Verteporfin therapy and triamcinolone acetonide: convergent modes of action for treatment of neovascular age-related macular degeneration.
Choroidal neovascularization associated with age-related macular degeneration is the primary cause of blindness in the elderly in developed countries, due to a number of pathogenic effects, including angiogenesis, cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix remodeling. By producing photochemical effects at the site of target tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood flow stasis, leading to occlusion of vascularization and lesion leakage. PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective in reducing the risk of vision loss in patients with classic containing subfoveal CNV and occult with no classic CNV. However, in predominantly occult CNV, the treatment may be most effective in smaller lesions, and less in larger lesions. Most important, visual acuity rarely is improved. Pilot studies and large case series suggest that a combination of PDT and intravitreal triamcinolone acetonide has the potential to improve visual outcomes and reduce the need for additional treatments. Randomized, prospective clinical trials are underway to confirm the efficacy and safety of this novel treatment modality.


The prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma.
To evaluate the prognostic significance of surgical margin in liver resection of patients with hepatocellular carcinoma. Retrospective study. The Center for Adult Diseases, Osaka, Japan, between 1980 and 1989. One hundred eighty-five patients with hepatocellular carcinoma who underwent liver resection with complete extirpation. Cumulative survival rate. The patients were divided into a wide surgical margin group, in which the lesion was excised with a margin of 1.0 cm or more, and a narrow surgical margin group, in which the margin was less than 1.0 cm. No significant differences could be detected in survival rates for 3 years or longer. Mean +/- SE tumor sizes were 3.4 +/- 0.4 cm and 4.4 +/- 0.3 cm, respectively, in the wide and narrow surgical margin groups. The patients were divided into three groups according to tumor size: group 1, 2.0 cm or less in diameter; group 2, greater than 2.0 cm but 5.0 cm or less in diameter; and group 3, greater than 5.0 cm in diameter. In groups 2 and 3, no significant differences in survival rates were found between the wide and narrow surgical margin groups. In group 1, the survival rate was significantly higher in the wide surgical margin group than in the narrow surgical margin group (P < .05). Small hepatocellular carcinomas of 2.0 cm or less in diameter should be resected with an adequate surgical margin. However, surgical margin was not a significant factor in the resection of hepatocellular carcinomas larger than 2.0 cm.


Integrated Metabolomics Assessment of Human Dried Blood Spots and Urine Strips.
(1) Background: Interest in the application of metabolomics toward clinical diagnostics development and population health monitoring has grown significantly in recent years. In spite of several advances in analytical and computational tools, obtaining a sufficient number of samples from patients remains an obstacle. The dried blood spot (DBS) and dried urine strip (DUS) methodologies are a minimally invasive sample collection method allowing for the relative simplicity of sample collection and minimal cost. (2) Methods: In the current report, we compared results of targeted metabolomics analyses of four types of human blood sample collection methods (with and without DBS) and two types of urine sample collection (DUS and urine) across several parameters including the metabolite coverage of each matrix and the sample stability for DBS/DUS using commercially available Whatman 903TM paper. The DBS/DUS metabolomics protocols were further applied to examine the temporal metabolite level fluctuations within hours and days of sample collection. (3) Results: Several hundred polar metabolites were monitored using DBS/DUS. Temporal analysis of the polar metabolites at various times of the day and across days identified several species that fluctuate as a function of day and time. In addition, a subset of metabolites were identified to be significantly altered across hours within a day and within successive days of the week. (4) Conclusion: A comprehensive DBS/DUS metabolomics protocol was developed for human blood and urine analyses. The described methodology demonstrates the potential for enabling patients to contribute to the expanding bioanalytical demands of precision medicine and population health studies.


Vitamin D3 inhibits fatty acid synthase expression by stimulating the expression of long-chain fatty-acid-CoA ligase 3 in prostate cancer cells.
FAS and FACL3 are enzymes of fatty acid metabolism. In our previous studies, we found that FAS and FACL3 genes were vitamin D3-regulated and involved in the antiproliferative effect of 1alpha,25(OH)2D3 in the human prostate cancer LNCaP cells. Here, we elucidated the mechanism behind the downregulation of FAS expression by vitamin D3. Triacsin C, an inhibitor of FACL3 activity, completely abolished the downregulation of FAS expression by vitamin D3, whereas an inhibitor of FAS activity, cerulenin, had no significant effect on the upregulation of FACL3 expression by vitamin D3 in LNCaP cells. In human prostate cancer PC3 cells, in which FACL3 expression is not regulated by vitamin D3, no regulation of FAS expression was seen. This suggests that the downregulation of FAS expression by vitamin D3 is mediated by vitamin D3 upregulation of FACL3 expression. Myristic acid, one of the substrates preferential for FACL3, enhanced the repression of FAS expression by vitamin D3. The action of myristic acid was abrogated by inhibition of FACL3 activity, suggesting that the enhancement in the downregulation of FAS expression by vitamin D3 is due to the formation of myristoyl-CoA. The data suggest that vitamin D3-repression of FAS mRNA expression is the consequence of feedback inhibition of FAS expression by long chain fatty acyl-CoAs, which are formed by FACL3 during its upregulation by vitamin D3 in human prostate cancer LNCaP cells.


Higher Burden of Cerebral Small Vascular Disease Predicts Major Adverse Cardiac and Cerebrovascular Events and Is Related to Abnormal Blood Pressure Variability Pattern in Hypertension Patients.
The study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden. We retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression. Among the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393-2.703; P < 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669-0.791; P < 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129-2.633; P = 0.012). Total CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.


Excess risk of sickness and disease in bus drivers: a review and synthesis of epidemiological studies.
In an extensive search of available literature, 22 epidemiological studies that have examined health risks of bus drivers were identified. These studies focus on three main disease categories: (1) cardiovascular disease, including hypertension, (2) gastrointestinal illnesses, including peptic ulcer and digestive problems, and (3) musculoskeletal problems including back and neck pain. The studies consistently report that bus drivers have higher raes of mortality, morbidity, and absence due to illness when compared to employees from a wide range of other occupational groups. Increased disease rates have been found for drivers regardless of the use of different research methodologies, measurement techniques and comparison groups. When evaluating the impact of bias on the estimates of risk, it appears likely that findings are conservative: strong systematic selective factors have probably favoured the elimination of those in poorer health both at the time of entry into and exit from the job of bus driving and other sources of bias have most likely caused underestimations of risk. Nevertheless, there remain questions that need careful assessment before firm conclusions can be made about whether increased disease rates result from driving a bus. Such questions, coupled with the consistent findings of heightened risk of disease, make urban bus drivers an appropriate and promising occupational group in which to study further the potential adverse effects of the work environment on employee health.


Biomarkers of homeostasis, allostasis, and allostatic overload in decapod crustaceans of distinct habitats and osmoregulatory strategies: an empirical approach.
The term "allostasis", meaning the assumption that homeostasis may not be as static as the term implies, has been vastly employed for mammals, and other vertebrates, for which the degree of internal stability is maximal, according to their higher complexity. We have here investigated how these states of homeostasis, allostasis, and allostatic overload could be diagnosed in decapod crustaceans, upon acute salinity challenges. Decapods of distinct lineages and habitats have been submitted to 3 salinity levels for 6 and 12 h. The first salinity was the habitat salinity (control), considered as the one that allows the homeostatic condition. The next salinity represented a mild challenge, that would potentially lead to allostasis, and the third salinity was intended to represent an overload, albeit not lethal. Species used were: the marine crab Hepatus pudibundus (Hp, osmoconformer, salinities 33, 25, and 20‰), the marine/estuarine swimming crab Callinectes danae (Cd, weak regulator, salinities 30, 20, and 10‰), and the diadromous freshwater prawn Macrobrachium acanthurus (Ma, strong regulator, salinities <0.5, 15, and 30‰). These 3 species follow a sequence of growing regulatory capacity (Hp<Cd<Ma), and euryhalinity (Hp<Ma<Cd). The biomarker of allostatic overload in Hp was the dramatic build-up of hemolymph lactate in 10‰; Cd was so euryhaline that had its homeostasis barely disturbed by the treatments, and the overload biomarker for Ma was low reduced muscle hydration in 30‰. The concept of allostasis can be successfully applied to comparative osmoregulation of decapods, with potential implications in areas of applied physiology such as aquaculture.


[Development and application of reference materials containing mixed degradation products of amoxicillin and ampicillin].
Reference materials containing mixed degradation products of amoxicillin and ampicillin were developed after optimization of preparation processes. The target impurities were obtained by controlled stress testing, and each major component was identified with HPLC-MS and compared with single traceable reference standard each. The developed reference materials were applied to system suitability test for verifying HPLC system performed in accordance with set forth in China Pharmacopeia and identification of major impurities in samples based on retention and spectra information, which have advantages over the methods put forth in foreign pharmacopoeias. The development and application of the reference materials offer an effective way for rapid identification of impurities in chromatograms, and provide references for analyzing source of impurities and evaluation of drug quality.


Serological evidence of Coxiella burnetii infection in wild animals in Japan.
One hundred and thirty-four (26%) of 511 sera from 11 wild animal species in eight prefectures in Japan had antibody titers to Coxiella burnetii by the enzyme-linked immunosorbent assay. High prevalences were observed in Japanese black bears (Ursus thibetanus) (78%), Hokkaido deer (Cervus nippon yesoensis) (69%), Japanese hares (Lepus brachyurus) (63%), Japanese deer (Cervus nippon centralis) (56%), and to some extent in Japanese monkeys (Macaca fuscata) (28%). A low prevalence (13%) was observed in nutrias (Myocastor coypus). Japanese serows (Capricornis crispus), wild rats (Muroides sp.), raccoon dogs (Nyctereutes procyonoides viverrinus), wild pigs (Sus scrofa leucomystax), and masked palm civets (Paguma larvata) had no detectable antibodies to C. burnetii. Thus, six of 11 wild animal species in Japan were exposed to C. burnetii. Based on the high prevalences in some species, they may be a potential source of infection to both domestic animal and human populations.


Ultrasonic wave transmission and bandgap in multidirectional composite laminates with spring-type interlayer interfaces.
The ultrasonic wave transmission through multidirectional composite laminates is studied theoretically by accounting for the effect of thin interlayer resin-rich regions based on the spring-type interface model. Using the stiffness-matrix method, the energy transmission spectrum of the longitudinal wave impinging obliquely on cross-ply and quasi-isotropic laminates immersed in water is calculated. The location and bandwidth of the frequency ranges where the transmissivity becomes vanishingly small are shown to be significantly influenced by the incident angle, the laminate lay-up, and the interlayer interfacial stiffnesses. By examining the energy flux density of partial waves inside the laminate, these frequency ranges are shown to be the bandgaps due to the constructive interference of scattered waves from the interlayer interfaces. The mode combination causing the interference is found to vary remarkably with the bandgap location. Furthermore, the interference in the finite laminate structure is shown to occur in almost the same manner as the Floquet wave does in the infinitely extended laminate structure. The energy transmission spectrum is experimentally measured for 16-ply carbon/epoxy cross-ply and quasi-isotropic composite laminates using the through-transmission technique. The transmission and bandgap characteristics observed in the experimental results are reasonably reproduced by the present theory incorporating the interlayer resin-rich regions.


Staining-free malaria diagnostics by multispectral and multimodality light-emitting-diode microscopy.
We report an accurate optical differentiation technique between healthy and malaria-infected erythrocytes by quasi-simultaneous measurements of transmittance, reflectance, and scattering properties of unstained blood smears using a multispectral and multimode light-emitting diode microscope. We propose a technique for automated imaging, identification, and counting of malaria-infected erythrocytes for real-time and cost-effective parasitaemia diagnosis as an effective alternative to the manual screening of stained blood smears, now considered to be the gold standard in malaria diagnosis. We evaluate the performance of our algorithm against manual estimations of an expert and show a spectrally resolved increased scattering from malaria-infected blood cells.


Spindle microtubule dynamics: modulation by metabolic inhibitors.
Recent experiments have shown that spindle microtubules are exceedingly dynamic. Measurements of fluorescence recovery after photobleaching (FRAP), in cells previously microinjected with fluorescent tubulin, provide quantitative information concerning the rate of turnover, or exchange, of tubulin subunits with the population of microtubules in living cells at steady state. In an effort to elucidate the pathways and factors that regulate tubulin exchange with microtubules in living cells, we have investigated the energy requirements for tubulin turnover as measured by FRAP. Spindle morphology was not detectably altered in cells incubated with 5 mM sodium azide and 1 mM 2-deoxyglucose (Az/DOG) for 5 minutes, as assayed by polarized light microscopy and antitubulin immunofluorescence. In FRAP experiments on these ATP-depleted cells, the average rate of recovery and the average percent of bleached fluorescence recovered were reduced to 37% and 30% of controls, respectively. When the inhibitors were removed, cells continued through mitosis, and rapid FRAP was restored. In the presence of azide and glucose, the rate of recovery and percent of fluorescence recovered were only slightly reduced, demonstrating that energy production via glycolysis can support microtubule turnover. Longer incubations with Az/DOG altered the microtubule organization in mitotic cells: astral microtubules lengthened and spindle fibers shortened. Furthermore, both astral and spindle microtubules became resistant to nocodazole-induced disassembly under these conditions. Together these observations indicate that microtubule dynamics require ATP and suggest a relationship between microtubule organization and turnover.


Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro.
To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro. The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting. Treatment of U251 and U87 cells with anisomycin (0.01-8 μmol/L) inhibited the cell growth in time- and concentration-dependent manners (the IC(50) values at 48 h were 0.233±0.021 and 0.192±0.018 μmol/L, respectively). Anisomycin (4 μmol/L) caused 21.5%±2.2% and 25.3%±3.1% of apoptosis proportion, respectively, in U251 and U87 cells. In the two cell lines, anisomycin (4 μmol/L) activated p38 MAPK and JNK, and inactivated ERK1/2. However, neither the p38 MAPK inhibitor SB203580 (10 μmol/L) nor the JNK inhibitor SP600125 (10 μmol/L) prevented anisomycin-induced cell death. On the other hand, anisomycin (4 μmol/L) reduced the level of PP2A/C subunit (catalytic subunit) in a time-dependent manner in the two cell lines. Treatment of the two cell lines with the PP2A inhibitor okadaic acid (100 nmol/L) caused marked cell death. Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit. The regulation of PP2A/C exression by anisomycin provides a clue to further study on its role in glioma therapy.


Exploiting Mitochondrial Vulnerabilities to Trigger Apoptosis Selectively in Cancer Cells.
The transformation of normal cells to the cancerous stage involves multiple genetic changes or mutations leading to hyperproliferation, resistance to apoptosis, and evasion of the host immune system. However, to accomplish hyperproliferation, cancer cells undergo profound metabolic reprogramming including oxidative glycolysis and acidification of the cytoplasm, leading to hyperpolarization of the mitochondrial membrane. The majority of drug development research in the past has focused on targeting DNA replication, repair, and tubulin polymerization to induce apoptosis in cancer cells. Unfortunately, these are not cancer-selective targets. Recently, researchers have started focusing on metabolic, mitochondrial, and oxidative stress vulnerabilities of cancer cells that can be exploited as selective targets for inducing cancer cell death. Indeed, the hyperpolarization of mitochondrial membranes in cancer cells can lead to selective importing of mitocans that can induce apoptotic effects. Herein, we will discuss recent mitochondrial-selective anticancer compounds (mitocans) that have shown selective toxicity against cancer cells. Increased oxidative stress has also been shown to be very effective in selectively inducing cell death in cancer cells. This oxidative stress could lead to mitochondrial dysfunction, which in turn will produce more reactive oxygen species (ROS). This creates a vicious cycle of mitochondrial dysfunction and ROS production, irreversibly leading to cell suicide. We will also explore the possibility of combining these compounds to sensitize cancer cells to the conventional anticancer agents. Mitocans in combination with selective oxidative-stress producing agents could be very effective anticancer treatments with minimal effect on healthy cells.


Responses to Cortical Spreading Depression under Oxygen Deficiency.
The effect of cortical spreading depression (CSD) on extracellular K(+) concentrations ([K(+)](e)), cerebral blood flow (CBF), mitochondrial NADH redox state and direct current (DC) potential was studied during normoxia and three pathological conditions: hypoxia, after NOS inhibition by L-NAME and partial ischemia. A SPECIAL DEVICE (MPA) WAS USED FOR MONITORING CSD WAVE PROPAGATION, CONTAINING: mitochondrial NADH redox state and reflected light, by a fluorometry technique; DC potential by Ag/AgCl electrodes; CBF by laser Doppler flowmetry; and [K(+)](e) by a mini-electrode. CSD under the 3 pathological conditions caused an initial increase in NADH and a further decrease in CBF during the first phase of CSD, indicating an imbalance between oxygen supply and demand as a result of the increase in oxygen requirements. The hyperperfusion phase in CBF was significantly reduced during hypoxia and ischemia showing a further decline in oxygen supply during CSD. CSD wave duration increased during the pathological conditions, showing a disturbance in energy production.Extracellular K(+) levels during CSD, increased to identical levels during normoxia and during the three pathological groups, indicating correspondingly increase in oxygen demand. 5. The special design of the MPA enabled identifying differences in the simultaneous responses of the measured parameters, which may indicate changes in the interrelation between oxygen demand, oxygen supply and oxygen balance during CSD propagation, under the conditions tested. 6. In conclusion, brain oxygenation was found to be a critical factor in the responses of the brain to CSD.


The effect of tenotomy and tendon transfers on muscle fiber types in the dog.
Different muscle groups have been shown to have variable muscle-fiber type patterns that may be, in part, due to function and use. In an attempt to identify any changes in fiber composition following surgical alteration of function, eleven beagle dogs had the fibularis longus tendon severed. Four dogs had the tendon reattached 6-24 weeks later. After 6-24 weeks, four dogs had the tendon surgically transferred to the tendon of the tibialis anterior, a functionally different muscle. Three dogs had the tendon immediately transferred to the tendon of the tibialis longus. Biopsies were performed after each procedure to assess fiber changes, and late biopsies were performed in one dog from each group at 27-29 months. Fiber characteristics in the biopsy specimens were identified using histochemical staining. In the first group (tenotomy-reattachment), variable atrophy occurred early but disappeared following reattachment. In the second group (tenotomy and tendon transfer), variable atrophy occurred along with an increased percentage of Type I and Type IIB fibers. Early biopsies performed in the third group (direct transfer) revealed mild Type II hypertrophy. In the late biopsy specimen, an increase of Type I and Type IIB fibers was noted and was similar to the fiber composition of the tibialis anterior to which it was transferred. These findings indicate that muscle-fiber remodeling does occur and that multiple operative procedures are not intrinsically harmful to the muscles. The best evidence from this and previous studies suggests that changes in muscle-fiber type are manifestations of functional adaptation.


Long-term preservation of unstable bacteriophages of enterobacteria.
Bacteriophages are integral components of bacterial communities. Their practical applications and significance for humans are various. Thus, keeping phage collections along with their specific host bacteria is an urgent and important mission for biologists. The problems of the long-term storage of phages steel are not completely solved. The main difficulties may occur due to the structural instability of virions as well as an accelerated genetic variability in phage genomes both in vivo and in vitro. In the paper the results of 10-years observation over unstable bacteriophage storage process was presented as well the method of their long-term preservation was proposed. It consisted of the optimization of STMG buffer system (200 mM NaCl, 10 mM Tris-HCl, pH 7.4, 1 mM MgCl, 100 microg/ml gelatin) [Serwer P, Pichler ME. Electrophoresis of bacteroiphage T7 capsids in agarose gels//J. Virol. - 1978 - V28, N3. - P.917-928] by higher gelatin concentration or its replacement by ficoll (2 - 6%), and increasing of Mg(2-) concentration to 10 mM. The proposed buffer composition allowed saving structural entirety of unstable phage virions during their long-term storage.


Double-Door or "French-Door" Cervical Laminoplasty.
Cervical spondylotic myelopathy (CSM) is a condition resulting from cervical stenosis. Manifestations of CSM include paresthesia in the extremities, loss of fine motor skills, balance problems, and bowel and bladder dysfunction in advanced disease. Laminoplasty is one surgical treatment option. The goal of laminoplasty is to reposition the laminae to expand the spinal canal, allowing the spinal cord to migrate posteriorly. There are various laminoplasty techniques; the main ones being open-door laminoplasty and double-door laminoplasty. This manuscript demonstrates a double-door laminoplasty otherwise known as a "French-door" laminoplasty discusses the indications and outcomes of this procedure. The double-door laminoplasty creates an opening in the midline of the spinous processes and a symmetrical expansion with hinges on both laminae. Bilateral troughs are drilled on each laminae using a bur, and opened liked a French-door, allowing the spinal cord to move posteriorly in the enlarged spinal canal. The space between the gapped laminae are then stabilized by allograft. This manuscript presents the case of a 56-year-old man with CSM caused by multilevel cervical stenosis. The patient had classic signs and symptoms of CSM including problems with fine motor skills and walking difficulty. The video demonstrates the spinal cord decompression achieved with the French-door technique from C4 to C6 with a dome laminectomy at C3. There are many surgical treatments for cervical stenosis including anterior cervical discectomy and fusions and posterior procedures such as laminoplasty or laminectomy and fusion. The indications and technical pearls for French-door laminoplasty are presented as an effective option for the treatment of multilevel cervical stenosis.


Palmar-plantar erythema associated with combination chemotherapy.
We report three cases of a distinctive palmar-plantar erythema associated with the treatment of non-Hodgkin's lymphoma and acute myeloid leukaemia. The rash is characterized by a painful, sharply demarcated, intense erythema of the palms and/or soles followed by bulla formation, desquamation and healing. The eruption is self limiting in nature and did not adversely affect prognosis. Treatment need be neither altered nor stopped; only symptomatic measures are required.


Significance of cyanide in medicolegal investigations involving fires.
This article presents the significance of cyanide in medicolegal investigation of fires. It discusses the various aspects of fire investigation and the pathophysiology of cyanide toxicity and evidence interpretation in fire investigations.


Subsequent Fracture Prevention in Patients 50 Years and Older With Fragility Fractures: A Quality Improvement Initiative.
Because of osteoporosis, patients older than 50 years with fragility fractures are at risk of further fractures. We developed a quality improvement initiative based on an evidence-based Fracture Liaison Service (FLS) model of care to help prevent subsequent fractures. Previous to the implemented FLS model, less than 13% of patients with fragility fractures were assessed for osteoporosis at our institution. We created a registry tool to identify patients with fractures who were older than 50 years. Our interventions focused on identifying, contacting, and educating patients; and coordinating screening tests and an outpatient follow-up visit with an endocrinologist. Identification of patients older than 50 years with fragility fractures increased from 0% to 74.5%, with implementation of the fracture registry. Of those identified, 33.9% were screened and had a follow-up visit. The fragility fracture population older than 50 years is at risk of subsequent fractures and should be identified, contacted, educated, screened, and assessed for osteoporosis to prevent subsequent fractures.


[Molecular basis of breast cancer related to BRCA 1 and BRCA2 genes: characteristics and targeting therapy].
Breast cancer is one of the most frequent tumors in women, and BRCA1 and BRCA2 genes play a major role in the hereditary susceptibility for this disease. Until the age of 70 women carrying a mutation in BRCA1 or BRCA2 gene have a 45-85% probability of developing breast cancer, and 11-62% probability of developing ovarian cancer. Mutation carrier's tumors contain nonfunctional BRCA1 or BRCA2 genes, which in healthy cells are involved in DNA repair. These tumors show an increased sensitivity to DNA damaging chemical agents and to PARP (poly(adenosine diphosphate-ribose) polymerase1) inhibitors. New targeted therapies already in use are directed toward tumors of mutation carriers. Successful treatment is most likely to be achieved through cooperation of a pathologist, oncologist and a genetic laboratory performing BRCA genes mutation screening.


Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain.
Calmodulin (CaM), a 16 kDa ubiquitous calcium-sensing protein, is known to bind tightly to the calcium release channel/ryanodine receptor (RyR), and modulate RyR function. CaM binding studies using RyR fragments or synthetic peptides have revealed the presence of multiple, potential CaM-binding regions in the primary sequence of RyR. In the present study, we inserted GFP into two of these proposed CaM-binding sequences and mapped them onto the three-dimensional structure of intact cardiac RyR2 by cryo-electron microscopy. Interestingly, we found that the two potential CaM-binding regions encompassing, Arg3595 and Lys4269, respectively, are in close proximity and are adjacent to the previously mapped CaM-binding sites. To monitor the conformational dynamics of these CaM-binding regions, we generated a fluorescence resonance energy transfer (FRET) pair, a dual CFP- and YFP-labeled RyR2 (RyR2R3595-CFP/K4269-YFP) with CFP inserted after Arg3595 and YFP inserted after Lys4269. We transfected HEK293 cells with the RyR2R3595-CFP/K4269-YFP cDNA, and examined their FRET signal in live cells. We detected significant FRET signals in transfected cells that are sensitive to the channel activator caffeine, suggesting that caffeine is able to induce conformational changes in these CaM-binding regions. Importantly, no significant FRET signals were detected in cells co-transfected with cDNAs encoding the single CFP (RyR2R3595-CFP) and single YFP (RyR2K4269-YFP) insertions, indicating that the FRET signal stemmed from the interaction between R3595-CFP and K4269-YFP that are in the same RyR subunit. These observations suggest that multiple regions in the RyR2 sequence may contribute to an intra-subunit CaM-binding pocket that undergoes conformational changes during channel gating.


Inhibition of human mammary carcinoma cell proliferation by retinoids and intracellular cAMP-elevating compounds.
Retinoids and cAMP-elevating agents markedly inhibited the proliferation of human mammary tumor cells. Their response has been previously correlated with the presence of estrogen receptor (ER) positivity. MDA-MB-231 cells were ER negative and insensitive to the antiproliferative effects of retinoids. However, their growth was markedly inhibited by agents that elevated intracellular cAMP levels, i.e., 8-bromo-cAMP, cholera toxin (CT), forskolin, and the phosphodiesterase inhibitor papaverine. The CT and forskolin inhibition of the ER-positive cells (MCF-7) was associated with an elevation of adenylate cyclase activity and intracellular cAMP levels; however, similar elevations in intracellular cAMP levels were not observed following CT or forskolin inhibition of MDA-MB-231 cells but only following the addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine.


Blood glucose responses of diabetes mellitus type II patients to some local fruits.
To determine the glucose responses of diabetes mellitus type II subjects to fruits, four locally available fruits (containing 25 g of available carbohydrates per serving portion) of chico, mango, pineapple, and papaya were tested among ten type II diabetic subjects, using wheat bread as the control. Results of the in vivo test indicated that chico and mango had significantly lower (P ≤ 0.05) blood glucose areas compared to wheat bread. Chico and mango also had a much lower glycemic index (GI), 57 and 59, respectively, compared to pineapple, 73 and papaya, 86. Differences in glucose responses to fruits and their varying GI are attributed to the amount of fiber, type and amount of sugars found, presence of antinutrients, acidity and physical characteristics of the fruits when chewed. The high fiber content of chico (7.9%), its fructose content (5.3%), its grainy texture when chewed and the presence of antinutrients (saponin, sapotin and achrasaponin) may contribute to its slow digestion and absorption. The low GI and blood glucose response of mango may be because of its fructose content (3.0%), acidity content (malic, citric and tartaric) and its phytic acid content (0.03%). Furthermore, starch, which is a possible factor contributing to low GI, is present in chico (0.8%) and mango (0.3%). Pineapple and papaya, the test fruits that elicited higher blood glucose responses and GI, have much lower fiber contents, less acids and contain glucose and sucrose sugars.


Real-space vortex glass imaging and the vortex phase diagram of SnMo6S8.
Using scanning tunneling microscopy at 400 mK, we have obtained maps of around 100 vortices in SnMo(6)S(8) from 2-9 T. The orientational and positional disorder at 5 and 9 T show that these are the first large-scale images of a vortex glass. At higher temperature a magnetization peak effect is observed, whose upper boundary coincides with a lambda anomaly in the specific heat. Our data favor a kinetic glass description of the vortex melting transition, indicating that vortex topological disorder persists at fields and temperatures far below the peak effect in low-T(c) superconductors.


The deuterostome ancestor.
Hemichordates, the phylum of bilateral animals closest to chordates, can illuminate the evolutionary origins of various chordate traits to determine whether these were already present in a shared ancestor (the deuterostome ancestor) or were evolved within the chordate line. We find that an anteroposterior map of gene expression domains, representing 42 genes of neural patterning, is closely similar in hemichordates and chordates, though it is restricted to the neural ectoderm in chordates whereas in hemichordates, which have a diffuse nervous system, it encircles the whole body. This map allows an accurate alignment of the anterioposterior axes of members of the two groups. We propose that this map dates back at least to the deuterostome ancestor. The map of dorsoventral expression domains, organized along a Bmp-Chordin developmental axis, is also similar in the two groups in terms of many gene expression domains and for the placement of the gill slits, heart, and post-anal tail. The two groups, however, differ in two major respects along this axis. The nervous system and epidermis are not segregated into distinct territories in hemichordates, as they are in chordates, and furthermore, the mouth is on the Chordin side in hemichordates but the Bmp side in chordates. The dorsoventral dimension has undergone extensive modification in the chordate line, including centralization of the nervous system, segregation of epidermis, derivation of the notochord, perhaps from the gut midline, and relocation of the mouth. Based on the shared domain maps, speculations can be made for the remodeling of the body axis in the chordate line.


Use of Laser in Sleep Disorders: A Review on Low Laser Uvulopalatoplasty.
A comprehensive and systematic literature review was conducted using PubMed, Google Scholar, Cochrane Central Register of Controlled Trials, Embase, Web of Science, the US National Institutes of Health Trials Registry, WHO Library, and Medline. The search strategies were developed to cover publications from January 2010 through March 2020. The past 10 years of the search were performed to report the data following systematic review and meta-analysis protocol (PRISMA-P) 2015 statement. With the help of keywords, the total number of abstracts identified was 946. These abstracts were further reviewed as per inclusion and exclusion criteria, and 106 abstracts were identified to match the selection criteria. Further review of full articles resulted in 12 articles that matched the inclusion criteria for the study. Er:YAG can be a good alternative and least invasive therapy for managing snoring and obstructive sleep apnea. Er:YAG therapy is considered to nonsurgical intervention with minimum side effects and can be performed chairside.


Production of anti-microbial substances by probiotics.
Bacterial antagonism has been recognised for over a century but in recent years this phenomenon has received more scientific attention, particularly in the use of various strains of lactic acid bacteria (LAB). Antimicrobial compounds produced by LAB have provided these organisms with a competitive advantage over other microorganisms. Lactic acid bacteria have a natural ecological niche in many foods as well as in the intestinal tract. The efficacy and spectrum of antimicrobial products of lactic acid bacteria are broad and include lactic and acetic acid, hydrogen peroxide, carbon dioxide, diacetyl as well as bacteriocins or bacteriocin-like substances. Further screening for agents with a broad spectrum of activity is required. This will involve genetic or protein engineering of such compounds to commercialise these agents.


Anaerobic digestion of wood ethanol stillage using upflow anaerobic sludge blanket reactor.
The anaerobic digestion of wood ethanol stillage in a UASB reactor was studied. At organic loading rates be low 16 kg COD/m(3) day the reactor performed effectively, achieving soluble COD and BOD removals in excess of 86 and 93%, respectively. Removal of color averaged 40%. At a loading rate of 16 kg COD/m(3) day the methane yield was 0.302 L CH(4) (STP)/g COD removed, and the observed cell yield was 0.112 g VSS/g COD removed. Operation of the reactor at higher loading rates was unsuccessful. Nitrogen, phosphorus, and alkalinity were supplemented. No additions of the essential trace elements Fe, Co, and Ni were required.


Covalent docking predicts substrates for haloalkanoate dehalogenase superfamily phosphatases.
Enzyme function prediction remains an important open problem. Though structure-based modeling, such as metabolite docking, can identify substrates of some enzymes, it is ill-suited to reactions that progress through a covalent intermediate. Here we investigated the ability of covalent docking to identify substrates that pass through such a covalent intermediate, focusing particularly on the haloalkanoate dehalogenase superfamily. In retrospective assessments, covalent docking recapitulated substrate binding modes of known cocrystal structures and identified experimental substrates from a set of putative phosphorylated metabolites. In comparison, noncovalent docking of high-energy intermediates yielded nonproductive poses. In prospective predictions against seven enzymes, a substrate was identified for five. For one of those cases, a covalent docking prediction, confirmed by empirical screening, and combined with genomic context analysis, suggested the identity of the enzyme that catalyzes the orphan phosphatase reaction in the riboflavin biosynthetic pathway of Bacteroides.


Relationship between bilirubin, apolipoprotein B, and coronary artery disease.
Lipoprotein lipids and apo B from 254 male patients were compared with bilirubin as a risk factor for coronary artery disease (CAD). Patients were classified as: 1, Normal, all vessels < 20% stenosis, n = 83; or 2, CAD, at least one vessel > 70%, n = 171. Diagnostic accuracy was assessed by receiver operator characteristic curves (ROC). Corrections were made for possible confounding variables in the multivariate analysis. Upon ROC analysis, bilirubin showed an inverse relationship with risk of CAD, with areas under the ROC curve comparable to lipoprotein: however, bilirubin showed no discrimination below false positive frequencies of approximately 0.3. Logistic regression indicated that bilirubin was a weaker global marker than the lipoproteins and interacted with apo B. A highly significant correlation was found between bilirubin and apo B (p = 0.0025), but not with cholesterol, triglycerides, or high density lipoprotein cholesterol. Compared to lipoprotein markers, bilirubin provides little practical power of discrimination for CAD. Further studies of the affect of bilirubin on CAD must take its interaction with apo B into consideration.


A potentiometric SO2 gas sensor based on the Li3PO4-Li2SiO3 solid electrolyte thin film.
A potentiometric sulfur dioxide (SO2) gas sensor based on the Li3PO4-Li2SiO3 solid electrolyte thin film was developed. The sensor was based on a galvanic cell O2, SO2, Au, Li2SO4-V2O5|Li3PO4-Li2SiO3|Au, SO2, O2. The Li3PO4-Li2SiO3 thin film was deposited on the Al2O3 substrate by RF magnetron sputtering, and the Au patterns were fabricated as the electrodes. The sensing electrode materials of Li2SO4-V2O5 with different dopants TiO2 and MgO were prepared, and as the ratio of Li2SO4:TiO2 is 1:1 (mol) with 5 wt. % V2O5 and 5 wt. % MgO, the sensor showed relatively good response characteristics to SO2 at 450 °C. Then, the sensor was further tested at the working temperature from 400 °C to 500 °C. The results show that the sensor has good response to SO2 at 400-450 °C, and the sensitivity is 90.15-57.19 mV/dec. The response and recovery times are 20-40 s and 2.5-4 min, respectively, when the gas concentration of SO2 increases from 10 ppm to 100 ppm and then decreases to 10 ppm. At 425 °C, the sensitivity is close to the theoretical values, and the final recovery potential of the sensor is almost consistent with the initial potential.


Cholecystokinin, bombesin and neurotensin in brain tissue from obese animals.
The concentration of cholecystokinin (the octapeptide, CCK-8), bombesin, and neurotensin was measured by radioimmunoassay in the cortex, hypothalamus and diencephalon of brains from lean, genetically obese and hypothalamic (VMH) obese rodents. Highest concentration of CCK-8 was found in the cortex whereas highest concentrations of bombesin and neurotensin were in the hypothalamus. When food was provided ad libitum, there was no difference in concentration of any of these peptides between lean and the respective genetically obese mice (ob/ob) and fatty (fa/fa) rats, or between lean and hypothalamic (VMH lesioned) obese rats. Adrenalectomy, which arrested the progression of obesity in both ob/ob and fatty rats, did not result in significant change in concentration of any of the three peptides studied in comparison with the respective sham-operated animals. Though significant differences in cholecystokinin and bombesin concentrations were detectable in some instances between adrenalectomized lean and adrenalectomized obese rats, these differences did not appear to be related to fall in food intake or slowing of body weight gain. Thus a variety of manipulations which altered the nutritional plane of the experimental rodents was not accompanied by significant changes in brain concentrations of cholecystokinin, bombesin or neurotensin.


Microbial synthesis of violacein pigment and its potential applications.
Violacein is a pigment synthesized by Gram-negative bacteria such as Chromobacterium violaceum. It has garnered significant interest owing to its unique physiological and biological activities along with its synergistic effects with various antibiotics. In addition to C. violaceum, several microorganisms, including: Duganella sp., Pseudoalteromonas sp., Iodobacter sp., and Massilia sp., are known to produce violacein. Along with the identification of violacein-producing strains, the genetic regulation, quorum sensing mechanism, and sequence of the vio-operon involved in the biosynthesis of violacein have been elucidated. From an engineering perspective, the heterologous production of violacein using the genetically engineered Escherichia coli or Citrobacter freundii host has also been attempted. Genetic engineering of host cells involves the heterologous expression of genes involved in the vio operon and the optimization of metabolic pathways and gene regulation. Further, the crystallography of VioD and VioE was revealed, and mass production by enzyme engineering has been accelerated. In this review, we highlight the biologically assisted end-use applications of violacein (such as functional fabric development, nanoparticles, functional polymer composites, and sunscreen ingredients) and violacein activation mechanisms, production strains, and the results of mass production with engineered methods. The prospects for violacein research and engineering applications have also been discussed.


Speeding up Batch Alignment of Large Ontologies Using MapReduce.
Real-world ontologies tend to be very large with several containing thousands of entities. Increasingly, ontologies are hosted in repositories, which often compute the alignment between the ontologies. As new ontologies are submitted or ontologies are updated, their alignment with others must be quickly computed. Therefore, aligning several pairs of ontologies quickly becomes a challenge for these repositories. We project this problem as one of batch alignment and show how it may be approached using the distributed computing paradigm of MapReduce. Our approach allows any alignment algorithm to be utilized on a MapReduce architecture. Experiments using four representative alignment algorithms demonstrate flexible and significant speedup of batch alignment of large ontology pairs using MapReduce.


Teased Fiber Preparation of Myelinated Nerve Fibers from Peripheral Nerves for Vital Dye Staining and Immunofluorescence Analysis.
Glial cells regulate a wide variety of neuronal functions during physiological and pathological conditions. Therefore, the study of glial cells and their association with axons is of paramount importance in order to understand the physiology of the nervous system. This chapter describes a detailed protocol to prepare and stain teased nerve fibers from peripheral nerves using fluorescent indirect immunolabeling and staining with vital dyes. For immunofluorescence analysis, we describe techniques to study the axonal compartment and the expression of cytoplasmic and plasma membrane proteins in Schwann cells.


Reliable method for generating double-stranded DNA vectors containing site-specific base modifications.
Cells of all living organisms are continuously exposed to physical and chemical agents that damage DNA and alter the integrity of their genomes. Despite the relatively high efficiency of the different repair pathways, some lesions remain in DNA when it is replicated or transcribed. Lesion bypass by DNA and RNA polymerases has been the subject of numerous investigations. However, knowledge of the in vivo mechanism of transcription lesion bypass is very limited because no robust methodology is available. Here we describe a protocol based on the synthesis of a complementary strand of a circular, single-stranded DNA molecule, which allows for the production of large amounts of double-stranded DNA containing a lesion at a specific position in a transcribed sequence. Such constructs can subsequently be used for lesion bypass studies in vivo by RNA polymerase and to ascertain how these events can be affected by the genetic background of the cells.


Amniotic fluid index and fetal bladder outlet obstruction. Do we really need more?
With the constant advances in technology and expertise of prenatal diagnosis, necessity of early counseling in cases of bilateral obstructive uropathy has become of paramount importance. To better evaluate fetal renal function new biochemical (serum and urine) fetal markers have been introduced in the literature. However, they are only available at select centers and always requiring an invasive approach. Furthermore, paucity of normal controls sometimes makes interpretation of results difficult. Owing to this growing interest towards biochemical evaluation of fetal renal function, assessment of amniotic fluid, which is mostly expression of fetal urination, has progressively fallen into disrepute, and studies comparing the amount of amniotic fluid with renal function are scant. In a 3-year period 28 cases of bilateral obstructive uropathy were seen prenatally at the Artemisia Medical Center. All cases were initially reviewed at 17 to 20 weeks of gestation when a distended fetal bladder with thickened wall and enlarged kidneys were visualized. At the same time ultrasonographic assessment of amniotic fluid was performed by calculating the amniotic fluid index. An amniotic fluid index less than the 25th percentile was considered below average and an index less below the 5th percentile was considered oligohydramnios, whereas an index between 50th and 75th percentiles was considered normal. All cases were subsequently evaluated for renal function up to age 1 year. Impaired renal function was defined as a serum creatinine greater than 1.2 mg/dl before age 1 year. Of the 28 cases 18 had an index of oligohydramnios (group 1) and 10 had a normal index (group 2). No significant variations were observed in amniotic fluid index at repeated consultations throughout pregnancy. Two cases in group 1 and 1 case in group 2 were lost to followup while in the other group 1 cases intrauterine death occurred. Bilateral obstructive uropathy was confirmed in all instances after birth as valves in 18 cases and urethral atresia in 3. Of the 12 surviving group 1 cases there were 3 neonatal deaths from severe lung hypoplasia, and in the remaining 9 cases mean serum creatinine at each evaluation before age 1 year was 1.3 +/- 0.2 mg/dl. All patients in group 2 survived with a mean serum creatinine at each evaluation of 0.6 +/- 0.1 mg/dl (p <0.05). Despite widespread use of prenatal biochemistry, evaluation of amniotic fluid by the amniotic fluid index remains a reproducible and inexpensive method to predict renal function in cases of bilateral obstructive uropathy of any origin. It retains its validity not only in severe, but also in milder reductions. Conversely, intact amniotic fluid mostly invariably predicts normal renal function at long-term evaluation. For a better understanding of the disease such information is to be promptly conveyed to the prospective parents at each prenatal consultation.


Reading Words or Pictures: Eye Movement Patterns in Adults and Children Differ by Age Group and Receptive Language Ability.
This study was conducted to explore the differences in the degree of attention given to Chinese print and pictures by children and adults when they read picture books with and without Chinese words. We used an eye tracker from SensoMotoric Instruments to record the visual fixations of the subjects. The results showed that the adults paid more attention to Chinese print and looked at the print sooner than the children did. The stronger the children's receptive language abilities were, the less time it took them to view the pictures. All participants spent the same amount of time looking at the pictures whether Chinese words were present or absent.


Port--site metastases following bariatric surgery.
Morbid obesity is a huge problem of the twenty-first century, mostly treated by bariatric surgery. The authors report the case of a patient with port site metastases from an unknown rectal adenocarcinoma when bariatric surgery took place. Implants in the site of the subcutaneous access port to the band are problematic, particularly in patients with occult intra-abdominal malignancy. This case underlines the importance of preventive measures to avoid cell implant in port sites in benign such as malignant diseases.


[A descriptive study of Hafnia alvei isolated from stool samples: an approach to its clinical assessment].
The importance in human diarrhoeal disease of Hafnia alvei is unclear. The objective of the study was to describe the population which was isolated H. alvei in stool cultures and the therapeutic management of these cases in our Health Area. A descriptive retrospective study was carried out in 2014 and 2015. Epidemiological, clinical, treatment and evolution variables were collected in the computerized clinical history. A collection of 7,290 stool specimens were processed, 3,321 in 2014 and 3,969 in 2015, of which 58 (1.7%) and 53 (1.3%) were positive for H. alvei, respectively. A 60.4% of samples were isolated in women. The mean age was 38.68 years. A 68.5% of samples were from primary care. In 71.2% there was related clinic, diarrhoea in 57.7%. In 75.7% of the cases there was not associated underlying disease. A 43.2% of the cases received treatment. A 66.7% of treated patients came from Primary Care. The mean duration of treatment was 8 days. The evolution was favourable in 85.4% of the cases treated. All strains were susceptible to ciprofloxacin and trimethoprim/sulfamethoxazole. More evidence is needed to support H. alvei as a cause of gastroenteritis.


Possible immune adverse events as predictors of durable response to BRAF inhibitors in patients with BRAF V600-mutant metastatic melanoma.
BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are among the cornerstones of metastatic melanoma therapy demonstrating excellent response rates with duration of 7-12 m. Long-term benefit from these agents was reported in patients with normal lactate dehydrogenase (LDH) and less than three disease sites. However, a treatment-dependent marker for long-term efficacy is lacking. Data suggest that immune-related adverse events (irAEs) are associated with clinical benefit in patients treated with immunotherapy and that response to BRAF/MEK therapy may have an underlying immune mechanism. We hypothesised that AEs with an underlying immune mechanism may be associated with a durable response to targeted therapy. We retrospectively identified a cohort of 78 BRAF V600-mutant metastatic melanoma patients treated with BRAFi or BRAFi + MEKi between November 2010 and November 2013. Four treatment-related AEs including vitiligo, uveitis, erythema nodosum and keratitis sicca were defined as irAEs of interest. Retrospective analysis of AEs in relationship to progression-free survival (PFS), disease burden and LDH levels was performed. Median PFS (mPFS) for all patients was 7.5 months with responses ongoing in eight patients as of April 2017. Ten patients were identified with the AEs defined previously. Cox regression analysis revealed a very strong association between those AEs and PFS; mPFS was 42.8 m in patients with at least one AE versus 6.1 m in those without an AE (hazard ratio [HR] 0.22, p = 0.002). This association was independent of LDH levels and disease burden (HR 0.24, p = 0.035). This analysis demonstrates a strong association between immune AEs and durable response to targeted therapy and may provide a treatment-related biomarker to estimate the outcome of therapy.


Different modes of hydrocarbon uptake by two Pseudomonas species.
The mode of n-hexadecane uptake by two organisms-Pseudomonas M 1 and Pseudomonas N 1-was studied. During the growth of Pseudomonas M 1 on n-hexadecane, no extracellular biosurfactant/bioemulsifier was produced, no significant n-hexadecane pseudosolubilization was observed, and the reduction of surface and interfacial tensions in the cell-free culture broth was negligible. EDTA, a known inhibitor of hydrocarbon pseudosolubilization, did not inhibit the growth of the organism on n-hexadecane. Normal hexadecane-grown cells showed strong surface-active properties and capacity to adhere firmly to hydrocarbon phase. It was concluded that in this organism, surface-active properties of the cells facilitate attachment of cells to the hydrocarbon-water interface generated by agitation, and promote substrate uptake and growth; no hydrocarbon pseudosolubilization or extracellular mediator is involved in the substrate uptake. Pseudomonas N 1 grew on n-hexadecane much faster than Pseudomonas M 1. Growth of this organism on n-hexadecane was associated with the extracellular production of biosurfactant-bioemulsifier and n-hexadecane pseudosolubilizing factor; the growth was strongly inhibited by 5 mM EDTA, indicating that hydrocarbon pseudosolubilization was the dominant factor in substrate uptake. The rate of n-hexadecane pseudosolubilization was high enough to account for the substrate up take rate. Hydrocarbon emulsifying and n-hexadecane pseudosolubilizing factors were isolated and tentatively characterized as lipoprotein and glycoprotein, respectively. Both factors act in a synergistic manner to provide enhanced hydrocarbon transport to cells through pseudosolubilization. It is proposed that this facility of mediated hydrocarbon transport is the basis for the relatively fast rate of growth of Pseudomonas N 1 on hydrocarbon.


High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors.
We treated 49 patients with recurrent or poor-prognosis CNS malignancies with high-dose chemotherapy regimens followed by autologous marrow rescue with or without peripheral-blood stem-cell augmentation to determine the toxicity of and event-free survival after these regimens. Nineteen patients had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had ependymomas, three had primitive neuroectodermal tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7) or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and -3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received standard supportive care. Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after transplantation, including nine of 16 treated before recurrence and nine of 33 treated after recurrence. There was one transplant-related death from pulmonary aspergillosis. Of five patients assessable for disease response, one had a partial remission (2 months), one has had stable disease (55+ months), and three showed progression 2, 5, and 8 months after transplantation. The toxicity of these regimens was tolerable. Certain patients with high-risk CNS malignancies may benefit from such a treatment approach. Subsequent trials should attempt to determine which patients are most likely to benefit from high-dose chemotherapy with autologous stem-cell rescue.


Maspin expression in oral squamous cell carcinoma.
Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily of protease inhibitors and it has a role as a tumor suppressor. Maspin has been reported to be important in processes relevant to tumor growth and metastasis such as cell invasion, angiogenesis, and apoptosis. A high expression of maspin was correlated with better rates of survival and absence of nodal metastases in head and neck squamous cell carcinoma. In contrast, some studies have shown that maspin overexpression is correlated with a poor prognosis in pancreatic and ovarian cancers and in lung adenocarcinoma. The aim of this study was an immunohistochemical evaluation of the maspin expression in oral squamous cell carcinoma and thus 89 patients were evaluated. Maspin expression in oral squamous cell carcinoma was significantly associated with the tumor differentiation grade (chi test: P = 0.0318) and the lymph node status (chi test: P < 0.005), but not with the tumor stage (chi test: P = 0.666). Metastatic involvement of lymph nodes was observed more frequently in maspin-negative cases than in tumors with more than 5% of positive cells (P = 0.0024). The present results confirm that maspin expression predicts a better prognosis in oral squamous cell carcinoma and that maspin probably plays a role in tumor progression.


Investigation of Social, Emotional, and Cognitive Factors with Effect on Suicidal Behaviour in Adolescents with Depression.
Our study aimed at investigating social, emotional, and cognitive factors playing a role in the development of suicidal ideation in depressed adolescents and its turning into a suicide attempt. Sixty-three adolescents (48 female, 15 male) aged 12 to 18 years were included in the study. In face-to-face interviews, suicide ideation, suicide plans, and previous suicide attempts were evaluated, sociodemographic data were collected. Additionally, the Children's Depression Inventory, State-Trait Anxiety Inventory (STAI-I, II), Beck Hopelessness Scale, Coopersmith Self-Esteem Inventory, Multidimensional Scale of Perceived Social Support, Strengths and the Difficulties Questionnaire (SDQ) parent forms were applied. SPSS version 13.0 for Windows was used for statistical analysis. It has been established that in the last six months, 71.4% of cases (n=45) had suicidal ideation and 27% (n=17) attempted suicide. Factors associated with suicidal ideation in depressed adolescents were: high depression and anxiety levels, hopelessness and low self-esteem (p<0.05). Factors associated with suicide attempts were: separated family background, lower perceived family support and high rates of conduct difficulties (p<0.05). Patients with suicide attempt differed from patients with suicidal ideation but without suicide attempt in lower perceived family support only (p<0.05). It is thought that keeping in mind the factors associated with the development of suicidal ideation and its turning into a suicide attempt, will help clinicians in preventing suicide attempts in depressed adolescents.


The Relationship between Erythrocytes and Diabetes Mellitus.
High blood glucose level (hyperglycemia) is a leading indicator of diabetes mellitus (DM). Erythrocytes are the most abundant cells in the circulation and the first to perceive changes in plasma composition. Long-lasting hyperglycemia affects the structure and function of erythrocytes. The detection of erythrocyte-related indicators can provide a valuable reference for the prevention, diagnosis, and treatment of DM and its complications. This paper reviews the normal structure and function of erythrocytes, the changes in erythrocytes in patients with diabetes, and the role of erythrocytes in the development of diabetic complications to provide more indicators for the early prevention of DM complications and to monitor the therapeutic effect of DM.


Report on the open discussion on the future of life extension research.
Following a highly stimulating series of talks on the social and ethical implications of greatly extended life spans, a discussion of the issues was held, in which a series of straw polls was conducted. An alarming conclusion from these polls was that most participants thought it either probable or "not improbable" that comprehensive functional rejuvenation of middle-aged mice would be possible within 10-20 years, but also felt that biogerontologists should not yet discuss timescales (either for mouse rejuvenation or similar progress in humans) in society at large. This combination of views may be very dangerous, as it assumes that humanity will need little forward planning to transition smoothly from its current almost universal fatalism concerning the defeat of aging to a widespread appreciation of its foreseeability or even imminence.


Arrythmias and ischemic changes of the heart induced by gastric endoscopic procedures.
Changes in the heart rate, blood pressure, ECG, occurring at the time of endoscopy of the stomach were studied in a group of 59 cases of cardiovascular disease and in a control group of 27 cases. With regard to arrythmias appearing at the time of endoscopy of the stomach, ventricular and atrial premature beats were the most numerous. Atrial fibrillation, as well as ventricular bigeminy were encountered. Two cases of atrial fibrillation continued even after the end of the examination. ST-T changes during endoscopy were found most frequently in the ischemic heart disease group and the valvular heart disease group. There were three cases in which severe ST depression made it necessary to stop the examination. The cardiovascular changes generally occurred at the beginning of the endoscopy examination. Two milligrams of propranolol i.v. seemed to be effective in preventing changes of heart rate.


Safety, pharmacokinetics, and immunomodulatory effects of lenalidomide in children and adolescents with relapsed/refractory solid tumors or myelodysplastic syndrome: a Children's Oncology Group Phase I Consortium report.
To determine the maximum-tolerated or recommended phase II dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and immunomodulatory effects of lenalidomide in children with recurrent or refractory solid tumors or myelodysplastic syndrome (MDS). Cohorts of children with solid tumors received lenalidomide once daily for 21 days, every 28 days at dose levels of 15 to 70 mg/m(2)/dose. Children with MDS received a fixed dose of 5 mg/m(2)/dose. Specimens for PK and immune modulation were obtained in the first cycle. Forty-nine patients (46 solid tumor, three MDS), median age 16 years (range, 1 to 21 years), were enrolled, and 42 were fully assessable for toxicity. One patient had a cerebrovascular ischemic event of uncertain relationship to lenalidomide. DLTs included hypercalcemia at 15 mg/m(2); hypophosphatemia/hypokalemia, neutropenia, and somnolence at 40 mg/m(2); and urticaria at 55 mg/m(2). At the highest dose level evaluated (70 mg/m(2)), zero of six patients had DLT. A maximum-tolerated dose was not reached. No objective responses were observed. PK studies (n = 29) showed that clearance is faster in children younger than 12 years of age. Immunomodulatory studies (n = 26) showed a significant increase in serum interleukin (IL) -2, IL-15, granulocyte-macrophage colony-stimulating factor, natural killer (NK) cells, NK cytotoxicity, and lymphokine activated killer (LAK) cytoxicity, and a significant decrease in CD4(+)/CD25(+) regulatory T cells. Lenalidomide is well-tolerated at doses up to 70 mg/m(2)/d for 21 days in children with solid tumors. Drug clearance in children younger than 12 years is faster than in adolescents and young adults. Lenalidomide significantly upregulates cellular immunity, including NK and LAK activity.


The use of the Rx spin label in orientation measurement on proteins, by EPR.
The bipedal spin label Rx is more restricted in its conformation and dynamics than its monopodal counterpart R1. To systematically investigate the utility of the Rx label, we have attempted to comprehensively survey the attachment of Rx to protein secondary structures. We have examined the formation, structure and dynamics of the spin label in relation to the underlying protein in order to determine feasibility and optimum conditions for distance and orientation measurement by pulsed EPR. The labeled proteins have been studied using molecular dynamics, CW EPR, pulsed EPR distance measurement at X-band and orientation measurement at W-band. The utility of different modes and positions of attachment have been compared and contrasted.


Effects of feeding increasing levels of iron from iron sulfate or iron carbonate on nursery pig growth performance and hematological criteria.
A total of 140 weanling pigs (241 × 600, DNA, Columbus, NE; initially 5.5 ± 0.79 kg body weight) were used in a 32-d study evaluating the effects of increasing dietary Fe from either iron sulfate (FeSO4) or iron carbonate (FeCO3) on nursery pig growth performance and blood Fe status. The pigs used for this trial did not receive an Fe injection after birth in order to increase the sensitivity to added dietary Fe after weaning. Pigs were weaned at approximately 21 d and allotted to pens based on the initial weight in a completely randomized block design with five pigs in each pen and four pens per treatment. Experimental treatments were arranged as a 2 × 3 + 1 factorial with main effects of dietary Fe source (FeSO4 vs. FeCO3) and level (10, 30, or 50 mg/kg of added Fe) plus a negative control with no additional dietary Fe. The basal diet contained 40 mg/kg total dietary Fe based on ingredient contributions and was formulated with an Fe-free trace mineral premix. Experimental diets were formulated below the pigs recommended Fe requirement based on NRC (2012) estimates. Experimental diets were fed in pellet form in a single phase for the duration of the trial. From day 0 to 32, there was no evidence for source × level interactions for growth performance, hemoglobin (Hb), or hematocrit (Hct) values. There was no evidence for a difference (P > 0.10) in dietary Fe source. Providing increasing Fe levels in the diet from either FeSO4 or FeCO3 improved (P < 0.05) average daily gain, average daily feed intake, gain-to-feed ratio, and increased (P < 0.05) Hb and Hct values. A day effect (P = 0.001) was observed for both Hb and Hct with values increasing throughout the study. Increasing dietary Fe levels in the diet from either FeSO4 or FeCO3 increased (linear; P < 0.05) Hb and Hct values on days 14, 21, and 32. In summary, these data suggest that the micronized form of FeCO3 is a source of Fe that can be added to nursery diets to yield similar responses to those observed from FeSO4 supplementation. Similar to previous research, increasing dietary Fe improved the growth performance and increased Hb and Hct values when pigs have low Fe status at weaning.


Late gestation increase in 11beta-hydroxysteroid dehydrogenase 1 expression in human fetal membranes: a novel intrauterine source of cortisol.
Late human gestation is associated with an increase in the concentration of cortisol (F) in the fetal circulation and amniotic fluid. It had been assumed that most of the F measured in the amniotic fluid came from the fetal adrenal gland. However, local production of F can also occur in human intrauterine tissues from inactive cortisone under the influence of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1. Recent studies have shown that 11beta-HSD 1 activity is up-regulated by prostaglandins (PG) E2 and F2alpha, hormones that are produced in the fetal membranes (FM) at term. In the present study, we hypothesized that 11beta-HSD 1 expression would increase in FM during pregnancy and at labor, creating the potential for local increase in F production at term. We examined 11beta-HSD 1 expression in placenta and FM obtained during normal pregnancy from nonlaboring women [26-28 wk (n = 3); 29-30 wk (n = 3); 32-33 wk (n = 3); 35-36 wk (n = 3)] and from uncomplicated term pregnancies after elective cesarean section (n = 6). 11beta-HSD 1 expression was also examined in amnion and chorionic tissues in relation to term labor (n = 12). Immunohistochemistry and Western blot analysis were used to examine 11beta-HSD 1 localization and expression. 11beta-HSD 1 activity was also measured in microsomal fractions prepared from whole fetal membranes. At term, immunoreactive 11beta-HSD 1 expression was localized predominantly to the chorion trophoblast cells, attached decidua, and amnion epithelial cells. 11beta-HSD 1 expression in FM increased with gestational age and reflected increased enzyme reductase activity. No change in 11beta-HSD 1 expression was found in placental tissue from the same patients. There was a significant increase in 11beta-HSD 1 expression in amnion but not in chorion with the onset of labor. We suggest that increases in 11beta-HSD 1 expression/activity by intrauterine membranes during late gestation may result in increased potential for a local increase in F production and that FM should be considered as an extraadrenal source of F during late gestation. This local F production may be involved in different pathways contributing to the regulation of parturition.


Integrated bioinformatics and validation reveal SOX12 as potential biomarker in colon adenocarcinoma based on an immune infiltration-related ceRNA network.
The primary objective of this study was to construct competing endogenous RNA (ceRNA) networks and evaluate the prognostic significance of tumor-infiltrating immune cells (TIICs) and key biomarkers within the ceRNA networks in colon adenocarcinoma (COAD) patients. Comprehensive bioinformatics tools were used to screen differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) related to COAD, leading to the creation of ceRNA networks. The CIBERSORT technique was employed to assess the significance of TIICs in COAD, and an immune-related prognosis prediction model was subsequently developed. Co-expression analyses were conducted to determine the relationship between key genes in ceRNA networks and immunologically significant TIICs. The study also utilized 5 GEO datasets and web-based databases to externally validate the findings. The study revealed a statistically significant relationship between key hub genes and immune cells, as determined through co-expression analysis. Two hub regulators (SOX12 and H19) demonstrated significant prognostic value in the ceRNA-related prognostic model, and their elevated expression levels were verified across multiple CRC cell lines. Additionally, the knockdown of SOX12 led to a suppression of proliferation, migration, and invasion in colon cancer cells. Through the construction of ceRNA networks and evaluation of TIICs, the study successfully established two risk score models and nomograms. These models serve as valuable tools for understanding the molecular processes and predicting the prognosis of COAD patients. Further validation of hub regulators SOX12 and H19 substantiates their potential role as key biomarkers in COAD.


Anomalous behavior of plasma response functions at strong coupling.
Using data from equilibrium molecular dynamics computer simulations we have built up a catalog of response functions for the Coulomb one-component plasma over a wide range of Γ coupling values, including the strongly coupled Γ>1 liquid regime. We focus on the domain of negative compressibility (Γ>3), where the proper response displays an acausal behavior, implying a modification of the relation between its real and imaginary parts in the Kramers-Kronig relations. We give a description of the details of this acausal feature, in both the frequency and time domains. We show that the viscoelastic pole of the density response function morphs into an imaginary pole in the upper ω half-plane that is responsible for the anomalous behavior of the response in this coupling range. By examining the plasmon dispersion relation through the dielectric response function, rather than via the peaks of the dynamical structure function, we obtain a more reliable representation for the dispersion. We demonstrate that there is an intimate link between the formation of the roton minimum in the dispersion and the negative compressibility of the system. The feasibility of the extension of our analysis to systems with a short-range interaction is explored.


Stem cells for obstetricians and gynecologists.
Stem cells are a subject of immense research interest, and may in the not too far future provide the basis for a number of new therapies aimed at substituting damaged or lacking cells, tissues, and even organs. A number of stem cell types have been identified, including embryonal stem cells, umbilical cord blood stem cells, and bone marrow stem cells. Two of the most promising stem cell types, embryonal stem cells and umbilical cord blood stem cells, are obtained from sources within the field of gynecology and obstetrics, namely fertility clinics performing in-vitro fertilization, and labor wards, respectively. This review focuses on the biological potentials of stem cells with a primarily gynaecological-obstetrical perspective. It is not the aim of this review to discuss the many important ethical aspects of stem cell technologies.


Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease.
We studied the effects of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during a maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing. The electrical activity of the diaphragm was recorded with an esophageal electrode during the fatigue runs, and the high-low ratio of the electrical signal was analyzed to assess diaphragmatic fatigue. Studies were performed before and after 7 and 30 days of theophylline administration (mean plasma level, 13 +/- 2 mg per liter). A control group received a placebo instead of theophylline. Theophylline increased maximal transdiaphragmatic pressure by 16 per cent after 7 days of administration (P less than 0.01), and this increase persisted after 30 days. No significant change in maximal transdiaphragmatic pressure was observed in the group given the placebo. Theophylline also suppressed diaphragmatic fatigue in all patients who received it. We conclude that theophylline has a potent and long-lasting effect on diaphragmatic strength and fatigue in patients with fixed airway obstruction.


Investigation of the Shear Behavior of Concrete Beams Reinforced with FRP Rebars and Stirrups Using ANN Hybridized with Genetic Algorithm.
The shear strength prediction of concrete beams reinforced with FRP rebars and stirrups is one of the most complicated issues in structural engineering applications. Numerous experimental and theoretical studies have been conducted to establish a relationship between the shear capacity and the design variables. However, existing semi-empirical models fail to deliver precise predictions due to the intricate nature of shear mechanisms. To provide a more accurate and reliable model, machine learning (ML) techniques are adopted to study the shear behavior of concrete beams reinforced with FRP rebars and stirrups. A database consisting of 120 tested specimens is compiled from the reported literature. An artificial neural network (ANN) and a combination of ANN with a genetic optimization algorithm (GA-ANN) are implemented for the development of an ML model. Through neural interpretation diagrams (NID), the critical design factors, i.e., beam width and effective depth, shear span-to-depth ratio, compressive strength of concrete, FRP longitudinal reinforcement ratio, FRP shear reinforcement ratio, and elastic modulus of FRP longitudinal reinforcement rebars and FRP stirrups, are identified and determined as input parameters of the models. The accuracy of the proposed models has been verified by comparing the model predictions with the available test results. The application of the GA-ANN model provides better statistical results (mean value Vexp/Vpre equal to 0.99, R2 of 0.91, and RMSE of 22.6 kN) and outperforms CSA S806-12 predictions by improving the R2 value by 18.2% and the RMSE value by 52.5%. Furthermore, special attention is paid to the coupling effects of design parameters on shear capacity, which has not been reasonably considered in the models in the literature and available design guidelines. Finally, an ML-regression equation considering the coupling effects is developed based on the data-driven regression analysis method. The analytical results revealed that the prediction agrees with the test results with reasonable accuracy, and the model can be effectively applied in the prediction of shear capacity of concrete beams reinforced with FRP bars and stirrups.


Metabonomics: systems biology in pharmaceutical research and development.
Metabonomics uses a combination of data-rich analytical chemical methods such as nuclear magnetic resonance spectroscopy and mass spectrometry together with chemometrics for profiling metabolism and interpreting metabolic fingerprints in complex biological systems. The methods have been applied in many areas of relevance to pharmaceutical research and development, including drug safety assessment, characterization of genetically modified animal models of disease, diagnosis of human disease, understanding physiological variation and drug therapy monitoring. As well as providing a novel means of sample classification and effect evaluation, the approach can lead to identification of combinations of biomarkers for those effects. These attributes mean that metabonomics will be integral in the drive towards personalized healthcare.


Significance of DMBT1 in Papillary Thyroid Carcinoma Concurrent With Hashimoto's Thyroiditis.
Papillary thyroid carcinoma (PTC) concurrent with Hashimoto's thyroiditis (HT) was associated with a better clinical prognosis. This study aimed to investigate a potential mRNA gene that affects the development of PTC, which helps PTC concurrent with HT patients have a better prognosis. PTC data were obtained from The Cancer Genome Atlas (TCGA) database. And the validation data of tissue specimens were collected from Guangzhou First People's Hospital. The thyroid tissue sections were hybridized with deleted in malignant brain tumor 1 (DMBT1) probes by situ hybridization. Survival rates were analyzed using Kaplan-Meier curves, and the log-rank test was used to compare group survival rates. Prognosis clinicopathological factors were analyzed by Cox regression. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) pathway enrichment analyses were performed using single-sample gene set enrichment analysis (ssGSEA). Finally, the correlation of deletion in DMBT1 expression with overall immune status, tumor purity, and human leukocyte antigen (HLA) gene expression profile was analyzed. HT was significantly associated with sex, tumor foci, extrathyroidal extension (ETE), residual tumor, and tumor stage (T stage). Moreover, PTC concurrent with HT had a lower risk of recurrence versus non-HT groups. A total of 136 differentially expressed mRNAs (DEMs) were identified between HT and non-HT groups. Among them, the expression level of DMBT1 in HT groups was statistically higher than that in non-HT groups. A significant association with ETE and recurrence was revealed in the high expression and the low expression of DMBT1. Furthermore, DMBT1 was an independent predictor of survival. The overall immune activity of high expression of DMBT1 was higher than that of the low-expression group. The PTC patients with HT had better behavior features and prognosis than those with simple PTC. DMBT1 in PTC-HT patients was a potential possible factor that inhibits tumors. High expression of DMBT1 may improve PTC prognosis by immune-related pathways.


Insights into the reaction mechanism of the coagulation of soy protein isolates induced by subtilisin carlsberg.
The reaction mechanism of the coagulation of soy protein isolates (SPIs) induced by subtilisin Carlsberg was investigated. Formation of the coagula was monitored by measuring the turbidity (OD660) of the SPI solution, which decreased at the initial stage (phase 1 or digestion phase) of the reaction, and then increased (phase 2 or coagulation phase) and finally reached the plateau level. The velocity of the coagulation increased with increasing enzyme concentration. The coagulation was inhibited dramatically by adding a serine protease inhibitor (phenylmethanesulfonyl fluoride, PMSF) when the turbidity reached the minimum value. This indicates that the SPI digests participating in the coagulation are produced mainly in phase 2; in other words, production of the coagulating fragments and their coagulation occur simultaneously in phase 2. Structural changes of SPI during proteolysis were measured by observing fluorescence changes of aromatic amino acids of SPI and an externally added hydrophobic probe. It was suggested that the hydrophilic surface areas of SPIs might be cleaved preferentially in phase 1, and that the hydrophobic inner areas might be cleaved in phase 2 with extensive decomposition of the 3-D structure of SPI proteins. The fragments formed in phase 2 are considered to coagulate through hydrophobic interactions.


Hydatidiform mole.
Hydatidiform mole is the most common form of gestational trophoblastic disease. It is an abnormally formed placental tissue with characteristic changes in karyotype, arising in fertilization disorders. The presence of abundant paternal genetic information plays a key role in the pathogenesis of complete and partial hydatidiform moles. These lesions are characterized by a relatively wide spectrum of morphological changes that may not be fully expressed, especially in the early stages of pregnancy. In addition, some changes can be observed in non-molar gravidities, which, unlike hydatidiform moles, lack any risk of malignant transformation. Although conventional histological examination still plays a key role in the diagnosis, it should be supplemented by other methods that reliably differentiate individual lesions. Accurate diagnosis of molar gravidities is important not only for determining the correct therapeutic approach, but the obtained data may also contribute to further research of these pathological entities.


Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies.
Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration.


Polyurethane Foam Skeleton-Based Phase Change Hydrogel for Efficient Battery Thermal Management with Favorable Antivibration Performance.
Efficient thermal management is critical to ensure the safe and reliable operation of lithium-ion batteries (LIBs) as they are highly sensitive to temperature changes. Meanwhile, LIBs are exposed to various external forces during operation, such as vibration, shock, and oscillation, which may disrupt the physical and chemical processes inside the battery and lead to a decreased performance and shortened life. Here, we designed a phase change hydrogel (PCH) pad based on the polyurethane (PU) foam skeleton and demonstrated its effectiveness in efficient thermal management and improving antivibration performance. The thermal conductivity of the prepared composite is 0.65 W/(m·K), while the thermal contact resistance could decrease to ∼20 K·cm2/W under 60 °C. It exhibits a flexible contact transformation during the phase transition, resulting in enhanced interfacial heat transfer and storage rate, as well as improved resistance against external impacts. The temperature of the battery module wrapped with a composite plate decreases by 11.4 °C during the 6C discharge. Moreover, the additional heat generated by external vibration is only half that of the bare battery, and the temperature difference could reach 5.2 °C, demonstrating the effective buffering effect of PCH@PU in mitigating long-term discharge-induced increases in internal resistance. The developed PCH@PU, known for its exceptional thermal management and favorable antivibration performance, holds promising potential for widespread utilization in the field of power battery heat dissipation.


Impact of Problematic Smartphone Use on Mental Health of Adolescent Students: Association with Mood, Symptoms of Depression, and Physical Activity.
Problematic smartphone use in adolescent students can impair their mental health and behavior, thereby affecting academic performance and interpersonal relationships as well as reducing time spent on physical activity. This study investigated the association between problematic smartphone use and mood, symptoms of depression, and level of physical activity in adolescent students. The sample consisted of 308 boys (46.1 percent, 16.04 ± 1.30 years) and 359 girls (53.9 percent, 15.54 ± 1.44 years), aged 13-18 years (15.77 ± 1.40 years). Four instruments were used: the Sociodemographic, School, and General Health Characteristics Questionnaire; Smartphone Addiction Scale (to measure problematic smartphone use); Brunel Mood Scale; and Beck Depression Inventory. The study found that physically inactive adolescent students were more likely to present with problematic smartphone use than those who were physically active, and girls were more likely to exhibit problematic smartphone use than boys. Adolescent students with problematic smartphone use presented with more mood disturbances and symptoms of depression than did adolescent students without problematic smartphone use. Overall, physical inactivity and problematic smartphone use can reduce vigor and increase symptoms of depression in adolescent students.


Merge to emerge - An interdisciplinary approach for management of periodontally compromised orthodontically treated patient.
In the modern day dental practice, synergy is fundamental. This synergistic effect must exist among various disciplines of dentistry for proper diagnosis, treatment planning, sequencing and execution of treatment in complex and challenging dental situations. Such collaborative effect between an orthodontist and a periodontist is essential as both works with same element, the tooth as crown-root unit with its supporting tissues. The orthodontic treatment is carried out through the medium of periodontium, so a healthy tooth supporting system is an essential prerequisite. Every potential candidate for orthodontic treatment should undergo a thorough periodontal examination. Any lousily diagnosed or conducted orthodontic treatment could be a facilitator of periodontal inflammatory or infectious process especially when the patient's oral hygiene is explicitly deficient. This case report demonstrates a challenging situation to a periodontist where patient had completed her orthodontic treatment but ended up with severe periodontal disease. The patient was thoroughly examined and a comprehensive treatment was planned and executed. Regenerative surgical procedures were done using platelet rich fibrin and hydroxyapitatite bone graft. Patient was followed up for 2 years. As sequelae of surgical procedures, patient had developed black triangles in the anterior region. The patient was unwilling for further perioplastic surgical procedures and further orthodontic treatment, so a gingival prosthesis using valplast was fabricated addressing her esthetic concerns.


Comprehending envy.
The authors reviewed the psychological research on envy. The authors examined definitional challenges associated with studying envy, such as the important distinction between envy proper (which contains hostile feelings) and benign envy (which is free of hostile feelings). The authors concluded that envy is reasonably defined as an unpleasant, often painful emotion characterized by feelings of inferiority, hostility, and resentment caused by an awareness of a desired attribute enjoyed by another person or group of persons. The authors examined questions such as why people envy, why envy contains hostile feelings, and why it has a tendency to transmute itself. Finally, the authors considered the role of envy in helping understand other research domains and discussed ways in which people cope with the emotion.


Behavioral dimensions in fourth-, fifth-, and sixth-grade students as rated by teachers.
The St. Francis Boys' Homes early intervention program for inadequately coping fourth-, fifth-, and sixth-grade students depends upon school teachers' nominations and employs their descriptions of pupil characteristics. In the interest of behavioral science, as well as the potential screening-in, selective placement, predictor purpose, and clinical gain within the tailored treatment program, the teachers completed a 99-item, favorable and unfavorable item description of 852 youths who were participating for 45 days in "Passport for Adventure." This large array of items yielded 14 first-order and four second-order factors, many of which have been found in the extensive literature. These measures of 14 first-order factors obtained through ratings by numerous teachers in 122 school settings demonstrated the wide span of the usual teacher's perception of youths in a formative period of their lives. It included interpersonal and intrapersonal descriptors. Most prior studies entered analysis with a low number of items and therefore could describe only a few simpler dimensions and could name them with less certainty. In addition, the factor analysis was sometimes unrealistically orthogonal and not finally hand rotated for clearest simple structure. This study gives a more comprehensive understanding of what teachers can and do perceive within and among their students, made manifest by a more extensive sampling of behavior.


Parallel and cross-resistances of clinical yeast isolates determined by susceptibility pattern analysis.
For calculated initial antifungal therapy, knowledge on parallel and cross-resistances are vitally important particularly in the case of multiresistant isolates. Based on a strain collection of 1,062 yeast isolates from a German/Austrian multicentre study, susceptibility pattern analysis (SPA) was used to determine the proportion of parallel and cross-resistances to eight antifungal agents (AFAs) encompassing flucytosine, amphotericin B, azoles (fluconazole, voriconazole and posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin). A total of 414 (39.0%) isolates were resistant for one or more of the AFAs. Resistance to one AFA was shown for 18.1% of all isolates. For 222 isolates (20.9%), resistance to two to seven AFAs was noted (7.7%; 7.7%; 3.6%; 1.0%; 0.7% and 0.2% to 2, 3, 4, 5, 6 and 7 antifungal compounds, respectively). Partial parallel resistances within the azole and echinocandin classes, respectively, were found for 81 (7.6%) and 70 (6.6%) isolates. Complete parallel resistances for azoles, echinocandins and combined for both classes were exhibited by 93 (8.8%), 18 (1.7%) and 6 (0.6%) isolates, respectively. Isolates displaying cross-resistances between azoles and echinocandins were infrequently found. Highly resistant isolates (resistance to ≥6 AFAs) were almost exclusively represented by Candida albicans. Highly standardized testing of AFAs in parallel and from the same inocula followed by SPA allows detailed insights in the prevalence and distribution of susceptibility patterns of microbial isolates.


Traumatic and non-traumatic adrenal emergencies.
Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.


Reduced viscosity of the free surface in entangled polymer melt films.
By embedding "dilute" gold nanoparticles in single polystyrene thin films as "markers", we probe the local viscosity of the free surface at temperatures far above the glass transition temperature (T(g)). The technique used was x-ray photon correlation spectroscopy with resonance-enhanced x-ray scattering. The results clearly showed the surface viscosity is about 30% lower than the rest of the film. We found that this reduction is strongly associated with chain entanglements at the free surface rather than the reduction in T(g).