Noncovalent triblock copolymers based on a coiled-coil peptide motif.
The formation of a noncovalent triblock copolymer based on a coiled-coil peptide motif is demonstrated in solution. A specific peptide pair (E and K) able to assemble into heterocoiled coils was chosen as the middle block of the polymer and conjugated to poly(ethylene glycol) (PEG) and polystyrene (PS) as the outer blocks. Mixing equimolar amounts of the polymer-peptide block copolymers PS-E and K-PEG resulted in the formation of coiled-coil complexes between the peptides and subsequently in the formation of the amphiphilic triblock copolymer PS-E/K-PEG. Aqueous self-assembly of the separate peptides (E and K), the block copolymers (PS-E and K-PEG), and equimolar mixtures thereof was studied by circular dichroism, dynamic light scattering, and cryogenic transmission electron microscopy. It was found that the noncovalent PS-E/K-PEG copolymer assembled into rodlike micelles, while in all other cases, spherical micelles were observed. Temperature-dependent studies revealed the reversible nature of the coiled-coil complex and the influence of this on the morphology of the aggregate. A possible mechanism for these transitions based on the interfacial free energy and the free energy of the hydrophobic blocks is discussed. The self-assembly of the polymer-peptide conjugates is compared to that of polystyrene-b-poly(ethylene glycol), emphasizing the importance of the coiled-coil peptide block in determining micellar structure and dynamic behavior.


Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo.
Clinical management of chondrosarcoma remains a challenging problem, largely due to the toxicity and resistance of this tumor to conventional chemotherapy. Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different cell types in response to various stimuli, and has been shown to be down-regulated in many cancer tissues. In this study, mRNA and protein levels of PDCD5 were found to be up-regulated in cisplatin-treated SW1353 chondrosarcoma cells compared with untreated cells. Recombinant human PDCD5 (rhPDCD5) was also shown to sensitize chondrosarcoma cells to cisplatin-based chemotherapy, with inhibition of cell growth and apoptosis detected both in vitro and in vivo. Increased expression of Bax and decreased expression of Bcl-2 were also observed, along with release of cytochrome c from mitochondria into the cytosol. Additionally, cleavage of caspase-9 and caspase-3, as well as the cleavage of poly (ADP-ribose) polymerase (PARP), were detected, suggesting that sensitization of chondrosarcoma cells involves the intrinsic mitochondrial apoptosis pathway. In vivo, the treatment of a xenograft model of chondrosarcoma with rhPDCD5 and cisplatin significantly inhibited tumor cell proliferation and induced apoptosis compared to treatment with cisplatin alone. Overall, these data provide a theoretical basis for the administration of rhPDCD5 and cisplatin for the treatment of patients with chondrosarcoma.


The Significance of Surgical Intervention for Metasynchronous Liver Metastasis in Gastric Cancer: A Single-centre Analysis.
This study investigated the influence of surgery for metasynchronous liver metastasis in gastric cancer on prognosis. A retrospective study was conducted involving 21 consecutive patients with gastric cancer with metasynchronous distant metastasis only in the liver after curative gastrectomy. The patients were divided into two groups: those who underwent hepatic resection and those who did not. The clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were analysed. Among 981 gastrectomies performed in Tottori University Hospital between 2005 and 2019, 930 were curative. Among 153 cases of recurrence during the follow-up, 21 consecutive cases involving the liver only and metasynchronous recurrent metastasis on imaging were included in this study. The study included 16 males and five females with a median age of 70 years. No statistical difference in RFS (237 vs. 201 days; p=0.788) was observed between the hepatectomy and non-hepatectomy groups; however, OS (1,564 vs. 608 days, p=0.008) and DSS (1,597 vs. 608 days, p=0.006) were significantly prolonged in the hepatectomy group. Univariate and multivariate analyses revealed that hepatectomy was the only independent prognostic factor (hazard ratio=0.33; p=0.042). Hepatic resection of heterogeneous liver metastases in gastric cancer seems to be a useful option that can be expected to cure the disease, which cannot be achieved by chemotherapy alone.


Draft Genome Sequence of Multidrug-Resistant Cellulosimicrobium sp. Strain KWT-B, Isolated from Feces of Hirundo rustica.
Migratory birds have been postulated as potential spreaders of antibiotic resistance. Multidrug-resistant Cellulosimicrobium sp. strain KWT-B was isolated from the feces of Hirundo rustica A draft genome sequence indicated that the strain harbors multidrug-resistant transporters, multidrug efflux pumps, a vancomycin-resistant protein, and metallo-beta-lactamases.


United States Physical Therapists' Knowledge About Joint Hypermobility Syndrome Compared with Fibromyalgia and Rheumatoid Arthritis.
Joint hypermobility syndrome (JHS) is one of the most common inherited connective tissue disorders. It causes significant pain and disability for all age groups, ranging from developmental delay among children to widespread chronic pain in adults. Experts in JHS assert that the condition is under-recognized and poorly managed. The aim of this study was to assess US physical therapists' knowledge about JHS compared with other causes of widespread pain and activity limitations: fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis. Cross-sectional, Internet-based survey of randomly selected members of the American Physical Therapy Association and descriptive statistics were used to explore physical therapists' knowledge about JHS, fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis, and chi square was used to compare knowledge about the different conditions. The response rate was 15.5% (496). Although 36% recognized the Beighton Scale for assessing joint hypermobility, only 26.8% of respondents were familiar with the Brighton Criteria for diagnosing JHS. Few respondents (11-19%) realized that JHS has extra-articular features such as anxiety disorder, fatigue, headache, delayed motor development, easy bruising and sleep disturbance. Physical therapists working in environments most likely to see patients with JHS underestimated the likely prevalence in their patient population. The results suggest that many physical therapists in the United States are not familiar with the diagnostic criteria, prevalence or common clinical presentation of JHS.


Superior microwave absorption properties of ultralight reduced graphene oxide/black phosphorus aerogel.
Through a facile self-assembled process, an ultralight reduced graphene oxide/black phosphorus (rGO/BP) composite aerogel was successfully fabricated. The BP nanosheets were homogeneously distributed throughout the rGO 3D framework, and the interfaces between rGO and BP possessed four kinds of interconnections, such as wrapping, wearing, bridging and weak linking. As an ultralight composite, the rGO/BP aerogel could easily stand on the stamen of a flower. Compared with pure rGO aerogel, the rGO/BP composite aerogel exhibited enhanced microwave absorption ability. The minimum reflection loss value of -46.9 dB with a thickness of 2.53 mm was obtained, and a wide absorption band of 6.1 GHz (RL < -10 dB) was achieved. The superior microwave absorption property was demonstrated to stem from the interfacial polarization loss mechanism in which the multiform interface interactions between the rGO skeleton and BP nanosheets played critical roles. The rGO/BP aerogel has great potential to be used as an ultralight microwave absorber.


ARL6IP5 Ameliorates α-Synuclein Burden by Inducing Autophagy via Preventing Ubiquitination and Degradation of ATG12.
Recent advanced studies in neurodegenerative diseases have revealed several links connecting autophagy and neurodegeneration. Autophagy is the major cellular degradation process for the removal of toxic protein aggregates responsible for neurodegenerative diseases. More than 30 autophagy-related proteins have been identified as directly participating in the autophagy process. Proteins regulating the process of autophagy are much more numerous and unknown. To address this, in our present study, we identified a novel regulator (ARL6IP5) of neuronal autophagy and showed that the level of ARL6IP5 decreases in the brain with age and in Parkinson's disease in mice and humans. Moreover, a cellular model of PD (Wild type and A53T mutant α-synuclein overexpression) has also shown decreased levels of ARL6IP5. ARL6IP5 overexpression reduces α-synuclein aggregate burden and improves cell survival in an A53T model of Parkinson's disease. Interestingly, detailed mechanistic studies revealed that ARL6IP5 is an autophagy inducer. ARL6IP5 enhances Rab1-dependent autophagosome initiation and elongation by stabilizing free ATG12. We report for the first time that α-synuclein downregulates ARL6IP5 to inhibit autophagy-dependent clearance of toxic aggregates that exacerbate neurodegeneration.


Dexamethasone Modulates Nonvisual Opsins, Glucocorticoid Receptor, and Clock Genes in Danio rerio ZEM-2S Cells.
Here we report, for the first time, the differential cellular distribution of two melanopsins (Opn4m1 and Opn4m2) and the effects of GR agonist, dexamethasone, on the expression of these opsins and clock genes, in the photosensitive D. rerio ZEM-2S embryonic cells. Immunopositive labeling for Opn4m1 was detected in the cell membrane whereas Opn4m2 labeling shows nuclear localization, which did not change in response to light. opn4m1, opn4m2, gr, per1b, and cry1b presented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression of per1b and cry1b transcripts to ZT16, which corresponds to the highest opn4m1 expression. Interestingly, DEX promoted an increase of per1b expression when applied in LD condition but a decrease when the cells were kept under DD condition. Although DEX effects are divergent with different light conditions, the response resulted in clock synchronization in all cases. Taken together, these data demonstrate that D. rerio ZEM-2S cells possess a photosensitive system due to melanopsin expression which results in an oscillatory profile of clock genes in response to LD cycle. Moreover, we provide evidence that glucocorticoid acts as a circadian regulator of D. rerio peripheral clocks.


[A case of metastatic breast cancer successfully treated with weekly low-dose epirubicin (EPI), cyclophosphamide (CPA), 5-fluorouracil (5-FU) and medroxyprogesterone (MPA)].
We reported a case of successful treatment of disseminated breast cancer with epirubicin (EPI), 5-fluorouracil (5-FU), and medroxyprogesterone (MPA). The patient was a 49-year-old female with bone and liver metastasis developed 5 years after surgery. The primary tumor was ER-positive, and she had been treated previously with adjuvant therapy using UFT and tamoxifen. The treatment consisted of 3 cycles of thrice-weekly EPI (40mg), 5-FU (500mg) and CPA (500mg). The patient was then treated with a weekly schedule of EPI (10mg), 5-FU (50mg/day), CPA (50mg/day) and MPA (400mg/day). After 2 years, her bone and liver metastasis showed remarkable remission (PR). No side effects of this chemotherapy were observed. In the search for palliative treatments which have a minimal impact on normal lifestyle, low toxicity is important. PR was continued for 2 years, and the patient enjoyed a favorable quality of life. This low dose-weekly approach was very well tolerated, yet was effective.


Effects of Akt signaling on nuclear reprogramming.
Reprogramming of the epigenetic state from differentiated to pluripotent cells can be attained by cell fusion of differentiated somatic cells with embryonic stem (ES) cells or transfer of the nucleus of a differentiated cell into an enucleated oocyte. Activation of Akt signaling is sufficient to maintain pluripotency of ES cells and promotes derivation of embryonic germ (EG) cells from primordial germ cells (PGCs). Here we analyzed the effects of Akt signaling on somatic cell nuclear reprogramming after cell fusion and nuclear transfer. We found that forced activation of Akt signaling stimulated reprogramming after cell fusion of ES cells with thymocytes or mouse embryonic fibroblasts. These hybrid cells showed ES cell characteristics, including in vitro and in vivo differentiation capacity. In contrast, Akt signaling significantly reduced the efficiency of reprogramming with nuclear transfer. Our results demonstrate that Akt signaling plays important roles on the nuclear reprogramming of somatic cells.


Properties of two-dimensional resonant reflectors with zero-contrast gratings.
The spectral properties of high-reflection mirrors imbued with two-dimensional (2D) subwavelength periodicity are investigated. The reflectors are designed in a silicon-on-glass film that is partially etched to implement a zero-contrast interface between the grating pillars and the sublayer, thereby annulling the local reflections and phase changes associated with hard interfaces. This approach has shown impressive results for 1D polarized reflectors; here we strive to discover analogous wideband unpolarized reflectors. Using particle swarm optimization, we report wideband unpolarized reflectors in the 1.4-2.0 μm wavelength band. A 2D reflector with square pillars exhibits 99% reflectance across a bandwidth exceeding 350 nm and possesses tolerance against angular deviations. The complementary structure with rectangular periodic voids achieves a bandwidth of 370 nm. A comparable, optimized 2D high-contrast grating reflector with grating pillars residing directly on the substrate yields a 99% bandwidth of 240 nm.


Effect of introducing biologics to patients with rheumatoid arthritis on the risk of venous thromboembolism: a nationwide cohort study.
In the United States, 100,000-300,000 patients die from venous thromboembolism (VTE) each year, with more than 500,000 people related hospitalizations. While in Europe, 500,000 people die from VTE each year. Patients with rheumatoid arthritis are at increased risk of VTE. The use of biologics in patients with rheumatoid arthritis may be associated with an increased risk of VTE. We identified all patients who had been newly approved for Catastrophic Illness Card of rheumatoid arthritis extracted the claims data from the National Health Insurance research database and Registry for Catastrophic Illness Patient Database from 2003 to 2016. VTE was defined as the presence of inpatient VTE diagnostic codes (including DVT or PE) according to the discharge diagnosis protocol. An analysis of VTE variables indicated that the incidence of VTE in the biologic group (14.33/10,000 person-years) was higher than that in the conventional drug group (12.61/10,000 person-years). As assessed by the Cox proportional hazards model, the relative HR for VTE in the biologic group (HR: 1.11; 95% CI 0.79-1.55) versus that in the conventional drug group did not reach a significant difference. In conclusion, this study found no significant differences in risk were observed between the use of conventional DMARDs and biologics.


The long-term functional outcome of type II odontoid fractures managed non-operatively.
Odontoid fractures currently account for 9-15% of all adult cervical spine fractures, with type II fractures accounting for the majority of these injuries. Despite recent advances in internal fixation techniques, the management of type II fractures still remains controversial with advocates still supporting non-rigid immobilization as the definitive treatment of these injuries. At the NSIU, over an 11-year period between 1 July 1996 and 30 June 2006, 66 patients (n = 66) were treated by external immobilization for type II odontoid fractures. The medical records, radiographs and CT scans of all patients identified were reviewed. Clinical follow-up evaluation was performed using the Cervical Spine Outcomes Questionnaire (CSOQ). The objectives of this study were to evaluate the long-term functional outcome of patients suffering isolated type II odontoid fractures managed non-operatively and to correlate patient age and device type with clinical and functional outcome. Of the 66 patients, there were 42 males and 24 females (M:F = 1.75:1) managed non-operatively for type II odontoid fractures. The mean follow-up time was 66 months. Advancing age was highly correlated with poorer long-term functional outcomes when assessing neck pain (r = 0.19, P = 0.1219), shoulder and arm pain (r = 0.41, P = 0.0007), physical symptoms (r = 0.25, P = 0.472), functional disability (r = 0.24, P = 0.0476) and psychological distress (r = 0.41, P = 0.0007). Patients >65 years displayed a higher rate of pseudoarthrosis (21.43 vs. 1.92%) and established non-union (7.14 vs. 0%) than patients <65 years. The non-operative management of type II odontoid fractures is an effective and satisfactory method of treating type II odontoid fractures, particularly those of a stable nature. However, patients of advancing age have been demonstrated to have significantly poorer functional outcomes in the long term. This may be linked to higher rates of non-union.


A 5-YEAR REVIEW OF ULTRASONOGRAPHIC EVALUATION OF OCULAR DISEASES AT THE UNIVERSITY COLLEGE HOSPITAL IBADAN, SOUTH-WEST, NIGERIA.
Orbito-ocular diseases are a major public health issue, often causing visual impairment with serious socioeconomic implications on individual lives. Ocular ultrasonography is an invaluable diagnostic tool when clinical examination of the ocular fundus is difficult. To describe the indications, sonographic findings, and contribution of orbito-ocular ultrasonography to the management of orbito-ocular diseases in the University College Hospital, Ibadan. A retrospective review of B-mode ocular ultrasound findings and hospital data of all patients referred to the Radiology department of the University College Hospital, Ibadan for ocular Ultrasound between January 2014 - December 2018. There were 142 patients, aged 1-85 years, (median age =28 years). 72 (50.7%) patients were under 30 years of age, and 50 (35.2%) were pediatric cases. Male to female ratio was 1.84:1. The commonest presenting complaint was blurred vision in 97 (68.3%) cases, followed by eye trauma in 54 (38.0%). B-mode Ultrasound, demonstrated cataract in 63 (44.4%,) cases, vitreous hemorrhage in 42 (29.6%), retinal detachment in 27 (19.0%), vitreous detachment in 19 (13.4%), normal findings in 17 (12%) and orbital tumors in 13 (9.2%) patients. B-mode ultrasound scan and clinical diagnosis demonstrated good agreement in 91 /142 cases (64.1%), partial agreement in 23/142 (16.2%) cases, and no agreement in 28 (19.7%). Kappa agreement scores, K were 74.3% and 70.9%, for ruptured globe and cataract respectively. Orbito-ocular ultrasonography contributes significantly to the diagnosis of orbito-ocular disease and shows good correlation with clinical diagnoses. However, a future study with larger numbers is required.


Atomistic simulation and the mechanism of graphene amorphization under electron irradiation.
Real-time reconstruction of a divacancy in graphene under electron irradiation (EI) is investigated by nonequilibrium molecular dynamic simulation (NEMD). The formation of the amorphous structure is found to be driven by the generalized Stone-Wales transformations (GSWTs), i.e. C-C bond rotations, around the defective area. The simulation reveals that each step of the reconstruction can be viewed as a quasi-thermal process and thus the reconstruction from a point defect to an amorphous structure favors the minimum energy path. On the other hand, the formation of a high energy large defective area is kinetically dominated by the balance between its expansion and shrinkage, and a kinetic model was proposed to understand the size of the defective area. The current study demonstrates that the route of the reconstruction from the point defective graphene toward an amorphous structure is predictive, though under stochastic EI.


[Juvenile onset of idiopathic interstitial pneumonia].
A 22-year-old first man came to our hospital because of dyspnea on exertion in February 1993, and was admitted in September 1994 because of progression of dyspnea. A chest roentgenogram showed diffuse ground-glass-opacities in the middle and lower lung fields, and an elevated diaphragm. Pulmonary-function testing revealed a low %VC and a low diffusing capacity. Examination of a specimen obtained by thoracoscopic lung biopsy revealed usual interstitial pneumonia. Immunohistochemical examinations showed the expression of intercellular adhesion molecule-1 on vascular endothelial cells and on alveolar epithelial cells. Dust inhalation and collagen vascular disease were ruled out and the diagnosis was idiopathic interstitial pneumonia. This condition develops only rarely in patients under 60 years old.


Tritium movement in soil of tropical rain forest.
Tritiated water applied to the surface of soil in a tropical rain forest was found in free water of the litter and top 18 centimeters of soil as long as 7 months after the application. Plant roots, even in the high-rainfall environment of a tropical rain forest, therefore are exposed to tritiated water for considerable periods of time after release.


Rapid recovery of genetic diversity of dogwhelk (Nucella lapillus L.) populations after local extinction and recolonization contradicts predictions from life-history characteristics.
The dogwhelk Nucella lapillus is a predatory marine gastropod populating North Atlantic rocky shores. As with many other gastropod species, N. lapillus was affected by tributyltin (TBT) pollution during the 1970s and 1980s, when local populations became extinct. After a partial ban on TBT in the United Kingdom in 1987, vacant sites have been recolonized. N. lapillus lacks a planktonic larval stage and is therefore expected to have limited dispersal ability. Relatively fast recolonization of some sites, however, contradicts this assumption. We compared levels of genetic diversity and genetic structuring between recolonized sites and sites that showed continuous population at three localities across the British Isles. No significant genetic effects of extinction/recolonization events were observed in SW Scotland and NE England. In SW England we observed a decrease in genetic diversity and an increase in genetic structure in recolonized populations. This last result could be an artefact, however, due to the superposition of other local factors influencing the genetic structuring of dogwhelk populations. We conclude that recolonization of vacant sites was accomplished by a relatively high number of individuals originating from several source populations (the 'migrant-pool' model of recolonization), implying that movements are more widespread than expected on the basis of development mode alone. Comparison with published data on genetic structure of marine organisms with contrasted larval dispersal supports this hypothesis. Our results also stress the importance of local factors (geographical or ecological) in determining genetic structure of dogwhelk populations.


CDK5RAP2 functions in centrosome to spindle pole attachment and DNA damage response.
The centrosomal protein, CDK5RAP2, is mutated in primary microcephaly, a neurodevelopmental disorder characterized by reduced brain size. The Drosophila melanogaster homologue of CDK5RAP2, centrosomin (Cnn), maintains the pericentriolar matrix (PCM) around centrioles during mitosis. In this study, we demonstrate a similar role for CDK5RAP2 in vertebrate cells. By disrupting two evolutionarily conserved domains of CDK5RAP2, CNN1 and CNN2, in the avian B cell line DT40, we find that both domains are essential for linking centrosomes to mitotic spindle poles. Although structurally intact, centrosomes lacking the CNN1 domain fail to recruit specific PCM components that mediate attachment to spindle poles. Furthermore, we show that the CNN1 domain enforces cohesion between parental centrioles during interphase and promotes efficient DNA damage-induced G2 cell cycle arrest. Because mitotic spindle positioning, asymmetric centrosome inheritance, and DNA damage signaling have all been implicated in cell fate determination during neurogenesis, our findings provide novel insight into how impaired CDK5RAP2 function could cause premature depletion of neural stem cells and thereby microcephaly.


Topoisomerase II and tubulin inhibitors both induce the formation of apoptotic topoisomerase I cleavage complexes.
Topoisomerase I (Top1) is a ubiquitous enzyme that removes DNA supercoiling generated during transcription and replication. Top1 can be trapped on DNA as cleavage complexes by the anticancer drugs referred to as Top1 inhibitors as well as by alterations of the DNA structure. We reported recently that Top1 cleavage complexes (Top1cc) are trapped during apoptosis induced by arsenic trioxide and staurosporine. In the present study, we generalize the occurrence of apoptotic Top1cc in response to anticancer drugs, which by themselves do not directly interact with Top1: the topoisomerase II inhibitors etoposide, doxorubicin, and amsacrine, and the tubulin inhibitors vinblastine and Taxol. In all cases, the Top1cc form in the early phase of apoptosis and persist throughout the apoptotic process. Their formation is prevented by the caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp(OMe)-fluoromethylketone and the antioxidant N-acetyl-L-cysteine. We propose that the trapping of Top1cc is a general process of programmed cell death, which is caused by alterations of the DNA structure (oxidized bases and strand breaks) induced by caspases and reactive oxygen species.


Segmented targeted least squares estimator for material decomposition in multibin photon-counting detectors.
We present a fast, noise-efficient, and accurate estimator for material separation using photon-counting x-ray detectors (PCXDs) with multiple energy bin capability. The proposed targeted least squares estimator (TLSE) is an improvement of a previously described A-table method by incorporating dynamic weighting that allows the variance to be closer to the Cramér-Rao lower bound (CRLB) throughout the operating range. We explore Cartesian and average-energy segmentation of the basis material space for TLSE and show that, compared with Cartesian segmentation, the average-energy method requires fewer segments to achieve similar performance. We compare the average-energy TLSE to other proposed estimators-including the gold standard maximum likelihood estimator (MLE) and the A-table-in terms of variance, bias, and computational efficiency. The variance and bias were simulated in the range of 0 to 6 cm of aluminum and 0 to 50 cm of water with Monte Carlo methods. The Average-energy TLSE achieves an average variance within 2% of the CRLB and mean absolute error of [Formula: see text]. Using the same protocol, the MLE showed variance within 1.9% of the CRLB ratio and average absolute error of [Formula: see text] but was 50 times slower in our implementations. Compared with the A-table method, TLSE gives a more homogenously optimal variance-to-CRLB ratio in the operating region. We show that variance in basis material estimates for TLSE is lower than that of the A-table method by as much as [Formula: see text] in the peripheral region of operating range (thin or thick objects). The TLSE is a computationally efficient and fast method for material separation with PCXDs, with accuracy and precision comparable to the MLE.


The effects of two monophasic oral contraceptives containing 30 mcg of ethinyl estradiol and either 2 mg of chlormadinone acetate or 0.15 mg of desogestrel on lipid, hormone and metabolic parameters.
This study was conducted to compare the effects of two monophasic oral contraceptives (OCs) containing ethinyl estradiol (EE) 30 mcg+either chlormadinone acetate (CMA) 2 mg (Belara) or 0.15 mg desogestrel (Marvelon) on lipid, hormone and other relevant metabolic parameters. Markers of lipid and carbohydrate metabolism, and reproductive hormone levels, were measured in 45 subjects randomly assigned to 6 months of treatment with one of the two OCs. The cortisol response to adrenocorticotrophic hormone (ACTH) stimulation was also evaluated. In both treatment groups, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and Apo AII levels increased; low-density lipoprotein cholesterol (LDL-C) and the LDL-C/HDL-C ratio decreased; and total cholesterol and lipoprotein(a) were unchanged during treatment. Effects on HDL-C, Apo AI, LDL-C and the LDL-C/HDL-C ratio were more evident in the EE 30 mcg+CMA 2 mg group. Follicle-stimulating hormone, luteinizing hormone and androgen levels decreased and sex hormone-binding globulin levels increased in both groups. Both OCs increased basal cortisol levels and cortisol response to ACTH. Oral contraceptive did not have a clinically significant impact on carbohydrate metabolism. Both low-dose monophasic OCs had comparable effects on lipid, hormone and metabolic parameters during six cycles of treatment in healthy female subjects. There was some evidence of a beneficial effect on atherogenic cardiovascular risk markers, which was slightly more pronounced with EE 30 mcg+CMA 2 mg.


Metabolism-Mediated Thrombotic Microangiopathy in an Older Patient Without Malnutrition.
Vitamin B12 deficiency can cause thrombotic microangiopathy (TMA)-like symptoms such as purpura caused by platelet reduction, general fatigue caused by anemia, and renal and hepatic abnormalities caused by malnutrition. TMA-like symptoms are known as metabolism-mediated TMA (MM-TMA). In MM-TMA, blood cell production is altered, and both pancytopenia and schistocytes appear. The initial presentation of MM-TMA makes it challenging to distinguish between primary and secondary TMA when patients do not present risk factors for malnutrition. We encountered an older female patient with a chief complaint of unconsciousness and loss of appetite for two days. Laboratory tests revealed pancytopenia with schistocytes. Moreover, the laboratory data revealed low serum levels of vitamin B12, indicating MM-TMA. The patient was successfully treated with intravenous vitamin B12 supplementation and discharged home. The patient had atrophic gastritis, which could have impeded the absorption of vitamin B12 from food. Among older patients without prolonged appetite loss, TMA-like symptoms should be investigated as MM-TMA induced by vitamin B12 deficiency, and prompt initiation of appropriate treatment is essential to differentiate between MM-TMA and true TMA.


Hyperoxic condition prevents bacterial translocation and elevation of plasma microorganism components during hemorrhagic shock.
To evaluate the influence of hyperoxic conditions on bacterial translocation (BT) and microorganism components during hemorrhagic shock, rats were divided into a group breathing 100% oxygen and a group breathing room air. The groups were then subjected to hemorrhagic shock. Systemic blood and mesenteric lymph nodes were cultured for BT, and systemic plasma concentrations of microorganism components were measured by the silkworm larvae plasma (SLP) test and the endotoxin test. Hyperoxic conditions prevented both BT and plasma SLP-reactive substance (peptidoglycan and beta-glucan) elevation during hemorrhagic shock. Our findings suggest that hyperoxic treatment might improve host conditions during hemorrhagic shock.


Contagious Ecthyma, Rangiferine Brucellosis, and Lungworm Infection in a Muskox ( Ovibos moschatus ) from the Canadian Arctic, 2014.
An adult male muskox ( Ovibos moschatus ), harvested on 26 August 2014 on Victoria Island, Nunavut, in the Canadian Arctic, had proliferative dermatitis on the muzzle and fetlocks suggestive of contagious ecthyma or orf (Parapoxvirus). Histopathologic features of the lesions were consistent with this diagnosis. Orf virus DNA, phylogenetically similar to an isolate from a captive muskox of the Minnesota Zoo, US, was detected in the lesions by PCR using Parapoxvirus primers. Additionally, there was a metaphyseal abscess with a cortical fistula in the right metacarpus from which Brucella suis biovar 4 was isolated and identification supported by PCR. Brucella spp. antibodies were detected in serum. Finally, 212 nodules were dissected from the lungs. Fecal analysis and lung examination demonstrated co-infection with the lungworms Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis. The zoonotic potential of orf and rangiferine brucellosis adds an important public health dimension to this case, particularly given that muskoxen are a valuable source of food for Arctic residents. Careful examination of these pathogens at a population level is needed as they may contribute to muskox population decline and potentially constitute a driver of food insecurity for local communities. This case underscores the importance of wildlife health surveillance as a management tool to conserve wildlife populations and maintain food security in subsistence-oriented communities.


'Chemical stabilization of oils rich in long-chain polyunsaturated fatty acids during storage' by F. Pop.
At the request of the Managing Editor the following paper has been retracted: F. Pop. (2011). 'Chemical stabilization of oils rich in long-chain polyunsaturated fatty acids during storage', Food Science and Technology International 17: 111-117, DOI: 10.1177/1082013210368738.


Time-dependent variation in coronary flow velocity reserve induced by adenosine triphosphate: comparison to low-dose dipyridamole.
Measuring the coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) has been widely performed using adenosine. Although adenosine infusion is known to induce transient variation of hyperemia, the timing to measure the CFVR has not been well addressed. Therefore, we aimed to clarify the difference between the peak CFVR and at 2 min following adenosine triphosphate (ATP) infusion compared to the CFVR after low-dose dipyridamole infusion. A total of 26 patients with coronary artery diseases underwent TTDE. The coronary flow velocity (CFV) of the left anterior descending artery (LAD) was monitored during ATP infusion at 0.14 mg/kg/min. The CFVR was measured both at the first peak and at 2 min following ATP infusion, and after dipyridamole infusion at 0.56 mg/kg/min for 4 min. The first peak of hyperemia occurred 63.7 ± 8 s after starting ATP infusion. The value of the peak CFVR was significantly higher than the CFVR at 2 min following ATP stress, which was equivalent to the CFVR after dipyridamole infusion (2.30 ± 0.92, 1.83 ± 0.77, and 1.70 ± 0.68, respectively, P < 0.001). Applying a cut-off value of 2.0 to predict angiographic LAD stenosis, the CFVR at 2 min following ATP stress was significantly correlated to the angiographic findings. However, the peak CFVR after ATP infusion did not correlate with the angiographic findings. During ATP infusion, the peak CFVR was significantly higher than the CFVR at 2 min, which was equivalent to the CFVR after low-dose dipyridamole. This finding should be considered for the standardization of CFVR measurements.


[Infection in sickle cell disease].
Bacterial infection is frequent in patients with sickle cell disease. Pneumococcal bacteremia is particularly severe in young children. The risk persists in adults, especially for nosocomial infections. Prevention is directed against pneumococcal disease and includes both vaccination and prophylactic antibiotics.


Active or passive guidance? Decision-making in fetal health consultation.
Prenatal consults are full of uncertainty. But, what are physicians contributing to this, and what is parents understanding of the intricacies of the complex decisions we present to them? Might the way we actively or passively guide parents affect how they make decisions in the complex world of fetal health consultations? For instance, how does "recommending" versus "not recommending" impact how parents view their choices? Reviewing the literature, there is a paucity of data on this topic. There are studies detailing experience but not of how guidance affects decision-making. We review some of this literature and discuss concepts relevant to this observation. We hypothesize that passive or active guidance by fetal health consultation members influences the moral deliberation and ethical decision-making of parents in different ways and propose a possible research idea.


Impact of trial design and patient heterogeneity on the identification of clinically effective therapies for progressive MS.
Clinically effective immunomodulatory therapies have been developed for relapsing-remitting multiple sclerosis (RRMS), but they have generally not translated to a corresponding slowing of disability accumulation in progressive forms of multiple sclerosis (MS). Since disability is multifaceted, progressive patients are heterogeneous, and the drivers of disease progression are still unclear, it has been difficult to identify the most informative outcome measures for progressive trials. Historically, secondary outcome measures have focused on inflammatory measures, which contributed to the recent identification of immunomodulatory therapies benefiting younger patients with more inflammatory progressive MS. Meanwhile, agents capable of treating late-stage disease have remained elusive. Consequently, measures of neurodegeneration are becoming common. Here, we review completed clinical trials testing immunomodulatory therapies in primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS) and discuss the features contributing to trial design variability in relation to trial outcomes, and how efforts toward better patient stratification and inclusion of reliable progression markers could improve outcomes.


Energy expenditure, lipid profile, oxidative stress, and cardiac energy metabolism after growth hormone treatment in obese young rats.
Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n=16): control (C) was fed standard-chow and water and hypercaloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n=8): C+PL was fed standard-chow, water and received saline subcutaneously; C+GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H+PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H+GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H+PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C+PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO (2))/body weight. H+GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H+PL. Comparing C+GH with C+PL, despite no effects on morphometric parameters, lipid profile, myocardial LH, and LDH activity, GH enhanced fed RMR and myocardial pyruvate dehydrogenase. In conclusion, the present study brought new insights into the GH effects on obesity related cardiovascular damage demonstrating, for the first time, that GH regulated cardiac metabolic pathways, enhanced energy expenditure and improved the lipid profile in obesity condition. Growth hormone in standard fed condition also offered promising therapeutic value enhancing pyruvate-dehydrogenase activity and glucose oxidation in cardiac tissue, thus optimizing myocardial energy metabolism.


Short-term couplings of the cardiovascular system in pregnant women suffering from pre-eclampsia.
Pre-eclampsia (PE), a serious pregnancy-specific disorder, causes significant neonatal and maternal morbidity and mortality. Recent studies showed that cardiovascular variability parameters as well as the baroreflex sensitivity remarkably improve its early diagnosis. For a better understanding of the dynamical changes caused by PE, in this study the coupling between respiration, systolic and diastolic blood pressure, and heart rate is investigated. Thirteen datasets of healthy pregnant women and 10 of subjects suffering from PE are included. Nonlinear additive autoregressive models with external input are used for a model-based coupling analysis following the idea of Granger causality. To overcome the problem of misdetections of standard methods in systems with a dominant driver, a heuristic ensemble approach is used here. A coupling is assumed to be real when existent in more than 80 per cent of the ensemble members, and otherwise denoted as artefacts. As the main result, we found that the coupling structure between heart rate, systolic blood pressure, diastolic blood pressure and respiration for healthy subjects and PE patients is the same and reliable. As a pathological mechanism, however, a significant increased respiratory influence on the diastolic blood pressure could be found for PE patients (p=0.003). Moreover, the nonlinear form of the respiratory influence on the heart rate is significantly different between the two groups (p=0.002). Interestingly, the influence of systolic blood pressure on the heart rate is not selected, which indicates that the baroreflex sensitivity estimation strongly demands the consideration of causal relationships between heart rate, blood pressure and respiration. Finally, our results point to a potential role of respiration for understanding the pathogenesis of PE.


Human safety review of "nano" titanium dioxide and zinc oxide.
Based on the current weight of evidence of all available data, the risk for humans from the use of nano-structured titanium dioxide (TiO(2)) or zinc oxide (ZnO) currently used in cosmetic preparations or sunscreens is considered negligible. There is a large body of information that when viewed in its entirety is considered as sufficient to demonstrate that these nano-structured ultraviolet (UV) filters, irrespective of various treatments (coatings) or crystalline structure, can be regarded as safe for use at concentrations up to 25% in cosmetic products to protect the skin from harmful effects of solar UV radiation. "Nano" TiO(2) and ZnO formulated in topically applied sunscreen products exist as aggregates of primary particles ranging from 30-150 nm in size. These aggregates are bonded such that the force of sunscreen product application onto the skin would have no impact on their structure or result in the release of primary particles. Multiple studies have shown that under exaggerated test conditions neither nano-structured TiO(2) nor ZnO penetrates beyond the stratum corneum of skin. Further, the distribution and persistence of these nano-structured metal oxides is the same compared to larger pigment-grade (i.e., >100 nm) particles, demonstrating equivalence in the recognition and elimination of such material from the body. Finally, the in vitro genotoxic and photogenotoxic profiles of these nano-structured metal oxides are of no consequence to human health. Whereas the most logical, straightforward conclusion based on data from internationally-recognized guideline studies and current 20+ year history of human use is that nano-structured TiO(2) and ZnO are safe, there will continue to be questions as "nano" conjures images of technology gone awry. Despite this rather sober view, the public health benefits of sunscreens containing nano TiO(2) and/or ZnO outweigh human safety concerns for these UV filters.


A nor-diterpene from Salvia sahendica leaves.
Phytochemical investigation of n-hexane extract of Salvia sahendica by normal phase column chromatography resulted in the isolation of six compounds. Structures were established by 1D and 2D NMR spectroscopy, and HRMS, as a new norditerpene 1, and known terpenoids, sclareol (2), oleanolic acid (3), β-sitosterol (4), salvigenin (5) and 3α-hydroxy-11α,12α-epoxyoleanan-28,13β-olide (6). The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis and electronic circular dichroism spectroscopy. In vitro cytotoxic activity on breast cancer cell line (MDA-MB-231) and also the antimicrobial activity of the pure compounds were tested against Staphylococcus aureus, Bacilus cereus and Escherichia coli.


Sex-linked peptidase-1 patterns in Pleurodeles waltlii Michah (Urodele Amphibian): genetic evidence for a new codominant allele on the W sex chromosome and identification of ZZ, ZW and WW sexual genotypes.
In Pleurodeles waltlii, peptidase-1 is a dimeric enzyme which has been shown to be controlled by two codominant alleles, Pep-1A and Pep-1B (Ferrier et al., 1980, 1983), linked respectively to the Z and W sex chromosomes. The enzymatic patterns obtained after starch gel electrophoresis were used routinely to identify the sexual genotypes of animals reared in our laboratory. We describe here three new patterns that were encountered in standard females, in sex-reversed animals and in thelygenous females. The inheritance data indicated the occurrence of a third codominant allele, Pep-1 beta, linked to the W sex chromosome. The discovery of this new allele does not impair peptidase-1 polymorphism as a reliable tool for ZZ, ZW and WW genotype identification.


[Rheumatology education in quality circles of office-based general practitioners: A novel andragogic concept for continuing medical education].
Continuing medical education is essential to improve the quality of health care delivery. The efficacy of postgraduate medical education generally improves when participants feel that their specific needs are met by a particular educational activity. Audit circles of general practitioners allow for a discussion of relevant issues. The present paper describes a novel concept for delivering knowledge and skills in arthritis and rheumatic conditions to general practitioners. A well-designed paper case was used for discussion in established audit circles of general practitioners, and a specially trained expert rheumatologist participated as an external expert to answer all those questions that could not be solved by the other participants. The participation of such as an expert-on-demand was found extremely helpful, as an evaluation during pilot sessions in 6 pre-existing audit circles of general practitioners revealed.


Impact of depressive symptomatology on alcohol problems in women.
The association between the amount of depression manifest at time of an alcoholic woman's admission to treatment, the course of alcoholism and its consequences, and early psychosocial vulnerabilities was examined in a sample of women in treatment for alcoholism (n = 301). Two indices of depression, one reflecting low self-esteem and the other current mood were constructed by factor analysis of interview items measuring depression (drawn from Center for Epidemiological Studies Depression scale, Diagnostic Interview Scale, and Personal Attributes Questionnaire). Both depression indices were associated with earlier age of onset and earlier loss of control. Binge drinking was associated with current mood, while daily/weekend drinking was associated with low self-esteem. Both measures were associated with the consequences of alcoholism. An examination of alcoholic women's background revealed that there are some influences in the early family environment that are associated with increased levels of depression in alcoholic women.


Considerable slowdown of short DNA fragment translocation across a protein nanopore using pH-induced generation of enthalpic traps inside the permeation pathway.
A pressing challenge in the realm of nanopore-based sensing technologies for nucleic acid characterization has been the cheap and efficient control of analyte translocation. To address this, a plethora of methods were tested, including mutagenesis, molecular motors, enzymes, or the optimization of experimental conditions. Herein, we present a paradigm exploiting the manipulation of electrostatic interactions between 22-mer single-stranded DNAs (22_ssDNA) and low pH-induced charges in the alpha-hemolysin (α-HL) nanopore, to efficiently control the passage of captured molecules. We discovered that in electrolytes buffered at pH = 5 and pH = 4.5 where the nanopore's vestibule and lumen become oppositely charged as compared to that at neutral pH, the electrostatic anchoring at these regions of a 22_ssDNA fragment leads to a dramatic increase of the translocation time, orders of magnitude larger compared to that at neutral pH. This pH-dependent tethering effect is reversible, side invariant, and sensitive to the ionic strength and ssDNA contour length. In the long run, our discovery has the potential to provide a simple read-out of the sequence of bases pertaining to short nucleotide sequences, thus extending the efficacy of current nanopore-based sequencers.


[Rehabilitation and return-to-work after laryngectomy: the role of industrial otolaryngologists].
Rehabilitation and return-to-work are important problems for laryngectomized patients. Here, we report 2 cases of laryngectomized middle-aged men, and discuss the role of otolaryngologists from the viewpoint of an industrial physician. The first case is a 55-year-old post-office male clerk, who underwent radical and reconstructive surgery for hypopharyngeal carcinoma. He started light work following 3-month-rest at home after discharge, and fully returned to his previous work 3 years later. The second case is a 50-year-old mailman who also underwent radical and reconstructive surgery for hypopharyngeal carcinoma. He could not return to work because of the recurrence of tumor during rehabilitation. In such cases, comprehensive management including medical, mental and social supports is essential according to the occupational environment. Industrial otolaryngologists should play an important role in rehabilitation and return-to-work of laryngectomized patients.


A Comparative Evaluation of Two Commonly Used GP Solvents on Different Epoxy Resin-based Sealers: An In Vitro Study.
This study evaluates epoxy resin-based sealers after their final set, immersed in Endosolve-R or xylene for 1-2 minutes, for its easy removal mechanically after softening. Sixty Teflon molds were grouped with 20 samples in each of the three commercially available sealers, i.e., AH 26, AH Plus, and Adseal. The sealers were put in the specific molds after their manipulation as per the instructions given in the literature by the manufacturer. They were allowed to harden for 2 weeks at 37°C in 100% humidity. Two subgroups, A-Xylene and B-Endosolv-R, of 10 samples each, were formed from 20 set specimens based on solvents to which they were immersed for 1 and 2 minutes, respectively. The data obtained was subjected to the Mauchly's test one-way ANOVA and two-way ANOVA for analysis. It was proved that for all the sealers immersed in solvents, there was a significant reduction in the mean Vickers hardness as the time increases. There was a significant difference in the initial hardness between the mentioned sealers with AH plus showing the highest followed by AH 26 and Adseal showing the lowest. AH Plus and Adseal sealers were softened by xylene after 2 minutes of their initial microhardness (p < 0.001); least effect was seen on AH 26. After 2 minutes, Endosolv-R softened initial microhardness of all the three sealers (p < 0.001). It was concluded that Endosolv-R was more effective in softening the epoxy-based resin sealer than xylene, after 2 minutes of exposure. Tyagi S, Choudhary E, Choudhary A, et al. A Comparative Evaluation of Two Commonly Used GP Solvents on Different Epoxy Resin-based Sealers: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(1):35-37.


Taking culture seriously: Can we improve the developmental health and well-being of Australian Aboriginal children in out-of-home care?
Children in out-of-home care have well-documented health and developmental needs. Research suggests that Aboriginal children in care have unmet health and intervention needs. In metropolitan Sydney, Kari Aboriginal Resources Inc. (KARI), an Aboriginal organization, provides support to indigenous children in care, including clinical assessment and intervention. We wanted to determine the health and developmental needs of a subset of children in out-of-home care with KARI, who had been in stable care for at least a year. We wanted to identify child, carer, and intervention characteristics that contributed to children doing well. We also wanted to identify enablers and barriers to providing culturally competent intervention. We used mixed methods. From the KARI clinic database over the past 3 years, we identified children who had been in stable care with KARI for >12 months. We compared clinical measures and outcomes for these children with results from previous audits. We carried out a group discussion and key informant interviews with therapists and caseworkers to identify risk and resilience factors for each child, as well as enablers and barriers to culturally competent intervention. The health and developmental profile of the 26 children identified as being in stable care was similar to that of previous audits. Most (88%) were getting speech pathology intervention; one third were getting occupational therapy and psychological intervention; most children and their carers attended cultural programmes. The majority of children (25/26) improved in their developmental health. Caseworkers and therapists identified risk and resilience factors related to child, carer, and home characteristics. They also identified elements of good practice; systemic issues prevented some interventions from being carried out. There are challenges delivering a trauma-informed, culturally respectful service to Aboriginal children in out-of-home care in an urban setting, but it can be done if attention is paid to culture and the enablers and barriers are identified.


Platelet-derived extracellular vesicles infiltrate and modify the bone marrow during inflammation.
During inflammation, steady-state hematopoiesis switches to emergency hematopoiesis to repopulate myeloid cells, with a bias toward the megakaryocytic lineage. Soluble inflammatory cues are thought to be largely responsible for these alterations. However, how these plasma factors rapidly alter the bone marrow (BM) is not understood. Inflammation also drives platelet activation, causing the release of platelet-derived extracellular vesicles (PEVs), which package diverse cargo and reprogram target cells. We hypothesized that PEVs infiltrate the BM, providing a direct mode of communication between the plasma and BM environments. We transfused fluorescent, wild-type (MPL+) platelets into recipient cMpl-/-mice before triggering systemic inflammation. Twenty hours postinfusion, we observed significant infiltration of donor platelet-derived particles in the BM, which we tracked immunophenotypically (MPL+ immunohistochemistry staining) and quantified by flow cytometry. To determine if this phenomenon relates to humans, we extensively characterized both megakaryocyte-derived and PEVs generated in vitro and in vivo, and found enrichment of extracellular vesicles in bone marrow compared with autologous peripheral blood. Last, BM from cMpl-/- mice was cultured in the presence or absence of wild-type (MPL+) PEVs. After 72 hours, flow cytometry revealed increased megakaryocytes only in cultures with added PEVs. The majority of CD41+ cells were bound to PEVs, suggesting a PEV-mediated rescue of megakaryopoiesis. In conclusion, we report for the first time that plasma-residing PEVs infiltrate the BM. Further, PEVs interact with BM cells in vivo and in vitro, causing functional reprogramming that may represent a novel model of inflammation-induced hematopoiesis.


Low Relative Lean Mass is Associated with Increased Likelihood of Abdominal Aortic Calcification in Community-Dwelling Older Australians.
Age-related loss of skeletal muscle is associated with increased risk of functional limitation and cardiovascular (CV) mortality. In the elderly abdominal aortic calcification (AAC) can increase CV risk by altering aortic properties which may raise blood pressure and increase cardiac workload. This study investigated the association between low muscle mass and AAC in community-dwelling older Australians. Data for this cross-sectional analysis were drawn from a 2010 sub-study of the Melbourne Collaborative Cohort Study in the setting of community-dwelling older adults. Three hundred and twenty-seven participants [mean age = 71 ± 6 years; mean BMI = 28 ± 5 kg/m(2); females n = 199 (62 %)] had body composition determined by dual-energy x-ray absorptiometry (DXA) and AAC determined by radiography. Participants were stratified into tertiles of sex-specific BMI-normalised appendicular lean mass (ALM). Those in the lowest tertile were considered to have low relative muscle mass. Aortic calcification score (ACS) was determined visually as the extent of calcification on the aortic walls between L1 and L4 vertebrae (range: 0-24). Severe AAC was defined as ACS ≥ 6. Prevalence of any AAC was highest in participants with low relative muscle mass (74 %) compared to the middle (65 %) and upper (53 %) tertiles (p trend = 0.006). The lower ALM/BMI tertile had increased odds (Odds ratio = 2.3; 95 % confidence interval: 1.1-4.6; p = 0.021) of having any AAC; and having more severe AAC (2.2; 1.2-4.0; p = 0.009) independent of CV risk factors, serum calcium and physical activity. AAC is more prevalent and severe in community-dwelling older adults with low relative muscle mass. Maintaining muscle mass could form part of a broader primary prevention strategy in reducing AAC.


Delta sleep-inducing peptide modulates the stimulation of rat pineal N-acetyltransferase activity by involving the alpha 1-adrenergic receptor.
Delta sleep-inducing peptide (DSIP) has been isolated and characterized by its capacity to enhance delta sleep in rabbits. Up to now, sleep was the main target of DSIP research, but different extra-sleep effects of the peptide have been reported as well. Several mechanisms of action have been proposed, though no convincing evidence for any of them has been obtained so far. We recently detected that DSIP reduced the nocturnal increase of N-acetyltransferase (NAT) activity in rat pineal in a dose-dependent manner. The activity of this enzyme is known to be induced by adrenergic agonists and several studies have suggested that stimulation of alpha 1-adrenergic receptors potentiates the "basic" effect of beta-receptors. DSIP in the range between 20 and 300 nM significantly enhanced NAT activity induced by 10(-6) M norepinephrine in vitro, and a similar effect was observed with 2nMP-DSIP, a phosphorylated analog. Incubation with prazosin eliminated the enhancement, whereas propranolol reduced norepinephrine stimulation that was still increased by P-DSIP and probably DSIP. It was concluded that the sleep-peptide and its analog modulate the alpha 1-adrenergic receptor of rat pineal in its response to adrenergic agonists. The same mechanism may also be responsible for other biological activities of DSIP such as sleep-induction and stress-tolerance.


Dimensional Analysis of Atypical Functional Connectivity of Major Depression Disorder and Bipolar Disorder.
Literatures have reported considerable heterogeneity with atypical functional connectivity (FC) pattern of psychiatric disorders. However, traditional statistical methods are hard to explore this heterogeneity pattern. We proposed a "brain dimension" method to describe the atypical FC patterns of major depressive disorder and bipolar disorder (BD). The approach was firstly applied to a simulation dataset. It was then utilized to a real resting-state functional magnetic resonance imaging dataset of 47 individuals with major depressive disorder, 32 individuals with BD, and 52 well matched health controls. Our method showed a better ability to extract the FC dimensions than traditional methods. The results of the real dataset revealed atypical FC dimensions for major depressive disorder and BD. Especially, an atypical FC dimension which exhibited decreased FC strength of thalamus and basal ganglia was found with higher severity level of individuals with BD than the ones with major depressive disorder. This study provided a novel "brain dimension" method to view the atypical FC patterns of major depressive disorder and BD and revealed shared and specific atypical FC patterns between major depressive disorder and BD.


Achieving integrative, collaborative ecosystem management.
Although numerous principles have been identified as being important for successfully integrating social and ecological factors in collaborative management, few authors have illustrated how these principles are used and why they are effective. On the basis of a review of the ecosystem management and collaboration literature, we identified eight factors important for integrative, collaborative ecosystem management-integrated and balanced goals, inclusive public involvement, stakeholder influence, consensus group approach, collaborative stewardship, monitoring and adaptive management, multidisciplinary data, and economic incentives.We examined four cases of successful ecosystem management to illustrate how the factors were incorporated and discuss the role they played in each case's success. The cases illustrate that balancing social and ecosystem sustainability goals is possible. Collaborative efforts resulted in part from factors aimed at making plans economically feasible and from meaningful stakeholder participation in ongoing management. It also required participation in monitoring programs to ensure stakeholder interests were protected and management efforts were focused on agreed-upon goals. Data collection efforts were not all-inclusive and systematic; rather, they addressed the ecological, economic, and social aspects of key issues as they emerged over time. Economic considerations appear to be broader than simply providing economic incentives; stakeholders seem willing to trade some economic value for recreational or environmental benefits. The cases demonstrate that it is not idealistic to believe integrative, collaborative ecosystem management is possible in field applications.


In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis.
The oxidative stress hypothesis links neurodegeneration in the later, progressive stages of multiple sclerosis (MS) to the loss of a major brain antioxidant, glutathione (GSH). We measured GSH concentrations among major MS subtypes and examined the relationships with other indices of disease status including physical disability and magnetic resonance imaging (MRI) measures. GSH mapping was performed on the fronto-parietal region of patients with relapsing-remitting multiple sclerosis (RRMS, n = 21), primary progressive multiple sclerosis (PPMS, n = 20), secondary progressive multiple sclerosis (SPMS, n = 20), and controls ( n = 28) using GSH chemical shift imaging. Between-group comparisons were performed on all variables (GSH, T2-lesion, atrophy, Expanded Disability Status Scale (EDSS)). Patients with MS had substantially lower GSH concentrations than controls, and GSH was lower in progressive MS (PPMS and SPMS) compared with RRMS. GSH concentrations were not significantly different between PPMS and SPMS, or between RRMS and controls. Brain atrophy was significant in both RRMS and progressive MS compared with controls. Markedly lower GSH in progressive MS than RRMS indicates more prominent involvement of oxidative stress in the progressive stage of MS than the inflammatory stage. The association between GSH and brain atrophy suggests the important role of oxidative stress contributing to neurodegeneration in progressive MS, as suggested in other neurodegenerative diseases.


Electrical Manipulation of Quantum Coherence in a Two-Level Molecular System.
We report the manipulation of ultrafast quantum coherence of a two-level single hydrogen molecular system by employing static electric field from the sample bias in a femtosecond terahertz scanning tunneling microscope. A H_{2} molecule adsorbed on the polar Cu_{2}N surface develops an electric dipole and exhibits a giant Stark effect. An avoided crossing of the quantum state energy levels is derived from the resonant frequency of the single H_{2} two levels in a double-well potential. The dephasing time of the initial wave packet can also be changed by applying the electric field. The electrical manipulation for different tunneling gaps in three dimensions allows quantification of the surface electrostatic fields at the atomic scale. Our work demonstrated the potential application of molecules as controllable two-level molecular systems.


Functional dissection of osteoprotegerin and its interaction with receptor activator of NF-kappaB ligand.
The receptor activator of NF-kappaB (RANK) belongs to the neuregulin/tumor necrosis factor (TNF) receptor superfamily and is activated by RANK ligand (RANK-L), a homotrimeric, TNF-like cytokine. RANK is present on the surface of osteoclast cell precursors, where its interaction with RANK-L induces their terminal differentiation into osteoclasts, thus increasing bone breakdown. The secreted, soluble receptor osteoprotegerin (OPG) interrupts this activation by binding directly to RANK-L. Therefore, osteoclast maturation (and bone homeostasis) is regulated in vivo by OPG levels of expression. We have studied the assembly state and affinity of OPG for RANK-L by sedimentation analyses and surface plasmon resonance (Biacore). Full-length, homodimeric OPG binds to RANK-L with a KD of 10 nM. OPG is also a member of the TNF receptor superfamily and contains four disulfide-rich ligand-binding domains, yet lacks a transmembrane region separating the ligand-binding region from the two death domains, as observed for other receptor family members. We showed that dimerization of OPG results from noncovalent interactions mediated by the death domains and to a lesser extent by a C-terminal heparin-binding region. In contrast, a C-terminal intermolecular disulfide bond does not contribute to the formation or stability of OPG dimers. A truncate of osteoprotegerin, containing the ligand-binding domains but lacking the dimerization domains, bound RANK-L with a KD of approximately 3 microM, indicating that monomer oligomerization for the OPG provides an increase of 3 orders of magnitude in the affinity for RANK-L. Therefore, OPG dimer formation is required for the mechanism of inhibition of the RANK-L/RANK receptor interaction.


Movement therapy with the aged.
This study examined effect of participation in a movement therapy group on morale and self-esteem in a population of institutionalized aged persons. Control group subjects participated in the usual treatment program at the nursing home, and experimental group subjects participated in a series of movement therapy sessions. Scores on morale and self-esteem scales were used to compare differences between the groups. Movement therapy group members demonstrated greater improvement in total morale and attitudes toward their own aging. Findings from the study contribute to the body of knowledge of nursing science as well as to gerontological theory development by further defining types of activities which are compatible with successful aging and by providing empirical support for specific nursing interventions.


Critical role of Glu40-Ser48 loop linking actuator domain and first transmembrane helix of Ca2+-ATPase in Ca2+ deocclusion and release from ADP-insensitive phosphoenzyme.
The functional importance of the length of the A/M1 linker (Glu(40)-Ser(48)) connecting the actuator domain and the first transmembrane helix of sarcoplasmic reticulum Ca(2+)-ATPase was explored by its elongation with glycine insertion at Pro(42)/Ala(43) and Gly(46)/Lys(47). Two or more glycine insertions at each site completely abolished ATPase activity. The isomerization of phosphoenzyme (EP) intermediate from the ADP-sensitive form (E1P) to the ADP-insensitive form (E2P) was markedly accelerated, but the decay of EP was completely blocked in these mutants. The E2P accumulated was therefore demonstrated to be E2PCa(2) possessing two occluded Ca(2+) ions at the transport sites, and the Ca(2+) deocclusion and release into lumen were blocked in the mutants. By contrast, the hydrolysis of the Ca(2+)-free form of E2P produced from P(i) without Ca(2+) was as rapid in the mutants as in the wild type. Analysis of resistance against trypsin and proteinase K revealed that the structure of E2PCa(2) accumulated is an intermediate state between E1PCa(2) and the Ca(2+)-released E2P state. Namely in E2PCa(2), the actuator domain is already largely rotated from its position in E1PCa(2) and associated with the phosphorylation domain as in the Ca(2+)-released E2P state; however, in E2PCa(2), the hydrophobic interactions among these domains and Leu(119)/Tyr(122) on the top of second transmembrane helix are not yet formed properly. This is consistent with our previous finding that these interactions at Tyr(122) are critical for formation of the Ca(2+)-released E2P structure. Results showed that the EP isomerization/Ca(2+)-release process consists of the following two steps: E1PCa(2) --> E2PCa(2) --> E2P + 2Ca(2+); and the intermediate state E2PCa(2) was identified for the first time. Results further indicated that the A/M1 linker with its appropriately short length, probably because of the strain imposed in E2PCa(2), is critical for the correct positioning and interactions of the actuator and phosphorylation domains to cause structural changes for the Ca(2+) deocclusion and release.


G.B. Morgagni: the father and founder of contemporary pathology.
Giovanni Morgagni (1682-1771) who lived in the 18th century was the greatest pathologist that ever existed. His fame extended beyond his country, Italy, and his name became universally known, being the Father of Contemporary Pathology. He set the basis for the creation of a new medical specialisation, pathology, which was unknown at the time. His brilliant mind made a big step in the formation of a new type of clinical thought in every day medicine. He managed to make the clinician, physician and surgeon think and act in a different scientific manner; to think in an anatomo-clinical way. In other words, by correlating the symptoms of a certain disease with the corresponding pathological alterations, he also discovered many new diseases and wrote many books which were unique for their wisdom.


[Protocol of nursing care to traumatized patients in the aerospace environment: care before flight].
The study aimed to present a protocol for nursing care in pre aerospace removing of adult victims of trauma. A qualitative convergent care research was performed at the Division of Air Operations in the municipality of San Jose-SC, Brazil, from April to June 2010. The study was based on the principles of the Pre-hospital Trauma Life Support. Individual interviews and group meetings were used. Eight nurses participated in the service. The proposed protocol includes safety boarding, disembarking, assessment of the scene, primary assessment, secondary assessment and stabilization of the patient. The protocol will provide a safer nursing practice care to patients aero removed.


Development of a thin high-frequency and high-precision magnetic probe array in Sino-United Spherical Tokamak.
Since the major/minor radius of the Sino-United Spherical Tokamak (SUNIST) is 0.3/0.23 m, respectively, the space left for magnetic diagnostics in the high field side (HFS) is quite limited. At the same time, a good signal-to-noise ratio and a high-frequency response (up to 1 MHz) are required for equilibrium reconstruction (ER) and Alfven eigenmode studies. Such a magnetic probe array must be extremely thin and tightly close to the central column, not exceeding the inner limiter and leaving the aspect ratio of the spherical tokamak unchanged. Therefore, the turn number and the shape of windings should be highly optimized to enable both a high-frequency response and an enough effective area. A 32-channel magnetic probe array fulfilling these requirements on the central column is designed, calibrated, and installed in the SUNIST. The array consists of 16 probes. Each of them consists of two perpendicular windings, which can measure toroidal and poloidal magnetic fields simultaneously. The effective area and frequency response of each probe are calibrated using a Helmholtz coil and an LCR bridge based on an equivalent probe-and-cable circuit model. After that, an expression of the magnetic diagnostic response to the field coil currents is used to calibrate the installation error. With the full coverage of magnetic probes in the poloidal direction, more reliable ER can be obtained, and the features of magnetohydrodynamic activities in the HFS can be studied.


Value of peritoneal lavage cytology during laparoscopic staging of patients with gastric carcinoma.
Forty-nine consecutive patients with advanced gastric carcinoma underwent preoperative staging by laparoscopy between June 1991 and June 1992. Peritoneal lavage with cytologic examination was performed when ascites was not present. In eight cases (16.3%), laparoscopy revealed carcinomatosis and/or multiple hepatic metastases, so laparotomy was not performed. Intraperitoneal free cancer cells (IFCCs) were detected in 41% of patients (65% in patients with ascites and 28% by peritoneal lavage). In the absence of macroscopic peritoneal dissemination, IFCCs were encountered in 29% of patients. IFCCs were present only when invasion of the gastric serosa was >3 cm2 or when adjacent organs and structures were already invaded. Mucinous adenocarcinoma, Borrmann class IV tumors, and Stage IV patients had higher incidence of IFCCs. Cytologic results were similar at laparoscopy and laparotomy (p > 0.05). Therefore, cytologic evaluation of peritoneal lavage added sensitivity to laparoscopy in assessing patients with advanced gastric carcinoma and may alter their therapeutic approach.


Computational nanomechanics and thermal transport in nanotubes and nanowires.
Representative results of computer simulation and/or modeling studies of the nanomechanical and thermal transport properties of an individual carbon nanotube, silicon nanowire, and silicon carbide nanowire systems have been reviewed and compared with available experimental observations. The investigated nanomechanical properties include different elastic moduli of carbon nanotubes, silicon nanowires, and silicon carbide nanowires, all obtained within their elastic limits. Moreover, atomistic mechanisms of elastic to plastic transition under external stresses and yielding of carbon nanotubes under experimentally feasible temperature and strain rate conditions are discussed in detail. The simulation and/or modeling results on thermal properties, presented in this work, include vibrational modes, thermal conductivity and heat pulse transport through single carbon nanotubes, and thermal conductivity of silicon nanowires.


An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers.
As regards central nervous system (CNS) effects there are three types of antihistamines. Those that cross the blood-brain barrier and cause widespread impairment of cognitive and psychomotor function; those that cross into the brain and, although without much impairment at low clinical doses, have a dose-related relationship to impairment; and those that do not cross into the brain and therefore possess no intrinsic potential for impairing CNS function. [corrected] To investigate the acute effects of fexofenadine (360 mg) on various aspects of cognitive and psychomotor function in comparison to placebo and promethazine (positive internal control), an antihistamine known to produce psychomotor and cognitive impairment. Fifteen healthy volunteers received fexofenadine 360 mg, promethazine 30 mg and placebo in a 3-way cross-over, double-blind study. For each treatment condition, subjects were required to perform a series of tests of cognitive function and psychomotor performance at baseline and 1, 3, 5 and 7 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and a subjective assessment of sedation (LARS). Fexofenadine was not distinguishable from placebo in any of the objective and subjective tests for up to seven hours following drug administration. However, all measures were significantly impaired following the administration of promethazine, which confirms the sensitivity of the test battery for sedation. The effects of fexofenadine and placebo were not significantly different from one another, whereas promethazine caused an overall reduction in CFF thresholds when compared to placebo (P < 0.05). There was an overall significant increase (impairment) in recognition, motor and total reaction time (P < 0.05), and both the tracking accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05) following the administration of promethazine. In contrast, the effects of fexofenadine could not be distinguished from the placebo condition. Subjective ratings of sedation were significantly higher with promethazine when compared to placebo (P < 0.05) and fexofenadine (P< 0.05). Fexofenadine at a dose of 360mg is demonstrably free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg. The identification of an antihistamine (fexofenadine) devoid of central effects even at supraclinical doses separates it from currently available first and second generation drugs with no objective evidence of CNS side-effects on cognition and psychomotor function, and highlights the need for the introduction of a third generation of non-sedative antihistamines.


Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridization.
A polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary tuberculosis was developed by using oligonucleotide primers to amplify a fragment of IS6110, an insertion sequence repeated multiple times in the chromosome of Mycobacterium tuberculosis. Sediment obtained from sputa processed by the N-acetyl-L-cysteine-NaOH method was suspended in a simple lysis buffer and was heated at 100 degrees C for 30 min prior to amplification. A dUTP-uracil N-glycosylase PCR protocol was used to prevent false-positive test results because of the carryover of products from previous amplification reactions. The 317-bp amplicon was detected by direct gel analysis and Southern blotting and then hybridization with a biotin-labeled internal probe. Hybrid molecules were detected by using a commercially available avidin-alkaline phosphatase-chemiluminescent substrate system (Tropix, Inc., Bedford, Mass.). The analytical sensitivity of the assay was 10 fg of purified mycobacterial DNA. The limits of detection by culture (Middlebrook 7H11 agar and Lowenstein-Jensen medium) and by PCR were equivalent in terminal dilution experiments for organism suspensions and positive sputa. An internal control was used to detect the presence of amplification inhibitors in each negative reaction mixture. DNA was purified from inhibitory specimens by phenol-chloroform extraction and ethanol precipitation. PCR results were compared with results of microscopy and conventional culture for the detection of M. tuberculosis in 313 sputum specimens. There were 124 specimens that were positive for M. tuberculosis by conventional methods and 113 (91%) that were positive by PCR. PCR detected 105 of 110 (95%) of the smear-positive and 8 of 14 (57%) of the smear-negative specimens. There were no false-positive results by PCR (specificity, 100%). This PCR assay innovations that make application of this new technology feasible in clinical microbiology laboratories.


C-terminal calmodulin-binding motif differentially controls human and rat P2X7 receptor current facilitation.
P2X(7) receptors (P2X(7)R) are ATP-gated calcium-permeable cationic channels structurally unique among the P2X family by their much longer intracellular C-terminal tail. P2X(7)Rs show several unusual biophysical properties, in particular marked facilitation of currents and leftward shift in agonist affinity in response to repeated or prolonged agonist applications. We previously found the facilitation at rat P2X(7)R resulted from a Ca(2+)-calmodulin-dependent process and a distinct calcium-independent process. However, P2X(7)Rs show striking species differences; thus, this study compared the properties of ATP-evoked facilitation of currents in HEK293 cells transiently expressing the human or rat P2X(7)R as well as rat/human, human/rat chimeric, and mutated P2X(7)Rs. Facilitation at the human P2X(7)R was 5-fold slower than at the rat P2X(7)R. Facilitation did not resulting from an increase of receptor addressing the plasma membrane. We found the human P2X(7)R shows only calcium-independent facilitation with no evidence for calmodulin-dependent processes, nor does it contain the novel 1-5-16 calmodulin binding domain present in the C terminus of rat P2X(7)R. Replacement of three critical residues of this binding domain from the rat into the human P2X(7)R (T541I, C552S, and G559V) reconstituted the Ca(2+)-calmodulin-dependent facilitation, leaving the calcium-independent facilitation unaltered. The leftward shift in the ATP concentration-response curve with repeated agonist applications appears to be a property of the calcium-independent facilitation process because it was not altered in any of the chimeric or mutated P2X(7)Rs. The absence of Ca(2+)-dependent facilitation at the human P2X(7)R may represent a protective adaptation of the innate immune response in which P2X(7)R plays significant roles.


Effect of Naringenin, Quercetin, and Sesamin on Xenobiotica-Metabolizing CYP1A and CYP3A in Mice Offspring after Maternal Exposure to Persistent Organic Pollutants.
The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin with Ki values from 1.7 to 2.6 μM. BROD activity was inhibited by quercetin with Ki values from 64.9 to 75.3 μM and naringenin with Ki values from 39.3 to 45.8 μM. The IC50 and Ki values did not differ between the groups of mice with different levels of POPs exposure in any of the experimental sets. Sesamin did not inhibit either EROD or BROD. We concluded that the interactions of quercetin and naringenin with CYP1A and CYP3A in mice liver were not affected by the levels of POPs exposure.


Study of the Role of CREB, BDNF, and VGF Neuropeptide in Long Term Antidepressant Activity of Crocin in the Rat Cerebellum.
Antidepressant activity of crocin, saffron main component, has been established before. Based on previous study, it is suggested that elevation in the levels of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide could be considered as one probable molecular mechanisms involved in antidepressant activity of long term crocin administration in the rat hippocampus. In this study we further investigated whether the antidepressant activity of crocin in long term administration was associated with alteration in these factors in the rat cerebellum. Crocin (12.5, 25 and 50 mg/kg/day) and imipramine (10 mg/kg/day) were administered interaperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were dissected. BDNF, VGF, CREB, and phospho-CREB (P-CREB) protein and mRNA levels in the rat cerebellum were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the current study significant increases in mRNA and protein levels of VGF, CREB and (BDNF) in long term crocin treatment were not observed in the rat cerebellum. Although a slight increase was observed in protein level of P-CREB compared to normal saline, but it was not significant. It is concluded that antidepressant activity of crocin might be partially mediated to CREB. Moreover, other factors rather than BDNF and VGF neuropeptides may alter following long term crocin treatment in the cerebellum. To understand the precise mechanism of crocin antidepressant effects in the cerebellum, longer duration of crocin treatment in further studies is recommended.


Recognizing young children in need of mental health assessment: Development and preliminary validity of the early childhood screening assessment.
The Early Childhood Screening Assessment (ECSA) is a primary care screening measure developed to identify very young children (1½-5 years old) who need further emotional or behavioral assessment. The ECSA was developed specifically to meet the logistical constraints of primary care settings. This study assessed the preliminary psychometric properties of the ECSA by comparing it with extant validated measures of young children's emotional and behavioral development, comparing it with a diagnostic interview, and measuring test-retest reliability. In the study, 309 mothers in two primary care clinics completed the ECSA and the Child Behavior Checklist (CBCL; T. Achenbach & L. Rescorla, 2000). A subset (n = 69) also completed the Diagnostic Interview for the Preschool Age (DIPA; M. Scheeringa & N. Haslett, 2010). ECSA score correlated significantly and strongly with the CBCL Total Problem T score (Spearman's rho = 0.86, p ⩽ .01). The ECSA was 86% sensitive and 83% specific in identifying DIPA diagnoses. Internal consistency of the ECSA was 0.91. Test-retest reliability at 10 days was excellent (Spearman's rho = 0.81, p ⩽ .01). The ECSA is an easy-to-use screening measure that demonstrates strong convergent validity, criterion validity, and test-retest reliability in the pediatric setting. It shows potential as a feasible and psychometrically strong tool for busy primary care providers to identify preschoolers who need further socioemotional assessment.


[The identification and comparison of gram-negative Enterobacteriaceae and non-fermentative bacteria by the conventional manual method and the Quantum II microbiology system].
In this study a total of 1065 clinically isolated enteric and non-fermentative bacteria were tested and compared with a commercially manufactured "Quantum II Microbiology System", and the conventional manual biochemical tests. We are able to say that, "Quantum II Microbiology System" will be very useful in clinical laboratories due to making an identification in a very short time and in species level when an attentive study is made.


Review of study reporting guidelines for clinical studies using artificial intelligence in healthcare.
High-quality research is essential in guiding evidence-based care, and should be reported in a way that is reproducible, transparent and where appropriate, provide sufficient detail for inclusion in future meta-analyses. Reporting guidelines for various study designs have been widely used for clinical (and preclinical) studies, consisting of checklists with a minimum set of points for inclusion. With the recent rise in volume of research using artificial intelligence (AI), additional factors need to be evaluated, which do not neatly conform to traditional reporting guidelines (eg, details relating to technical algorithm development). In this review, reporting guidelines are highlighted to promote awareness of essential content required for studies evaluating AI interventions in healthcare. These include published and in progress extensions to well-known reporting guidelines such as Standard Protocol Items: Recommendations for Interventional Trials-AI (study protocols), Consolidated Standards of Reporting Trials-AI (randomised controlled trials), Standards for Reporting of Diagnostic Accuracy Studies-AI (diagnostic accuracy studies) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis-AI (prediction model studies). Additionally there are a number of guidelines that consider AI for health interventions more generally (eg, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), minimum information (MI)-CLAIM, MI for Medical AI Reporting) or address a specific element such as the 'learning curve' (Developmental and Exploratory Clinical Investigation of Decision-AI) . Economic evaluation of AI health interventions is not currently addressed, and may benefit from extension to an existing guideline. In the face of a rapid influx of studies of AI health interventions, reporting guidelines help ensure that investigators and those appraising studies consider both the well-recognised elements of good study design and reporting, while also adequately addressing new challenges posed by AI-specific elements.


Cardiac response to repeated doses of isoproterenol aerosol.
We studied 18 patients with moderate to severe asthma for cardiac response to repeated doses of isoproterenol aerosol. In only 1 patient was there a significant increase in heart rate immediately after inhalation of isoproterenol aerosol, and it lasted only for 1 minute. In 2 patients increased heart rate was either due to breathholding or to the propellant in the aerosol. There was no cumulative effect on heart rate. Arrhythmias did not develop at any time despite repeated doses of aerosol every 5 to 20 minutes. Peak expiratory flow rate increased 5 minutes after the first dose, and it increased even further after repeated doses; at no time did it decrease after repeated doses.


Spinon Fermi Surface in a Cluster Mott Insulator Model on a Triangular Lattice and Possible Application to 1T-TaS_{2}.
1T-TaS_{2} is a cluster Mott insulator on the triangular lattice with 13 Ta atoms forming a star of David cluster as the unit cell. We derive a two-dimensional XXZ spin-1/2 model with a four-spin ring exchange term to describe the effective low energy physics of a monolayer 1T-TaS_{2}, where the effective spin-1/2 degrees of freedom arises from the Kramers degenerate spin-orbital states on each star of David. A large scale density matrix renormalization group simulation is further performed on this effective model and we find a gapless spin liquid phase with a spinon Fermi surface at a moderate to large strength region of the four-spin ring exchange term. All peaks in the static spin structure factor are found to be located on the "2k_{F}" surface of a half-filled spinon on the triangular lattice. Experiments to detect the spinon Fermi surface phase in 1T-TaS_{2} are discussed.


Superiority of group counseling to individual coaching for parents of children with learning disabilities.
Abstract Two interventions for parents of children with learning disabilities (LD)-individual coaching and group counseling-were compared. Participants were 169 parents, non-randomly assigned to three experimental conditions: coaching (n=45), group counseling (n=93) and control (n=31). Variables included outcomes (parental stress and parental coping), personal (perceived social support) and process (bonding with therapist/group). Findings indicated more favorable outcomes for parents in both treatment conditions compared to control, more favorable outcomes on the stress index for parents treated in groups compared to individual coaching, and bonding was the most consistent predictor of outcomes. The discussion focuses on the power of group counseling for parents of children with LD.


Phase-sensitive black-blood coronary vessel wall imaging.
Black-blood MR coronary vessel wall imaging may become a powerful tool for the quantitative and noninvasive assessment of atherosclerosis and positive arterial remodeling. Although dual-inversion recovery is currently the gold standard, optimal lumen-to-vessel wall contrast is sometimes difficult to obtain, and the time window available for imaging is limited due to competing requirements between blood signal nulling time and period of minimal myocardial motion. Further, atherosclerosis is a spatially heterogeneous disease, and imaging at multiple anatomic levels of the coronary circulation is mandatory. However, this requirement of enhanced volumetric coverage comes at the expense of scanning time. Phase-sensitive inversion recovery has shown to be very valuable for enhancing tissue-tissue contrast and for making inversion recovery imaging less sensitive to tissue signal nulling time. This work enables multislice black-blood coronary vessel wall imaging in a single breath hold by extending phase-sensitive inversion recovery to phase-sensitive dual-inversion recovery, by combining it with spiral imaging and yet relaxing constraints related to blood signal nulling time and period of minimal myocardial motion.


Mycobacterial disease: epidemiology, diagnosis, treatment, and prevention.
TB is common in the setting of HIV-induced immunosuppression, especially among demographic groups with a high background prevalence of tuberculous infection. It is often the first (sentinel) infectious disease to appear, extrapulmonary and disseminated disease is common, the chest x-ray picture is frequently atypical, and the tuberculin skin test is often falsely negative. It therefore requires a high index of suspicion and an aggressive diagnostic approach to avoid missing HIV-related tuberculous disease, which is communicable from man to man by the aerosol route and which appears to be highly treatable with conventional anti-TB drugs. Identification and INH prophylaxis of tuberculous-infected, HIV-seropositive persons is likely to be very important in the prevention of tuberculous disease. MAI is also a very common pathogen that frequently produces extrapulmonary and disseminated disease among patients with AIDS. In contrast to TB, AIDS-related MAI disease occurs more uniformly among the AIDS risk groups, occurs late among the HIV-related infections, and is not effectively treated with current drug regimens.


Studies on the mechanism of luteinizing hormone-induced desensitization of the rabbit follicular adenylyl cyclase system in vitro.
In vitro studies were conducted to evaluate the possible mechanisms of LH-induced desensitization of the rabbit follicular adenylyl cyclase (AC) system. We tested the effects of cAMP, dibutyryl cAMP, and inhibitors of various cellular functions on LH-stimulated AC activity as well as the reversibility of AC desensitization. Refractoriness of the AC to LH was induced by a1 1- or 2-h incubation of Graafian follicles with 10 microgram/ml LH. We fund that the initial 60-min phase of AC desensitization to LH in Graafian follicles was not prevented by a 60-min preincubation of follicles with 11 microM puromycin, 30 microM cycloheximide, 8 microM actinomycin D, 5 microgram/ml cytochalasin B, 50 microM colchicine, or 1 or 10 mM trinitrophenol or by a 90-min preincubation of follicles with 50 microM colchicine. We evaluated the effects of cAMP and dibutyryl cAMP on LH-stimulated AC activity by incubating Graafian follicles with these nucleotides for 30-min to 4 h. While LH-stimulated AC activity was not significantly reduced in follicles which had been incubated 30-min or 1-h with either nucleotide, 2 h incubations resulted in significant reductions in LH-stimulated AC activity, and 4-h incubations promoted a complete refractoriness of the LH-stimulable AC. cAMP also caused desensitization of the FSH-stimulable AC in 4-h incubations, but not in the 1-h incubations. Lastly, once the follicular AC was desensitized to LH, neither 4-guanylyl imidodiphosphate nor ATP could reverse desensitization. These results indicate that AC desensitization in rabbit Graafian follicles is biphasic event. The initial 60-min phase is not mediated by cAMP, RNA, or protein synthetic events, by energy-requiring events inhibited by trinitrophenol, or by microtubule- or micro-filament-associated processes. A secondary phase occurs within 2-h and appears to be mediated, at least in part, by cAMP.


Does the aqueous humor have a role in mitogen-activated protein kinase (MAPK) intracellular signaling in Glaucoma?
Glaucoma is a common blinding disease worldwide. Glaucoma treatment today is based on reduction of aqueous humor production or increase aqueous humor drainage. By medical manipulation, the treatment goal is to reduce the main risk factor, elevated intra ocular pressure. Here we hypothesize that the aqueous humor has a role, beside oxygen and nutrient supply, in transferring signaling to the trabecular meshwork. This signaling might be delivered from the ciliary body were the aqueous humor is produced, or from the lens or the cornea. Recently in our lab we proposed that MAPKs present in the aqueous humor are a novel signal involved in glaucoma pathology. Here we show that this pathway exists at an unexpected, extracellular media. Western blot analysis of aqueous humor from congenital glaucomatic rabbits and a rat model of induced elevated intra ocular pressure (IOP) were found to express several signaling members of the MAPK family. Although these members are usually found in an intracellular environment, they can be detected at an extracellular environment, namely the aqueous humor. These signaling proteins are found also in normal eyes. Moreover the MAPK signaling proteins are found in the active phosphorylated form and in non-active form in elevated IOP animals as well as in the control, normal IOP groups. Understanding the signaling cascade, at the aqueous humor, opens a new area for treatment of glaucoma patients. By interfering with the signaling cascade, taking place at a reachable location, the anterior chamber, we will be able to manipulate these protein effects on the trabecular meshwork.