Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse.
Thymosin beta-4 (Tbeta4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tbeta4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8-10 weeks old, were treated with 150 microg of Tbeta4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tbeta4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tbeta4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tbeta4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tbeta4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy.


PRNP haplotype distribution in Moroccan goats.
Susceptibility/resistance to scrapie in sheep and goats is influenced by host prion protein gene (PRNP) genotype. In this study, we report the analysis of prion protein gene polymorphisms in 137 goats of two Moroccan populations: D'man and Chaouni. We found seven previously described amino acid polymorphisms at codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent mutations. In addition, we identified three new allelic variants: 101R and 139S in D'man goats and 145D in D'man and Chaouni individuals. The high frequency of the resistant allele 154H could offer genetic protection against the disease to the analysed animals. A total of 12 haplotypes and 28 genotypes were found, the distribution of which shows significant differences between both groups. Moreover, haplotype frequencies were compared with bibliographic data showing that the haplotype distribution of PRNP in Moroccan populations is genetically similar to Southern Italian and Greek goats.


Accurate ab initio dipole moment surfaces of ozone: First principle intensity predictions for rotationally resolved spectra in a large range of overtone and combination bands.
Ab initio dipole moment surfaces (DMSs) of the ozone molecule are computed using the MRCI-SD method with AVQZ, AV5Z, and VQZ-F12 basis sets on a dense grid of about 1950 geometrical configurations. The analytical DMS representation used for the fit of ab initio points provides better behavior for large nuclear displacements than that of previous studies. Various DMS models were derived and tested. Vibration-rotation line intensities of 16O3 were calculated from these ab initio surfaces by the variational method using two different potential functions determined in our previous works. For the first time, a very good agreement of first principle calculations with the experiment was obtained for the line-by-line intensities in rotationally resolved ozone spectra in a large far- and mid-infrared range. This includes high overtone and combination bands up to ΔV = 6. A particular challenge was a correct description of the B-type bands (even ΔV3 values) that represented major difficulties for the previous ab initio investigations and for the empirical spectroscopic models. The major patterns of various B-type bands were correctly described without empirically adjusted dipole moment parameters. For the 10 μm range, which is of key importance for the atmospheric ozone retrievals, our ab initio intensity results are within the experimental error margins. The theoretical values for the strongest lines of the ν3 band lie in general between two successive versions of HITRAN (HIgh-resolution molecular TRANsmission) empirical database that corresponded to most extended available sets of observations. The overall qualitative agreement in a large wavenumber range for rotationally resolved cold and hot ozone bands up to about 6000 cm-1 is achieved here for the first time. These calculations reveal that several weak bands are yet missing from available spectroscopic databases.


Genetic profiling of Hypericum (St. John's Wort) species by nuclear ribosomal ITS sequence analysis.
A PCR-based DNA amplification method was applied to genetically distinguish the popular dietary supplement Hypericum perforatum L. (common St. John's Wort) from other related Hypericum species. Nuclear ribosomal gene sequences of the internal transcribed spacer (ITS) region were analyzed for 50 Hypericum taxa native to the Old and New Worlds, representing 11 of the 36 currently accepted taxonomic sections. This study provides a genetic method for authentication of commercial H. perforatum preparations. In addition, these data allow a preliminary assessment of phylogenetic relationships within the genus, revealing three strongly supported monophyletic clades, plus several secondary monophyletic groupings. Using ITS gene sequences, we were able to distinguish H. perforatum from all other species of Hypericum included in this study.


Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy.
To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH. Subjects were consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders. A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio [HR] 7.7, 95% confidence interval [CI] 1.4-15.7), number of lobar microbleeds (HR 2.93 with 2-4 microbleeds present, 95% CI 1.3-4.0; HR = 4.12 when >or=5 microbleeds present, 95% CI 1.6-9.3), and presence of CT-defined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01-12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6-8.3, p = 0.021). Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk.


Facilitated case conferences on end-of-life care for persons with advanced dementia-a qualitative study of interactions between long-term care clinicians and family members.
Prognostic uncertainty and the need for proxy decision-making owing to cognitive impairment in advanced dementia, adds complexity to end-of-life care planning within the long-term care setting. Case conferences provide a structure to facilitate difficult conversations and an opportunity for family and clinicians to engage in prospective planning, and reach agreement on goals of end-of-life care. To explore interactions between multidisciplinary healthcare clinicians and families during facilitated case conferences on end-of-life care for residents with advanced dementia. A qualitative approach was used. Transcripts of audio-recorded case conferences facilitated by a trained registered nurse were coded by two independent researchers and analysed inductively. Transcripts were selected from an available pool until thematic saturation was reached. Emerging themes were confirmed with the wider research group. Thematic saturation was reached after 25 transcripts. An overarching theme concerned the ways in which clinicians and families bridged medical and person-centred perspectives. Subthemes included: details of day-to-day care versus establishing overall goals of care; expression of emotion versus retreat from emotion; and missed opportunities versus expressed cues. Successful facilitation served to 'bridge the gap' between family and clinicians. Facilitation of case conferences for residents with advanced dementia should focus on ensuring that: clinicians do not miss opportunities to discuss end-of-life care; discussions on the minutiae of care regularly return to the resident's broader goals of care; and information on dementia and treatments provided by clinicians is integrated with advice by family members regarding the resident's premorbid values and likely preferences.


Mortality supposedly due to intoxication by pyrrolizidine alkaloids from Heliotropium indicum in a horse population in Costa Rica: a case report.
This article describes a case of massive mortality among horses which was probably due to intoxication by pyrrolizidine alkaloids from Heliotropium indicum. Over 4 years more than 75% of a population of about 110 horses on a farm in Costa Rica died after showing nervous neurological symptoms. Two clinical manifestations were encountered, an acute and a chronic one, both with a fatal outcome. Pathological findings in 2 horses coincided with those reported in the literature for intoxication by pyrrolizidine alkaloids and were not specific for VEE. However Venezuelan equine encephalitis (VEE) was the main differential diagnosis and could not completely be excluded because this disease was endemic in the region and VEE titres were found to be high. Taxonomic and toxicological investigations implicated Heliotropium indicum as the most probable principal cause of the intoxication.


Effect of vitamin A nutriture on experimental esophageal carcinogenesis.
The effect of mild vitamin A deficiency or vitamin A supplementation on methylbenzylnitrosamine (MBN; CAS: 937-40-6)-induced esophageal carcinogenesis was examined in Sprague-Dawley rats. The animals were fed semipurified diets containing levels of retinyl acetate, which were adequate (2.2 mg/kg diet), deficient (0.30 mg/kg diet), or supplemented (29.9 mg/kg diet) with respect to vitamin A content. Carcinogen-treated rats received 2.5 mg MBN/kg (body wt) twice a week for 5 weeks; they were then sacrificed for evaluation of esophageal tumorigenesis 15 weeks later. Liver levels of retinol reflected vitamin A nutriture, but there were no clinical signs of deficiency or toxicity. There were no significant differences in the frequency or incidence of esophageal tumors (either carcinomas or papillomas) among the dietary groups. There was also no indication that either vitamin A deficiency or vitamin A supplementation influenced the formation of preneoplastic lesions. Although the time was short for the neoplastic development, tumors were observed. These data suggest that vitamin A is selective in tissues it may protect from cancer induction and that the esophagus is less involved than other tissues.


Induction of mononuclear precursor cells with osteoclastic phenotypes in a rat bone marrow culture system depleted of stromal cells.
The importance of bone stromal cell involvement in osteoclast differentiation has been suggested. However, the detailed mechanism of its regulation is unclear. We investigated whether the soluble factors from osteoblastic cells influence osteoclast lineage cells in a population of rat bone marrow cells depleted of stromal cells. We show here that hematopoietic progenitor cells differentiate into mononuclear precursor cells, the preosteoclasts, that strongly express certain osteoclastic phenotypes in the absence of stromal cells. The multinucleation of the preosteoclasts occurred only in the presence of 1,25 dihydroxyvitamin D3 and stromal cells. The preosteoclasts themselves did not have dentine-resorbing activity, but they could differentiate into multinucleate osteoclast-like cells having such activity in the presence of rat primary osteoblasts. This culture system is a unique differentiation system for preosteoclast induction.


Carcinosarcoma of the prostate. Report of 21 cases.
Carcinosarcoma of the prostate is an unusual malignancy characterized by adenocarcinoma intimately admixed with sarcoma. The authors reviewed the clinical and pathologic findings of 21 cases of carcinosarcoma of the prostate from the files of the Mayo Clinic. Patient age ranged from 50 to 89 years (mean, 68 years). Ten patients (48%) had a previous diagnosis of prostatic acinar adenocarcinoma 2-73 months (mean, 33 months) before the diagnosis of carcinosarcoma, 8 of whom had received androgen deprivation therapy and/or radiation therapy in the interim. The Gleason score of adenocarcinoma ranged from 7 to 10 (mean, 9; median, 9). The sarcomas consisted of osteosarcoma (13), leiomyosarcoma (5), fibrosarcoma (1), malignant fibrous histiocytoma (1), and rhabdomyosarcoma (1), and the grade of the sarcoma component ranged from 2 to 4 (mean, 4; median, 4). Adenocarcinoma was the dominant histologic pattern in 7 cases and sarcoma in 14. Immunohistochemical staining revealed cytoplasmic reactivity for prostate specific antigen or keratin in 16 of 16 cases in the adenocarcinoma component. The sarcoma component was positive for vimentin in 16 of 16 cases, actin in 8 of 16 (focal in 2), S-100 protein in 2 of 16, and desmin in 1 of 16. At the time of diagnosis of carcinosarcoma, 11 patients had metastases, including 4 with metastatic adenocarcinoma before the diagnosis of carcinosarcoma. Treatment varied, and nonsurgical therapy was ineffective. Sites of metastases included lung (10 cases), bone (7), brain (4), liver (1), and peritoneum (1). Follow-up ranged from 1 to 107 months after the diagnosis of carcinosarcoma (mean, 34 months; median, 10 months). Mean time to tumor progression was 23 months (range, 1-96 months; median, 18 months). Eighteen patients died of carcinosarcoma from 2 to 107 months (mean, 34 months; median, 9.5 months) after diagnosis. Five-year survival was 41%, and 7-year survival was 14%. Progression and survival were not affected by histologic pattern. Carcinosarcoma of the prostate is an aggressive malignancy, regardless of histologic type.


Effect of long-term storage temperatures on the bond strength of self-etch adhesives.
Manufacturers often recommend refrigerated storage of self-etching enamel and dentin adhesives. The purpose of this study was to compare the shear-bond strength of composite resin to dentin using two different self-etching adhesives after extended storage at room or refrigerated temperatures. One- and two-step self-etching bonding agents were stored separately at room (23 degrees C) or refrigerated temperatures (5 degrees C) per manufacturer recommendations for 1, 4, or 18 months before testing. After each time period, composite resin was bonded to the dentinal surface of extracted human third molars using a mold and tested in shear on a universal-testing machine. Data were analyzed with analysis of variance/Tukey's test. No significant difference in bond strengths was found on the basis of storage temperature for either adhesive type. The one-step adhesive had a significant loss in bond strength over the 18 months of storage. However, the two-step self-etch adhesive had no loss in bond strength, regardless of storage temperature.


Predicting clinical outcomes after thrombolysis using the iScore: results from the Virtual International Stroke Trials Archive.
The ischemic stroke risk score (iScore) is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. Our goal was to determine the ability of the iScore to estimate clinical outcomes after intravenous thrombolysis tissue-type plasminogen activator (tPA) in the Virtual International Stroke Trials Archive (VISTA). We applied the iScore (www.sorcan.ca/iscore) to patients with an acute ischemic stroke within the VISTA collaboration to examine the effect of tPA. We explored the association between the iScore (<200 and ≥200) and the primary outcome of favorable outcome at 3 months defined as a modified Rankin scale score of 0 to 2. Secondary outcomes included death at 3 months, catastrophic outcomes (modified Rankin scale, 4-6), and Barthel index >90 at 3 months. Among 7140 patients with an acute ischemic stroke, 2732 (38.5%) received tPA and 711 (10%) had an iScore ≥200. Overall, tPA treatment was associated with a significant improvement in the primary outcome among patients with an iScore <200 (38.9% non-tPA versus 47.5% tPA; P<0.001) but was not associated with a favorable outcome among patients with an iScore ≥200 (5.5% non-tPA versus 7.6% tPA; P=0.45). In the multivariable analysis after adjusting for age, baseline National Institutes of Health Stroke Scale, and onset-to-treatment time, there was a significant interaction between tPA administration and iScore; tPA administration was associated with 47% higher odds of a favorable outcome at 3 months among patients with an iScore <200 (odds ratio, 1.47; 95% confidence interval, 1.30-1.67), whereas the association between tPA and favorable outcome among those with an iScore ≥200 remained nonsignificant (odds ratio, 0.80; 95% confidence interval, 0.45-1.42). A similar pattern of benefit with tPA among patients with an iScore <200, but not ≥200, was observed for secondary outcomes including death. The iScore is a useful and validated tool that helps clinicians estimate stroke outcomes. In stroke patients participating in VISTA, an iScore <200 was associated with better outcomes at 3 months after tPA.


Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis.
Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.


NADPH oxidase-derived H(2)O(2) contributes to angiotensin II-induced aldosterone synthesis in human and rat adrenal cortical cells.
The Renin-Angiotensin-Aldosterone-System plays a pivotal role in hypertension. Angiotensin II (Ang II) is a major regulator of aldosterone synthesis and secretion, and it is known to facilitate reactive oxygen species (ROS) generation in many cell types. Here, we assessed the role of ROS signaling in Ang II-induced aldosterone synthesis by focusing on the regulation of aldosterone synthase (CYP11B2), a cytochrome P450 oxidase that catalyzes the final step in aldosterone biosynthetic pathway. Ang II increased CYP11B2 activity, mRNA and protein with a concomitant elevation of 6-Carboxy- 2',7'-dichlorodihydrofluorescein diacetate fluorescence, malondialdehyde and protein carbonyl levels (indices of ROS), NADPH oxidase (Nox) activity, and H(2)O(2) levels in human and rat adrenal cortical cells. The expression of nuclear receptor related 1 protein, a transcription factor known to regulate CYP11B2 expression, was also augmented by Ang II. These Ang II-evoked effects were either abolished or attenuated by pretreatment of cells with either Ang II type I receptor (AT(1)R) antagonist, or antioxidants or Nox inhibitor or siRNA silencing of Nox1, 2 and 4, or inhibitors of phospholipase C and protein kinase C. Exogenous H(2)O(2) mimicked the facilitatory effects of Ang II on CYP11B2 activity, mRNA, and protein expression, and these changes were significantly reduced by PEG-catalase. ROS, particularly H(2)O(2), is identified as a key regulator of aldosterone production. Our results suggest that Ang II facilitates CYP11B2 activity and the ensuing aldosterone production via activation of AT(1)R-Nox-H(2)O(2) signaling pathway.


Surgical treatment of pulmonary metastases in germ-cell testicular cancer patients--long-term results.
The aim of this prospective clinical study is to evaluate our 20-year experience with surgical treatment of pulmonary metastases in germ-cell testicular cancer and discuss the optimal therapeutical approach. Authors presents 63 patients who were surgically treated in the period from 1988 to 2008 for pulmonary metastases in germ cell testicular cancer. All patients were allocated for surgical treatment after undergoing cisplatin-based combination chemotherapy. In a group of 63 patients, 57 thoracotomias and 27 sternotomias were performed. In pulmonary procedures small atypical resections prevailed--84%. Postoperative mortality was 1.2%. Decision for follow-up treatment was made on basis of histological investigation of metastases. In some cases when viable tumor tissue was found (16% patients), further chemotherapy was administered. The rest of patients were monitored intensively. In a long-term follow-up, remission was achieved in almost 60% of patients. We suggest that lung metastasectomy as the secondary treatment in generalized germ cell testicular cancer should be fully warranted (Fig. 3, Ref. 16). Full Text (Free, PDF) www.bmj.sk.


Interrater reliability of scores derived from two methods for scoring the clock drawing test.
Scores on the Clock Drawing Test have long been considered a useful screening tool for neuropsychological dysfunction, and a number of scoring methods have been developed to evaluate various aspects of performance. This study compared quantitative and qualitative scoring by briefly trained students on 145 clock drawings produced by patients in a geriatric psychiatry outpatient clinic to estimate the interrater reliability of the methods, user's acceptance of the methods, and whether the methods provide differential diagnosis. Both systems showed acceptable interrater reliability. Using the quantitative method, raters scored drawings by patients with organic mental disease as more impaired than those patients diagnosed as depressed or schizophrenic. Results suggest that the Clock Drawing Test is a reliable screening tool for cognitive impairment in a geropsychiatric population, but the scoring methods examined do not yet appear psychometrically sound enough to provide a differential diagnosis.


Subunit arrangement in beef heart complex III.
Beef heart mitochondrial complex III was separated into 12 polypeptide bands representing 11 different subunits by using the electrophoresis conditions described by Schägger et al. [(1986) Methods Enzymol. 126, 224-237]. Eight of the 12 polypeptide bands were identified from their NH2-terminal sequences as obtained by electroblotting directly from the NaDodSO4-polyacrylamide gel onto a solid support. The topology of the subunits in complex III was explored by three different approaches. (1) Protease digestion experiments of submitochrondrial particles in the presence and absence of detergent showed that subunits II and VI are on the M side of the inner membrane and subunits V and XI on the C side. (2) Labeling experiments with the membrane-intercalated probes [125I]TID and arylazidoPE indicated that cytochrome b is the predominant bilayer embedded subunit of complex III, while the non-heme iron protein appears to be peripherally located. (3) Cross-linking studies with carbodiimides and homobifunctional cleavable reagents demonstrated that near-neighbor pairs include subunits I+II, II+VI, III+VI, IV+V, V+X, and reagents demonstrated that near-neighbor pairs include subunits I+II, II+VI, III+VI, IV+V, V+X, and VI+VII. The cytochrome c binding site was found to include subunits IV, VIII, and X. The combined data are used to provide an updated model for the topology of beef heart complex III.


A new method for stability analysis of recurrent neural networks with interval time-varying delay.
This brief deals with the problem of stability analysis for a class of recurrent neural networks (RNNs) with a time-varying delay in a range. Both delay-independent and delay-dependent conditions are derived. For the former, an augmented Lyapunov functional is constructed and the derivative of the state is retained. Since the obtained criterion realizes the decoupling of the Lyapunov function matrix and the coefficient matrix of the neural networks, it can be easily extended to handle neural networks with polytopic uncertainties. For the latter, a new type of delay-range-dependent condition is proposed using the free-weighting matrix technique to obtain a tighter upper bound on the derivative of the Lyapunov-Krasovskii functional. Two examples are given to illustrate the effectiveness and the reduced conservatism of the proposed results.


International Scientific Collaboration on Pituitary Research: A Social Network Analysis.
Background: Social network analysis (SNA) evaluates the connections and behavior of individuals in social groups. The scientific collaboration network is a kind of SNAs. A social network could be defined as a collection of nodes (social existence) and links (connections) associated with the nodes. The aim of this study was to evaluate the scientific outputs and collaboration networks of the countries and authors using indicators of SNA in the field of pituitary disorders between 2000 and 2020. Methods: This is a practical study performed by applying a scientometric approach and SNA. We retrieved 31257 papers in the field of pituitary disorders between 2000 and 2020. Data were analyzed using scientific software, namely, VOSviewer, UciNet, and Netdarw. Results: Based on degree centrality, Colao and Pivonello in the world, Shimon and Kadioghlu in the Middle-East (ME), and Khamseh, Ghorbani in Iran achieved the top ranking. Based on the betweenness centrality, Pivonello, Colao, and Chanson in the world, Laws, and Kadioghlu in the Middle-East, and Larijani, Mohseni, and Khamseh in Iran were known as the top authors. According to closeness centrality, Pivonello, Colao, and Chanson in the world, Kadioghlu and Kelestimur in the Middle-East, and Mohseni, Khamseh, and Larijani in Iran were the top authors. The map of the authors' collaboration in the field of pituitary disorders consists of 92 nodes. A total number of 77313 authors had global collaboration. The global collaboration network was comprised of 129 nodes (country) and 2694 links (country's collaboration). The Middle-East collaboration network revealed 69 nodes and 1708 links. The collaboration network of the Middle-East countries consists of 13 nodes and 50 links. Conclusion: Authors with a higher degree, betweenness and closeness centrality have greater efficiency (the number of articles) and effectiveness (the number of received citations). Moreover, the authors and countries that published more scientific products received more citations. In addition, in the Middle-East countries, the interdisciplinary scientific collaboration between the researchers in the fields of endocrinology, neurosurgery, pathology, and radiology has a significant impact on improving scientific outputs.


Effect of risperidone on serum cytokines.
A variety of cytokines are dysregulated in schizophrenia, and some antipsychotic drugs effect cytokines. In order to examine the effect of risperidone on plasma cytokines, we measured the serum level of IL-1b, IL-2, IL-6, IL-12, and INF-g during acute states of illness, and after 4 weeks of treatment with risperidone in 19 schizophrenic patients. The patients' psychopathology was assessed by PANSS. Plasma IL-12 levels increased significantly after 4 weeks of treatment (p = .002). Plasma IL-b, IL-2, IL-6, and INF-g levels were not significantly different before and after treatment. There were no significant correlations between the changes in cytokine levels and the changes in PANSS scores. Increased IL-12 may contribute to activation of immune responses during treatment with risperidone. IL-12 may play an important role in immune responses related to neuropsychiatry.


Materials discovery and crystal growth of zeolite A type zeolitic-imidazolate frameworks revealed by atomic force microscopy.
A new zeolitic-imidazolate framework (ZIF), [Zn(imidazolate)2-x(benzimidazolate)x], that has the zeolite A (LTA) framework topology and contains relatively inexpensive organic linkers has been revealed using in situ atomic force microscopy. The new material was grown on the structure-directing surface of [Zn(imidazolate)1.5(5-chlorobenzimidazolate)0.5] (ZIF-76) crystals, a metal-organic framework (MOF) that also possesses the LTA framework topology. The crystal growth processes for both [Zn(imidazolate)2-x(benzimidazolate)x] and ZIF-76 were observed using in situ atomic force microscopy; it is the first time the growth process of a nanoporous material with the complex zeolite A (LTA) framework topology has been monitored temporally at the nanoscale. The results reveal the crystal growth mechanisms and possible surface terminations on the {100} and {111} facets of the materials under low supersaturation conditions. Surface growth of these structurally complex materials was found to proceed through both "birth-and-spread" and spiral crystal-growth mechanisms, with the former occurring through the nucleation and spreading of metastable and stable sub-layers reliant on the presence of non-framework species to bridge the framework during formation. These results support the notion that the latter process may be a general mechanism of surface crystal growth applicable to numerous crystalline nanoporous materials of differing complexity and demonstrate that the methodology of seeded crystal growth can be used to discover previously unobtainable ZIFs and MOFs with desirable framework compositions.


The algicidal activity of Aeromonas sp. strain GLY-2107 against bloom-forming Microcystis aeruginosa is regulated by N-acyl homoserine lactone-mediated quorum sensing.
Cyanobacterial blooms have disrupted the efficient utilization of freshwater worldwide. A new freshwater bacterial strain with strong algicidal activity, GLY-2107, was isolated from Lake Taihu and identified as Aeromonas sp. It produced two algicidal compounds: 2107-A (3-benzyl-piperazine-2,5-dione) and 2107-B (3-methylindole). Both compounds exhibited potent algicidal activities against Microcystis aeruginosa, the dominant bloom-forming cyanobacterium in Lake Taihu. The EC50 values (concentration for 50% maximal effect) of 3-benzyl-piperazine-2,5-dione and 3-methylindole were 4.72 and 1.10 μg ml-1 respectively. Based on a thin-layer chromatography biosensor assay and ultra-performance liquid chromatography-coupled high resolution-tandem mass spectrometry (UPLC-HRMS/MS), the N-acyl homoserine lactone (AHL) profile of strain GLY-2107 was identified as two short side-chain AHLs: N-butyryl-homoserine lactone (C4-HSL) and N-hexanoyl-homoserine lactone (C6-HSL). The production of the two algicidal compounds was controlled by AHL-mediated quorum sensing (QS), and C4-HSL was the key QS signal for the algicidal activity of the strain GLY-2107. Moreover, 3-methylindole was found to be positively regulated by C4-HSL-mediated QS, whereas 3-benzyl-piperazine-2,5-dione might be negatively controlled by C4-HSL-mediated QS. This study suggests that a QS-regulated algicidal system may have potential use for the development of a novel control strategy for harmful cyanobacterial blooms.


Increased Angiogenesis and Decreased Programmed Cell Death Increases the Risk of Uterine Cervical Cancer.
Cervical cancer is one of the most common female malignancies and leading cause for high mortality rate. In the present study we made an attempt to determine the extent of angiogenesis, apoptosis, accumulation of mutant p53 protein, cell proliferation rate in the uterine cervical cancer tissues. Cervical cancer samples were obtained from patients and they were subjected to PCR analysis and immunocytochemistry. A total of 30 cervical cancer tissue samples were analyzed, by PCR, we found 25 collected cervical cancer samples showed HPV-16 and E6 positive. Further, we observed the increased CD34 expression was associated with HPV-16 and E6 positive cancer tissues when compared to the corresponding control tissues. This elevated level of CD34 confirms the increased extent of angiogenesis in cervical cancer tissues. Further by immunocytochemistry we have demonstrated that the rate of apoptosis is reduced, over expression of bcl-2, Ki 67 and thus increases rate of cell proliferation. Therefore, our data suggest that development of new anticancer or antiviral drugs could efficiently compromise the HPV-16 mediated angiogenesis and reduced apoptosis in cervical cancer and thus will improve the survival rate of patients.


Resting-state brain correlates of instantaneous autonomic outflow.
A prominent pathway of brain-heart interaction is represented by autonomic nervous system (ANS) heartbeat modulation. While within-brain resting state networks have been the object of intense functional Magnetic Resonance Imaging (fMRI) research, technological and methodological limitations have hampered research on the central correlates of cardiovascular control dynamics. Here we combine the high temporal and spatial resolution as well as data volume afforded by the Human Connectome Project with a probabilistic model of heartbeat dynamics to characterize central correlates of sympathetic and parasympathetic ANS activity at rest. We demonstrate an involvement of a number of brain regions such as the Insular cortex, Frontal Gyrus, Lateral Occipital Cortex, Paracingulate and Cingulate Gyrus and Precuneous Cortex, as well as subcortical structures (Thalamus, Putamen, Pallidum, Brain-Stem, Hippocampus, Amygdala, and Right Caudate) in the modulation of ANS-mediated cardiovascular control, possibly indicating a broader definition of the central autonomic network (CAN). Our findings provide a basis for an informed neurobiological interpretation of the numerous studies which employ HRV-related measures as standalone biomarkers in health and disease.


Violence exposure and burn-out among Turkish nursing home staff.
The aim of this study was to describe the frequency of violence against personnel from residents and to identify the prevalence of burn-out among staff working in nursing homes. The study was performed in two cities in the west of Turkey. A semi-structured questionnaire on violence and Pines' Burnout scale were distributed among all the staff working in six nursing homes, and 214 of them responded. Of the total number of respondents, 56% stated that they had been exposed to violence during the preceding year. More than 20% stated that they had reported violence to their supervisor. Less than 10% had received medical or psychological support following the event. Violent incidents were reported significantly more frequently among staff who reported problems working with elderly residents. There was no relationship between violence towards staff and burn-out. Violence is commonly experienced by care workers in nursing homes for the elderly. Strategies to improve occupational conditions in nursing homes are required.


Immune regulation effect of lienal polypeptides extract in Lewis lung carcinoma-bearing mice treated with cyclophosphamide.
Polypeptides extracted from animal immune organs have been proved to exert immunomodulatory activities in previous reports. However, relative experimental data regarding the influence of a polypeptide mixture extracted from healthy calf spleen (lienal polypeptide [LP]) on the immune function in tumor therapy are limited, and the components in LP remain unclear. In the present study, the immune regulatory effect of LP was investigated in normal mice and Lewis lung carcinoma (LLC)-bearing mice treated with cyclophosphamide (CTX). The components of LP were identified by liquid chromatography-electrospray ionization-coupled with tandem mass spectrometry (LC-MS/MS) analysis and bioinformatic analysis. In LLC-bearing mice, LP showed a synergic antitumor effect with CTX, whereas LP alone did not present direct antitumor activity. Further, LP was found to enhance immune organ indexes, splenocyte number, and T lymphocyte subsets in normal mice and LLC-bearing mice treated with CTX. The decline of white blood cell and platelet counts, splenocyte proliferation activity, and peritoneal macrophage phagocytic function caused by CTX were also significantly suppressed by LP treatment in LLC-bearing mice. Notably, LP treatment significantly decreased the expression of phagocytosis-related proteins including CD47/signal regulatory protein α/Src homology phosphatase-1 in the tumor tissue of LLC-bearing mice treated with CTX. LC-MS/MS-based peptidomics unraveled the main polypeptides in LP with a length from 8 to 25 amino acids. Bioinformatics analysis further confirmed the possibility of LP to regulate immunity, especially in phagocytosis-related pathway. Our above findings indicated that LP can relieve the immunosuppression induced by chemotherapy and is a beneficial supplement in cancer therapy. Impact statement The immunomodulatory activities of polypeptides extracted from animal immune organs have incurred people's interests since a long time ago. In this study, we investigated the immune regulation effects of a polypeptide mixture extracted from health calf spleen (lienal polypeptide [LP]) in Lewis lung carcinoma-bearing mice treated with cyclophosphamide (CTX). Liquid chromatography-electrospray ionization-coupled with tandem mass spectrometry-based peptidomics and bioinformatics analysis unraveled the main polypeptides in LP and further confirmed that LP is mainly associated with immune regulating pathway, especially in tumor cell phagocytosis-related pathway. Our study for the first time revealed that polypeptides from spleen can relieve the immunosuppression induced by CTX and is a beneficial supplement in cancer therapy.


Structural property-induced different phonon-twin-boundary scattering in diamond.
Twin boundaries (TBs), as one kind of crystal defect, have often been observed in various material systems, and the (111)/[110] TB has been verified to show weak phonon scattering. However, it's still not clear whether other TBs can show similar thermal properties to the (111)/[110] TB. To solve this issue, in this work, we perform a systematic study of heat transport across six kinds of twin boundaries in diamond, including the (111)/[110], (221)/[110], (331)/[110], (113)/[110], (112)/[110] and (310)/[001] TBs, by both molecular dynamics simulations and first-principles calculations. The results indicate that the thermal boundary resistance of the six TBs ranges from 1.01 × 10-11 to 6.35 × 10-10 m2 K W-1; specifically, the (111)/[110] TB shows much weaker phonon scattering than the others. The different phonon scattering at TBs mainly depends on the transmission coefficients across the twin boundaries for boundaries with the same symmetry, as well as the combined action of group velocity and phonon mean free path. Furthermore, by analyzing the structural properties of TBs, it can be observed that TB thermal resistance varies significantly with the TB structure, and is strongly correlated with TB energy and bond difference parameter. Our findings will provide useful guidelines for designing efficient thermoelectric and thermal management materials based on phonon-TB scattering.


Stress factors of nursing students in their final year.
To identify the stress factors of the university environment and the repercussions on the quality of sleep and life of students in their last year of undergraduate nursing. A cross-sectional, comparative, quantitative study conducted with students in their last year of undergraduate nursing in a private institution in the south of Minas Gerais. The Instrument for the Assessment of Stress in Nursing Students (ASNS), the Pittsburgh Sleep Quality Index (PSQI), the WHOQOL-Bref quality of life questionnaire and the sociodemographic characterization questionnaire were applied for data collection; association, comparison and correlation coefficient tests and descriptive statistics were performed for data analysis. The sample consisted of 55 participants. There was a strong correlation between Time Management of stress with sleep and the physical, psychological and environmental domains of quality of life, in addition to the significant association for insomnia and some sociodemographic variables. Stress factors were associated with poor quality sleep and changes in quality of life. Time Management was the factor with the greatest potential for stress. The ninth semester had greater exposure to stressors, worse quality of sleep and life.


Emotional Speech Recognition Method Based on Word Transcription.
The emotional speech recognition method presented in this article was applied to recognize the emotions of students during online exams in distance learning due to COVID-19. The purpose of this method is to recognize emotions in spoken speech through the knowledge base of emotionally charged words, which are stored as a code book. The method analyzes human speech for the presence of emotions. To assess the quality of the method, an experiment was conducted for 420 audio recordings. The accuracy of the proposed method is 79.7% for the Kazakh language. The method can be used for different languages and consists of the following tasks: capturing a signal, detecting speech in it, recognizing speech words in a simplified transcription, determining word boundaries, comparing a simplified transcription with a code book, and constructing a hypothesis about the degree of speech emotionality. In case of the presence of emotions, there occurs complete recognition of words and definitions of emotions in speech. The advantage of this method is the possibility of its widespread use since it is not demanding on computational resources. The described method can be applied when there is a need to recognize positive and negative emotions in a crowd, in public transport, schools, universities, etc. The experiment carried out has shown the effectiveness of this method. The results obtained will make it possible in the future to develop devices that begin to record and recognize a speech signal, for example, in the case of detecting negative emotions in sounding speech and, if necessary, transmitting a message about potential threats or riots.


Functional characterization of tlmH in Streptoalloteichus hindustanus E465-94 ATCC 31158 unveiling new insight into tallysomycin biosynthesis and affording a novel bleomycin analog.
Tallysomycins (TLMs) belong to the bleomycin (BLM) family of anticancer antibiotics and differ from the BLMs principally by the presence of a 4-amino-4,6-dideoxy-L-talose attached to C-41 of the TLM backbone as part of a glycosylcarbinolamide. To facilitate an understanding of the differences in anticancer activities observed between TLMs and BLMs, we thought to generate des-talose TLM analogs by engineering TLM biosynthesis in Streptoalloteichus hindustanus E465-94 ATCC 31158. Here we report (i) the engineering of the DeltatlmH mutant SB8005 strain that produces the two TLM analogs, TLM H-1 and TLM H-2, (ii) production, isolation, and structural elucidation of TLM H-1 and TLM H-2 by NMR and mass spectroscopic analyses as the desired des-talose TLM analogs, and (iii) comparison of the DNA cleavage activities of TLM H-1 with selected TLMs and BLMs. These findings support the previous functional assignment of tlmH to encode an alpha-ketoglutarate-dependent hydroxylase and unveil the TlmH-catalyzed hydroxylation at both C-41 and C-42 and the TlmK-catalyzed glycosylation of a labile carbinolamide intermediate as the final two steps for TLM biosynthesis. TlmH is apparently distinct from other enzymes known to catalyze carbinolamide formation. The availability of TLM H-1 now sets the stage to study the TlmH enzymology in vitro and to elucidate the exact contribution of the l-talose to the anticancer activities of TLMs in vivo.


Numerical method for studying the detectability of inclusions hidden in optically turbid tissue.
We introduce an efficient numerical method for studying the detectability of absorptive inclusions in a multiple-scattering optical medium. Use of the method is demonstrated by the forward calculation of integrated and time-gated photon intensities. Schemes for positioning the light source above an inclusion and otherwise determining the location of a hidden object, involving either reflected or transmitted reemissions, are discussed as examples. They are investigated for several illustrative models, and images are calculated as a function of the size and shape of the inclusion.


[Somatostatin receptor scintigraphy. Methodology, indications, results].
Somatostatin-receptor scintigraphy has been in clinical use for several years. Most of the experience with somatostatin tumor scintigraphy has been obtained with gastro-enteropathic (GEP) tumors and carcinoids. Clinical applications of somatostatin imaging have been reported in small-cell lung carcinomas, malignant lymphomas, renal-cell carcinomas, breast cancers and medullary thyroid cancers. Somatostatin analogues were initially applicable in larger medical institutions because of the necessity for radioactive labeling with iodine (octreotide to [123I-Tyr3]-octreotide); however, the clinical results with iodinated analogues were worse than the relatively new analogue [111In-DTPA-D-Phe1]octreotide, now available as Octreoscan. This review describes the current status of the clinical application of somatostatin receptor imaging, together with our own experience in carcinoids, GEP tumors and medullary thyroid carcinomas.


New developments in the clinical use of didanosine.
Didanosine (ddI) is a purine analogue that demonstrates in vitro anti-human immunodeficiency virus (HIV) activity, effects on the surrogate markers CD4+ T-lymphocytes and p24 antigen, and has adequate oral bio-availability. Recently, 500 mg/day of ddI in sachet form demonstrated clinical effectiveness compared with zidovudine (ZDV) for delaying HIV disease progression in patients with AIDS or AIDS related complex (ARC) and less than 300 CD4+ T-lymphocytes, or asymptomatic individuals with less than 200 CD4+ T-lymphocytes. All patients tolerated a minimum of 16 weeks of prior ZDV treatment. ddI treatment was associated with an increase in serum amylase and pancreatitis, however, there was no significant difference in the incidence of pancreatitis between the 500 mg ddI and ZDV groups. There was significantly more hematologic toxicity associated with ZDV and no difference between ddI and ZDV groups with respect to peripheral neuropathy. ddI is presently available in tablet form with 125% the bioavailability of the sachet form of ddI; therefore, the 500-mg sachet formulation corresponds to a 400-mg daily tablet dose of ddI. Future studies of ddI will involve ddI's effects on antiretroviral naive patients and the potential of combining ddI with other agents.


Design of curcumin loaded cellulose nanoparticles for prostate cancer.
Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural diphenol, has shown potent anti-cancer efficacy in various types of cancers. However, suboptimal pharmacokinetics and poor bioavailability limit its effective use in cancer therapeutics. Several successful CUR nanoformulations have recently been reported which improve upon these features; however, there is no personalized safe nanoformulation for prostate cancer. This study contributes two important scientific aspects of prostate cancer therapeutics. The first objective was to investigate the comparative cellular uptake and cytotoxicity evaluation of β-cyclodextrin (CD), hydroxypropyl methylcellulose (cellulose), poly(lactic-co-glycolic acid) (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR) formulation exhibited the highest cellular uptake and caused maximum ultrastructural changes related to apoptosis (presence of vacuoles) in prostate cancer cells. Secondly, the anti-cancer potential of the cellulose-CUR formulation was evaluated in cell culture models using cell proliferation, colony formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose-CUR formulation showed improved anti-cancer efficacy compared to free curcumin. Our study shows, for the first time, the feasibility of cellulose-CUR formulation and its potential use in prostate cancer therapy.


Universal Near-Infrared and Mid-Infrared Optical Modulation for Ultrafast Pulse Generation Enabled by Colloidal Plasmonic Semiconductor Nanocrystals.
Field effect relies on the nonlinear current-voltage relation in semiconductors; analogously, materials that respond nonlinearly to an optical field can be utilized for optical modulation. For instance, nonlinear optical (NLO) materials bearing a saturable absorption (SA) feature an on-off switching behavior at the critical pumping power, thus enabling ultrafast laser pulse generation with high peak power. SA has been observed in diverse materials preferably in its nanoscale form, including both gaped semiconductor nanostructures and gapless materials like graphene; while the presence of optical bandgap and small carrier density have limited the active spectral range and intensity. We show here that solution-processed plasmonic semiconductor nanocrystals exhibit superbroadband (over 400 THz) SA, meanwhile with large modulation depth (∼7 dB) and ultrafast recovery (∼315 fs). Optical modulators fabricated using these plasmonic nanocrystals enable mode-locking and Q-switching operation across the near-infrared and mid-infrared spectral region, as exemplified here by the pulsed lasers realized at 1.0, 1.5, and 2.8 μm bands with minimal pulse duration down to a few hundreds of femtoseconds. The facile accessibility and superbroadband optical nonlinearity offered by these nonconventional plasmonic nanocrystals may stimulate a growing interest in the exploiting of relevant NLO and photonic applications.


[Detection of respiratory allergies using the Phadiatop test in children 1 to 6 years of age].
Phadiatop, a new test for detecting hypersensitivity to airborne allergens, was used in 83 children aged 9 months to 6 years with recurrent respiratory manifestations, i.e. recurrent expiratory obstruction and/or recurrent respiratory infections. A good correlation was found between this test and both the prick tests (95%) and the specific IgE assays (91% for RASTS of classes greater than or equal to 1, and 95% for RASTS of classes greater than or equal to 2). However, the correlation was less strong with the total IgE level (68%). The overall correlation with the specialist's prediction based on history and physical evaluation was excellent (94%). In this study, Phadiatop was found to have a 90% sensitivity and a 98% specificity. Furthermore, this test costs 40% less than the often used strategy combining skin tests and determinations of total and specific IgE levels. In the age group studied, Phadiatop is most useful above the age of two, since in younger patients true respiratory allergies are fairly infrequent in recurrent ENT and lower respiratory tract infections, whereas infections are far more common.


Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines.
Non-small cell lung cancer (NSCLC) cells have constitutively high expression of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX) 2. These NSCLC cells also have increased prostaglandin expression (PGE2). Many lung cancers also express 12-lipoxygenase RNA and 12-lipoxygenase protein and biosynthesize 12(S)-hydroxyeicosatetraenoic acid, which correlates with their metastatic potential. Several studies have demonstrated that COX-1 and COX-2 inhibitors could inhibit the in vitro growth of human lung cancer cell lines. In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines. We compared these effects with those of 13-cis-retinoic acid, a chemoprevention agent, and with the cytotoxic chemotherapeutic agents paclitaxel and cisplatin, alone or in combination. Our goal was to develop new chemoprevention and treatment strategies. Each of the six agents tested inhibited the in vitro growth of three NSCLC and three SCLC cell lines at the highest concentration. Paclitaxel was the most potent agent (IC50 = 0.003-0.150 microM); sulindac sulfide, NDGA, and 13-cis-retinoic acid had intermediate potency (IC50 = 4-80 microM), and cisplatin and exisulind were the least potent (IC50 = 150-500 microM). Combination studies showed synergistic interactions for sulindac sulfide, exisulind, and NDGA with paclitaxel, cisplatin, and 13-cis-retinoic acid, regardless of drug-resistance phenotype. At high concentrations, the combination of 13-cis-retinoic acid and each of the five other drugs resulted in a strong synergistic effect. These studies provide a rationale for chemoprevention (exisulind +/- retinoic acid +/- NDGA) and therapeutic (exisulind +/- paclitaxel +/- cisplatin) studies in patients at risk for, or with, lung cancer.


A sensitive and specific radiochromatographic assay of fatty acid amide hydrolase activity.
A radiochromatographic method has been set up in order to determine fatty acid amide hydrolase (FAAH) activity, based on reversed-phase high-performance liquid chromatography and on-line scintillation counting. The reaction products were separated using a C18 column eluted with methanol-water-acetic acid and quantitated with an external standard. Baseline separation of the acid product from the substrate was completed in less than 4 min, with a detection limit of 2.5 fmol arachidonic acid at a signal to noise ratio of 4:1. The method enabled to determine the kinetic constants (i.e., apparent Km of 2.0 +/- 0.2 microM and Vmax of 800 +/- 75 pmol. min-1. mg protein-1 toward anandamide) and the substrate specificity of human brain FAAH, as well as the extent of enzyme inhibition by some anandamide congeners. The femtomole sensitivity and the accuracy of the method allow detection and characterization of the activity of FAAH in very minute tissue samples or in samples where the enzymatic activity is very low.


Intraoperative pediatric laryngeal electromyography: experience and caveats with monopolar electrodes.
We report our experience with intraoperative laryngeal electromyography (L-EMG) using direct laryngoscopy and placement of monopolar electrodes under general anesthesia in the evaluation and management of laryngeal dysfunction in pediatric patients. In this series of case studies, we present clinical data on 30 pediatric patients with known or suspected anatomic or neurologic laryngotracheal disorders evaluated with placement of shielded monopolar electrodes into the thyroarytenoid muscles during direct laryngoscopy under general anesthesia. Diagnoses included congenital vocal fold paralysis (VFP), laryngotracheal stenosis, cerebral palsy, laryngeal tumors, traumatic vocal fold dysfunction, and postsurgical VFP. The impact of L-EMG on patient management was assessed. We found that L-EMG objectively supported clinical findings, but provided new objective data relevant toward management recommendations in only a few selected pediatric patients with new-onset vocal fold paralysis or paresis or infiltrative laryngeal tumors, and in selected postsurgical cases involving decannulation decisions. The prognostic utility of L-EMG in newborns with congenital VFP has not been established. A normal L-EMG recording indicates an intact neuromuscular axis, but does not guarantee vocal fold mobility or guarantee muscle function in a partially denervated or deconditioned muscle. The potential for false-negative recordings is the major limitation of this technique.


The effect of tolcapone on the pharmacokinetics of benserazide.
This study investigated the potential interaction between tolcapone, a catechol-O-methyltransferase (COMT) inhibitor, and the decarboxylase inhibitor, benserazide. In an open-labelled six-week study, patients with Parkinson's disease (PD), treated with levodopa/benserazide, were given tolcapone at 200 mg t.i.d. Blood samples for analysis of benserazide, its main active metabolite, trihydroxybenzylhydrazine, levodopa and 3-O- methyldopa (3-OMD) were collected immediately before and repeatedly after the first drug intake of the day at baseline and after 1-2 and 6 weeks of treatment. Furthermore, animal experiments were performed to determine the levels of benserazide and trihydroxybenzylhydrazine at doses for which safety had previously been established. It was shown that tolcapone can cause an increase in benserazide plasma concentrations and that this effect is dependent on the benserazide dose. When tolcapone was combined with 25 mg benserazide the elevation was small. Although the increase was more pronounced when tolcapone was combined with 50 mg benserazide, the levels were still substantially lower than concentrations causing toxicity in animals. The safety margin derived from this study, together with the absence of any organic toxic effects in clinical trials, show that the observed interaction between tolcapone and benserazide does not represent a safety concern for PD patients treated with this combination.


The metrics of spatial distance traversed during mental imagery.
The authors conducted 2 experiments to study the metrics of spatial distance in a mental imagery task. In both experiments, participants first memorized the layout of a building containing 10 rooms with 24 objects. Participants then received mental imagery instructions and imagined how they walked through the building from one room to another. The authors manipulated Euclidean distance involved in these imaginary motions: Spatial distance measured in centimeters on the layout was either short or long. Independently, they varied categorical distance: The motions led through one room or two rooms. The time needed to imagine motions and response times to test probes indicated that both Euclidean distance and categorical distance affected mental imagery. The authors discuss the new finding of categorical distance effects in mental imagery and relate the results to earlier failures to find Euclidean distance effects in formally equivalent studies of narrative comprehension.


Radiation damage to bull sperm motility. II. Proton irradiation and respiration measurements.
Diluted bull semen samples were bombarded with a 24 Mev proton beam. Dose response curves for the fraction of cells which survived the bombardment and for the average velocity of the surviving cells were measured. Target theory indicated a cross section of the sensitive volume of 2.1 x 10(-10) cm(2). Respiration measurements showed that the oxidative phosphorylation in the sperm remained coupled after the bombardments. The efficiency with which free energy from ATP hydrolysis was converted into mechanical work by the sperm was found to decrease after proton bombardment. The half-value dose for this effect was two and a half times higher than the half-value dose for motility damage. These respiration measurements indicate that the damage due to the bombardment is not to the metabolic system or to the contractile system in the sperm flagellum, but to a control system for the motility. The results of the target theory shows that this control system is localized in a small element of approximately 1600 A diameter. The centriole is tentatively proposed as being this control element.


[Autoimmune dysthyroidism induced by alpha interferon in two female patients with chronic non-A, non-B hepatitis].
We report two cases of autoimmune thyroid disorders which appeared after 6 months of recombinant alpha interferon therapy given for chronic non-A, non-B hepatitis. There was no family or personal history of thyroid disease, or had the patients taken any hepatic or thyroid toxic drugs. The other causes of hepatic and thyroid diseases were ruled out. The first case concerned a 33-year-old woman with sporadic hepatitis C. Therapy was complicated by the appearance of antimicrosomal thyroid antibodies and hypothyroidism. At 22 months, substitutive therapy was still necessary in one case. The second case involved a 37-year-old woman with post-transfusional non-A, non-B hepatitis which was complicated by transient hypothyroidism preceding thyrotoxicosis (with TSH-receptor antibodies). We observed a return to euthyroidism and loss of associated antibodies after withdrawal of interferon and institution of hormonal therapy.


Corneal shape evaluation by using laser keratopography.
Corneal topography assessment plays a fundamental role in the detection of keratoconus and the evaluation of the refractive surgery patient. The main drawbacks of the methods based on the use of Placido's disk (the most commonly used technique) have been pointed out recently, and new techniques are being sought that allow clinicians to be more confident about the measurement. Some years ago, we proposed a new technique based on a scan of the corneal surface with a low power HeNe laser beam; by measuring the deflection of the reflected beam, it is possible to compute the shape of the scanned cornea. In this paper, we explain the basic theory behind the method and present numerical simulations which show that errors in the surface heights of less than 1 microm may be obtained. In this work, we do not consider the effect of experimental errors. We discuss some possible extensions and improvements to the theory.


Discoid Lateral Meniscus in Children: Diagnosis, Management, and Outcomes.
Discoid meniscus is a congenital variant of the knee joint that typically involves abnormal morphology and potential instability of the lateral meniscus. Some discoid menisci have abnormal peripheral attachments and are unstable. Discoid menisci are prone to tearing secondary to increased thickness, poor tissue quality, and instability. Patients may or may not be symptomatic. Torn or unstable discoid menisci cause mechanical symptoms, pain, and swelling. Symptomatic patients in whom nonsurgical management fails most frequently are treated with arthroscopic surgery. Historically, complete meniscectomy has successfully alleviated symptoms but has resulted in poor midterm results, with degenerative changes to the knee joint. Current treatment emphasizes the saucerization of the meniscus, with removal of the central disk and retention of the peripheral crescent. Peripheral meniscal repair is performed when instability is present. Short-term results are good; however, degenerative changes have been reported at intermediate follow-up.


[Protective role of kartolin-4 in soil drought in wheat plants].
Parameters of photosynthesis, heat-resistance, and osmotic pressure of cell exudate of leaves of the drought-sensitive cultivar Lyutestsens 758 of wheat, Triticum aestivum, were studied under conditions of normal water supply, soil drought, and subsequent rehydration. The plants preliminarily treated with kartolin-4 were compared to untreated plants. Kartolin-4, a preparation with cytokininlike activity, partially prevented the drought-induced inhibition of the photosynthetic assimilation of carbon dioxide and carboxylation activities of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 220.127.116.11), the key enzyme of carbon metabolism in plants. Upon a subsequent rehydration, kartolin-4 stimulated the reparation reactions and facilitated rapid recovery of normal photosynthetic activity. Kartolin-4 also increased plant resistance to overheating and water deficiency.


Transfedotr of Allergic Encephalomyelitis by Lymph Node Cells in Inbred Guinea Pigs.
Severe or lethal allergic encephalomyelitis was transferred between histocompatible guinea pigs by lymphoid cells capable of persistence in a viable state in the recipient. For optimum induction of passive disease, cells must be transferred before the day on which the disease becomes manifest in the donor.


Detection of a porcine-like rotavirus in a child with enteritis in Italy.
During a 1-year rotavirus surveillance of children hospitalized with acute gastroenteritis in Brescia Hospital, Italy, a chimerical rotavirus strain, G3P[6], was detected, displaying the VP7 and VP4 genes of porcine origin and the NSP4 and VP6 genes of human origin. The reassortant nature of the virus rules out a direct zoonotic event.


Poverty in Eritrea: challenges and implications for development.
Poverty, one of the world's most serious problems, is particularly severe in Africa. Eritrea is a 16-year-old nation that gained its independence from Ethiopia in 1993. The country's economy was doing relatively well between 1993 and 1997. Eritrea was then exposed to numerous challenges such as drought, famines and recurrent war. As a result, poverty has become more rampant in a country where over 66 per cent of people live below the poverty line. Some families live on remittances. The government has taken some poverty alleviation measures. However, it has not mitigated poverty due to a lack of resources and a poorly implemented poverty alleviation programme. This article attempts to explore the incidence of poverty. It also provides details of poverty surveys that have been conducted since independence. It discusses various poverty challenges and provides some policy implications for development.


Enhanced thermoelectric properties of Pb-doped BiCuSeO ceramics.
A high-performance thermoelectric oxyselenide BiCuSeO ceramic with ZT > 1.1 at 823 K and higher average ZT value (ZTave ≈0.8) is obtained. The heavy doping element and nanostructures can effectively tune its electronic structure, hole concentration, and thermal conductivity, resulting in substantially enhanced mobility, power factor, and thus ZT value. This work provides a path to high-performance thermoelectric ceramics.


In search and proof of human beings, not machines.
My intentions are twofold in this autobiographical account. On one hand, I hope to present empirical and theoretical evidence for a freely willing human being. On the other, I carefully record the developing stages I lived through to cement my confidence in the image of humanity I would like my readers to accept. I have, in my career development, worked hard to redefine psychological terminology, defend traditional scientific practices, and provide support for all those colleagues who can no longer stand the mechanistic characterization that so many psychology departments insist on. I have spent over 40 years pursuing such goals. It is not likely that I will ever give up my quest for what I take to be a genuine humanity.


Assembly of Human Stem Cell-Derived Cortical Spheroids and Vascular Spheroids to Model 3-D Brain-like Tissues.
Human cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neurons, pericytes, astrocytes, and brain microvascular endothelial cells, in brain-like tissues are less investigated. The objective of this study is to investigate the impacts of neural spheroids and vascular spheroids interactions on the regional brain-like tissue patterning in cortical spheroids derived from human iPSCs. Hybrid neurovascular spheroids were constructed by fusion of human iPSC-derived cortical neural progenitor cell (iNPC) spheroids, endothelial cell (iEC) spheroids, and the supporting human mesenchymal stem cells (MSCs). Single hybrid spheroids were constructed at different iNPC: iEC: MSC ratios of 4:2:0, 3:2:1 2:2:2, and 1:2:3 in low-attachment 96-well plates. The incorporation of MSCs upregulated the secretion levels of cytokines VEGF-A, PGE2, and TGF-β1 in hybrid spheroid system. In addition, tri-cultured spheroids had high levels of TBR1 (deep cortical layer VI) and Nkx2.1 (ventral cells), and matrix remodeling genes, MMP2 and MMP3, as well as Notch-1, indicating the crucial role of matrix remodeling and cell-cell communications on cortical spheroid and organoid patterning. Moreover, tri-culture system elevated blood-brain barrier gene expression (e.g., GLUT-1), CD31, and tight junction protein ZO1 expression. Treatment with AMD3100, a CXCR4 antagonist, showed the immobilization of MSCs during spheroid fusion, indicating a CXCR4-dependent manner of hMSC migration and homing. This forebrain-like model has potential applications in understanding heterotypic cell-cell interactions and novel drug screening in diseased human brain.


Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines.
The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment.


Remarkable anticancer activity of ferrocenyl-terpyridine platinum(ii) complexes in visible light with low dark toxicity.
Ferrocenyl platinum(ii) complexes (), viz. [Pt(Fc-tpy)Cl]Cl (), [Pt(Fc-tpy)(NPC)]Cl (, HNPC = N-propargyl carbazole) and [Pt(Fc-bpa)Cl]Cl (), were prepared, characterized and their anti-proliferative properties in visible light in human keratinocyte (HaCaT) cell lines have been studied. [Pt(Ph-tpy)Cl]Cl () was prepared and used as a control. Complexes and , structurally characterized by X-ray crystallography, show distorted square-planar geometry for the platinum(ii) centre. Complexes and having the Fc-tpy ligand showed an intense absorption band at ∼590 nm. The ferrocenyl complexes are redox active showing the Fc(+)-Fc couple near 0.6 V vs. SCE in DMF-0.1 M tetrabutylammonium perchlorate (TBAP). Complexes showed external binding to calf thymus DNA. Both and showed remarkable photocytotoxicity in HaCaT cell lines giving respective IC50 values of 9.8 and 12.0 μM in visible light of 400-700 nm with low dark toxicity (IC50 >60 μM). Fluorescent imaging studies showed the spread of the complexes throughout the cell localising both in cytoplasm and the nucleus. The ferrocenyl complexes triggered apoptosis on light exposure as evidenced from the Annexin V-FITC/PI and DNA ladder formation assays. Spectral studies revealed the formation of ferrocenium ions upon photo-irradiation generating cytotoxic hydroxyl radicals via a Fenton type mechanism. The results are rationalized from a TDDFT study that shows involvement of ferrocene and the platinum coordinated terpyridine moiety as respective HOMO and LUMO.


Transcriptome analysis and comparison reveal divergence between the Mediterranean and the greenhouse whiteflies.
Both the Mediterranean (MED) species of the Bemisia tabaci whitefly complex and the greenhouse whitefly (Trialeurodes vaporariorum, TV) are important agricultural pests. The two species of whiteflies differ in many aspects such as morphology, geographical distribution, host plant range, plant virus transmission, and resistance to insecticides. However, the molecular basis underlying their differences remains largely unknown. In this study, we analyzed the genetic divergences between the transcriptomes of MED and TV. In total, 2,944 pairs of orthologous genes were identified. The average identity of amino acid sequences between the two species is 93.6%. The average nonsynonymous (Ka) and synonymous (Ks) substitution rates and the ratio of Ka/Ks of the orthologous genes are 0.0389, 2.23 and 0.0204, respectively. The low average Ka/Ks ratio indicates that orthologous genes tend to be under strong purified selection. The most divergent gene classes are related to the metabolisms of xenobiotics, cofactors, vitamins and amino acids, and this divergence may underlie the different biological characteristics between the two species of whiteflies. Genes of differential expression between the two species are enriched in carbohydrate metabolism and regulation of autophagy. These findings provide molecular clues to uncover the biological and molecular differences between the two species of whiteflies.


In vivo MR angiography and velocity measurement in mice coronary arteries at 9.4 T: assessment of coronary flow velocity reserve.
To demonstrate the feasibility of coronary magnetic resonance (MR) angiography in living mice and to evaluate a dynamic MR angiographic method for coronary flow measurement at 9.4-T field strength. This study was conducted according to European law and was in full compliance with National Institutes of Health recommendations for animal care and a local institutional animal care committee. Mice were anesthetized by using isoflurane. First, time-of-flight MR angiography was performed in 10 mice to measure coronary diameters at 80-mum isotropic resolution. Second, left coronary artery (LCA) velocity measurements were performed at seven cardiac phases in nine other mice to assess the velocity curve profile. Third, coronary velocities were measured at the middiastolic phase in 13 mice at rest and during adenosine-induced hyperemia to calculate coronary flow velocity reserve (CFVR). The Pearson coefficient compared the correlation between isoflurane dose and CFVR. Paired t tests compared R-R intervals and respiratory rates between rest and hyperemia. Proximal diameters were, respectively, 404 mum +/- 34 [standard deviation] and 259 mum +/- 22 for the LCAs and the right coronary arteries, which were in accordance with reported values. The velocity curve profile throughout the cardiac cycle was similar to values from the literature. Baseline and hyperemic velocities were, respectively, 19.0 cm/sec +/- 4.4 and 33.7 cm/sec +/- 4.7 (P<.001), resulting in a CFVR of 1.77 +/- 0.19. CFVR did not correlate with isoflurane dose (r = 0.05, P = .88). R-R intervals shortened by 2.5% during hyperemia (P = .04). Respiratory rates showed no difference between rest and hyperemia (P = .39). High-spatial-resolution three-dimensional coronary MR angiography is feasible in living mice. Dynamic MR angiography depicts coronary velocity changes throughout the cardiac cycle and between rest and maximum hyperemia, providing a tool for CFVR assessment.


Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis.
Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16-0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58-2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: -1.11 to -0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.


[Acute inguinal swelling--unusual presentation of postoperative necrotising pancreatitis].
Necrotising pancreatitis presenting as an acute inguinal swelling is an extremely rare condition. We report on a 61-year-old male who underwent explorative laparotomy for pancreatic tumour. Intraoperatively, the diagnosis of a locally advanced carcinoma of the head of the pancreas was confirmed histologically. During the postoperative course, the patient developed an acute inguinal swelling, which was suspected to be an incarcerated hernia. Intraoperatively, exploration of both abdomen and inguinal canal revealed an acute necrotising pancreatitis. This case is, to the best of our knowledge, the first case report on a postoperative necrotising pancreatitis masquerading as an incarcerated inguinal hernia in an adult male, and the diagnostic problems are discussed.


Invisible in aging research: Arab Americans, Middle Eastern immigrants, and Muslims in the United States.
Recent worldwide events have focused greater attention on the Middle East. Little is known about the diverse populations of older persons living in the United States who have Middle Eastern origins and/or practice Islam. Stereotypes and backlash can negatively influence the quality of life for mid- and later-life individuals and their families. Gerontologists can improve conditions by incorporating new knowledge of these groups into research, policy, and practice to dispel stereotypes and provide appropriate services. This article focuses on the demographic characteristics and diversity among mid- and later-life Arab Americans, Muslims, and Middle Eastern immigrants and their descendants. Further research is needed to shed light on the family support, social patterns, housing environments, health care needs, service utilization, and quality of life among immigrants and their descendants across the life course.


A rapid, high-volume cervical screening project using self-sampling and isothermal PCR HPV testing.
Rapid, high-volume screening programs are needed as part of cervical cancer prevention in China. In a 5-day screening project in Inner Mongolia, 3345 women volunteered following a community awareness campaign, and self-swabbed to permit rapid HPV testing. Two AmpFire™ HPV detection systems (Atila Biosystems) were sufficient to provide pooled 15-HPV type data within an hour. HPV+ patients had same-day digital colposcopy (DC) performed by 1 of 6 physicians, using the EVA™ system (MobileODT). Digital images were obtained and, after biopsy of suspected lesions for later confirmatory diagnosis, women were treated immediately based on colposcopic impression. Suspected low- grade lesions were offered treatment with thermal ablation (Wisap), and suspected high-grade lesions were treated with LLETZ. Of 3345 women screened, 624 (18.7%) were HPV+. Of these, 88.5% HPV+ women underwent same-day colposcopy and 78 were treated. Later consensus histology results obtained on 197 women indicated 20 CIN2+, of whom 15 were detected and treated/referred at screening (10 by thermal ablation, 4 by LLETZ, 1 by referral). Global control of cervical cancer will require both vaccination and screening of a huge number of women. This study illustrates a cervical screening strategy that can be used to screen-and-treat large numbers of women. HPV self-sampling facilitates high-volume screening. Specimens can be tested rapidly, promoting minimal loss-to-follow-up. Specifically, the AmpFire™ system used in this study is highly portable, simple, rapid (92 specimens per 65 min per unit), and economical. Visual triage can be performed on HPV+ women with a portable digital colposcope that provides magnification, lighting, and a recorded image. Diagnosis and appropriate treatment remain the most subjective elements. The digital image is under study for deep-learning based automated evaluation that could assist the management decision, either by itself or combined with HPV typing.


Metallization on Sapphire and Low-Temperature Joining with Metal Substrates.
To meet the packaging requirements of sapphire in special electronic components, there is an urgent need for a joining process that can realize a good connection between sapphire and dissimilar metals at a low temperature. In this work, the surface of a sapphire substrate was successfully catalytically activated and metallized by an electroless nickel plating process. Moreover, the solderability and interconnection of metallized sapphire with Sn-based solders were evaluated and investigated at 250 °C, and the wetting angle of the Sn-based solders on sapphire on sapphire without and with metallization was 125° and 51°, respectively. The interfacial microscopic morphology and element distribution in the Cu/Sn-Ag solder/sapphire solder joints were analyzed. It was found that the middle solder layer has diffused during the reflow process, inferring good adhesion between sapphire and Cu substrate with the aid of the Ni-P deposition. Thus, a sapphire welding method with a simple process suitable for practical applications is demonstrated.


Leishmania donovani mucosal leishmaniasis in Malta.
We report a case of a 76-year-old British man living in Malta who presented with a 7-month history of recurrent epistaxis and an enlarging right nasal vestibular lesion. Of note, his medical history included rheumatoid arthritis for which he was on long-term methotrexate. Blood results were unremarkable other than a mild lymphopaenia. Despite the use of various antibiotics and intranasal steroids, the lesion failed to resolve. This was eventually biopsied, and the histological picture was that of mucosal leishmaniasis. Leishmania donovani complex was detected by PCR. The patient was treated with liposomal amphotericin B on alternate days for a total of 20 doses. The lesion was found to have healed well at follow-up and the patient denied any further episodes of epistaxis.


Physician duties in the conduct of human subject research.
In this article, I examine a skeptical argument against the possibility of ethically justifying risky human subject research (rHSR). That argument asserts that such research is unethical because it holds the possibility of wronging subjects who are harmed and whose consent to participate was less than fully voluntary. I conclude that the skeptical argument is not in the end sufficient to undermine the ethical foundation of rHSR because it fails to take account of the special positive duty researchers owe their clients and future patients. Although the skeptical argument is defeated, it exacts certain novel concessions from the pro-research position. Of particular importance are the admissions (a) that researchers presumptively owe a fiduciary duty to research subjects, (b) that because the most important risks of rHSR are unknown and unquantifiable that duty must be explicitly waived by all subjects before they participate in any protocol, and (c) that such waivers must be made by individuals who satisfy objective criteria of competence for giving fully voluntary consent. The implementation of procedures responsive to these concerns might have a dampening effect on the conduct of research. However, the article concludes with a consideration of the likely benefits to researchers and society of a more cautious ethical regime.


Wear Analysis of Forging Tools Used in an Industrial Production Process-Hot Forging in Closed Dies of the "Head-Disk" of an Engine Valve Forging.
The article performs an analysis of the durability of punches applied in the process of producing a valve forging from chromium-nickel steel. A forging of this type is made in two operations: coextrusion of a long shank, followed by finishing forging in closed dies of the valve head. The product obtained in this way (after other additional finishing procedures) constitutes the key element of the combustion engine (resistant to high pressures and temperatures) in motor trucks. Unfortunately, a significant problem in this production process is a relatively low durability of the forging tools, especially the punch used in the second forging operation. The key element at this stage, deciding about the punch's further operation, is the area of the so-called "calotte". The short-term life of the tools results from very hard performance conditions present during the forging process (periodical high mechanical and thermal loads, long path of friction). The latter cause intensive abrasive wear as well as high adhesion of the forging material to the tool surface. Based on the performed studies, including the following: technology analysis, numerical modelling, macro analyses combined with 3D scanning of tool sections as well as microstructural tests and hardness measurements, it was established that it is crucial to properly select the process parameters (charge and tool temperature, tribological conditions), as even slight changes introduced into them significantly affect the operation time of the forging tools. Mastering and proper implementation of the analyzed forging technology requires numerous further studies and tests, which will enable its perfection and thus increase the durability of the tools as well as the quality of the produced items.


Dental Treatments under the General Anesthesia in a Child with Keratitis, Ichthyosis, and Deafness Syndrome.
KID syndrome is a rare genodermatosis characterized by keratitis, ichthyosis, and sensorineural deafness. Although the dermatological, ophthalmologic, and sensorineural defects are emphasized in the literature, oral and dental evaluations are so superficial. In this case report, dental and oral symptoms of a three year and five months old boy with KID syndrome, suffering severe Early Childhood Caries (s-ECC) and dental treatments done under General Anesthesia (GA) were reported.


A stochastic version of the Malthusian Trap Model: consequences for the empirical relationship between economic growth and population growth in LDC's.
A stochastic version of the Malthusian trap model relating the growth rate of income per capita to the population growth rate of a given country is described. This model is applied to the a priori evaluation of the cross-sectional correlation between these 2 growth rates under 2 additional assumptions: 1) the relations in the model at national levels include country-specific and time-invariant random components, and 2) these growth rates are measured with a certain degree of temporal aggregation. It is shown that these 2 assumptions can explain near-0 correlations between the 2 growth rates even if there exist a strongly negative effect of population growth on economic growth. However, it is not clear whether these assumptions fully explain such insignificant correlations. Indeed, the implementation of the model is complicated by the structural shifts which are likely to occur in the equations over the course of the demographic transition.


Why We Still Need To Speak About Sex Differences and Sex Hormones in Pain.
In the world of pain, we must always consider the presence of gender. In nociception, as well as in pain, women are different from men in many, if not all, aspects of the system. Nociception is the sum of several events that occur from the periphery to the CNS, and there is much evidence that female nociception differs from male nociception. Moreover, it has to be considered that pain results from a male or a female cortex. Genetic, anatomical, physiological, hormonal, psychological, and social factors have been considered to explain the differences present at both levels. Notwithstanding all the evidence, it is still difficult to observe the application of this knowledge to the treatment of pain. Drugs are still given per kilogram, and clinical studies, albeit including women, often mix data from both sexes. Moreover, reports on these studies often fail to mention the women's age and reproductive status, i.e., sex hormones. Hormone levels vary from hour to hour, from day to day, and, as repeatedly confirmed, are affected by several pain killers commonly used in pain therapy. All the data confirm the urgent need to include sex differences and sex hormones among the key factors that play an important role in pain and pain treatment.


Screenieboppers and extreme screenies: the place of screen time in the time budgets of 10-13 year-old Australian children.
Excessive 'screen time' has been associated with a range of psychosocial disturbances and increasing pediatric obesity. This study describes the magnitude, distribution, composition and time-distribution of children's screen use; examines correlates of screen use; and characterises 'extreme' screen users (top quartile). 1,039 South Australian children aged 10-13 years old completed a multimedia 24-hour activity recall diary on 2-4 occasions in 2002, including at least one school day and one non-school day. The median screen time was 229 minutes.d(-1). This was higher in boys (264 vs. 196 minutes; p<0.001) and on non-school days (260 vs. 190 minutes; p<0.001), increased with age (p=0.003), and decreased with socio-economic status (SES; p=0.003). Television consumed 73% of all screen time, video games 19%, non-game computer use 6%, and cinema 2%. The top quartile of screen users were more likely to be boys (OR=3.8), have low physical activity (OR=4.3), spend >25% of screen time playing video games (OR=1.8), sleep less, and be of lower SES. Interventions to reduce screen time should target inactive, low-SES boys, encourage earlier bedtimes, and limit video game use.


Expression Analyses of Rac3, a Rho Family Small GTPase, during Mouse Brain Development.
Rac3 is a member of Rho family small GTPases which regulate cellular signaling and cytoskeletal dynamics. The RAC3 gene abnormalities have been shown to cause neurodevelopmental disorders with structural brain anomalies, including polymicrogyria/dysgyria, callosal abnormalities, brainstem anomalies, and cerebellar dysplasia. Although this evidence indicates that Rac3 is essential in brain development, not only its molecular mechanism but also the expression profile is yet to be elucidated. In this study, we carried out expression analyses of Rac3 with mouse brain tissues. In immunoblotting, Rac3 exhibited a tissue-dependent expression profile in the young adult mouse and was expressed in a developmental stage-dependent manner in brain. In primary cultured hippocampal neurons, while Rac3 was distributed mainly in the cytoplasm, it was visualized in axon and dendrites with partial localization at synapses, in consistent with the observation in biochemical fractionation analyses. In immunofluorescence analyses with brain slices, Rac3 was distributed strongly and moderately in the axon and cytoplasm, respectively, of cerebral cortex at postnatal day (P) 2 and P18. Similar distribution profile was also observed in hippocampus. Taken together, the results obtained strongly suggest that Rac3 plays an important physiological role in neuronal tissues during corticogenesis, and defects in the Rac3 function induce structural brain anomalies leading to pathogenesis of neurodevelopmental disorders.


A cohort study of racing performance in Japanese Thoroughbred racehorses using genome information on ECA18.
Using 1710 Thoroughbred racehorses in Japan, a cohort study was performed to evaluate the influence of genotypes at four single nucleotide polymorphisms (SNPs) on equine chromosome 18 (ECA18), which were associated in a previous genome-wide association study for racing performance with lifetime earnings and performance rank. In males, both g.65809482T>C and g.65868604G>T were related to performance rank (P= 0.005). In females, g.65809482T>C (P = 1.76E-6), g.65868604G>T (P=6.81E-6) and g.66493737C>T (P=4.42E-5) were strongly related to performance rank and also to lifetime earnings (P < 0.05). When win-race distance (WRD) among all winning racehorses and best race distance (BRD) among elite racehorses were considered as the phenotypes, significant associations (P<0.001) were observed for all four SNPs. The favourable race distance of both elite (BRD) and novice racehorses (WRD) was also associated with genotypes in the ECA18 region, indicating the presence of a gene in this region influencing optimum race distance in Thoroughbred racehorses. Therefore, the association with performance rank is likely due to the bias in the race distances. The location of the SNPs within and proximal to the gene encoding myostatin (MSTN) strongly suggests that regulation of the MSTN gene affects racing performance. In particular, the g.65809482T>C, g.65868604G>T and g.66493737C>T SNPs, or their combinations, may be genetic diagnostic markers for racing performance indicators such as WRD and BRD.


Trajectories of intrusive parenting during infancy and toddlerhood as predictors of rural, low-income African American boys' school-related outcomes.
Stability and change in maternal intrusiveness during early childhood is rarely explored, particularly within African American families. The current study examined the prediction of maternal intrusiveness during the first 3 years of life among mothers of rural, low-income African American boys and its relation to school-related outcomes. Observations of mothers (N = 230) interacting with children at 6, 24, and 36 months were coded and analyzed. Predictors of the trajectories and child outcomes were assessed using questionnaires and various tasks. On average, mothers of African American boys increased in intrusiveness across the first 3 years of life. Cumulative sociodemographic risk was associated with initial levels of intrusiveness, and child fearfulness and maternal negative regard predicted increases in intrusiveness over time. After controlling for sociodemographic risk, child temperament, and parental negativity, increases in intrusiveness over the first 3 years of life were associated with lower levels of expressive communication, inhibitory control, and intellectual functioning but not with attention focusing. Comprehensive parenting intervention efforts aimed toward improving children's outcomes must take into consideration the broader socioeconomic and affective context in which parenting behaviors occur as well as stability and change in parenting over time.


Lung parenchymal changes secondary to cigarette smoking: pathologic-CT correlations.
To determine the histopathologic basis for computed tomographic (CT) interpretation of smokers' lung and the accuracy of CT in the detection of alterations related to cigarette smoking, parenchymal lung lesions were studied from 41 heavy smokers who underwent thoracotomy for removal of a solitary pulmonary nodule. CT scanning of the resected lungs, corresponding exactly to the sections seen on preoperative CT scans, resulted in the following pathologic-CT correlations. Areas of ground-glass attenuation seen on preoperative CT scans (n = 11 [27%]) were related to three main histologic features: (a) accumulation of pigmented macrophages and mucus in the alveolar spaces, associated with mild interstitial inflammation and/or fibrosis (n = 7); (b) thickening of the alveolar walls with inflammatory cells with normal alveolar spaces (n = 3); and (c) presence of organizing alveolitis (n = 1). Parenchymal micronodules depicted presurgically (n = 4 [10%]) corresponded to bronchiolectases with peribronchiolar fibrosis (n = 4) associated with obliterative bronchiolitis in one patient. When emphysema was detected presurgically (n = 21 [51%]), it was always present at pathologic study to a higher extent than initially suspected.