[Needle crystal detector technology in mammography--relationship between image quality and dose depending on beam quality].
Compared with traditional CR storage phosphor plates, CR needle crystal technology used in mammography claims to allow for better image quality using a lower dose. Image quality and dose behavior are evaluated for multiple breast thicknesses (simulated with PMMA slabs) on the Agfa DX-M system with needle crystal detectors (HM5.0) and optimized for possible different beam qualities. Technical image quality was determined using the CDMAM phantom with subsequent "automatic readout" by considering limiting values as specified in the EUREF guideline. For dose, the calculated average glandular dose was used. With CR needle crystal detectors, comparable image quality can already be achieved with an approximately 50% lower dose than required for traditional plates. In addition, CR needle crystal technology makes it possible to also reach the achievable EUREF limit values without exceeding the dose limit values specified in EUREF. It was also found that the usage of W/Rh instead of Mo/Rh is beneficial for a 50 mm as well as 70 mm PMMA with regards to better image quality and a lower dose. The needle crystal technology with the Agfa DX-M system supports equivalent CDMAM image quality with an approximately 50% lower AGD compared to powder-based CR. An additional dose reduction can be achieved by using W/Rh instead of Mo/Rh.


The dietary supplement Cyplexinol® alleviates joint pain in men and women.
Joint pain afflicts millions of adults worldwide. The effect of a bone morphogenetic protein complex on joint pain is assessed in this study. We compared the impact of a dietary supplement protein complex (Cyplexinol®) and placebo in 18 men and women (aged 43 ± 10 years) with self-reported joint pain. Subjects were randomly assigned to each condition, consumed twice daily for 14 days (900 mg/day). Subjects completed questionnaires (e.g., Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective pain using a visual analog scale [VAS]) at the start and end of each treatment phase. Blood samples were analyzed for bone morphogenic protein (BMP), alkaline phosphatase, and cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, IL-1β, and TGF-β). Blood was also collected on days 1 and 15 to determine the acute impact of treatment on these measures. Pain and discomfort scores improved (P ≤ 0.05) for subjects following use of Cyplexinol® but not placebo. Improvements were noted for WOMAC pain (P = 0.05), stiffness (P = 0.039), and total pain (P = 0.026), as well as VAS pain (P = 0.015), recreational activity interference (P = 0.023), mood interference (P = 0.012), and total pain (P = 0.024). A trend was noted for WOMAC physical function (P = 0.052). An approximate 50% increase in BMP5 was noted following Cyplexinol® (P = 0.01), with a similar increase noted for placebo (P = 0.022). A near doubling in TGF-β (P = 0.001) was noted for Cyplexinol®. No other changes of significance were noted across time, nor were any differences noted in cytokines following acute intake of the conditions (P > 0.05). Cyplexinol® can alleviate joint pain in middle-aged men and women, while elevating BMP5 and TGF-β. Cyplexinol® does not influence cytokines, at least within a short 2-week supplementation period or within the 2-h post-ingestion period. Individuals suffering with joint pain in the knee and/or hip may benefit from daily use of Cyplexinol®, as we observed decreased pain and stiffness following treatment.


Highly selective detection of 2,4,6-trinitrophenol and Cu(2+) ions based on a fluorescent cadmium-pamoate metal-organic framework.
A luminescent cadmium-pamoate metal-organic framework, [Cd2 (PAM)2 (dpe)2 (H2 O)2 ]⋅0.5(dpe) (1), has been synthesized under hydrothermal conditions by using π-electron-rich ligands 4,4'-methylenebis(3-hydroxy-2-naphthalenecarboxylic acid) (H2 PAM) and 1,2-di(4-pyridyl)ethylene (dpe). Its structure is composed of both mononuclear and dinuclear Cd(II) building units, which are linked by the PAM and dpe ligands, resulting in a (4,8)-connected 3D framework. The π-conjugated dpe guests are located in a 1D channel of 1. The strong emission of 1 could be quenched efficiently by trace amounts of 2,4,6-trinitrophenol (TNP), even in the presence of other competing analogues such as 4-nitrophenol, 2,6-dinitrotoluene, 2,4-dinitrotoluene, nitrobenzene, 1,3-dinitrobenzene, hydroquinone, dimethylbenzene, and bromobenzene. The high sensitivity and selectivity of the fluorescence response of 1 to TNP shows that this framework could be used as an excellent sensor for identifying and quantifying TNP. In the same manner, 1 also exhibits superior selectivity and sensitivity towards Cu(2+) compared with other metal ions such as Zn(2+) , Mn(2+) , Mg(2+) , K(+) , Na(+) , Ni(2+) , Co(2+) , and Ca(2+) . This is the first MOF that can serve as a dual functional fluorescent sensor for selectively detecting trace amounts of TNP and Cu(2+) .


Spontaneous transient outward currents: modulation by nociceptin in murine dentate gyrus granule cells.
Spontaneous transient outward currents have been found in peripheral neurons and smooth muscle cells, but rarely in central neurons. Using a nystatin-perforated patch clamp technique, we succeeded in recording spontaneous transient outward currents in mouse dentate gyrus granule cells. Nociceptin/orphanin FQ increased the amplitude and frequency of transient outward currents. We consider modulation of spontaneous transient outward currents to be a new means to regulate cell activity in central neurons, and studied their characteristics and mechanism of augmentation. The whole-cell current-voltage relationship showed outward rectification and the reversal potential was close to the equilibrium potential for K+. The frequency of spontaneous transient outward currents increased at depolarized potentials. Tetraethylammonium, iberiotoxin and a Ca2+ chelator BAPTA-AM inhibited spontaneous transient outward currents. These results suggest the involvement of large-conductance Ca2+-activated K+ channels. Single-channel recordings in the inside-out configuration revealed Ca2+-activated K+ channels with a conductance ranging from 82 to 352 pS. The augmenting effect of nociceptin/orphanin FQ was cancelled by [Phe1psi(CH2-NH)Gly2]Nociceptin(1-13)NH2. Cd2+ did not affect the transient outward currents or augmentation by nociceptin/orphanin FQ. Whereas nociceptin/orphanin FQ, theophylline and cyclic ADP ribose induced transient outward currents with short duration observed under control conditions, inositol 1,4,5-trisphosphate induced transient outward currents with long duration, in addition to those with short duration. Ryanodine inhibited nociceptin/orphanin FQ from augmenting spontaneous transient outward currents. Our data suggest that Ca2+ sparks transiently activate large-conductance Ca2+-activated K+ channels to induce transient outward currents. Nociceptin/orphanin FQ probably sensitizes ryanodine receptors and increases transient outward currents to reduce cell excitability.


How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia?
Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC. Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice. Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals. Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.


Anion-directed formation and degradation of an interlocked metallohelicate.
Although there are many examples of catenanes, those of more complex mechanically interlocked molecular architectures are rare. Additionally, little attention has been paid to the degradation of such interlocked systems into their starting complexes, although formation and degradation are complementary phenomena and are equally important. Interlocked metallohelicate, [(Pd(2)L(4))(2)](8+) (2(8+)), is a quadruply interlocked molecular architecture consisting of two mechanically interlocked monomers, [Pd(2)L(4)](4+) (1(4+)). 2(8+) has three internal cavities, each of which encapsulates one NO(3)(-) ion (1:3 host-guest complex, 2⊃(NO(3)|NO(3)|NO(3))(5+)) and is characterized by unusual thermodynamic stability. However, both the driving force for the dimerization and the origin of the thermodynamic stability remain unclear. To clarify these issues, BF(4)(-), PF(6)(-), and OTf(-) have been used to demonstrate that the dimerization is driven by the anion template effect. Interestingly, the stability of 2(8+) strongly depends on the encapsulated anions (2⊃(NO(3)|NO(3)|NO(3))(5+) ≫ 2⊃(BF(4)|BF(4)|BF(4))(5+)). The origins of this differing thermodynamic stability have been shown through detailed investigations to be due to the differences in the stabilization of the interlocked structure by the host-guest interaction and the size of the anion. We have found that 2-naphthalenesulfonate (ONs(-)) induces the monomerization of 2⊃(NO(3)|NO(3)|NO(3))(5+) via intermediate 2⊃(ONs|NO(3)|ONs)(5+), which is formed by anion exchange. On the basis of this finding, and using p-toluenesulfonate (OTs(-)), the physical separation of 2⊃(NO(3)|NO(3)|NO(3))(5+) and 1(4+) as OTs(-) salt was accomplished.


Myalgia.
Myalgia, a common symptom resulting from a variety of disease processes, often escapes a specific etiologic diagnosis. Despite the poorly understood pathogenetic mechanisms underlying myalgia, logical classification and clinical evaluation can lead to successful treatment in many cases.


Evaluation of intra-abdominal solid organ injuries in children.
In our study we investigated characteristics and degree of intra-abdominal solid organ injuries according to tomographic imaging in pediatric patients who presented to our emergency clinic with possible abdominal injuries and to whom US and/or abdominal tomography were applied. 1066 pediatric patients were included in the study. The age, gender, injury localization, injury type, injury mechanism, abdominal US and CT results, and treatment specifics of patients were evaulated. 58.5% of cases were male. Average age of children was 7.1±4.6 70.8% of the injuries occured in the outdoors. As for injury type, 92.8% of the injuries were blunt and 7.2% were penetrating traumas. The most common mechanism of injury was motor vehicle accidents at 41.4%. The most common abdominal physical examination finding was tenderness with a prevelance of 67%. In patients with solid organ injury, liver injury was detected in 47% of patients, spleen injury was detected in 36% of patients and renal injury was detected in 17% of patients. Grade II injury was the most common grade. 96.5 of patients were provided conservative treatment and 3.5% of patients were treated surgically. Solid organ injuries due to abdominal trauma in children are generally related to blunt trauma and are severe injuries. CT angio is an important imaging method for detecting solid organ injuries, classification of the injury and treatment determination. Greater than 90% of solid organ injuries in children can be treated successfully with conservative methods.


Compression neuropathy: a late finding in the postburn population: a four-year institutional review.
Nerve compression syndromes may cause postburn morbidity that can often be difficult to recognize and manage. This study reviewed patients in the authors' institution who needed nerve decompression secondary to thermal or electrical burns. The objective was to evaluate the timing of nerve decompression in the burn population. A 4-year review of the authors' institution's database found 22 patients who underwent peripheral neuroplasty. This patient population included both thermal and electrical burn patients. Two patients were excluded from the study because they underwent rapid forearm amputation, and a third patient who had his initial burn care done in Europe was also excluded. The authors reviewed the mechanism of burn: percentage of body surface area burned, which nerves underwent decompression, and time from burn to decompression. Nerve compression syndromes were diagnosed and treated in this group of patients from day 46 to 1530 post-burn. Carpal tunnel was the most common site of compression accounting for 46% of the nerve decompressions. Sixteen of the 19 (84%) patients required that synchronous nerves be decompressed. The average body surface area burn in the thermal group was 43 and 5% in the electrical burn group. Nerve compression syndromes secondary to burns can be a challenging problem to diagnose and treat. Multiple studies have shown the importance of treating nerve compressions in the acute setting; however, this study shows the importance of long-term surveillance, secondary to the late presentation of nerve compression syndromes. Late nerve compression neuropathies were present in both the electrical and thermal burn patients. The authors also found that presentation of a single nerve compression should raise the suspicion of a synchronous nerve compression. Patients with thermal burns greater than 20% body surface area and electrical burns should be routinely questioned and examined for the peripheral nerve compression syndromes during long-term follow-up.


Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study.
RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials. In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss.


Malignant teratoma in Klippel-Feil syndrome: a case report and review of the literature.
Klippel-Feil syndrome is characterized by a congenital fusion of cervical vertebrae. Intracranial teratomas are nongerminomatous germ cell tumors and they account for 0.3 to 0.9% of all intracranial tumors. Teratomas with malignant transformation refer to lesions which give rise to malignant cancer of somatic type. The association between tumors of dermoid origin and Klippel-Feil malformation is extremely rare. Only 23 other cases have so far been reported, and only one case of dermoid tumor with areas of dedifferentiation on squamous cell carcinoma has been described. We report the case of a 72-year-old white man with a 2-year history of gait and balance disturbances. A brain magnetic resonance imaging revealed a fourth ventricle neoplastic process with infiltrative features. He was operated through a suboccipital craniectomy with a C1 laminotomy and bilateral vertebral artery transposition. At 6-months follow-up, magnetic resonance imaging showed an early regrowth of the fourth ventricle tumor, with the same radiological features. Patients with Klippel-Feil malformation could develop posterior fossa dermoid tumors. The malignant potential of such tumors must be considered and surgery is recommended. Particular attention must be focused on the histopathological analysis in order to identify possible foci of malignant transformation.


Ag/Brønsted Acid Co-Catalyzed Spiroketalization of β-Alkynyl Ketones toward Spiro[chromane-2,1'-isochromene] Derivatives.
A new Ag/Brønsted acid co-catalyzed spiroketalization of β-alkynyl ketones with para-quinone methides (p-QMs) has been established, enabling multiple C-C and C-O bond-forming events to access densely functionalized spiro[chromane-2,1'-isochromene] derivatives with generally excellent diastereoselectivity and good yields. A reasonable mechanism for forming these 6,6-dibenzannulated spiroketals involving 6-endo-dig oxo-cyclization and 1,6-addition-cyclization cascades is proposed.


The effect of human mesenchymal stem cells on tumour cell proliferation.
The therapeutic effect of mesenchymal stem cells (MSC) has been extensively investigated in recent decades, however this therapeutic effect has not been fully characterised. The aim of this study is to elucidate the inhibitory effect of MSC on haematopoietic tumour cells proliferation such as BV173 cell line. To this end, MSC generated from bone marrow, after immunophenotyping, they were co-cultured with tumour cell. The result shows that MSC profoundly inhibit the tumour cell proliferation via arresting the tumour cells at G0 and G1 phase of cell cycle.


The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis.
Ankylosing spondylitis (AS) or radiographic axial spondyloarthritis is a chronic immune-mediated rheumatic disorder characterized by the inflammation in the axial skeleton, peripheral joints, and soft tissues (enthesis, fascia, and ligament). In addition, the extra-skeletal complications including anterior uveitis, interstitial lung diseases and aortitis are found. The pathogenesis of AS implicates an intricate interaction among HLA (HLA-B27) and non-HLA loci [endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin-23 receptor (IL23R), gut dysbiosis, immune plasticity, and numerous environmental factors (infections, heavy metals, stress, cigarette smoking, etc.) The latter multiple non-genetic factors may exert a powerful stress on epigenetic regulations. These epigenetic regulations of gene expression contain DNA methylation/demethylation, histone modifications and aberrant non-coding RNAs (ncRNAs) expression, leading to inflammation and immune dysfunctions. In the present review, we shall discuss these contributory factors that are involved in AS pathogenesis, especially the aberrant ncRNA expression and its effects on the proinflammatory cytokine productions (TNF-α, IL-17 and IL-23), T cell skewing to Th1/Th17, and osteoclastogenic/osteogenic differentiation. Finally, some potential investigatory approaches are raised for solving the puzzles in AS pathogenesis.


Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell carcinomas in horses.
To assess expression of cyclooxygenase (COX)-1 and -2 in naturally occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in horses. Tissue samples collected from 3 conjunctival, 2 vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia. Tissue samples were snap frozen in liquid nitrogen and stored at -80 degrees C until analysis. Protein was extracted from the frozen tissues, and western blot analyses were performed. Nonneoplastic and abnormal tissues from each body region were run on the same blot, and blots were run in triplicate. Molecular-weight markers and COX-1 and 2 ovine standards (positive control samples) were run concurrently on the gels; negative control samples were not used. All tissues, including the nonneoplastic and SCC tissues, expressed both COX-1 and -2 proteins. Results indicated that the expression of COX proteins in both nonneoplastic and SCC-affected tissues in horses is markedly different from that in other species. The reason for the potential benefit of COX-2 inhibitors in horses and other species is unknown. Further research needs to be performed to evaluate the efficacy of COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms of tumor development in horses should be performed to increase understanding of this disease and ascertain how the mechanisms differ from those in other animals.


Small bowel stricture following blunt abdominal trauma.
Late presentation of small bowel strictures following blunt abdominal trauma is rather uncommon and there have been few previous reports of its occurrence. Most patients with blunt abdominal trauma without perforation or major bleeding are managed conservatively, making the diagnosis of less conspicuous intestinal injuries difficult. We reviewed our prospectively maintained surgical records over a period of 12 years and found that 8 patients developed small bowel obstruction subsequent to a history of blunt trauma abdomen which had been initially managed conservatively. A total of 7 males and 1 female with a mean age of 37 (range 23 - 48) years were examined in this study. The most common presentation was pain and vomiting with abdominal distension, noted in 5 patients; but three patients presented only with abdominal pain. The strictures were solitary in all cases, with the most common site being the terminal ileum. The average interval between the trauma and presentation of small bowel obstruction was 138 (range 7 to 550) days. Barium meal studies and computerized tomography were used to establish the diagnosis and laparotomy with resection of the involved bowel was curative. There was no mortality. Post traumatic small bowel obstruction should be kept in the differential diagnosis of patients who presented with abdominal pain, sometimes without distension and vomiting, and who have a history of blunt trauma abdomen.


Investigation of the enzymatic activity of the Na+,K+-ATPase via isothermal titration microcalorimetry.
Isothermal titration microcalorimetry (ITC) is shown here to be a sensitive and accurate method for assaying the steady-state enzyme activity of the Na+,K+-ATPase. Single ATP injection experiments yield an apparent enthalpy change for the ATP hydrolysis reaction catalyzed by the enzyme of -51 (+/-1) kJ mol(-1). This value is independent of the amount of ADP accumulated in the sample cell, which indicates that under the experimental conditions studied here (saturating Na+ and K+ concentrations) ADP does not inhibit enzyme activity by reversal of the phosphorylation reaction and resynthesizing ATP. Multiple ATP injection titration experiments in which varying concentrations of ADP were initially included in the sample cell could be adequately explained by a Michaelis-Menten kinetic model incorporating noncompetitive inhibition. This suggests that ADP inhibits the enzyme by binding to more than one enzyme intermediate and inhibiting forward reactions of the enzyme. Values of Km and KI obtained for the fits agree with literature values obtained by other methods. Because ITC is a direct method of continually monitoring enzyme activity, it is a valuable supplement to less direct or noncontinuous methods such as colorimetric, enzyme-coupled or radioactivity-based assays.


Focused Ion Beam Preparation of Specimens for Micro-Electro-Mechanical System-based Transmission Electron Microscopy Heating Experiments.
Micro-electro-mechanical systems (MEMS)-based heating holders offer exceptional control of temperature and heating/cooling rates for transmission electron microscopy experiments. The use of such devices is relatively straightforward for nano-particulate samples, but the preparation of specimens from bulk samples by focused ion beam (FIB) milling presents significant challenges. These include: poor mechanical integrity and site selectivity of the specimen, ion beam damage to the specimen and/or MEMS device during thinning, and difficulties in transferring the specimen onto the MEMS device. Here, we describe a novel FIB protocol for the preparation and transfer of specimens from bulk samples, which involves a specimen geometry that provides mechanical support to the electron-transparent region, while maximizing the area of that region and the contact area with the heater plate on the MEMS chip. The method utilizes an inclined stage block that minimizes exposure of the chip to the ion beam during milling. This block also allows for accurate and gentle placement of the FIB-cut specimen onto the chip by using simultaneous electron and ion beam imaging during transfer. Preliminary data from Si and Ag on Si samples are presented to demonstrate the quality of the specimens that can be obtained and their stability during in situ heating experiments.


Oil bio-degradation in permeable pavements by microbial communities.
This paper reports on continuing research at Coventry University into the improvement of highway water quality following flow through a permeable pavement. Such pavements have been shown elsewhere to be efficient in-situ bio-reactors, capable of degrading large quantities of clean motor oil. Further laboratory research, reported here, demonstrates that a commercially obtained oil degrading, microbial mixture was not significantly better at degrading clean motor oil than the indigenous microbial biomass established within the pavement over a 4-year period, when provided with an adequate nutrient supply. Scanning electron microscopy has been used to monitor biofilm development, which has also identified that the pavement has developed a complex community structure with high bio-diversity.


[Effect of dopexamine in splanchnic perfusion during surgery of the abdominal aorta].
Abdominal aortic surgery has significant effects on cardiac and splanchnic perfusion. The purpose of this study was to examine the effects of dopexamine, an inodilator drug, on hemodynamic and splanchnic perfusion with measurement of gastric intramucosal pH, by the method of gastric tonometry, during abdominal aneurysm resection. Twenty-five patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups. During aortic cross-clamping Group II patients received dopexamine infusion, at a dose of 1 microgram/kg/m, and at a dose of 0.5 micrograms/kg/m from declamping to the end of the surgery. Whereas Group I patients did not receive a dopexamine infusion. During aortic cross-clamping the intramucosal pH value decreased in Group I patients, but did not change in Group II patients. Heart rate, cardiac index, and mixed venous oxygen saturation increased significantly during dopexamine infusion, whereas systemic vascular resistance was reduced. During aortic cross-clamping dopexamine was a useful agent in improving splanchnic blood flow, cardiac index venous saturation. Also, since the drug produces dose related hemodynamic changes of rapid onset and reversibility, it is possible to interrupt the infusion before aortic declamping to avoid the decrease in the intramucosal pH value.


Evaluation of biomarkers of exposure to selected cigarette smoke constituents in adult smokers switched to carbon-filtered cigarettes in short-term and long-term clinical studies.
Cigarette smoke is a complex aerosol that includes a gas vapor phase and a particulate phase. Inclusion of activated carbon in the cigarette filter can reduce some of the gas-phase smoke constituents implicated as toxicologically relevant. The present study evaluated exposure to selected gas-phase constituents when adult smokers switched to prototype cigarettes with a highly activated carbon filter. Smokers (N = 160) in two separate studies were randomized to continue to smoke conventional cigarettes (either a 6-mg or 11-mg FTC tar product), to smoke test cigarettes containing carbon filters (comparable tar levels), or to stop smoking. After completing 8 days in controlled smoking conditions (short-term studies), smokers had the option to continue in 24-week long-term ambulatory studies with unrestricted smoking. Urinary excretion of mercapturic acid metabolites of 1,3-butadiene, acrolein, and benzene; nicotine and five of its metabolites, total NNAL, and 1-hydroxypyrene were measured at baseline in the conventional cigarette group, in all groups in the short-term studies, and every 4 weeks in the long-term studies. In the short-term studies, statistically significant reductions (>70%, p<.001) in gas-phase biomarker levels were observed in the test cigarette group for both tar level products compared with the conventional cigarette group. These reductions were similar to those observed in the stop-smoking groups. The reductions continued consistently (p<.001) throughout the long-term studies. Switching to test cigarettes minimally affected the particulate-phase biomarkers. Statistically significant and consistent reductions in selected gas vapor phase biomarkers were observed when smokers switched to activated carbon filter cigarettes.


[Development of newer antidepressant].
The development of antidepressant started from 1950's and it is based on monoamine hypothesis. Antidepressants enhance monoamine, such as serotonin, nor adrenaline and dopamine neurotransmission by blockade of monoamine transporter or monoamine oxydase. The antidepressants under clinical trials enhance those monoamine in various combinations. The development of newer antidepressants is still on pre-clinical trials. Those candidates such as neurotrophic factors and neuropeptides may show antidepressant effect without monoamine hypothesis and those are expected to overcome the limitation of existing antidepressant.


[A comparison of perceived maternal love and parentification in children of single-mothers and two-parent families].
Objectives: About 20 % of children in Germany grow up with a single mother - this is often associated with multiple strain for the mothers and may have adverse effects on the child-parent relationship. Methods: In two retrospective internet surveys (wave 1 born in 1960s, wave 2 born in 1990s) perceived maternal love and role reversal were assessed in children of single mothers and children grown up in two parent families. Results: In both waves high values of maternal love were reported. For children raised by single mothers, strong effects for age and occupational status were observed. Contrary to literature, no gender specific effects on role reversal were observed in this sample. Discussion: High occupational strain in a single mother was associated with less perceived love in the child.Multiple strain in singlemothers should findmore social and political attention. Regarding role reversal support should address daughters and sons similarly.


Barriers and more: functions of tight junction proteins in the skin.
Although the existence of tight junction (TJ) structures (or a secondary epidermal barrier) was postulated for a long time, the first description of TJ proteins in the epidermis (occludin, ZO-1, and ZO-2) was only fairly recent. Since then, a wealth of new insights concerning TJs and TJ proteins, including their functional role in the skin, have been gathered. Of special interest is that the epidermis as a multilayered epithelium exhibits a very complex localization pattern of TJ proteins, which results in different compositions of TJ protein complexes in different layers. In this review, we summarize our current knowledge about the role of TJ proteins in the epidermis in barrier function, cell polarity, vesicle trafficking, differentiation, and proliferation. We hypothesize that TJ proteins fulfill TJ structure-dependent and structure-independent functions and that the specific function of a TJ protein may depend on the epidermal layer where it is expressed.


ZnO Q-dots as a potent therapeutic nanomedicine for in vitro cytotoxicity evaluation of mouth KB44, breast MCF7, colon HT29 and HeLa cancer cell lines, mouse ear swelling tests in vivo and its side effects using the animal model.
Nanoformulations derived from fine porous ZnO quantum dot nanoparticles (QD NPs) can offer strong potential medical applications; especially in cancer therapy. ZnO QD NPs was synthesized by sol-gel hydrothermal process, fast cold quenching and further smart surface functionalization methods to obtain ultrasmall size (1-4 nm) NPs. ZnO nanopolymer, a wetting agent, PEG co-solvent and water/oil emulsion stabilizer were considered in our nanofluid formulation. The resulting nanofluid was characterized by SEM, FTIR, photoluminescence, band gap energy, zeta potential and UV-Vis spectroscopy. The cytotoxic effects on the growth of four cancer cell lines were evaluated by MTT assay. The IC50 (µg/ml) values of 30, 41, 40 and 35 for KB44, MCF-7, HT29 and HeLa cells, respectively, after 48 h of nanoformulation treatment suggested the cytotoxic effect of this nanoformulation on these cell lines in a concentration-dependent manner (p < .05). ZnO nanofluid destroyed cancer cell lines more efficiently than the normal HFF-2 (IC50 = 105 µg/ml). The reduction in cell viability in response to ZnO nanofluid treatment induced apoptosis in the cultured cells. Skin sensitization test plus antibacterial activity were also measured. Side effect tests on 70 white mice in vivo resulted in only 3-4 abnormal situations in hepatic tissue section possibly due to the idiosyncratic drug reactions.


Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.
The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.


Hypoplastic tibiae with postaxial polysyndactyly: a new dominant syndrome?
A five year old boy is reported with hypoplastic, bowed tibiae and postaxial polysyndactyly. Sixteen relatives of both sexes in four generations either have bilateral syndactyly or postaxial polydactyly or both. The nature of the condition and the possible mode of inheritance are discussed.


Proteinases from Bacillus intermedius secreted in the late stages of sporulation.
Proteinases are widely used in various fields of medicine, such as the treatment of burns, purulent wounds, or decubitus ulcers. On the basis of new microbial proteinases produced by nonpathogenic organisms, a new generation of medical preparations can be developed. Representatives of the Bacillus genera are nonpathogenic and are suitable for producing various proteases in large quantities. B. intermedius is shown to produce a set of alkaline proteases at the early and late stationary phase of growth. The activity of alkaline proteinases was determined using synthetic chromogenous substrates Z-Glu-pNA and Z-Ala-Ala-Leu-pNA. To determine beta-galactosidase activity, 2-nitro-beta-D-galactopyranosid was used. Spores were calculated by phase-contrast microscopy. During the late stages of sporulation B. intermedius 3-19 cells were shown to secrete two proteinases into the medium: glutamyl endopeptidase, with maximum activity at 40 hours of growth, and subtilisin, with maximum activity at 44 hours of growth. Evidence for the secretion of these enzymes into the medium was provided by measuring beta-galactosidase activity. Our results show that proteinases from B. intermedius (glutamyl endopeptidase 2 and subtilisin 2) in the late stationary phase of growth are secreted enzymes. This suggests that these enzymes play a role in sporulation.


[In vivo and in vitro degradation of fibrin adhesives (studies in rats)].
The fibrin seal (FS) is of indisputed value for hemostasis and atraumatic tissue synthesis in surgical therapy. In order to determine the optimal FS composition for resistance against fibrinolysis, in vivo lysis was tested by adding increasing amounts of the fibrinolysis-inhibitor aprotinine to 125I FS; urokinasis and plasminogen were administered in vitro while measuring protein and 125Iodine release. The correlation of protein and 125Iodine release clearly reflects the interdependence of both parameters; disjunction of radioactivity from the protein molecule was ruled out. In vitro, fibrinolysis is inhibited to a nearly unlimited extent by aprotinine. In vitro, aprotinine improves fibrinolysis inhibition only up to a maximum of 1500 KIE/ml clot, thereby significantly altering the maximum elimination of 125Iodine and FS half-life as well. Higher doses of aprotinine applied in vivo remain without effect upon FS stability. In human surgery, the addition of aprotinine to FS is recommended for strictly hemostyptic application only, but not for tissue synthesis such as nerve- and microvessel-anastomoses in plastic reconstructive surgery.


Observation of conical scattering cones from a two-dimensional hexagonal photonic crystal based on a polymer-dispersed liquid crystal.
We explore axial scattering from a two-dimensional hexagonal photonic crystal based on a polymer-dispersed liquid crystal at normal incidence. The scattering reveals symmetric cones over a range of frequencies. The observed cones disperse strongly outward, and their radii are determined by the wavelength of the probe beam. Such cones are generated by the coupling of forward-scattered beams of the refracted beams and the refracted beams themselves under momentum conservation.


Tinea gladiatorum: Pennsylvania's experience.
To describe the impact of ringworm infections in high school wrestlers (tinea gladiatorum) in Pennsylvania during the 1998-1999 scholastic wrestling season. Retrospective 23-item mail-out survey. Pennsylvania high schools with varsity wrestling programs in 1998-1999. Athletic trainers, athletic directors, and wrestling coaches who responded to the mail-out survey. Frequency of ringworm infection during the 1998-1999 season. Methods of prevention, diagnosis, and treatment of ringworm among respondent schools. Summary of beliefs concerning transmission and the way ringworm is approached compared with other skin infections. Any associations between the methods of prevention, diagnosis, and treatment and the frequency of ringworm infections. Response rate was 42.4%. Of the respondent schools, 84.7% had at least one wrestler diagnosed with ringworm. Of these teams with infected wrestlers 33% had a wrestler miss a match because of the infection. A majority of schools (68.7%) have a written guideline for return after a ringworm infection. Most respondents believe ringworm is transmitted by personal contact or from contact with mats. An overwhelming majority of schools (97%) use preventive practices. Interestingly, schools that used a greater number of preventive practices had more ringworm infections (p < 0.05). Larger teams were associated with more ringworm infections. In the respondent schools, 60% of coaches were involved in making a diagnosis of ringworm. Return decisions are made predominantly by a physician and/or the athletic trainer (79%). Ringworm infections in wrestlers are a common occurrence. There is a lot of variation among schools in Pennsylvania in regard to prevention, diagnosis, treatment, guidelines, and beliefs about ringworm. More study is needed to determine risk factors, transmission patterns, microbiology patterns, and evidence-based prevention and treatment recommendations.


Nonsymmetrical dithienylethenes bearing dithieno[3,2-b:2',3'-d]thiophene units with photochromic performance in the crystalline phase.
Four novel nonsymmetrical photochromic diarylethene compounds containing dithieno[3,2-b:2',3'-d]thiophene units were designed and synthesized to investigate their photochromic properties. All these molecules adopt a photoactive antiparallel conformation in single crystals, as revealed by X-ray crystallographic analysis, and exhibit excellent photochromism in solution as well as in the crystalline phase.


Sam68 regulates cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway in non-Hodgkin's lymphoma.
Sam68 (Src-associated in mitosis 68 kDa), a substrate for tyrosine kinase c-Src during mitosis, is up-regulated in a variety of human cancers and acts oncogenically promoting tumour progression. This study has explored biological function and clinical significance of Sam68 in non-Hodgkin's lymphoma (NHL). To examine Sam68 expression in NHL, clinically, eight diffuse large B-cell lymphomas and four reactive lymphoid hyperplasia fresh-frozen tissues were obtained for western blot and quantitative real-time PCR analyses. Using immunohistochemical staining, paraffin wax embedded sections from 164 cases of NHL patients were used to evaluate prognostic value of Sam68. Cell Counting Kit-8 (CCK-8) and soft agar colony assays were conducted to investigate the role of Sam68 in cell viability and cell proliferation respectively. Furthermore, effects of Sam68 on cell adhesion-mediated drug resistance (CAM-DR) was determined by CCK-8 assay and flow cytometric analysis. Expression status of Sam68 inversely correlated with clinical outcomes of patients with NHL, and it was also an independent prognostic factor for the outcomes. In addition, Sam68 was associated with proliferation of NHL cells. Knock-down of its gene inhibited cell proliferation and colony formation by delaying cell cycle progression. Furthermore, OCI-Ly8 and Jeko-1 cells adhering to FN and HS-5 expressed higher Sam68 protein, compared to their suspension counterparts. Sam68 promoted cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway. Increased Sam68 expression in NHL resulted in poor prognosis, and it promoted CAM-DR in NHL via AKT.


Activation of microglia in HIV-1 infected brains is not dependent on the presence of HIV-1 antigens.
The activation pattern of microglia in the cerebral cortex of AIDS patients with the neuropathological diagnosis of HIV-1 encephalitis was investigated by immunohistochemistry and morphometry. The number of activated microglial cells in the grey and white matter of five cortical regions was determined. In the grey and white matter of all cortical regions a significant increase in the number of microglial cells was demonstrated in HIV-1 infected brains. Moreover, the activation of microglia was not correlated with the presence of HIV-1 antigen in the brain region. The data show a significantly increased number of microglia in HIV-1 infected brains. These activated microglial cells could, among others, be those cells producing cytotoxic factors which, in turn, cause brain damage.


Time-resolved ARPES at LACUS: Band Structure and Ultrafast Electron Dynamics of Solids.
The manipulation of the electronic properties of solids by light is an exciting goal, which requires knowledge of the electronic structure with energy, momentum and temporal resolution. Time- and angle-resolved photoemission spectroscopy (tr-ARPES) is the most direct probe of the effects of an optical excitation on the band structure of a material. In particular, tr-ARPES in the extreme ultraviolet (VUV) range gives access to the ultrafast dynamics over the entire Brillouin zone. VUV tr-ARPES experiments can now be performed at the ASTRA (ARPES Spectrometer for Time-Resolved Applications) end station of Harmonium, at LACUS. Its capabilities are illustrated by measurements of the ultrafast electronic response of ZrSiTe, a novel topological semimetal characterized by linearly dispersing states located at the Brillouin zone boundary.


A high-order structure of plant storage proprotein allows its second conversion by an asparagine-specific cysteine protease, a novel proteolytic enzyme.
During seed embryogenesis, glycinin, the 11-S seed storage protein found in soybeans, undergoes post-translational proteolytic processing, in which a proprotein molecule is cleaved into an acidic and a basic subunit by a one-point cleavage that occurs at the carboxyl side of the asparaginyl residue located at the junction of the subunits. To elucidate the mechanism of this very limited proteolysis, we purified the cysteine endoprotease and used purified proglycinin produced by Escherichia coli as a substrate. This enzyme was separated by isoelectric focusing into three isomeric forms: two had a molecular mass of 33 kDa and the third, 33.8 kDa. The cysteine protease was found both in the proteinaceous vacuoles of cotyledonary tissue of immature seeds and in mature seeds, and is the first proteolytic enzyme to be classified as an asparagine-specific endoprotease. The results also indicate that the above proteolysis is largely attributable to the conformational accessibility of the enzyme to the asparaginyl residue in the cleavage site of proglycinin. The conformation of this single enzyme-accessible region on the proglycinin molecule is relatively flexible and becomes unstable under low salt conditions, or when heat is applied, causing the enzyme to lose its specificity.


[Purification, identification of acoagulatin, an anticoagulation factor from the venom of Chinese Agkistrodon, and observation of its anticoagulation effect].
To isolate and identify an anticoagulation factor, acoagulatin, from the venom of Chinese Agkistrodon and to observe its anticoagulation effect. The venom of Chinese Agkistrodon was isolated and purified using ion-exchange chromatography on DEAE-Sepharose Fast Flow and CM-sepharose Fast Flow. High-performance liquid chromatography (HPLC) was performed for determination of the purity of acoagulatin, and SDS-PAGE electrophoresis (with 5% concentrated gel of pH 6.8, 12% separation gel of pH 8.8, Tris-aminoacetic acid buffer of pH 8.3 as the electrode buffer) for determining the relative molecular mass. For observation of the anticoagulation effect, 20 microl acoagulatin solution at the concentration of 0.30, 0.20 and 0.15 microg/microl, respectively, was mixed with 100 microl rabbit anticoagulated plasma and the thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) were determined. Acoagulatin was found to consist of two subunits with relative molecular mass of 14 400 and 17 000 respectively, resulting in the total relative molecular mass of 31 400 as determined by SDS-PAGE. HPLC demonstrated good homogeneity of this protein, which significantly prolonged the PT and APTT without affecting TT. DEAE-Sepharose Fast Flow and CM-sepharose Fast Flow ion exchange column chromatographies are effective to isolate acoagulatin of high purity, which possesses anticoagulation effect.


Assessment on the leakage hazard of landfill leachate using three-dimensional excitation-emission fluorescence and parallel factor analysis method.
A large number of simple and informal landfills exist in developing countries, which pose as tremendous soil and groundwater pollution threats. Early warning and monitoring of landfill leachate pollution status is of great importance. However, there is a shortage of affordable and effective tools and methods. In this study, a soil column experiment was performed to simulate the pollution status of leachate using three-dimensional excitation-emission fluorescence (3D-EEMF) and parallel factor analysis (PARAFAC) models. Sum of squared residuals (SSR) and principal component analysis (PCA) were used to determine the optimal components for PARAFAC. A one-way analysis of variance showed that the component scores of the soil column leachate were significant influenced by landfill leachate (p<0.05). Therefore, the ratio of the component scores of the soil under the landfill to that of natural soil could be used to evaluate the leakage status of landfill leachate. Furthermore, a hazard index (HI) and a hazard evaluation standard were established. A case study of Kaifeng landfill indicated a low hazard (level 5) by the use of HI. In summation, HI is presented as a tool to evaluate landfill pollution status and for the guidance of municipal solid waste management.


Redescription of the mysid Petalophthalmus armiger Willemoes-Suhm, 1875 (Crustacea: Mysida: Petalophthalmidae) and distribution off western Mexico.
Specimens of Petalophthalmus armiger Willemoes-Suhm, 1875, were collected off western Mexico during a deep-water survey. Six males and 32 females were obtained from 18 sampling localities in western Mexico. The species is redescribed in detail, including illustrations of body and appendages, and SEM photographs of the mandibles. The new material indicates that P. armiger is widely distributed in the area and more common than previously thought in the eastern Pacific. Samples indicate that P. armiger inhabits water far offshore, where total depth exceeds 1000 m. Due to the lack of discrete samplings in the water column, however, the precise depth interval where P. armiger occurs cannot be defined.


Increased mRNA for corticotrophin releasing hormone in the amygdala of fawn-hooded rats: a potential animal model of anxiety.
Compared to the outbred Wistar rat strain, the Fawn-hooded rat strain has several characteristics which suggest that the Fawn-hooded strain is hyperaroused. Fawn-hooded rats exhibit more freezing behavior in response to stress, have an increased preference for alcohol, develop adult onset hypertension, and have elevated urinary catecholamine levels. We used quantitative in situ hybridization to investigate central components of the corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and noradrenergic stress response and arousal systems in these rats. We also measured basal corticosterone levels and adrenal weights to assess tonic hypothalamic-pituitary-adrenal axis activity. Compared to Wistar rats, Fawn-hooded rats had significantly increased CRH mRNA in the central nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of the hypothalamus. Fawn-hooded rats also bad reduced AVP mRNA expression in the parvocellular cells of the hypothalamic paraventricular nucleus. There were no differences between strains in glucocorticoid receptor mRNA in the hippocampus or the paraventricular nucleus or in mineralocorticoid receptor mRNA in the hippocampus. There was also no difference between strains in tyrosine hydroxylase mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced in the Fawn-hooded rats while basal corticosterone levels were similar in the two strains, which suggests central hypoactivity of the hypothalamic-pituitary-adrenal axis in Fawn-hooded rats compared to Wistar rats. Increased CRH mRNA in the central nucleus of the amygdala and reduced tonic hypothalamic-pituitary-adrenal axis activity may play a role in the unique behavioral and physiological characteristics of Fawn-hooded rats.


Ulnar artery as a coronary bypass graft.
The ulnar artery has been used as a coronary bypass graft in 8 patients when it was deemed unsafe to harvest the radial artery after evaluation of the arterial circulation in the forearm and hand. The ulnar artery was removed from the lower three quarters of the forearm, along with its satellite veins. Dissection was commenced distally near the wrist and extended proximally to where the ulnar artery passed between the two heads of origin of the flexor digitorum superficialis. The artery was divided distally above the wrist joint and proximally at a point immediately below the origin of the common interosseus artery. Ten ulnar arteries were removed for use as coronary artery bypass grafts; two were rejected, one because of severe calcification and the other because of atherosclerotic occlusion. The remaining eight ulnar arteries were grafted successfully to coronary arteries other than the left anterior descending. No early hand or cardiac complications were observed. The ulnar artery is an alternative coronary artery bypass graft that may be used when the radial artery is dominant and cannot be removed without risk. The ulnar artery is in close proximity to the ulnar nerve and harvesting has the potential to injure the nerve. Therefore, until the use of the ulnar artery has been more fully evaluated it should be used only when other options have been exhausted.


Boophilus microplus: passive transfer of resistance in cattle.
Plasma from cattle highly resistant to the tick Boophilus microplus conferred some resistance to unexposed calves. In contrast plasma from hosts of low resistance had no significant effect compared with plasma from unexposed donors.


KIN-MEDIATED MORPHOGENESIS IN FACULTATIVELY CANNIBALISTIC TADPOLES.
Inclusive fitness theory predicts that organisms can increase their fitness by helping or not harming relatives, and many animals modify their behavior toward kin in a manner consistent with this prediction. Morphogenesis also may be sensitive to kinship environment, particularly in species where certain individuals facultatively develop structures that can be used against conspecifics as weaponry. We tested this hypothesis by examining whether and how consanguinity affected the probability that a structurally distinctive carnivore phenotype, which is opportunistically cannibalistic, would be produced in plains spadefoot toad tadpoles (Spea bombifrons) and southern spadefoot toad tadpoles (S. multiplicata). For tadpoles of S. multiplicata, individuals were significantly more likely to express the carnivore phenotype in mixed sibship groups than in pure sibship groups. For tadpoles of S. bombifrons, individuals were significantly more likely to express the carnivore phenotype when reared alone than in pure sibship groups. Both outcomes were independent of food availability or sibship specific differences in size or growth rate, and waterborne chemical signals from nonkin were sufficient to trigger expression of the carnivore phenotype. Our results suggest that morphogenesis may be responsive to kinship environment in any species or population that occurs as multiple, environmentally induced forms (polyphenism) that differ in their ability to help or to harm others.


Cortical thickness, brain metabolic activity, and in vivo amyloid deposition in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease.
The natural history of preclinical late-onset Alzheimer's disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism. Given the importance of age in this sample of individuals potentially developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of β-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.


Particulate matter and health risk under a changing climate: assessment for Portugal.
The potential impacts of climate-induced changes in air pollution levels and its impacts on population health were investigated. The IPCC scenario (SRES A2) was used to analyse the effects of climate on future PM10 concentrations over Portugal and their impact on short-term population exposure and mortality. The air quality modelling system has been applied with high spatial resolution looking on climate changes at regional scale. To quantify health impacts related to air pollution changes, the WHO methodology for health impact assessment was implemented. The results point to 8% increase of premature mortality attributed to future PM10 levels in Portugal. The pollution episodes with daily average PM10 concentration above the current legislated value (50 μg·m⁻³) would be responsible for 81% of attributable cases. The absolute number of deaths attributable to PM10 under future climate emphasizes the importance of indirect effects of climate change on human health.


[Euthyroid sick syndrome].
The "euthyroid sick syndrome", representing the changes of thyroid hormone metabolism in disease, embraces the following hormonal changes: 1) A decrease in serum T3 levels which is often accompanied by an increase in rT3 levels. Serum T4 levels remain normal. These changes are extremely frequent in many varied diseases. 2) In very severe disease, serum T4 levels may also decrease. The free T4 index is often decreased and the free T4 may either be normal or decreased. These changes reflect alterations of thyroid hormone metabolism and can be distinguished from primary hypothyroidism by a normal serum TSH level. 3) Occasionally there are transient increases of total and free T4. This disturbance of serum thyroid hormone levels is mostly due to drug interference with thyroid hormone metabolism (amiodarone etc.). Differentiation from hyperthyroidism is difficult. It is important to diagnose the "euthyroid sick syndrome" since this will avoid erroneous diagnosis and treatment or hypo- and hyperthyroidism.


Iodide-Selective Synthetic Ion Channels Based on Shape-Persistent Organic Cages.
We report here a synthetic ion channel developed from a shape-persistent porphyrin-based covalent organic cage. The cage was synthesized by employing a synthetically economical dynamic covalent chemistry (DCC) approach. The organic cage selectively transports biologically relevant iodide ions over other inorganic anions by a dehydration-driven, channel mechanism as evidenced by vesicle-based fluorescence assays and planar lipid bilayer-based single channel recordings. Furthermore, the organic cage appears to facilitate iodide transport across the membrane of a living cell, suggesting that the cage could be useful as a biological tool that may replace defective iodide channels in living systems.


Resistance to vecuronium in patients with cerebral palsy.
To determine the electromyographic response of patients with cerebral palsy to vecuronium, 10 children (mean age, 6 yr 10 mo) without cerebral palsy and 11 children with cerebral palsy (mean age, 10 yr 3 mo) were studied. All patients were undergoing abdominal or orthopedic surgery and were anesthetized with isoflurane and nitrous oxide. The time from intravenous administration of 0.1 mg/kg of vecuronium to 25% recovery of control twitch height was 43.9 +/- 5.3 and 18.9 +/- 1.7 min (mean +/- SEM) in children without and with cerebral palsy, respectively (P less than 0.01). The authors conclude that patients with cerebral palsy are either resistant to vecuronium or have a rapid clearance as evidenced by the rapid recovery from neuromuscular blockade.


Efficacy of increasing levels of exposure therapy in the treatment of maladaptive behaviors and anxiety.
The present study examined the effectiveness of increasing levels of exposure therapy, which is applied for the treatment of maladaptive behaviors and anxiety. A total of 16 sessions were applied to the study group in the experimental group three times a week for 10 weeks. Patients aged ≥18 years whom the referring clinician evaluated as meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-V-TR) Generalized Anxiety Disorder were included in the study. For the control group, demographic characteristics and Spielberger's State-Trait Anxiety Inventory were applied in the first session, followed by Spielberger's State-Trait Anxiety Inventory as a post-test and follow-up. Electroencephalography (EEG) recordings of the study group were obtained at the cortical level. Electrodes for EEG measurements were recorded using the International 10/20 Electrode Placement System. EEG data were obtained using the EEG Analysis Program software. Following the data collection phase, all data were entered into cells based on items using SPSS 25 software. When the findings obtained in the study were examined, it was determined that the increasing levels of exposure and behavioral therapy applied for maladaptive anxiety decreased the anxiety levels compared to those before therapy. This finding can be interpreted as that the cortical function-oriented application method for anxiety effectively reduced the anxiety levels of the study group. However, EEG asymmetry revealed a change in the data before and after the application. These findings demonstrate that the application affects the EEG asymmetry changes at the cortical level.


Decay of postexercise augmentation in the Lambert-Eaton myasthenic syndrome: effect of cooling.
The effect of local cooling on surface recorded compound muscle action potential (CMAP) amplitude was studied in five patients with the Lambert-Eaton myasthenic syndrome (LEMS). The time course of decay of postexercise augmentation of CMAP amplitude characteristically seen in patients with LEMS was determined. We recorded the CMAP from abductor digiti minimi (ADM) in response to supramaximal stimulation of the ulnar nerve. Thirty consecutive stimuli were delivered at 1 Hz immediately after a 10-second period of maximal voluntary contraction. Skin surface temperature was recorded throughout. Initial testing at approximately 30 degrees C was repeated after cooling the hand and forearm by 6 to 12 degrees C. The effects of blood flow on temperature were counteracted by the application of a sphygmomanometer cuff, inflated above systolic blood pressure. The CMAP amplitude following contraction decayed in an exponential manner both during warm and cold conditions. The mean time constant for decay (1/b) in all patients was increased by approximately 25% after cooling. This prolongation of the period of postexercise augmentation of CMAP amplitude in LEMS after cooling concurs with patient reports of symptomatic improvement in cold weather. The mechanism for this benefit is thought to be due to reduction in the rate of removal of calcium ions from the nerve terminal following stimulation, similar to that seen in animal models of short-term synaptic enhancement.


Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report.
A 57-year-old man who was diagnosed with Wernicke-Korsakoff syndrome showed severe impairment of cognitive function and a craving for alcohol, even after sufficient supplementation with thiamine. After completing 10 sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) at 100% of the resting motor threshold over the left dorsolateral prefrontal cortex, dramatic improvement in cognitive function and a reduction in craving for alcohol were noted. This is the first case report of the efficacy of a high-frequency rTMS in the treatment of Wernicke-Korsakoff syndrome.


Invasive plants have scale-dependent effects on diversity by altering species-area relationships.
Although invasive plant species often reduce diversity, they rarely cause plant extinctions. We surveyed paired invaded and uninvaded plant communities from three biomes. We reconcile the discrepancy in diversity loss from invaders by showing that invaded communities have lower local richness but steeper species accumulation with area than that of uninvaded communities, leading to proportionately fewer species loss at broader spatial scales. We show that invaders drive scale-dependent biodiversity loss through strong neutral sampling effects on the number of individuals in a community. We also show that nonneutral species extirpations are due to a proportionately larger effect of invaders on common species, suggesting that rare species are buffered against extinction. Our study provides a synthetic perspective on the threat of invasions to biodiversity loss across spatial scales.


Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in the Netherlands, 1988-1999.
To assess pregnancy outcome after intrauterine transfusion (IUT) for fetal anemia due to red-cell alloimmunization in the Netherlands over 11 years, in order to improve care and counseling. A retrospective cohort study was conducted from January 1, 1988, to January 1, 1999. Data were collected prospectively on all red-cell alloimmunized pregnancies requiring intrauterine blood transfusions. Primary outcome variables were fetal and neonatal survival in relation to the type of antibody, gestational age and presence or absence of hydrops. In addition, we studied short-term neonatal morbidity and procedure-related complications. A total of 210 fetuses from 208 pregnancies received 593 transfusions. Overall survival rate was 86%. Survival of hydropic fetuses (78%) was significantly different from those without hydrops (92%). Low survival rates were especially found in hydropic fetuses with the first transfusion at gestational ages of 20 weeks or less (55%) or between 28 and 32 weeks (59%). In maternal rhesus D [Rh(D)] immunization 89% of fetuses survived, whereas survival in the case of Kell immunization was 58%. All fetuses with anemia due to Rh(c) immunization survived. The overall fatal procedure-related complication rate was 1.7% per procedure, resulting in a fetal loss rate of 4.8%. Intrauterine intravascular transfusions are effective in the management of fetal alloimmune anemia. Fetal hydrops, mostly associated with late referral, decreases the chance of survival. To improve the outcome of red-cell alloimmunized pregnancies early diagnosis of fetal anemia and referral to a specialized center are important, enabling the start of treatment before hydrops develops.


Managing fear in public health campaigns: a theory-based formative evaluation process.
The HIV/AIDS infection rate of Ethiopia is one of the world's highest. Prevention campaigns should systematically incorporate and respond to at-risk population's existing beliefs, emotions, and perceived barriers in the message design process to effectively promote behavior change. However, guidelines for conducting formative evaluation that are grounded in proven risk communication theory and empirical data analysis techniques are hard to find. This article provides a five-step formative evaluation process that translates theory and research for developing effective messages for behavior change. Guided by the extended parallel process model, the five-step process helps message designers manage public's fear surrounding issues such as HIV/AIDS. An entertainment education project that used the process to design HIV/AIDS prevention messages for Ethiopian urban youth is reported. Data were collected in five urban regions of Ethiopia and analyzed according to the process to develop key messages for a 26-week radio soap opera.


Direct production of OH radicals upon CH overtone activation of (CH3)2COO Criegee intermediates.
Ozonolysis of alkenes, a principle non-photolytic source of atmospheric OH radicals, proceeds through unimolecular decay of energized carbonyl oxide intermediates, known as Criegee intermediates. In this work, cold dimethyl-substituted Criegee intermediates are vibrationally activated in the CH stretch overtone region to drive the 1,4 hydrogen transfer reaction that leads to OH radical products. IR excitation of (CH3)2COO reveals the vibrational states with sufficient oscillator strength, coupling to the reaction coordinate, and energy to surmount the effective barrier (≤ 16.0 kcal mol(-1)) to reaction. Insight on the dissociation dynamics is gleaned from homogeneous broadening of the spectral features, indicative of rapid intramolecular vibrational energy redistribution and/or reaction, as well as the quantum state distribution of the OH X(2)Π (v = 0) products. The experimental results are compared with complementary electronic structure calculations, which provide the IR absorption spectrum and geometric changes along the intrinsic reaction coordinate. Additional theoretical analysis reveals the vibrational modes and couplings that permit (CH3)2COO to access to the transition state region for reaction. The experimental and theoretical results are compared with an analogous recent study of the IR activation of syn-CH3CHOO and its unimolecular decay to OH products [F. Liu, J. M. Beames, A. S. Petit, A. B. McCoy, and M. I. Lester, Science 345, 1596 (2014)].


Self-esteem and counterfactual thinking.
Two studies examined the relation between self-esteem and counterfactual thinking (consideration of "might-have-been" alternatives to reality). Ss imagined themselves in scenarios with another actor that resulted in either success or failure. Ss then "undid" the outcome by altering events that preceded the outcome. Following success, high self-esteem (HSE) Ss were more likely than low self-esteem (LSE) Ss to mutate their own actions. Following failure, LSE Ss were more likely than HSE Ss to mutate their own actions. Also, the structure of counterfactuals was influenced by outcome valence but not by self-esteem: Subtractive structures (in which antecedents are removed) were elicited by success, whereas additive structures (in which antecedents are added) were elicited by failure. The importance of the self and individual differences in self-esteem to counterfactual thinking is discussed.


[Indoor environment and heatstroke risk].
This paper describes the outline of heatstroke risk evaluation model for aged residents based on surveys done by the Heatstroke Surveillance Committee of Japanese Association for Acute Medicine and field measurements of indoor air temperature, humidity and so on. To reduce heatstroke of aged residents, promotion of thermal insulation, sun-shading, cross ventilation, air-condition of houses and living behavior of residents are needed.


Quantitative determination of pentaerythrityl tetranitrate and its metabolites in human plasma by gas chromatography/mass spectrometry.
Up to now, there has been no data available on the pharmacokinetics of pentaerythrityl tetranitrate (PETN, CAS 78-11-5) and its metabolites, pentaerythrityl-trinitrate (PE-tri-N), pentaerythrityl-dinitrate (PE-di-N), pentaerythrityl-mononitrate (PE-mono-N) in human plasma. Therefore, in order to determine PETN and its metabolites in plasma sensitive and highly selective GC/MS methods had to be developed and validated. PETN and its metabolite PE-tri-N were validated in the concentration range 50 pg/ml to 10 ng/ml. Isosorbide dinitrate (ISDN) was used as the internal standard and the analytes were extracted with dichloromethane from the plasma. The mass spectrometric tests were carried out using chemical ionization in the negative mode (NlCl) with the application of ammonia as a reagent gas. The nitrate ion m/z 62 was determined in the analytes and internal standard. The accuracy of the mean of the quality control samples during the three days (between days) was between 100 and 110% (PETN), as well as 90 and 106% (PE-tri-N). After an oral application of 100 mg PETN in a pilot study, unchanged PETN and PE-tri-N was measured in plasma. Both metabolites PE-di-N and PE-mono-N were validated at the concentration range of 0.25 ng/ml to 25 ng/ml plasma. After extraction, these analytes were derivatized with BSTFA (N,O-bis[trimethylsilyl]trifluoro-acetamide). The applied internal standard was isosorbide-5-mononitrate (IS-5-MN). The mass spectrometric tests were carried out in the same manner as for PETN and PE-tri-N with chemical ionization in the NlCl mode. The detected masses were m/z 324 for PE-di-N, m/z 351 for PE-mono-N and m/z 217 for IS-5-MN. The accuracy of the mean of the quality control samples during 5 days were between 104 and 107% (PE-di-N) and 102 and 106% (PE-mono-N). The maximum concentration of these analytes in the subject samples were on the average all over 5 ng/ml plasma after the oral administration of 100 mg PETN.


A unified framework for weighted parametric multiple test procedures.
We describe a general framework for weighted parametric multiple test procedures based on the closure principle. We utilize general weighting strategies that can reflect complex study objectives and include many procedures in the literature as special cases. The proposed weighted parametric tests bridge the gap between rejection rules using either adjusted significance levels or adjusted p-values. This connection is made by allowing intersection hypotheses of the underlying closed test procedure to be tested at level smaller than α. This may be also necessary to take certain study situations into account. For such cases we introduce a subclass of exact α-level parametric tests that satisfy the consonance property. When the correlation is known only for certain subsets of the test statistics, a new procedure is proposed to fully utilize this knowledge within each subset. We illustrate the proposed weighted parametric tests using a clinical trial example and conduct a simulation study to investigate its operating characteristics.


Human aminoacyl-tRNA synthetases in diseases of the nervous system.
Aminoacyl-tRNA synthetases (AaRSs) are ubiquitously expressed enzymes that ensure accurate translation of the genetic information into functional proteins. These enzymes also execute a variety of non-canonical functions that are significant for regulation of diverse cellular processes and that reside outside the realm of protein synthesis. Associations between faults in AaRS-mediated processes and human diseases have been long recognized. Most recent research findings strongly argue that 10 cytosolic and 14 mitochondrial AaRSs are implicated in some form of pathology of the human nervous system. The advent of modern whole-exome sequencing makes it all but certain that similar associations between the remaining 15 ARS genes and neurologic illnesses will be defined in future. It is not surprising that an intense scientific debate about the role of translational machinery, in general, and AaRSs, in particular, in the development and maintenance of the healthy human neural cell types and the brain is sparked. Herein, we summarize the current knowledge about causative links between mutations in human AaRSs and diseases of the nervous system and briefly discuss future directions.


Thermodynamics of the Flexible Metal-Organic Framework Material MIL-53(Cr) From First Principles.
We use first-principles density functional theory total energy and linear response phonon calculations to compute the Helmholtz and Gibbs free energy as a function of temperature, pressure, and cell volume in the flexible metal-organic framework material MIL-53(Cr) within the quasiharmonic approximation. GGA and metaGGA calculations were performed, each including empirical van der Waals (vdW) forces under the D2, D3, or D3(BJ) parameterizations. At all temperatures up to 500 K and pressures from -30 MPa to 30 MPa, two minima in the free energy versus volume are found, corresponding to the narrow pore (np) and large pore (lp) structures. Critical positive and negative pressures are identified, beyond which there is only one free energy minimum. While all results overestimated the stability of the np phase relative to the lp phase, the best overall agreement with experiment is found for the metaGGA PBEsol+RTPSS+U+J approach with D3 or D3(BJ) vdW forces. For these parameterizations, the calculated free energy barrier for the np-lp transition is only 3 to 6 kJ per mole of Cr4(OH)4(C8H4O4)4.


Surface Functionalization of a γ-Graphyne-like Carbon Material via Click Chemistry.
Surface functionalization of carbon materials is of interest in many research fields, such as electrocatalysis, interfacial engineering, and supercapacitors. As an emerging carbon material, γ-graphyne has attracted broad attention. Herein, we report that the surface functionalization of a γ-graphyne-like carbon material (γ-G1) is achieved by immobilizing functional groups via the click chemistry. Texture analysis of aberration-corrected microscopy, X-ray photoelectron spectroscopy, and electrochemistry confirm the successful surface modification of γ-G1 through a strong covalent linkage 1,2,3-triazole. The direct linkage of functional groups on γ-G1 via the click chemistry represents a general method for preparing other functional materials by using γ-graphyne-like materials as a skeleton.


Hub-organized parallel circuits of central circadian pacemaker neurons for visual photoentrainment in Drosophila.
Circadian rhythms are orchestrated by a master clock that emerges from a network of circadian pacemaker neurons. The master clock is synchronized to external light/dark cycles through photoentrainment, but the circuit mechanisms underlying visual photoentrainment remain largely unknown. Here, we report that Drosophila has eye-mediated photoentrainment via a parallel pacemaker neuron organization. Patch-clamp recordings of central circadian pacemaker neurons reveal that light excites most of them independently of one another. We also show that light-responding pacemaker neurons send their dendrites to a neuropil called accessary medulla (aMe), where they make monosynaptic connections with Hofbauer-Buchner eyelet photoreceptors and interneurons that transmit compound-eye signals. Laser ablation of aMe and eye removal both abolish light responses of circadian pacemaker neurons, revealing aMe as a hub to channel eye inputs to central circadian clock. Taken together, we demonstrate that the central clock receives eye inputs via hub-organized parallel circuits in Drosophila.


Necrotising fasciitis: experience with 32 children.
Necrotising fasciitis (NF) in children is rare, rapidly progressive and potentially fatal. A satisfactory outcome depends on early diagnosis and aggressive surgical debridement, along with appropriate antibiotic therapy. The aim was to describe the various presentations of NF and evaluate outcome of treatment. This was a 4-year prospective, descriptive study of all consecutive cases of NF aged 15 years and under treated at Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria from January 2001 to December 2004. Thirty-two children were treated during the study period. The male:female ratio was 1.7:1. Ages ranged from 6 days to 12 years (mean 2 yrs). The commonest predisposing factors were malnutrition (40.6%), boils (37.5%) and intravenous canulation (9.4%). Duration of symptoms ranged from 3 to 19 days (mean 6.4) and the total body surface areas involved ranged from 2% to 16% (mean 5.9%). Half of the patients presented with involvement of the trunk, followed by head/neck (28.1%), upper limbs (21.9%), lower limbs (6.3%) and perineum (6.3%). Most patients had polymicrobial infection, but the organism most commonly isolated was Staphylococcus aureus (71.9%). All patients were resuscitated and had surgical wound debridement, antibiotics and wound care. Final wound resurfacing was by secondary intention (46.9%), direct suturing (6.3%), split thickness skin grafting (21.9%) and local flap reconstruction (12.5%). Septicaemia was the commonest complication (71.9%). The mortality rate was 9.4%. Duration of hospital stay ranged from 14 to 96 days (mean 27.6). Follow-up ranged from 3 weeks to 6 months (mean 52.4 days). NF in children is not uncommon in Nigeria. It is associated with significant morbidity, but mortality can be reduced remarkably by early diagnosis and aggressive treatment.


Photocross-linking Kinetics Study of Benzophenone Containing Zwitterionic Copolymers.
The kinetics of benzophenone (BP) and its derivatives have been widely studied in different solvents by nanosecond laser flash photolysis as well as in the polymer matrix. With the development of functional polymer coating, BP, as well as other photocross-linkers, has been incorporated into the polymer backbone or side chain to form the covalent connection between polymer coatings and substrates, which can improve the mechanical and chemical stability of the coatings. In this work, a series of BP pendent zwitterionic copolymer kinetics were investigated using UV-vis for the first time. Because of the high hydrophilicity of the zwitterionic monomer, the influence of the polymer matrix's polarity on the cross-linking rate was observed. With a higher zwitterionic percentage in the copolymer, the polarity of the copolymer increases, BP reactivity decreases, and a hypothesis between the BP rate constant and partial coefficient log P was raised. Moreover, the thermal property is also an important factor affecting the BP reactivity. For polymers with high glass-transition temperature, the reactivity was not dominated by the chemical environment such as polarity, and the restricted segment movement reduces the cross-linking rate. Additionally, the ring substituents show similar effects to BP pendent copolymers as with small molecules. Electron-withdrawing groups help to stabilize the BP triplet radical and facilitate cross-linking, while electron-donating groups work conversely. Therefore, polarity, thermal properties, and substituents should be taken into consideration when designing BP-containing functional polymers.


Familial clustering of HBV in families with children who are diagnosed as chronic hepatitis B or inactive carriers of HBV.
The aim of this study was to assess and compare the spread of HBV infection in families with children who are diagnosed as chronic hepatitis B or are inactive carriers of HBV. A total of 570 patients aged 2-16 years and 2358 family members were included in the study. Patients were classified as inactive carriers (Group 1, 350 patients) or patients diagnosed as chronic active hepatitis B (Group 2, 220 patients). Demographic features of the families, HBV serological markers and routes of transmission were evaluated. Parental transmission was lower compared to nonparental transmission (34.8% and 65.1%, respectively). HBsAg positivity rate was found to be highest among mothers in both of the groups. HBeAg positivity and anti-HBs positivity were significantly higher in family members of Group 2. Transmission rates were significantly higher in families consisting of five or more members compared to families consisting of less than five members. HBsAg positivity of siblings was lowest when both parents were HbsAg negative and highest when both parents were HBsAg positive in both groups. A high risk of HBV transmission among mothers of HBsAg carriers and patients with chronic hepatitis B was demonstrated.


Surgical management of traumatic non-infective tenosynovitis of the wrist extensors.
Traumatic tenosynovitis of the wrist extensors is a common and disabling condition associated with overuse. It has been found to be associated with hypertrophy of the bellies of abductor pollicis longus and extensor pollicis brevis where they overlie the radial extensor tendons in the forearm, compressing these tendons and their enveloping paratenons against the deep structures beneath. Simple surgical decompression of the sheath of these overlying muscles has been found to give quick relief of symptoms and to allow a more rapid return to strenuous work than the conservative treatments usually employed.


Regulation of Kruppel-like factor 6 tumor suppressor activity by acetylation.
Krüppel-like factor 6 (KLF6) is a zinc finger transcription factor and tumor suppressor that is inactivated in a number of human cancers by mutation, allelic loss, and/or promoter methylation. A key mechanism of growth inhibition by wild-type KLF6 is through p53-independent up-regulation of p21(WAF1/cip1) (CDKN1A), which is abrogated in several tumor-derived mutants. Here we show by chromatin immunoprecipitation that transactivation of p21(WAF1/cip1) by KLF6 occurs through its direct recruitment to the p21(WAF1/cip1) promoter and requires acetylation by histone acetyltransferase activity of either cyclic AMP-responsive element binding protein-binding protein or p300/CBP-associated factor. Direct lysine acetylation of KLF6 peptides can be shown by mass spectrometry. A single lysine-to-arginine point mutation (K209R) derived from prostate cancer reduces acetylation of KLF6 and abrogates its capacity to up-regulate endogenous p21(WAF1/cip1) and reduce cell proliferation. These data indicate that acetylation may regulate KLF6 function, and its loss in some tumor-derived mutants could contribute to its failure to suppress growth in prostate cancer.


Chlamydomonas inner-arm dynein mutant, ida5, has a mutation in an actin-encoding gene.
Chlamydomonas flagellar inner-arm dynein consists of seven subspecies (a-g), of which all but f contain actin as subunits. The mutant ida5 and a new strain, ida5-t, lack four subspecies (a, c, d, and e). These mutants were found to have mutations in the conventional actin gene, such that its product is totally lost; ida5 has a single-base deletion that results in a stop codon at a position about two-thirds from the 5' end of the coding region, and ida5-t lacks a large portion of the entire actin gene. Two-dimensional gel electrophoresis patterns of the axonemes and inner-arm subspecies b and g of ida5 lacked the spot of actin (isoelectric point [pI] = approximately 5.3) but had two novel spots with pIs of approximately 5.6 and approximately 5.7 instead. Western blot with different kinds of anti-actin antibodies suggested that the proteins responsible for the two novel spots and conventional actin are different but share some antigenicity. Since Chlamydomonas has been shown to have only a single copy of the conventional actin gene, it is likely that the novel spots in ida5 and ida5-t originated from another gene(s) that codes for a novel actin-like protein(s) (NAP), which has hitherto been undetected in wild-type cells. These mutants retain the two inner-arm subspecies b and g, in addition to f, possibly because NAP can functionally substitute for the actin in these subspecies while they cannot in other subspecies. The net growth rate of ida5 and ida5-t cells did not differ from that of wild type, but the mating efficiency was greatly reduced. This defect was apparently caused by deficient growth of the fertilization tubule. These results suggest that NAP can carry out some, but not all, functions performed by conventional actin in the cytoplasm and raise the possibility that Chlamydomonas can live without ordinary actin.


A Study on THE Mechanism of Electroacupuncture to Alleviate Visceral Pain and NGF Expression.
Visceral pain is unbearable, and natural methods are needed to relieve it. Electroacupuncture is a relatively new technique that helps relieve visceral pain by improving blood circulation and providing energy to clogged parts of the body. However, its analgesic effect and mechanism in colorectal pain are still unknown. In this study, the visceral pain models of electroacupuncture in rats were compared and discussed, using nanocomponents to stimulate the expression and mechanism of the nerve growth factor in colorectal pain and electroacupuncture and to observe the expression and mechanism of nerve growth factor in visceral pain relief rats induced by nanocomponents and electroacupuncture. The results show that nanocomponents can effectively relieve visceral pain under the action of electroacupuncture. NGF can activate endogenous proliferation, migration, differentiation, and integration. NSC can promote nerve regeneration and recovery after injury.


Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics.
Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self-regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein.


Functional performance comparison between real and virtual tasks in older adults: A cross-sectional study.
Ageing is usually accompanied by deterioration of physical abilities, such as muscular strength, sensory sensitivity, and functional capacity, making chronic diseases, and the well-being of older adults new challenges to global public health. The purpose of this study was to evaluate whether a task practiced in a virtual environment could promote better performance and enable transfer to the same task in a real environment. The study evaluated 65 older adults of both genders, aged 60 to 82 years (M = 69.6, SD = 6.3). A timing coincident task was applied to measure the perceptual-motor ability to perform a motor response. The participants were divided into 2 groups: started in a real interface and started in a virtual interface. All subjects improved their performance during the practice, but improvement was not observed for the real interface, as the participants were near maximum performance from the beginning of the task. However, there was no transfer of performance from the virtual to real environment or vice versa. The virtual environment was shown to provide improvement of performance with a short-term motor learning protocol in a timing coincident task. This result suggests that the practice of tasks in a virtual environment seems to be a promising tool for the assessment and training of healthy older adults, even though there was no transfer of performance to a real environment. ISRCTN02960165. Registered 8 November 2016.


Efficacy of postoperative concurrent chemoradiation for resectable rectal cancer: a single institute experience.
For patients with Dukes' stage B and C rectal cancer, surgery followed by adjuvant chemoradiotherapy is considered to be the standard treatment. However, the drugs used in combination with 5-fluorouracil (5-FU), the method of administration, duration of adjuvant therapy and the frequencies of administration presently remain controversial topics. We investigated (1) the efficacy and safety of adjuvant radiotherapy and 5-FU/leucovorin (LV) chemotherapy for patients who had undergone curative resection and (2) the effect of dose related factors of 5-FU on survival. 130 rectal cancer patients with Dukes' B or C stage disease who were treated with curative resection were evaluated. The adjuvant therapy consisted of two cycles of 5-FU/LV chemotherapy followed by pelvic radiotherapy with chemotherapy, and then 4 approximately 10 more cycles of the same chemotherapy regimen were delivered based on the disease stage. The cumulative dose of 5-FU per body square meter (BSA), actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor, and the patients' survival rates were compared. With a median follow-up duration of 52 months, the 5-year disease-free survival and overall survival rates of 130 patients were 57% and 73%, respectively. Locoregional failure occurred in 17 (13%) of the 130 patients, and the distant failure rate was 27% (35/130). The chemotherapy related morbidity was minimal, and there was no mortality for these patients. The cumulative dose of 5-FU/BSA had a significant effect on the 5-year overall survival for Dukes' C rectal cancer patients (p=0.03). Multivariate analysis demonstrated that only the performance status affected the 5-year overall survival (p=0.003). An adjuvant therapy of radiotherapy and 5-FU/LV chemotherapy is effective and tolerable for Dukes' B and C rectal cancer patients. A prospective, multicenter, randomized study to evaluate the effects of the cumulative dose of 5-FU/BSA on survival is required.


IV Versus Subcutaneous Enoxaparin in Critically Ill Infants and Children: Comparison of Dosing, Anticoagulation Quality, Efficacy, and Safety Outcomes.
Subcutaneous enoxaparin is the mainstay anticoagulant in critically ill pediatric patients although it poses several challenges in this patient population. Enoxaparin infused IV over 30 minutes represents an attractive alternative, but there is limited experience with this route of administration in children. In this study, we assess dosing, anticoagulation quality, safety, and clinical efficacy of IV enoxaparin compared to subcutaneous enoxaparin in critically ill infants and children. Retrospective single-center study comparing dosing, anticoagulation quality, safety, and clinical efficacy of two different routes of enoxaparin administration (IV vs subcutaneous) in critically ill infants and children. Key outcome measures included dose needed to achieve target antifactor Xa levels, time required to achieve target antifactor Xa levels, proportion of patients achieving target anticoagulation levels on initial dosing, number of dose adjustments, duration spent in the target antifactor Xa range, anticoagulation-related bleeding complications, anticoagulation failure, and radiologic response to anticoagulation. Tertiary care pediatric hospital. All children admitted to the cardiac ICU, PICU, or neonatal ICU who were prescribed enoxaparin between January 2014 and March 2016 were studied. One hundred ten patients were identified who had received IV or subcutaneous enoxaparin and had at least one postadministration peak antifactor Xa level documented. Of the 139 courses of enoxaparin administered, 96 were therapeutic dose courses (40 IV and 56 subcutaneous) and 43 were prophylactic dose courses (20 IV and 23 subcutaneous). Dosing, anticoagulation quality measurements, safety, and clinical efficacy were not significantly different between the two groups. Our study suggests that anticoagulation with IV enoxaparin infused over 30 minutes is a safe and an equally effective alternative to subcutaneous enoxaparin in critically ill infants and children.