24-hour endocrine rhythms partially reflect the interaction of circadian rhythmicity with sleep-wake homeostasis but their relative contributions vary from one system to another. In older adults, many 24-hour rhythms are dampened and/or advanced, including those of cortisol and GH. Amplitude reduction and phase advance of 24-hour rhythms may represent age-related changes in the central nervous systems underlying circadian rhythmicity and sleep-wake homeostasis. Age-related alterations in circadian function could also reflect decreased exposure and/or responsivity to the synchronizing effects of both photic (e.g. light exposure) and nonphotic (e.g. social cues) inputs. There are pronounced age-related alterations in sleep quality in aging which consist primarily of a marked reduction of slow-wave sleep, a reduction in REM stages and a marked increase in the number and duration of awakenings interrupting sleep. Alterations in slow-wave sleep occur abruptly in young adulthood (30-40 years of age) whereas disturbances in amounts of REM and wake appear more gradually. This article reviews evidence indicating that deficits in characteristics of sleep-wake homeostasis and circadian function may mediate age-related alterations in somatotropic and corticotropic function. Because sleep loss in young subjects results in endocrine disturbances which mimic those observed in aging, it is conceivable that the decrease in sleep quality which characterizes aging may contribute to age-related alterations in hormonal function and their metabolic consequences.


Mammalian sensitivity to elemental gold (Au degrees).
There is increasing documentation of allergic contact dermatitis and other effects from gold jewelry, gold dental restorations, and gold implants. These effects were especially pronounced among females wearing body-piercing gold objects. One estimate of the prevalence of gold allergy worldwide is 13%, as judged by patch tests with monovalent organogold salts. Eczema of the head and neck was the most common response of individuals hypersensitive to gold, and sensitivity can last for at least several years. Ingestion of beverages containing flake gold can result in allergic-type reactions similar to those seen in gold-allergic individuals exposed to gold through dermal contact and other routes. Studies with small laboratory mammals and injected doses of colloidal gold showed increased body temperatures, accumulations in reticular cells, and dose enhancement in tumor therapy; gold implants were associated with tissue injuries. It is proposed that Au degrees toxicity to mammals is associated, in part, with formation of the more reactive Au+ and Au3+ species.


Pyroelectricity of Lead Sulfide (PbS) Quantum Dot Films Induced by Janus-Ligand Shells.
Asymmetry is an essential property to control. To do that in nanocrystalline systems we have developed methods to produce Janus-ligand shells on otherwise symmetric PbS quantum dots (QDs). Here, we demonstrate that control by constructing a system that exhibits pyroelectricity built from spherical PbS QDs. We observed a pyroelectric current in two different configurations. In one configuration, the QDs are self-assembled into close-packed arrays while in the second configuration, the QDs are dispersed into an electro-inactive polymer, polydimethylsiloxane. Both exhibit a pyroelectric response. In the first configuration we estimate a lower limit of the pyroelectric coefficient to be 1.97 × 10-7 C/m2·K, which is likely limited by the degree of QD alignment during film formation but is already on par with common pyroelectric systems. Compared with inorganic ceramic-like and polymeric pyroelectric materials, pyroelectric films self-assembled from polar QDs are easier to prepare, responsive to light with different energies based on QD exciton energy, and the polarization of each QD could be easily tuned by constructing different Janus-ligand shells.


Gravimetric Analysis of Particulate Matter using Air Samplers Housing Internal Filtration Capsules.
An evaluation was carried out to investigate the suitability of polyvinyl chloride (PVC) internal capsules, housed within air sampling devices, for gravimetric analysis of airborne particles collected in workplaces. Experiments were carried out using blank PVC capsules and PVC capsules spiked with 0,1 - 4 mg of National Institute of Standards and Technology Standard Reference Material® (NIST SRM) 1648 (Urban Particulate Matter) and Arizona Road Dust (Air Cleaner Test Dust). The capsules were housed within plastic closed-face cassette samplers (CFCs). A method detection limit (MDL) of 0,075 mg per sample was estimated. Precision Sr at 0,5 - 4 mg per sample was 0,031 and the estimated bias was 0,058. Weight stability over 28 days was verified for both blanks and spiked capsules. Independent laboratory testing on blanks and field samples verified long-term weight stability as well as sampling and analysis precision and bias estimates. An overall precision estimate Ŝrt of 0,059 was obtained. An accuracy measure of ±15,5% was found for the gravimetric method using PVC internal capsules.


Thyroid surgery: use of the LigaSure Vessel Sealing System versus conventional knot tying.
The aim of this work is to compare the use of conventional knot tying vs. LigaSuretrade mark Vessel Sealing System (Valley Lab, Boulder, CO) in patients undergoing thyroid surgery. We hypothesized that use of the LigaSure would reduce operating time while resulting in a similar rate of complications. This study was conducted in Endocrine Surgery Unit, Mansoura University Hospital on patients who underwent thyroid surgery from January 1, 2006 to December 31, 2006. One hundred and ten patients were operated upon by the same team of surgeons using conventional knot tying in 55 and the LigaSure in 55 patients for hemostasis. The medical records of the patients enrolled were reviewed and compared regarding age, sex, histopathological diagnosis, type of operation performed (lobectomy vs. subtotal thyroidectomy vs. total thyroidectomy), operating time, estimated intraoperative blood loss, postoperative complications, length of incision, hospital stay and cost, postoperative pain and outcome evaluation. The two groups had similar demographics, thyroid pathology, types of operations and complication rates. The LigaSure group had lower operating times, lower intraoperative blood loss, less postoperative pain and early pain-free return to normal activity and return to work. The LigaSure Vessel Sealing System was as safe as conventional knot tying for thyroidectomy, with the benefit of reduced operating time, postoperative pain severity and early pain-free return to normal activity and return to work.


[Effect of glucose control on lipid levels in patients with type 2 diabetes].
The dyslipoproteinemia characterizing patients with type 2 diabetes is a major risk factor for atherosclerosis. Prospective studies indicate that an improved glucose control is associated with lower lipid levels. In this study we evaluated whether an improvement of the lipid status can also be observed in a routine clinical setting. Furthermore, we evaluated how many patients achieve lipid target levels by improving glucose control. In 51 type 2 diabetics (60 +/- 12 ys., 29 men, 22 women) lipid values were determined before and after improvement of glucose metabolism (6 - 12 weeks, HbA1c 7.9 +/- 1.9 % vs. 7.1 +/- 1.3 %). Patients on lipid-lowering medication or with atherosclerosis were excluded. The improved glucose control was achieved by starting/intensifying treatment with diet (n = 5), acarbose (n = 5), metformin (n = 10), sulfonylurea/glinide (n = 12) or insulin (n = 19). The decrease in HbA1c was associated with a decrease in total cholesterol (232 +/- 64 vs. 216 +/- 35 mg/dl, p < 0.05) and triglycerides (348 +/- 448 vs. 216 +/- 139 mg/dl, p < 0.01), while HDL- and LDL-cholesterol did not change significantly. Only in patients with triglycerides > 200 mg/dl did changes in HbA1c-levels correlate with changes in triglyceride-levels (r(2) = 0.32, p = 0.012). Lipid target levels were reached in seven of 51 patients (five of 51 patients before improvement of HbA1c). Although in routine clinical practice an improvement in HbA1c results in better lipid values. This improvement is small and is usually not sufficient to reach lipid target levels.


High-Performance Rechargeable Aluminum-Selenium Battery with a New Deep Eutectic Solvent Electrolyte: Thiourea-AlCl3.
Aluminum-sulfur batteries (ASBs) have attracted substantial interest due to their high theoretical specific energy density, low cost, and environmental friendliness, while the traditional sulfur cathode and ionic liquid have very fast capacity decay, limiting cycling performance because of the sluggishly electrochemical reaction and side reactions with the electrolyte. Herein, we demonstrate, for the first time, excellent rechargeable aluminum-selenium batteries (ASeBs) using a new deep eutectic solvent, thiourea-AlCl3, as an electrolyte and Se nanowires grown directly on a flexible carbon cloth substrate (Se NWs@CC) by a low-temperature selenization process as a cathode. Selenium (Se) is a chemical analogue of sulfur with higher electronic conductivity and lower ionization potential that can improve the battery kinetics on the sluggishly electrochemical reaction and the reduction of the polarization where the thiourea-AlCl3 electrolyte can stabilize the side reaction during the reversible conversion reaction of Al-Se alloying processes during the charge-discharge process, yielding a high specific capacity of 260 mAh g-1 at 50 mA g-1 and a long cycling life of 100 times with a high Coulombic efficiency of nearly 93% at 100 mA g-1. The working mechanism based on the reversible conversion reaction of the Al-Se alloying processes, confirmed by the ex situ Raman, XRD, and XPS measurements, was proposed. This work provides new insights into the development of rechargeable aluminum-chalcogenide (S, Se, and Te) batteries.


Cadmium accumulation in Scenedesmus vacuolatus under freshwater conditions.
Cd accumulation in cultures of Scenedesmus vacuolatus, a freshwater alga, was investigated in water samples from freshwater systems (two hard- and one softwater system) and compared to accumulation from synthetic culture medium. The Cd accumulation in S. vacuolatus was compared to total, labile, and free Cd measured by various analytical methods. In the hardwater samples, Cd accumulation was similar to accumulation from the culture medium and approximately followed the free ion activity model. In the softwater system, Cd accumulation increased with increasing free and total Cd concentrations, but was lower than expected from the free Cd2+ concentrations compared to the other freshwaters and culture media. Cd accumulation in the various freshwaters was not simply related to labile and free Cd concentrations measured by several methods. From experiments using fulvic acid as a ligand in the culture medium, no influence on Cd accumulation other than by modifying the Cd speciation was detected. Modeling of the Cd uptake revealed that besides cation and proton competition, other factors such as dissolved organic carbon composition and the presence of colloids might reduce Cd accumulation in softwater systems.


Comparison of two oral health-related quality of life measures among adult dental patients.
The most commonly used oral health related quality of life measures, Oral Health Impact Profile (OHIP) and Oral Impact on Daily Performances (OIDP), are affected by cultural and linguistic factors, which may be intensified in a treatment-need driven society. This study therefore aimed to compare the psychometric properties of the OHIP-14 and OIDP measures in adult patients in Nigeria where patients typically visit the dentist when dental problems arise. This was a cross-sectional study in which 264 patients attending two dental clinics were recruited. Data were collected with OHIP-14 and OIDP structured interviewer-administered questionnaires, global self-report and perceived need for dental treatment questions and by oral examination. Data collected were subjected to statistical analysis using SPSS version 19 and the level of statistical significance was set at a p-value of 0.05. The majority (61.0%) rated their oral health status poorly and 203 (76.9%) perceived a need for treatment. The average OHIP and OIDP scores were 12.0 (range 0 to 56) and 8.9 (range 0 to 40), respectively. Both instruments showed a high index of validity and reliability; both had similar face and content validity, however, OIDP had better criterion validity while OHIP-14 had better construct validity and internal consistency. Both OHIP-14 and OIDP are precise, valid and reliable for evaluation of OHRQOL where dental care is treatment-need driven. They are able to discriminate between groups according to their perception of oral health status, but with OIDP detecting fewer impacts on daily activities.


Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes.
Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.


Aggregation of DNA by analogs of spermidine; enzymatic and structural studies.
A homologous series of spermidine analogs, with defined abilities to replace the natural polyamine in supporting cell growth, was examined for its influence on the structure of supercoiled, aggregated DNA and on the ability of the DNA aggregates to act as substrates for various enzymes. The concentration of amine necessary to aggregate negatively supercoiled Col E1 DNA was progressively increased as the diaminobutane moiety of spermidine was extended beyond 5 methylene groups. 1H- and 31P-NMR spectroscopy suggested that less rigid DNA aggregates were formed by spermidine analogs than by spermidine itself. Spermidine and its analogs differentially modulated the activities of bacterial and mammalian type I topoisomerases and EcoRI restriction endonuclease on aggregated DNA in a manner reminiscent of the abilities of the amines to stimulate cell growth. When DNA was not aggregated, the influence of the various amines on these reactions was almost identical. These results are discussed in relation to the structures of the DNA aggregates in the presence of the various triamines.


The changing landscape of diagnostic services for tuberculosis.
During the last decade there has been a dramatic change in the laboratory approach to tuberculosis (TB) diagnosis in the developing world. This change began with the realization that acid-fast bacillus smear microscopy alone was totally inadequate to deal with the dual problems of human immunodeficiency virus (HIV)-associated TB and drug-resistant TB that threaten to undermine global progress in TB control. Subsequently, increased financial resources for TB laboratory services and the establishment of a systematic process for endorsement of new TB diagnostic tools and approaches by the World Health Organization (WHO) have led to rapid expansion of TB laboratory services and the availability of several new diagnostic tests that have been introduced. These include both commercial automated and noncommercial systems for phenotypic mycobacterial liquid culture and drug susceptibility testing, a simple and inexpensive test for mycobacterial species identification in culture isolates, light-emitting diode fluorescence microscopy, and rapid molecular methods for TB case detection and the diagnosis of drug-resistant TB. The latter methodologies that include line probe assays and an automated cartridge-based real-time polymerase chain reaction (PCR)-based test are being scaled up at an unprecedented pace and are truly revolutionizing the diagnosis of drug-resistant TB. On the other hand, little progress has been made in the quest for a true point-of-care test for TB. Fortunately, this is being addressed in several discovery initiatives that hopefully will provide impetus for the development of rapid, accurate TB diagnostics for the lowest level of the health system.


Smac combined with DDP can inhibit drug resistance of ovarian cancer through regulation of Survivin expression.
Ovarian cancer has the highest mortality rate among gynecological malignancies, presenting a major threat to women's life and health. It is essential to study the mechanisms of drug resistance to chemotherapy to identify ways to enhance drug-sensitivity. In recent years, many studies have shown that Smac/DIABLO is closely related to tumor drug resistance. Smac/DIABLO expression is markedly different between drug-resistant and chemo sensitive tumor cells. Up-regulation of Smac/DIABLO has been shown to increase tumor cell chemotherapy sensitivity. We found that Smac, combined with DDP greatly inhibited proliferation of subcutaneous xenografts of ovarian cancer cell line SKOV3/DDP without side effects. Mechanistic studies showed that Smac can inhibit the expression of Survivin, promote cell apoptosis of drug-resistant ovarian cancer cells and reverse the drug resistance.


A risk management approach to the security of hospital information systems.
Risk management in today's technologically advanced health care system demands proactive rather than reactive strategies. Risk management is defined as a planned program for liability control and involves the identification, analysis and evaluation of legal risks followed by strategies to reduce or eliminate these risks. The concept of risk management is most often associated with quality assurance and direct patient care activities. For current purposes, the risk management concept is borrowed from arena of patient care and applied to the security measures surrounding hospital information systems. In this context, risk management/liability control is viewed as proactive activities designed to protect both the hospital information system and the confidentiality of patient information.


Valganciclovir for the prevention and treatment of CMV in solid organ transplant recipients.
Cytomegalovirus (CMV) infection is the most common viral infectious complication after solid organ transplantation (SOT). Ganciclovir is the first-line anti-CMV treatment, but its low oral bioavailability limits its use and generally intravenous treatment has been mandatory. Valganciclovir is a prodrug of ganciclovir with > 60% bioavailability and has become an alternative to intravenous ganciclovir. The review examines the use of valganciclovir both for prophylaxis and treatment of CMV disease in SOT. The reader will be provided an overview of the literature on valganciclovir related to efficacy and safety in SOT recipients. Furthermore, the use of valganciclovir in less well-documented areas, such as patients with potential problems with oral absorption of drugs, pediatric patients and patients with life-threatening CMV disease, is discussed. The major take home message is that valganciclovir is a documented option for prevention and treatment of CMV in most SOT recipients. Given the ease of use and clinical efficacy it allows for substituting intravenous treatment in the majority of cases and has resulted in a major change of therapy for CMV in solid organ transplanted patients.


Transcriptional regulation of endothelial-to-mesenchymal transition in cardiac fibrosis: role of myocardin-related transcription factor A and activating transcription factor 3.
The etiology of cardiac fibrogenesis is quite diverse, but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined. Myocardin-related transcription factor A facilitates the transcription of cytoskeletal genes by serum response factor during fibrosis; therefore, its specific role in cardiac EndMT might be of importance. Activation of activating transcription factor 3 (ATF-3) during cardiac EndMT is speculative, since ATF-3 responds to a transforming growth factor β (TGF-β) stimulus and controls the expression of the primary epithelial-to-mesenchymal transition markers Snail, Slug, and Twist. Although the role of TGF-β in EndMT-mediated cardiac fibrosis has been established, targeting of the TGF-β ligand has not proven to be a viable anti-fibrotic strategy owing to the broad functional importance of this ligand. Thus, targeting of downstream transcriptional mediators may be a useful therapeutic approach in attenuating cardiac fibrosis. Here, we discuss some of the transcription factors that may regulate EndMT-mediated cardiac fibrosis and their involvement in type 2 diabetes.


Relation between the pacing induced sequence of activation and left ventricular pump function in animals.
The main goal of this article was to review animal experimental work on the effect of asynchronous activation on ventricular pump function. During normal sinus rhythm and atrial pacing, the Purkinje system contributes significantly to the rapid electrical activation of the ventricles. In contrast, during ventricular pacing the impulse is almost exclusively conducted through the normal myocardium. As a consequence, electrical activation of the ventricles becomes asynchronous and has an abnormal sequence. The abnormal impulse conduction causes considerable disturbances to occur in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption; low values occurring in early activated regions and values above normal being present in late activated regions. Many animal studies have now shown that the abnormal electrical activation, induced by ventricular pacing, leads to a depression of systolic and diastolic LV function. Pacing at the right ventricular apex (the conventional pacing site) reduces LV function more than pacing at the high ventricular septum or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly improves LV pump function. Differences in LV pump function between (combinations of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of the depression of LV function during abnormal electrical activation appears to be a combination of the asynchrony and the sequence of activation. These experimental findings justify continuing attention for optimizing the site(s) of ventricular pacing in patients with normal and abnormal ventricular impulse conduction.


Evaluation of the hip.
This paper deals with clinical evaluation of the hip. Methods of testing for mobility in the hip joint are discussed. Analysis of gait and functional activities as related to muscle imbalance is presented. Gross techniques of manual muscle testing and basic principles of specific manual muscle testing are presented.


Role of c-Jun N-terminal kinase (JNK) in regulating tumor necrosis factor-alpha (TNF-alpha) mediated increase of acetaminophen (APAP) and chlorpromazine (CPZ) toxicity in murine hepatocytes.
Drug induced liver injury (DILI) accounts for more than 50% of the cases of acute liver failure in this country, and is the major cause of drug withdrawal from the market. DILI has been associated with the induction of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). Pro-inflammatory cytokines activate the mitogen activated protein kinase, c-Jun-N-terminal kinase (JNK) in the liver. Recent studies have shown that JNK can regulate the hepatotoxicity of the analgesic, acetaminophen (APAP). Several reports have shown that inflammation induced by the endotoxin, lipopolysaccharide (LPS) augments the toxic response to hepatotoxicants in vivo. However, the mechanism by which inflammation alters drug-induced hepatotoxicity is not known. This study investigated the role of inflammatory mediators in regulating the toxicity of the hepatotoxic drugs, APAP or chlorpromazine (CPZ) in primary mouse hepatocytes. We found that, pre-treatment with TNF-alpha resulted in approximately 50 to 60% increase in alanine aminotransferase (ALT) levels by APAP or CPZ, while interleukin-1beta (IL-1beta) or IL6 treatments showed only 15-20% increase in ALT release. The bacterial components, LPS or lipoteichoic acid (LTA) increased ALT release by approximately 35 to 38% upon drug treatment of the hepatocytes. The JNK inhibitor, SP600125 significantly diminished APAP and CPZ toxicity with or without TNF-alpha. Pre-treatment with TNF-alpha resulted in prolonged activation of JNK (upto 2 hr) in the presence of APAP or CPZ. These results show that TNF-alpha is the major cytokine involved in sensitizing hepatocytes to APAP- or CPZ-induced hepatotoxicity, likely by a mechanism involving sustained activation of JNK.


Visual hallucinations of autobiographic memory and asomatognosia: a case of epilepsy due to brain cysticercosis.
The current study describes the case of a woman with symptomatic epilepsy due to brain cysticercosis acquired during childhood. During her adolescence, she developed seizures characterized by metamorphopsia, hallucinations of autobiographic memory and, finally, asomatognosia. Magnetic brain imaging showed a calcified lesion in the right occipitotemporal cortex, and positron emission tomography imaging confirmed the presence of interictal hypometabolism in two regions: the right parietal cortex and the right lateral and posterior temporal cortex. We discuss the link between these brain areas and the symptoms described under the concepts of epileptogenic lesion, epileptogenic zone, functional deficit zone, and symptomatogenic zone.


High dose statin prophylaxis in cardiopulmonary bypass related surgery: clinical utility.
Previous studies from our group demonstrated the anti-inflammatory properties of statins on cardiopulmonary bypass (CPB), through inhibition of neutrophil transendothelial migration. We sought to determine the utility of preoperative statin on patients undergoing cardiac surgery, to investigate any moderating effects on the systemic inflammatory response (SIRS) with CPB, and to evaluate any clinical impact on our patients. This is a prospective, randomised controlled trial with national regulatory body approval. Eligible patients were already on oral statin therapy. They were then randomly assigned to either investigation arm (n = 15, atorvastatin 80 mg for 2 weeks before surgery) or control arm (n = 15, no change to current statin therapy). Blood and urine samples were collected at 3 timepoints. Postoperative clinical measures were documented. Patients in the investigation arm have significantly lower troponin level (p = 0.016), and lower level of urine neutrophil gelatinase-associated lipocalin (NGAL; p = 0.002); thus demonstrating a lesser degree of cardiac and renal injury in these patients. Higher level of Interleukin-8 (IL-8) at baseline (p = 0.036) and 4 h post cross-clamp removal (p = 0.035) in the investiation arm. A similar trend is also observed in Matrix Metalloproteinase-9 (MMP-9; p > 0.05). There were however no differences in clinical outcomes. Maximizing the dose of statin in patients waiting for cardiac surgery has measurable biological effects. There is evidence of less cardiac and renal damage. The use of preoperative statins and in particular, high dose preoperative statin therapy, may prove a useful new tool for optimal preparation of patients for cardiac surgery. EudraCT no. 2012-003396-20 . Registered 05 November 2012.


Cost-effectiveness of growth factors during hepatitis C anti-viral therapy.
Although the current standard of care for controlling anaemia and neutropenia during anti-viral therapy for hepatitis C is to use dose reduction of ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte colony-stimulating factor are now being advocated as alternatives to dose reduction. To determine the cost-effectiveness of erythropoietin and granulocyte colony-stimulating factor as an alternative to anti-viral dose reduction during antihepatitis C therapy. Decision analysis was used to assess cost-effectiveness by estimating the cost of using a growth factor per quality-adjusted life-year gained. Under baseline assumptions, the cost per quality-adjusted life-year of using growth factors ranged from 16,247 US dollars for genotype 1 with neutropenia to 145,468 US dollars for genotype 2/3 patients with anaemia. These findings are sensitive to the relationship between dose reduction and sustained virological response. Based upon our findings and the varying strength of the evidence for a relationship between dose reduction and sustained virological response: granulocyte colony-stimulating factor may be cost-effective for genotype 1 patients; erythropoietin is probably not cost-effective for genotype 2/3 patients; no conclusion can be reached regarding the cost-effectiveness of erythropoietin for genotype 1 patients or granulocyte colony-stimulating factor for genotype 2/3 patients. Randomized trials are needed to firmly establish the relationship between dose reduction and sustained virological response.


Introgressive hybridization and morphological transgression in the contact zone between two Mediterranean Solea species.
Hybrid zones provide natural experiments where new combinations of genotypes and phenotypes are produced. Studying the reshuffling of genotypes and remodeling of phenotypes in these zones is of particular interest to document the building of reproductive isolation and the possible emergence of transgressive phenotypes that can be a source of evolutionary novelties. Here, we specifically investigate the morphological variation patterns associated with introgressive hybridization between two species of sole, Solea senegalensis and Solea aegyptiaca. The relationship between genetic composition at nuclear loci and individual body shape variation was studied in four populations sampled across the hybrid zone located in northern Tunisia. A strong correlation between genetic and phenotypic variation was observed among all individuals but not within populations, including the two most admixed ones. Morphological convergence between parental species was observed close to the contact zone. Nevertheless, the samples taken closest to the hybrid zone also displayed deviant segregation of genotypes and phenotypes, as well as transgressive phenotypes. In these samples, deviant body shape variation could be partly attributed to a reduced condition index, and the distorted genetic composition was most likely due to missing allelic combinations. These results were interpreted as an indication of hybrid breakdown, which likely contributes to postmating reproductive isolation between the two species.


Novel variant in the FGD1 gene causing Aarskog-Scott syndrome.
Aarskog-Scott syndrome (ASS) is a rare, X-linked recessive inherited disorder. Affected individuals may develop short stature and exhibit distinctive skeletal and genital development. Mutations in the FYVE, rhogef and pleckstrin homology domain-containing protein 1 (FGD1) gene, located within the Xp11.21 region, are responsible for the occurrence of ASS. Since it is rare and complex, it can take a long time to obtain a definitive clinical diagnosis unless clinicians are familiar with the disease. In the present study, whole-exome sequencing (WES) was performed to screen for causal variants in a Chinese pediatric patient who exhibited a number of clinical symptoms of ASS, including short stature, facial abnormalities, stubby metacarpals and swollen testis. DNA sequencing revealed a novel c.1270 A>G mutation in exon 6 of the FGD1 gene, which led to an amino acid conversion of asparagine to aspartic acid on codon 424 and in silico analysis indicated that this novel missense mutation was pathogenic. The present study identified a novel variant of the FGD1 gene and to the best of our knowledge, is the first report of ASS in a Chinese individual. The results indicated that WES is an effective tool for the diagnosis of rare and complex syndromes such as ASS.


Delayed Transfer of the Extensor Carpi Radialis Brevis Branch of the Radial Nerve to the Anterior Interosseous Nerve for Restoration of Thumb and Index Finger Flexion: Case Report.
High median nerve injuries (HMNIs) are rare lesions involving the upper extremities and affect the median nerve from its origin to the emergence of the anterior interosseous nerve (AIN). Proximal reconstruction has long been considered the gold standard in treating HMNI, but thumb and index flexion and pinch and grip weakness are consistently not recovered. We report the surgical results of a patient affected by an HMNI with partial spontaneous recovery after a gunshot wound. AIN function was successfully restored in a delayed fashion by transferring the radial nerve branch to the extensor carpi radialis brevis to the AIN.


Airborne pollen sampling in Manoa Valley, Hawaii: effect of rain, humidity and wind.
Kramer-Collins pollen sampling was conducted over 24 hours for 25 consecutive months at two valley sites in Honolulu. Of 1,059 expected samples, 699 (66.0%) were collected. Only 25 were considered excellent, i.e., eight three-hour collection bands. Twenty eight were considered good, ie., two to six bands. The difficulties in the study were associated with the weather directly (17.5%), the power source (3.9%), inadequancy of the samplers (63.1%) and the inexperience of technicians (15.3%). Sampler problems were also indirectly attributable to the high humidity, rain and wind, which differed at the two sites.


Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose.
±3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic, psychoactive drug that is primarily used recreationally but also may have some therapeutic value. At low doses, MDMA produces feelings of relaxation, empathy, emotional closeness, and euphoria. Higher doses can produce unpleasant psychostimulant- and hallucinogen-like adverse effects and therefore are usually not taken intentionally. There is considerable evidence that MDMA produces neurotoxicity and cognitive deficits at high doses; however, these findings may not generalize to typical recreational or therapeutic use of low-dose MDMA. Here, we systematically review 25 years of research on the cognitive effects of MDMA in animals, with a critical focus on dose. We found no evidence that doses of less than 3 mg/kg MDMA-the dose range that users typically take-produce cognitive deficits in animals. Doses of 3 mg/kg or greater, which were administered most often and frequently ranged from 5 to 20 times greater than an average dose, also did not produce cognitive deficits in a slight majority of experiments. Overall, the preclinical evidence of MDMA-induced cognitive deficits is weak and, if anything, may be the result of unrealistically high dosing. While factors associated with recreational use such as polydrug use, adulterants, hyperthermia, and hyponatremia can increase the potential for neurotoxicity, the short-term, infrequent, therapeutic use of ultra low-dose MDMA is unlikely to pose significant cognitive risks. Future studies must examine any adverse cognitive effects of MDMA using clinically relevant doses to reliably assess its potential as a psychotherapeutic.


Active Information Manipulation via Optically Driven Acoustic-Wave Interference.
Implementing on-chip information processing systems through photonic-phononic interactions has attracted considerable interest owing to its potential for storing, sensing, and signal processing, but the generation and extinction of acoustic waves are determined by the existence of pump power and the phonon lifetime. Here, we demonstrate the acoustic-wave interference and active information manipulation by optically driven acoustic waves in a silicon photonic-phononic controller-emitter-receiver system. The filtered and transmitted information to the receiver has a narrow bandwidth of 6.2 MHz and can be amplified or canceled with a contrast greater than 40 dB by adjusting the relative microwave phase between the emitter and controller. The pulse-train signals can be transmitted, amplified, and canceled with a 3 dB cutoff frequency of 3.1 MHz. The proposed technique provides a potential solution for highly selective on-chip filtering, phase shifters, and information manipulation, offering new functions to optomechanical signal processing and silicon photonics.


Numerical solution of an inverse diffraction grating problem from phaseless data.
This paper is concerned with the numerical solution of an inverse diffraction grating problem, which is to reconstruct a periodic grating profile from measurements of the phaseless diffracted field at a constant height above the grating structure. An efficient continuation method is developed to recover the Fourier coefficients of the periodic grating profile. The continuation proceeds along the wavenumber and updates are obtained from the Landweber iteration at each step. Numerical results are presented to show that the method can effectively reconstruct the shape of the grating profile.


[Prophylactic systemic antibiotherapy with only ceftriaxone in neutropenic patients treated in a protected environment].
Prophylactic systemic antibiotherapy with ceftriaxone (CRO) alone was tested in aplastic patients receiving total gut decontamination and treated in protected environment. To enter the study, the patients had to be afebrile when their polymorphonuclear (PMN) count fell under 500/cumm. Seventy eight therapeutic aplasias (after allogeneic or autologous bone marrow transplant conditioning regimens or high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 D (11-93 D). Forty-three patients received during 51 aplasias one single injection of CRO per day as soon as PMN count was under 500/cumm. In 23 cases (45%) the patients remained afebrile until the end of aplasia. There were 3 Staphylococcus epidermidis bacteremias (6%), 3 bacteriologically documented fevers (6%) and 1 Cryptococcus septicemia. Twenty-nine of these aplasias were part of a randomized study between group A (prophylactic CRO) and group B (non prophylactic CRO: 27 cases). In group A, there were significantly more aplasias without fever (34.5% vs 4%), and less bacteremias (10% vs 48%). Fever appeared later in group A (mean 12.5 D vs 6 D). No death was recorded during the whole study. Thus, in protected environment, prophylactic systemic antibiotherapy could still lessen the risk of bacterial infections. The side effects and the cost of such a procedure appeared to be diminished by a monoantibiotherapy.


Facilitated distortion of the DNA site enhances EcoRI endonuclease-DNA recognition.
We have measured the binding of EcoRI endonuclease to a complete set of purine-base analogue sites, each of which deletes one functional group that forms a hydrogen bond with the endonuclease in the canonical GAATTC complex. For five of six functional group deletions, the observed penalty in binding free energy is +1.3 to +1.7 kcal/mol. For two of these cases (replacement of adenine N7 with carbon) a single protein-base hydrogen bond is removed without deleting an interstrand Watson-Crick hydrogen bond or causing structural "adaptation" in the complex. This observation establishes that the incremental energetic contribution of one protein-base hydrogen bond is about -1.5 kcal/mol. By contrast, deletion of the N6-amino group of the inner adenine in the site improves binding by -1.0 kcal/mol because the penalty for deleting a protein-base hydrogen bond is outweighed by facilitation of the required DNA distortion ("kinking") in the complex. This result provides direct evidence that the energetic cost of distorting a DNA site can make an unfavorable contribution to protein-DNA binding.


Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats.
Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.


[The Antonine plague].
During the reign of Marcus Aurelius, the Roman Empire was struck by a long and destructive epidemic. It began in Mesopotamia in late AD 165 or early AD 166 during Verus' Parthian campaign, and quickly spread to Rome. It lasted at least until the death of Marcus Aurelius in AD 180 and likely into the early part of Commodus' reign. Its victims were "innumerable". Galen had first-hand knowledge of the disease. He was in Rome when the plague reached the city in AD 166. He was also present during an outbreak among troops stationed at Aquileia during the winter of AD 168-169. His references to the plague are scattered and brief but enough information is available to firmly identify the plague as smallpox. His description of the exanthema is fairly typical of the smallpox rash, particularly in the hemorrhagic phase of the disease.


[A new mobile respiration and monitoring system for transporting critically ill patients].
This article introduces a compact versatile system that can be used when transporting high-risk patients. The equipment can be coupled to a standard hospital bed. An instrument carrier device mounted on rollers which is independent of the medical equipment manufacturer can take up every kind of storage-battery driven apparatus required for monitoring, infusion therapy and continuous drug supply, as well as an artificial respiration unit with sufficient O2 for more than 20 hours of artificial respiration. The entire setup occupies a minimum of space.


What makes a theme park experience less enjoyable? Evidence from online customer reviews of Disneyland China.
The aim of this study was to explore the causes of tourists' lesser enjoyment of theme parks through an unsupervised machine learning approach-structural topic modelling. Specifically, the research extracted a comprehensive list of discussion topics about the travel experience of tourists through the analysis of 112,000 customer reviews released by visitors to the Shanghai Disney Resort from 16 June 2016 to 4 March 2022. Then, we used sentiment analysis to distinguish positive and negative topics and to explore the relationship between tourists who buy different ticket types and sentiments in negative topics. The results show that problems such as "parking," "service attitude," "recommendation feeling," "experience comparison," and "entrance" may be the main reasons for an unpleasant experience. In addition, we also found that when tourists travel in groups (e.g., via family tickets), customers feel unhappy because of parking and fast track problems. Moreover, when tourists travel alone or with small groups, staff service attitudes, experience comparisons, and entrance processes are the sources of greater concern. Our findings can help theme park managers to better understand the expectations of tourists and take effective measures to tackle issues causing customer dissatisfaction, and they can also contribute to theme park studies in tourism management.


Synthesis and Structure-Activity Relationships of LP1 Derivatives: N-Methyl-N-phenylethylamino Analogues as Novel MOR Agonists.
The opioid pharmacological profile of cis-(-)-N-normetazocine derivatives is deeply affected by the nature of their N-substituents. Here, our efforts were focused on the synthesis and pharmacological evaluation of novel derivatives of the lead LP1, a multitarget opioid analgesic compound featuring an N-phenylpropanamido substituent. LP1 derivatives 5a-d and 6a-d were characterized by flexible groups at the N-substituent that allow them to reposition themselves relative to cis-(-)-N-normetazocine nucleus, thus producing different pharmacological profiles at the mu, delta and kappa opioid receptors (MOR, DOR and KOR) in in vitro and in vivo assays. Among the series, compound 5c, with the best in vitro and in vivo profile, resulted a MOR agonist which displays a KiMOR of 6.1 nM in a competitive binding assay, and an IC50 value of 11.5 nM and an Imax of 72% in measurement of cAMP accumulation in HEK293 cells stably expressing MOR, with a slight lower efficacy than LP1. Moreover, in a mouse model of acute thermal nociception, compound 5c, intraperitoneally administered, exhibits naloxone-reversed antinociceptive properties with an ED50 of 4.33 mg/kg. These results expand our understanding of the importance of N-substituent structural variations in the opioid receptor profile of cis-(-)-N-normetazocine derivatives and identify a new MOR agonist useful for the development of novel opioid analgesics for pain treatment.


A Severe Case of Lymphomatoid Papulosis Type E Successfully Treated with Interferon-Alfa 2a.
Lymphomatoid papulosis (LyP) is a benign papulonodular skin eruption with histologic features of malignant lymphoma. A new variant of LyP which was termed "type E" was recently described with similar clinical and histological features to angiocentric and angiodestructive T-cell lymphoma. LyP type E is characterized with recurrent papulonodular lesions which rapidly turn into hemorrhagic necrotic ulcers and spontaneous regression by leaving a scar. None of the available treatment modalities affects the natural course of LyP. For therapy various modalities have been used such as topical and systemic steroids, PUVA, methotrexate, bexarotene, and IFN alfa-2b. Here we present a severe and devastating case with a very rare variant of LyP type E, which is, to our knowledge, the first case successfully treated with IFN alfa-2a. Now disease has been maintaining its remission status for six months.


Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung.
Chronic colonization of the lungs by Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in cystic fibrosis (CF) patients. To gain insights into the characteristic biofilm phenotype of P. aeruginosa in the CF lungs, mimicking the CF lung environment is critical. We previously showed that growth of the non-CF-adapted P. aeruginosa PAO1 strain in a rotating wall vessel, a device that simulates the low fluid shear (LS) conditions present in the CF lung, leads to the formation of in-suspension, self-aggregating biofilms. In the present study, we determined the phenotypic and transcriptomic changes associated with the growth of a highly adapted, transmissible P. aeruginosa CF strain in artificial sputum medium under LS conditions. Robust self-aggregating biofilms were observed only under LS conditions. Growth under LS conditions resulted in the upregulation of genes involved in stress response, alginate biosynthesis, denitrification, glycine betaine biosynthesis, glycerol metabolism, and cell shape maintenance, while genes involved in phenazine biosynthesis, type VI secretion, and multidrug efflux were downregulated. In addition, a number of small RNAs appeared to be involved in the response to shear stress. Finally, quorum sensing was found to be slightly but significantly affected by shear stress, resulting in higher production of autoinducer molecules during growth under high fluid shear (HS) conditions. In summary, our study revealed a way to modulate the behavior of a highly adapted P. aeruginosa CF strain by means of introducing shear stress, driving it from a biofilm lifestyle to a more planktonic lifestyle. Biofilm formation by Pseudomonas aeruginosa is one of the hallmarks of chronic cystic fibrosis (CF) lung infections. The biofilm matrix protects this bacterium from antibiotics as well as from the immune system. Hence, the prevention or reversion of biofilm formation is believed to have a great impact on treatment of chronic P. aeruginosa CF lung infections. In the present study, we showed that it is possible to modulate the behavior of a highly adapted transmissible P. aeruginosa CF isolate at both the transcriptomic and phenotypic levels by introducing shear stress in a CF-like environment, driving it from a biofilm to a planktonic lifestyle. Consequently, the results obtained in this study are of great importance with regard to therapeutic applications that introduce shear stress in the lungs of CF patients.


Pathway analysis using information from allele-specific gene methylation in genome-wide association studies for bipolar disorder.
Bipolar disorder (BPD) is a complex psychiatric trait with high heritability. Despite efforts through conducting genome-wide association (GWA) studies, the success of identifying susceptibility loci for BPD has been limited, which is partially attributed to the complex nature of its pathogenesis. Pathway-based analytic strategy is a powerful tool to explore joint effects of gene sets within specific biological pathways. Additionally, to incorporate other aspects of genomic data into pathway analysis may further enhance our understanding for the underlying mechanisms for BPD. Patterns of DNA methylation play important roles in regulating gene expression and function. A commonly observed phenomenon, allele-specific methylation (ASM) describes the associations between genetic variants and DNA methylation patterns. The present study aimed to identify biological pathways that are involve in the pathogenesis of BPD while incorporating brain specific ASM information in pathway analysis using two large-scale GWA datasets in Caucasian populations. A weighting scheme was adopted to take ASM information into consideration for each pathway. After multiple testing corrections, we identified 88 and 15 enriched pathways for their biological relevance for BPD in the Genetic Association Information Network (GAIN) and the Wellcome Trust Case Control Consortium dataset, respectively. Many of these pathways were significant only when applying the weighting scheme. Three ion channel related pathways were consistently identified in both datasets. Results in the GAIN dataset also suggest for the roles of extracellular matrix in brain for BPD. Findings from Gene Ontology (GO) analysis exhibited functional enrichment among genes of non-GO pathways in activity of gated channel, transporter, and neurotransmitter receptor. We demonstrated that integrating different data sources with pathway analysis provides an avenue to identify promising and novel biological pathways for exploring the underlying molecular mechanisms for bipolar disorder. Further basic research can be conducted to target the biological mechanisms for the identified genes and pathways.


Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors.
Magnetic resonance imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice cone-beam CT (CBCT)-guided PT, and other MR-guided methods, i.e. offline MR-guided PT and MR-linac, for treatment of liver tumors. Clinical outcomes were assessed by quantifying the dosimetric and biological impact of target margin reduction enabled by each image-guided approach. Planning target volume (PTV) margins were calculated using random and systematic setup, delineation and motion uncertainties, which were quantified by analyzing longitudinal MRI data for 10 patients with liver tumors. Proton treatment plans were created using appropriate PTV margins for each image-guided PT method. Photon plans with margins equivalent to MRiPT were generated to represent MR-linac. Normal tissue complication probabilities (NTCP) of the uninvolved liver were compared. We found that PTV margin can be reduced by 20% and 40% for offline MR-guided PT and MRiPT, respectively, compared with CBCT-guided PT. Furthermore, clinical target volume expansion could be largely alleviated when delineating on MRI rather than CT. Dosimetric implications included decreased equivalent mean dose of the uninvolved liver, i.e. up to 24.4 Gy and 27.3 Gy for offline MR-guided PT and MRiPT compared to CBCT-guided PT, respectively. Considering Child-Pugh score increase as endpoint, NTCP of the uninvolved liver was significantly decreased for MRiPT compared to CBCT-guided PT (up to 48.4%,p < 0.01), offline MR-guided PT (up to 12.9%,p < 0.01) and MR-linac (up to 30.8%,p < 0.05). Target underdose was possible in the absence of MRI-guidance (D90 reduction up to 4.2 Gy in 20% of cases). In conclusion, MRiPT has the potential to significantly reduce healthy liver toxicities in patients with liver tumors. It is superior to other image-guided techniques currently available.


Impairment of glucose tolerance in copper-deficient rats: dependency on the type of dietary carbohydrate.
Copper deficiency was induced in weanling rats in order to study the possible interaction between the types of dietary carbohydrate and copper deficiency on glucose tolerance. Weanling male rats were fed copper-deficient or copper-supplemented diets containing either 62% starch, fructose or glucose. During week 5 the fructose portion of the copper-deficient diet was replaced (20 rats) by starch (10 rats) or glucose (10 rats). During the 9th week, an oral glucose tolerance test weas performed. Copper deficiency was associated with impaired glucose tolerance characterized by increased blood glucose and decreased insulin levels only in copper-deficient rats fed the monosaccharides fructose or glucose but not the polysaccharide starch. Changing the dietary carbohydrates in the copper-deficient diet from fructose to starch increased insulin levels and decreased blood glucose in response to the glycemic stress when compared to rats continuously fed fructose. Although both glucose and fructose feeding impaired the glucose tolerance, fructose was more diabetogenic. This could be demonstrated by some improvements in glucose tolerance when the copper-deficient rats were switched from the fructose to the glucose diet. The data indicate that copper deficiency per se does not impair glucose tolerance.


Health problems awareness during travel among faculty members of a large university in Latin America: preliminary report.
Health safety during trips is based on previous counseling, vaccination and prevention of infections, previous diseases or specific problems related to the destination. Our aim was to assess two aspects, incidence of health problems related to travel and the traveler's awareness of health safety. To this end we phone-interviewed faculty members of a large public University, randomly selected from humanities, engineering and health schools. Out of 520 attempts, we were able to contact 67 (12.9%) and 46 (68.6%) agreed to participate in the study. There was a large male proportion (37/44, 84.1%), mature adults mostly in their forties and fifties (32/44, 72.7%), all of them with higher education, as you would expect of faculty members. Most described themselves as being sedentary or as taking occasional exercise, with only 15.9% (7/44) taking regular exercise. Preexisting diseases were reported by 15 travelers. Most trips lasted usually one week or less. Duration of the travel was related to the destination, with (12h) or longer trips being taken by 68.2% (30/44) of travelers, and the others taking shorter (3h) domestic trips. Most travelling was made by air (41/44) and only 31.8% (14/44) of the trips were motivated by leisure. Field research trips were not reported. Specific health counseling previous to travel was reported only by two (4.5%). Twenty seven of them (61.4%) reported updated immunization, but 11/30 reported unchecked immunizations. 30% (9/30) reported travel without any health insurance coverage. As a whole group, 6 (13.6%) travelers reported at least one health problem attributed to the trip. All of them were males travelling abroad. Five presented respiratory infections, such as influenza and common cold, one neurological, one orthopedic, one social and one hypertension. There were no gender differences regarding age groups, destination, type of transport, previous health counseling, leisure travel motivation or pre-existing diseases. Interestingly, the two cases of previous health counseling were made by domestic travelers. Our data clearly shows that despite a significant number of travel related health problems, these highly educated faculty members, had a low awareness of those risks, and a significant number of travels are made without prior counseling or health insurance. A counseling program conducted by a tourism and health professional must be implemented for faculty members in order to increase the awareness of travel related health problems.


Hypochondroplasia.
Hypochondroplasia is an autosomal dominant discrete form of short-limbed dwarfism with roentgenographic changes similar to, but distinctive from, achondroplasia. The patients are normal at birth and in early childhood present with short-limbed dwarfism, thick body build, long trunk, normal head, moderate lumbar lordosis and broad, stubby hands and feet. A high incidence of mental retardation and absence of other neurologic complications is distinctive from achondroplasia. Diagnosis of hypochondroplasia is primarily radiogrpahic. No single diagnostic radiographic sign is present, and thus, a complete radiographic survey of the whole skeleton is required for diagnosis. Pertinent radiographic findings include a normal skull, short, broad long bones with prominent bony sites of muscle attachment, normal growth plate, prominent styloid process of the ulna and lateral malleolus of the fibula, shortened base of the iliac bones, horizontal hypoplastic low-set sacrum and mild narrowing of the interpediculate distance of the lumbar spine. Differential diagnosis is from other types of short-limbed dwarfism, particularly achondroplasia. Kozlowski, an authority on hypochondroplasia, believes this form of short-limbed dwarfism, if carfully searched for, may be more common than achondroplasia.


Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody.
The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1 Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria.


Fluorescence-based monitoring of PAD4 activity via a pro-fluorescence substrate analog.
Post-translational modifications may lead to altered protein functional states by increasing the covalent variations on the side chains of many protein substrates. The histone tails represent one of the most heavily modified stretches within all human proteins. Peptidyl-arginine deiminase 4 (PAD4) has been shown to convert arginine residues into the non-genetically encoded citrulline residue. Few assays described to date have been operationally facile with satisfactory sensitivity. Thus, the lack of adequate assays has likely contributed to the absence of potent non-covalent PAD4 inhibitors. Herein a novel fluorescence-based assay that allows for the monitoring of PAD4 activity is described. A pro-fluorescent substrate analog was designed to link PAD4 enzymatic activity to fluorescence liberation upon the addition of the protease trypsin. It was shown that the assay is compatible with high-throughput screening conditions and has a strong signal-to-noise ratio. Furthermore, the assay can also be performed with crude cell lysates containing over-expressed PAD4.


The taxonomic status of Long-tailed shrews (Mammalia: genus Sorex) from Nuclear Central America.
We examined 256 specimens of long-tailed shrews (Sorex) from 53 localities throughout the highlands of Nuclear Central America. We evaluate the efficacy of using three qualitative characteristics to identify populations of Sorex from Nuclear Central America: 1) the presence or the absence of a postmandibular foramen and canal; 2) relative size of U3 compared to U4; and, 3) the presence or absence of a pigmented ridge on the lingual side of each unicuspid tooth. In our data, the first character is invariable for the specimens we examined. Two species groups can be recognized based on the presence (S. salvini species group) or the absence of a postmandibular foramen and canal (S. veraepacis species group). The other two characteristics were useful, but not diagnostic. Based upon Principal Component Analysis we recognize nine species of Sorex in Nuclear Central America. Five species belong to the S. salvini species group: S. cristobalensis, S. salvini, S. sclateri, S. stizodon, and a new species from Honduras. Four species belong to the S. veraepacis species group: S. chiapensis, S. ibarrai, S. veraepacis, and a new species from western Guatemala. We also present evidence that the type locality (Cobán, Alta Verapaz, Guatemala) for S. veraepacis is not correct.


Collagen-based silver nanoparticles: Study on cell viability, skin permeation, and swelling inhibition.
Collagen is considered the most abundant protein in the animal kingdom, comprising 30% of the total amount of proteins and 6% of the human body by weight. Studies that examine the interaction between silver nanoparticles and proteins have been highlighted in the literature in order to understand the stability of the nanoparticle system, the effects observed in biological systems, and the appearance of new chemical pharmaceutical products. The objective of this study was to analyze the behavior of silver nanoparticles stabilized with collagen (AgNPcol) and to check the skin permeation capacity and action in paw edema induced by carrageenan. AgNPcol synthesis was carried out using solutions of reducing agent sodium borohydride (NaBH4), silver nitrate (AgNO3) and collagen. Characterization was done by using dynamic light scattering (DLS) and X-ray diffraction (XRD) and AFM. Cellular viability testing was performed by using flow cytometry in human melanoma cancer (MV3) and murine fibroblast (L929) cells. The skin permeation study was conducted using a Franz diffusion cell, and the efficiency of AgNPcol against the formation of paw edema in mice was evaluated. The hydrodynamic diameter and zeta potential of AgNPcol were 140.7±7.8nm and 20.1±0.7mV, respectively. AgNPcol failed to induce early apoptosis, late apoptosis, and necrosis in L929 cells; however, it exhibited enhanced toxicity in cancer cells (MV3) compared to normal cells (L929). AgNPcol demonstrated increased toxicological effects in cancer MV3 cells, promoting skin permeation, and preventing paw edema.


Missing data in quality of life research in Eastern Cooperative Oncology Group (ECOG) clinical trials: problems and solutions.
Incorporation of quality of life (QOL) investigation into Eastern Cooperative Oncology Group (ECOG) multi-centre clinical trials has led to innovative strategies for protocol design and high quality data collection. A scientific advisory committee reviews protocol design components, measurement selection, timing of assessments and compliance issues. Extensive educational programmes provide information about the scientific and clinical relevance of QOL protocols, as well as practical strategies for data collection and management. Compliance with QOL data collection standards is prospectively monitored and evaluated. Preliminary results from eight ECOG-run protocols found overall compliance to be approximately 85 per cent (94 per cent at baseline and 73 per cent during treatment). Selected patient and institutional factors were evaluated for their association with compliance.


Fluorescent probe for proton-coupled DNA folding revealing slow exchange of i-motif and duplex structures.
Ionized nucleobases participate in pairing interactions outside of Watson and Crick's rules. Base pairing and ionization can be coupled via global conformational changes to raise the apparent pKa of protonated nucleobases to values above physiological pH. To provide the first specific reporter of proton-coupled DNA folding, we developed a "push-pull" fluorescent nucleoside analog composed of dimethylaniline (DMA) fused to deoxycytidine. "(DMA)C" exhibits the same pKa and base pairing characteristics as native cytosine residues in the human telomeric repeat sequence, where it causes little or no perturbation of DNA structure or stability. Upon protonation of (DMA)C, enhanced charge transfer results in large red shifting (+40 nm) of its excitation/emission maxima. (DMA)C's fluorescence intensity, anisotropy, and energy transfer properties can be used to track conformational changes in real time. Strand displacement assays were conducted by mixing (DMA)C-labeled duplexes containing a 5' single-stranded overhang with an excess of unlabeled DNA to initiate thermodynamically favorable unfolding-refolding reactions that release the (DMA)C-labeled strand from its complement. Rate constants for strand displacement upon addition of i-motif DNA (k = 1.0 M(-1) s(-1), t1/2 ≈ 12 h) were 320-fold lower than those measured upon addition of unfolded DNA (k = 3.2 × 10(2) M(-1) s(-1), t1/2 ≈ 2 min). These results reveal that i-motif structures having only marginal thermodynamic stabilities (Tm < 40 °C) can still pose large kinetic barriers to duplex formation under near-physiological conditions of pH (5.75), temperature (25 °C), and salt (100 mM NaCl).


Characterizing Generalized Rate-Distortion Performance of Video Coding: An Eigen Analysis Approach.
Rate-distortion (RD) theory is at the heart of lossy data compression. Here we aim to model the generalized RD (GRD) trade-off between the visual quality of a compressed video and its encoding profiles (e.g., bitrate and spatial resolution). We first define the theoretical functional space W of the GRD function by analyzing its mathematical properties. We show that W is a convex set in a Hilbert space, inspiring a computational model of the GRD function, and a method of estimating model parameters from sparse measurements. To demonstrate the feasibility of our idea, we collect a large-scale database of real-world GRD functions, which turn out to live in a low-dimensional subspace of W. Combining the GRD reconstruction framework and the learned low-dimensional space, we create a low-parameter eigen GRD method to accurately estimate the GRD function of a source video content from only a few queries. Experimental results on the database show that the learned GRD method significantly outperforms state-of-the-art empirical RD estimation methods both in accuracy and efficiency. Last, we demonstrate the promise of the proposed model in video codec comparison.


Modulation versus Templating: Fine-Tuning of Hierarchally Porous PCN-250 Using Fatty Acids To Engineer Guest Adsorption.
Modulation and templating are two synthetic techniques that have garnered significant attention over the last several years for the preparation of hierarchically porous metal-organic frameworks (HP-MOFs). In this study, by using fatty acids with different lengths and concentrations as dual-functional modulators/templates, we were able to obtain HP-MOFs with tunable mesopores that exhibit different pore diameters and locations. We found that the length and concentration of the fatty acids can determine if micelle formation occurs, which in turn dictates the porosity of the resulting HP-MOFs. The HP-MOFs with different mesopores differed in their performance in gas uptake and dye adsorption, and the structure-performance relationships were ascribed to the pore diameters and locations. This approach could provide a potentially universal method to efficiently introduce hierarchal mesopores into existing microporous MOF adsorbents with tunable properties.


Coil geometry effects on scanning single-coil magnetic induction tomography.
Alternative coil designs for single coil magnetic induction tomography are considered in this work, with the intention of improving upon the standard design used previously. In particular, we note that the blind spot associated with this coil type, a portion of space along its axis where eddy current generation can be very weak, has an important effect on performance. The seven designs tested here vary considerably in the size of their blind spot. To provide the most discerning test possible, we use laboratory phantoms containing feature dimensions similar to blind spot size. Furthermore, conductivity contrasts are set higher than what would occur naturally in biological systems, which has the effect of weakening eddy current generation at coil locations that straddle the border between high and low conductivity features. Image reconstruction results for the various coils show that coils with smaller blind spots give markedly better performance, though improvements in signal-to-noise ratio could alter that conclusion.


[Ectopic pregnancy in intrauterine contraception].
39 patients between 24 and 40 years of age with ectopic pregnancy associated with an IUP comprised 17.9 per cent of ectopics in an 8 year period. The IUP is probably not causal in ectopic pregnancy but does not protect the predisposed patient from ectopic pregnancy.