Predictive factors of postoperative complications and hospital readmission after implementation of the single-port robotic platform: A single-center and single-surgeon experience.
To measure the incidence, and identify potential risk factors of conversion, postoperative complication and readmission for patients treated with urological robotic single-port surgery. All consecutive urological surgery procedures carried out with the single-port robotic platform by the same surgeon in a single institution between September 2018 and March 2020 were included in this retrospective analysis. Demographic data, main perioperative outcomes and information related to the surgical technique were gathered and analyzed. A logistic regression model was used to assess predictive factors for any grade and high-grade (e.g. Clavien grade ≥3) postoperative complications, as well as predictive factors for readmission. Analysis included 221 patients, of whom 194 (88%) underwent pelvic surgery and 27 (12.2%) underwent upper urinary tract surgery. Only one patient was converted to open surgery in the entire cohort. A total of 40 patients (18.1%) experienced postoperative complications, with grade ≥3 postoperative complications in 7.6% of the entire cohort. On multivariable analysis, the factors significantly associated with the risk of postoperative complication of any grade were diabetes (P < 0.001), perineal approach (P < 0.01) and postoperative pain management with opioids (P = 0.01). Only diabetes (P = 0.03) predicted a grade ≥3 complication. Overall, 17 patients (7.7%) were readmitted during the 3 months after surgery. A body mass index >30 kg/m2 was the only identified predictor of readmission (P = 0.01). A wide range of pelvic, extraperitoneal and upper-tract urological procedures can be carried out using the robotic single-port platform with a minimal conversion rate and low complication or readmission rate.


Botulinum toxin type A reduces inflammatory hypernociception induced by arthritis in the temporomadibular joint of rats.
This study aimed to investigate the antinociceptive effects of Botulinum toxin type A (BoNT-A) on persistent inflammatory hypernociception induced by arthritis in the temporomandibular joint (TMJ) of rats. Wistar rats were induced to persistent inflammatory hypernociception in the left TMJ. Then, animals were treated with intra-TMJ injections of BoNT-A, using doses of 3.5, 7 and 14 U/kg. Saline was used as control group. Behavioral tests were applied to evaluated the effect of BoNT-A in the inflammatory hypernociception. After that, animals were euthanized and samples from peri-articular tissues and trigeminal ganglia were obtained for further analyses. BoNT-A reduced the persistent inflammatory hypernociception induced by arthritis in the TMJ of rats. BoNT-A significantly reduced the peripheral release of the neurotransmitters Substance P and Calcitonin gene related peptide; and the pro-inflammatory cytokine IL-1β. Otherwise, BoNT-A had no effect in the peripheral release of glutamate and the cytokine TNF-α. These results demonstrate that intra-articular injection of BoNT-A reduces the albumin-induced arthritis persistent hypernociception in TMJ of rats by peripheral inhibition of neuropeptides release.


Transneuronal pathways to the vestibulocerebellum.
The alpha-herpes virus (pseudorabies, PRV) was used to observe central nervous system (CNS) pathways associated with the vestibulocerebellar system. Retrograde transneuronal migration of alpha-herpes virions from specific lobules of the gerbil and rat vestibulo-cerebellar cortex was detected immunohistochemically. Using a time series analysis, progression of infection along polyneuronal cerebellar afferent pathways was examined. Pressure injections of > 20 nanoliters of a 10(8) plaque forming units (pfu) per ml solution of virus were sufficient to initiate an infectious locus which resulted in labeled neurons in the inferior olivary subnuclei, vestibular nuclei, and their afferent cell groups in a progressive temporal fashion and in growing complexity with increasing incubation time. We show that climbing fibers and some other cerebellar afferent fibers transported the virus retrogradely from the cerebellum within 24 hours. One to three days after cerebellar infection discrete cell groups were labeled and appropriate laterality within crossed projections was preserved. Subsequent nuclei labeled with PRV after infection of the flocculus/paraflocculus, or nodulus/uvula, included the following: vestibular (e.g., z) and inferior olivary nuclei (e.g., dorsal cap), accessory oculomotor (e.g., Darkschewitsch n.) and accessory optic related nuclei, (e.g., the nucleus of the optic tract, and the medial terminal nucleus); noradrenergic, raphe, and reticular cell groups (e.g., locus coeruleus, dorsal raphe, raphe pontis, and the lateral reticular tract); other vestibulocerebellum sites, the periaqueductal gray, substantia nigra, hippocampus, thalamus and hypothalamus, amygdala, septal nuclei, and the frontal, cingulate, entorhinal, perirhinal, and insular cortices. However, there were differences in the resulting labeling between infection in either region. Double-labeling experiments revealed that vestibular efferent neurons are located adjacent to, but are not included among, flocculus-projecting supragenual neurons. PRV transport from the vestibular labyrinth and cervical muscles also resulted in CNS infections. Virus propagation in situ provides specific connectivity information based on the functional transport across synapses. The findings support and extend anatomical data regarding vestibulo-olivo-cerebellar pathways.


HIVAN phenotype: consequence of epithelial mesenchymal transdifferentiation.
Human immunodeficiency virus (HIV)-1-associated nephropathy (HIVAN) is characterized by proliferation of glomerular and tubular epithelial cells. We studied the role of epithelial mesenchymal transdifferentiation (EMT) in the development of HIVAN phenotype. Renal cortical sections from six FVB/N (control) and six Tg26 (HIVAN) mice were immunolabeled for PCNA, alpha-smooth muscle actin (alpha-SMA), fibroblast-specific protein-1 (FSP1), CD3, and F4/80. Since periglomerular cells (PGCs) and peritubular cells (PTCs) did not show any labeling for CD3 and F4/80 but showed labeling for alpha-SMA or FSP1, it appears that these were myofibroblasts that migrated from either glomerular or tubular sites, respectively. Occurrence of EMT was also supported by diminished expression of E-cadherin by renal epithelial cells in Tg26 mice. Interestingly, Tg26 mice also showed enhanced renal tissue expression of ZEB2; henceforth, it appears that transcription of molecules required for maintenance of de novo renal epithelial cell phenotype was suppressed. To evaluate the role of ANG II, Tg26 mice in groups of three were administered either normal saline or telmisartan (an AT1 receptor blocker) for 2 wk, followed by evaluation for renal cell EMT. Renal cortical section of Tg26 mice showed a sevenfold increase (P < 0.001) in parietal epithelial cell (PEC)-PGC and a threefold increase (P < 0.01) in tubular cell (TC)-PTC proliferation (PCNA-positive cells). Similarly, both PECs-PGCs and TCs-PTCs in Tg26 mice showed enhanced expression of alpha-SMA and FSP1. Both PECs and podocytes contributed to the glomerular proliferative phenotype, but the contribution of PECs was much greater. Telmisartan-receiving Tg26 mice (TRM) showed attenuated number of proliferating PECs-PGCs and TCs-PTCs compared with saline-receiving Tg26 mice (SRM). Similarly, TRM showed diminished expression of alpha-SMA and FSP1 by both PECs-PGCs and TCs-PTCs compared with SRM. We conclude that EMT contributes to the manifestation of the proliferative phenotype in HIVAN mice.


Effects of bacterial organic selenium, selenium yeast and sodium selenite on antioxidant enzymes activity, serum biochemical parameters, and selenium concentration in Lohman brown-classic hens.
This study compares the effects of sodium selenite, selenium yeast, and enriched bacterial organic selenium protein on antioxidant enzyme activity, serum biochemical profiles, and egg yolk, serum, and tissue selenium concentration in laying hens. In a 112-d experiment, 144 Lohman Brown Classic hens, 23-wks old were divided into four equal groups, each has six replicates. They were assigned to 4 treatments: 1) a basal diet (Con), 2) Con plus 0.3 mg/kg feed sodium selenite (SS); 3) Con plus 0.3 mg/kg feed Se-yeast (SY): 4) Con plus 0.3 mg/kg feed bacterial enriched organic Se protein (ADS18) from Stenotrophomonas maltophilia bacteria. On d 116, hens were euthanized (slaughtered) to obtain blood (serum), liver organ, and breast tissue to measure antioxidant enzyme activity, biochemical profiles, and selenium concentration. The results show that antioxidant enzyme activity of hens was increased when fed bacterial organic Se (ADS18), resulting in a significant (P < 0.05) increase in serum GSH-Px, SOD, and CAT activity compared to other treatment groups. However, ADS18 and SY supplementation increase (P < 0.05) hepatic TAC, GSH-Px, and CAT activity, unlike the SS and Con group. Similarly, dietary Se treatment reduced total cholesterol and serum triglycerides concentrations significantly (P < 0.05) compared to the Con group. At 16 and 18 weeks, selenium concentration in hen egg yolks supplemented with dietary Se was higher (P < 0.05) than in Con, with similar patterns in breast tissue and serum. Supplementation with bacterial organic Se (ADS18) improved antioxidant enzyme activity, decreased total serum cholesterol and serum lipids, and increased Se deposition in egg yolk, tissue, and serum. Hence, organic Se may be considered a viable source of Se in laying hens.


Binding of manumycin A inhibits IkappaB kinase beta activity.
IkappaB kinase (IKK) catalytic subunits play a key role in cytokinemediated nuclear factor (NF)-kappaB signaling, and a loss of NF-kappaB function appears to inhibit inflammation and oncogenesis. Manumycin A is a potent and selective farnesyltransferase inhibitor with antitumor activity. We found that manumycin A caused a rapid and potent inhibition of IKK activity induced by tumor necrosis factor alpha in a number of cell types. Most unexpectedly, other classes of farnesyltransferase inhibitors had no inhibitory effect. To identify the molecular mechanisms of manumycin A action, cultured human HepG2 hepatoma cells were transiently transfected with various IKKalpha and IKKbeta constructs, and a striking difference in manumycin A sensitivity was observed. Furthermore, cells expressing wild-type IKKbeta and IKKbeta mutated in the activation loop at Cys-179 exhibited covalent homotypic dimerization of IKKbeta in response to manumycin A, whereas substitution of Cys-662 and -716 conferred protection against dimer formation. Direct inhibition of IKK activity and formation of stable IKKbeta dimers were observed in the presence of manumycin A that could be blocked by dithiothreitol. IKK interaction with the adaptor protein IKKgamma/NEMO was disrupted in manumycin A-treated cells. Most importantly, administration of manumycin A to mice xenografted with murine B16F10 tumors caused potent IKK-suppressive effects. Thus, manumycin A with its epoxyquinoid moieties plays an important regulatory function in IKK signaling through pathways distinct from its role as a protein farnesylation inhibitor.


[Osteomyelitis in pregnancy].
Osteomyelitis is an infection of bone, which most frequently is found in weight-bearing bones of lower extremities. Only 4% of acute osteomyelitis cases have been found in the pubic bones in Finland. These cases of the pubic bones are usually related to gynecological or urological procedures or trauma. Osteitis, which is much more common than osteomyelitis, is a differential diagnosis for pregnant or postpartum women. These two diseases are difficult to distinguish based on the symptoms, even if it is important because osteomyelitis needs to be cured with antibiotics but to cure osteomyelitis NSAIDs are enough. The diagnosis of osteomyelitis is based on clinical examination, radiological imaging and laboratory tests.


Denitrification and DNRA in Urban Accidental Wetlands in Phoenix, Arizona.
Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) both require low oxygen and high organic carbon conditions common in wetland ecosystems. Denitrification permanently removes nitrogen from the ecosystem as a gas while DNRA recycles nitrogen within the ecosystem via production of ammonium. The relative prevalence of denitrification versus DNRA has implications for the fate of nitrate in ecosystems. Unplanned and unmanaged urban accidental wetlands in the Salt River channel near downtown Phoenix, Arizona, USA receive high nitrate relative to non-urban wetlands and have a high capacity for denitrification, but unknown capacity for DNRA. We conducted in-situ push-pull tests with isotopically labelled nitrate to measure denitrification and DNRA rates in three of the dominant vegetative patch types in these urban accidental wetlands. DNRA accounted for between 2 and 40% of nitrate reduction (DNRA plus denitrification) with the highest rates measured in patches of Ludwigia peploides compared to Typha spp. and non-vegetated patches. The wetland patches were similar with respect to dissolved organic carbon concentration but may have differed in carbon lability or strength of reducing conditions due to a combination of litter decomposition and oxygen supply via diffusion and aerenchyma. The ratio of DNRA to denitrification was negatively correlated with nitrate concentration, indicating that DNRA may become a more important pathway for nitrate attenuation at low nitrate concentration. Although DNRA was generally lower than denitrification, this pathway was an important component of nitrate attenuation within certain patches in these unmanaged urban accidental wetlands.


Preserving lessons learned in disease outbreaks and other emergency responses.
Public health departments often miss the opportunity to both learn from outbreaks and disasters and share any 'lessons learned' with other public health partners. These missed opportunities inhibit the public health system's ability to improve, change and adapt in an organized way. In 2003, Western Pennsylvania experienced the largest documented hepatitis A outbreak in US history. The authors documented the key facets of both the outbreak and the response, and in the process developed improved methods for capturing the historical record in an efficient and comprehensive fashion. This process incorporates key aspects of oral history, along with typical public health parameters such as epidemic curves and environmental risk factors, and allows for creation of unique tools for documentation and sharing with diverse audiences. Learning from experience is an essential part of reducing mistakes, improving public health response, and the methods described herein show one way that 'lessons learned' can become a valuable teaching/training tool for students and practitioners.


Modulation of fat-soluble vitamin concentrations and blood mononuclear leukocyte populations in milk replacer-fed calves by dietary vitamin A and beta-carotene.
Dairy calves (n = 18), separated from dams at birth, were fed 1 L of pooled-colostrum. For the remaining 7 wk of the study, they were fed one of three diets consisting of either a custom-formulated milk replacer without vitamin A (controls), or supplemented with retinyl palmitate (equivalent to 32,000 IU of vitamin A/d) or with beta-carotene (equivalent to 20,000 IU of vitamin A/d). Plasma retinol, beta-carotene, and RRR-alpha-tocopherol concentrations were lowest at birth, and increased substantially from birth to 1 wk postpartum in all groups, a probable consequence of ingestion of colostrum. From 1 to 7 wk of age, retinol concentrations were greatest in retinyl palmitate-supplemented calves, intermediate in beta-carotene-supplemented calves and lowest in control calves. At 2, 3, 5, 6, and 7 wk, RRR-alpha-tocopherol concentrations were lower in retinyl palmitate-supplemented calves than in control calves. A negative correlation between plasma retinol and vitamin E concentrations existed from wk 2 to 7, suggesting vitamin A influences the absorption and distribution of RRR-alpha-tocopherol. Supplemental retinyl palmitate, but not beta-carotene, was associated with a reduction in the percentage of blood mononuclear leukocytes expressing CD2, CD4, and CD8-T cell antigens and interleukin-2 receptors. By wk 7, leukocyte populations from retinyl palmitate-supplemented calves were more similar to those from adult cattle than those from control calves, suggesting that supplemental vitamin A, as retinyl palmitate, affects the maturation of the neonatal immune system. Differences in the composition of blood mononuclear leukocyte populations may represent changes in immune competency.


Correction of nonlinearities in series structure-based resistance thermometry readouts.
Series structure-based resistance thermometry readouts offer several advantages for multi-point temperature measurements. However, because of the diversity of nonlinear error sources and differences among channels in such readouts, existing nonlinear error correction methods are ineffective. In view of this situation, a nonlinear error correction method based on error source analysis is proposed. The proposed method first determines the impacts of error sources by analyzing the circuit architecture. The contributions of the common-mode rejection ratio and the mismatch between positive and opposite exciting currents are then eliminated using resistance bridge calibrators. Finally, the residuals are fitted to various polynomial functions. The results of experiments show that correction based on the proposed method results in a maximum nonlinear readout error of 1.87 × 10-5, compared with 4.01 × 10-5 using the classical method. Thus, the proposed method of nonlinear error correction is effective for series structure-based resistance thermometry readout.


Concomitant benzodiazepine and opioids decrease sleep apnoea risk in chronic pain patients.
The concurrent use of sedating centrally acting drugs and opioids by chronic pain patients occurs routinely despite concerns of negative impacts on respiration during sleep. The effects of centrally acting drugs and opioids on sleep apnoea have not been well characterised. The objective of this study was to assess the effect of concomitant centrally acting drugs and opioids on the prevalence and severity of sleep apnoea in chronic pain patients. We conducted a prospective cohort study at five chronic pain clinics. Each participant underwent an in-laboratory polysomnography and daily morphine milligram equivalents were calculated. Participants were grouped into centrally acting drugs and opioid users versus sole opioid users. Of the 332 consented participants, 204 underwent polysomnography and 120 (58.8%) had sleep apnoea (72% obstructive, 20% central, and 8% indeterminate sleep apnoea). Overall, 35% (71 of 204) were taking opioids alone, and 65% (133 of 204) were taking centrally acting drugs and opioids. There was a 69% decrease in the odds of having sleep apnoea (apnoea-hypopnoea index ≥5 events·h-1) in participants taking benzodiazepine/opioids versus sole opioid users (OR 0.31, 95% CI:0.12-0.80, p=0.015). Additionally, concomitant benzodiazepine/opioids versus sole opioid use was associated with a decrease in respiratory arousal index scores (p=0.03). Mean overnight S pO2 was approximately 1% lower in the concomitant benzodiazepine/opioids group versus sole opioid users (93.1±2.5 versus 94.4±2.1%, p=0.01). In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.


Laparoendoscopic single-site urethrovesical anastomosis training in an economical porcine model.
To develop an economical animal model for laparoendoscopic single-site surgery (LESS) urethrovesical anastomosis (UVA) training. A homemade single-port device was used and the uterus cervix and the ileum were chosen to simulate UVA to reduce costs. Ten trainees were randomly divided into two groups: the conventional LESS UVA (CLUVA) group and the transurethral assistant LESS UVA (TALUVA) group. In TALUVA, a laparoscopic forceps was inserted through the urethra to assist operation after the bladder neck was disconnected, whereas CLUVA followed the conventional steps. Anastomosis time and knotting time were recorded, and the learning curves of both groups were analyzed. After training, questionnaires were given to the trainees to assess the difficulties and the satisfaction of the training. The final mean operating time significantly declined in both groups. Except for the first lesson, the trainees in the TALUVA group operated faster than those in the other group. The results from the questionnaires show that all trainees were satisfied with the training, and LESS UVA was considered more difficult in the CLUVA group than in the TALUVA group. The female porcine model for LESS UVA was feasible and cost-effective. TALVUA could effectively reduce the difficulties involved in LESS UVA.


Ethnic-specific determinants of exercise capacity in a healthy high-risk population.
African Americans (AA) have been shown to have lower exercise capacities and a higher prevalence of related risk for cardiovascular disease (CVD) compared to European Americans (EA). Broad biopsychosocial models that may inform the design of ethnic-specific exercise programs have not been well examined. We thus examined exercise capacity and its biopsychosocial correlates in a healthy population of AA and EA at increased risk of CVD. Subjects underwent maximal graded treadmill testing with gated single-photon emission computed tomography (SPECT); exercise capacity was expressed in MET-minutes. Medical history, psychosocial variables, general well-being, physical activity, and anthropometrics were assessed. Peak filling rate, a measure of left ventricular function, and ejection fraction were obtained from SPECT imaging, and the presence of silent ischemia was determined from the treadmill and SPECT imaging. The sample (N = 1054) was 47% AA and 60% female. Mean age was 52.1 ± 9 yr for AA and 49.9 ± 10 yr for EA. Body mass index (BMI) was 32.5 ± 6.7 kg·m(-2) for AA and 29 ± 5.3 kg·m(-2) for EA. AA achieved a mean maximal exercise level of 31 MET·min less than EA did. In separate regression models by race, BMI (r(2) = 0 .30), age (r(2) = 0 .07), and sex (r(2) = 0 .03) explained 40% of the variance in MET-minutes in AA and 36% in EA, with a similar hierarchy of associated variables. The remaining variables had minimal effect on exercise capacity in either group. BMI, older age, and female sex together contribute most to exercise capacity in both ethnicities. Hypothetically important biopsychosocial variables that may help shape ethnic-specific exercise programs add little to the prediction of exercise capacity. Thus, programs designed to reduce disparities in exercise capacity still need to first and foremost be geared to the age and sex demographics and address obesity.


Adjuvant systemic therapy for older adults with early-stage breast cancer.
There is a relative paucity of evidence to guide the adjuvant therapy of breast cancer in older adults. Herein, we review data from relevant clinical trials and retrospective analyses that assess systemic therapies in older adults. Chemotherapy, endocrine therapy, HER2-directed agents and bisphosphonates in the adjuvant setting are discussed. Meta-analyses, such as the Oxford overview, suggest a decreasing benefit of chemotherapy with age. However, prospective trials do support a benefit from the addition of chemotherapy to endocrine therapy in older adults. In contrast to chemotherapy, the value of endocrine therapy appears to increase with age. In addition, available subset analyses suggest that the benefit from aromatase inhibitors relative to tamoxifen is independent of age. The use of HER2-directed therapy in older adults is challenged by the relatively low enrollment of this subset in prospective clinical trials. Nonetheless, the extent of enrollment may be proportional to the frequency of HER2 overexpression in this population. Finally, there are little data to support the use of adjuvant bisphosphonate therapy in older adults--ongoing prospective trials may address this issue. Each of the aforementioned therapeutic strategies will be augmented by efforts to personalize therapy for older adults. Clinical tools such as the geriatric assessment and biologic assays, such as the 21-gene recurrence score, may ultimately play a role in treatment algorithms for this unique demographic.


Effects of auricular acupuncture stimulation on healthy adults' upper limb motor-evoked potentials: A randomized, crossover, double-blind study.
The aim of this study was to determine whether auricular acupuncture has neuromodulatory effects on the motor cortex of healthy adults. Fourteen healthy subjects received a real auricular acupuncture stimulation (SF1) session and a sham acupuncture stimulation session. The interval between the two types of stimulation was more than 24 h. A finger dexterity test (taping score and taping speed by using ipad) was assessed, and motor-evoked potentials (MEP) were assessed before and after each stimulation. Before the treatment, there were no significant differences in MEP amplitude, tapping score, or tapping speed (P > 0.05) between the real and sham stimulation conditions. After the treatment, the MEP amplitude, tapping score, and tapping speed in the real stimulation condition increased significantly compared to the pre-stimulation measurements and were significantly higher than those in the sham stimulation condition (P < 0.01). In the sham stimulation condition, the MEP amplitude, tapping score, and tapping speed decreased significantly compared to the pre-stimulation measurements (P < 0.05). Acupuncture of auricular points can modulate the excitability of the motor cortex area of controlling the upper limbs. [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2100051608].


A critical role for the putative NCS2 nucleobase permease YjcD in the sensitivity of Escherichia coli to cytotoxic and mutagenic purine analogs.
The base analogs 6-N-hydroxylaminopurine (HAP) and 2-amino-HAP (AHAP) are potent mutagens in bacteria and eukaryotic organisms. Previously, we demonstrated that a defect in the Escherichia coli ycbX gene, encoding a molybdenum cofactor-dependent oxidoreductase, dramatically enhances sensitivity to the toxic and mutagenic action of these agents. In the present study, we describe the discovery and properties of a novel suppressor locus, yjcD, that strongly reduces the HAP sensitivity of the ycbX strain. Suppressor effects are also observed for other purine analogs, like AHAP, 6-mercaptopurine, 6-thioguanine, and 2-aminopurine. In contrast, the yjcD defect did not affect the sensitivity to the pyrimidine analog 5-fluorouracil. Homology searches have predicted that yjcD encodes a putative permease of the NCS2 family of nucleobase transporters. We further investigated the effects of inactivation of all other members of the NCS2 family, XanQ, XanP, PurP, UacT, UraA, RutG, YgfQ, YicO, and YbbY, and of the NCS1 family nucleobase permeases CodB and YbbW. None of these other defects significantly affected sensitivity to either HAP or AHAP. The combined data strongly suggest that YjcD is the primary importer for modified purine bases. We also present data showing that this protein may, in fact, also be a principal permease involved in transport of the normal purines guanine, hypoxanthine, and/or xanthine. Nucleotide metabolism is a critical aspect of the overall metabolism of the cell, as it is central to the core processes of RNA and DNA synthesis. At the same time, nucleotide metabolism can be subverted by analogs of the normal DNA or RNA bases, leading to highly toxic and mutagenic effects. Thus, understanding how cells process both normal and modified bases is of fundamental importance. This work describes a novel suppressor of the toxicity of certain modified purine bases in the bacterium Escherichia coli. This suppressor encodes a putative high-affinity nucleobase transporter that mediates the import of the modified purine bases. It is also a likely candidate for the long-sought high-affinity importer for the normal purines, like guanine and hypoxanthine.


Dactylolysis spontanea or ainhum involving the big toe.
We describe the case of an Italian Caucasian man with ainhum involving both big toes. Ainhum or dactylolysis spontanea is characterized by the development of a constricting band around a toe, which progresses to spontaneous autoamputation. It usually affects the fifth toe bilaterally, but in rare cases other toes may be involved. The disease occurs in Black people living in tropical regions but occasionally has been reported in persons having fair skin.


Focused attention during selective adaptation along a place of articulation continuum.
The current investigation manipulated subjects' attention to adaptor tokens in five selective adaptation experiments. All stimuli were synthetic consonant-vowel syllables, with the consonant varying from [b] to [d] by formant frequency transitions. Two distractor conditions (auditory and visual) were compared to a more typical endpoint-[d alpha] adaptor condition. Distraction from endpoint-[d alpha] adaptors to phonetically distinct [si] and [integral of i] was used to observe whether smaller adaptation effects would result when attention was not focused on adaptor stimuli. In contrast, a focused attention condition required subjects to whisper [b alpha] adaptors right after they were heard. Performance in the focused attention condition was compared to a more typical endpoint-[b alpha] adaptation condition. Results indicated that focused attention did not affect the size of the adaptation effect. Asymmetrical adaptation results for [d alpha] vs [b alpha] adaptors, and a larger amount of adaptation with the presence of contralateral "distractor" syllables, resembled findings in psychoacoustic studies of discrimination and loudness adaptation. These results suggest that two levels of auditory processing (not special to speech perception) were responsible for the observed adaptation effects.


Carrier-mediated extraction: Applications in extraction and microextraction methods.
The present review is mainly focused on the overview of carrier mediated extraction (principles and applications) being reported over the last two decades and discusses the extraction process through carriers in various extraction methods such as Bulk liquid membranes, supported liquid membranes, emulsion liquid membranes and polymer inclusion membranes. Several types of carriers such as neutral, anionic, cationic, macrocyclic and supramulecular carriers are discussed. Also their application for metal, anions, drugs and environmental compounds are investigated. Carriers have been demonstrated to be useful for the selective extraction and recovery of numerous cations and anions enhancing the extraction properties of traditional solvent extraction and ion-exchange processes. Several types of carriers have different transport mechanisms. In these mechanisms, transport configurations are addressed and emphasized and the detailed information on the type of carrier are presented along with their specific separation modes. The performance of different carriers in terms of selectivity as well as efficiency are also discussed. Finally, the application of different carriers for the extraction of various compounds are compared and reviewed. To our best knowledge no reviews have been published on carrier-mediated extraction methods.


Syngeneic living-donor liver transplantation without the use of immunosuppression.
Transplantation between monozygotic twins has been successfully performed using the kidney, small intestine, and pancreas. Identical HLA matching has enabled these individuals to be transplanted without the need for immunosuppressive medication. Liver transplantation without immunosuppression would lessen the risk of recurrent viral hepatitis and eliminate much of the morbidity associated with long-term use of immunosuppressive medication. Living-donor liver transplantation (LDLT) has been performed with increasing success in recent years without an opportunity arising to use a monozygotic twin as a donor. We report 2 cases of LDLT between identical twins wherein perfect haploidentity has allowed these recipients to be transplanted without the need for immunosuppression. Although HLA matched genotypically, there may be differences in anatomy between donor and recipient. Mild liver chemistry test abnormalities may occur after transplant despite the absence of immunosuppression.


Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections.
To determine observer agreement for a clinical score and oximetry in lower respiratory infection in children less than 2 yr of age, a convenience sample of 56 infants hospitalized with bronchiolitis or pneumonia was assessed independently by two observers. A total of 12 infants had chronic lung disease of prematurity or congenital heart disease. Infants in whom oxygen supplementation could not be discontinued for at least 5 min were excluded. A severity score was assigned for each of four categories (respiratory rate, retractions, wheeze, and general appearance). A total for each patient was obtained by summing the score for each category. Oxygen saturation was measured using a Nellcor oximeter. Agreement beyond chance was measured using the kappa statistic. The relationship between observers for total score and oximetry and the mean total score and mean oximetry value for each patient was expressed as a Pearson correlation coefficient. A total of 56 infants and children were studied: 2 had pneumonia, 11 had an exacerbation of pulmonary signs and symptoms with their underlying cardiac or pulmonary disease, and 43 had bronchiolitis. Kappa was 0.48 for general assessment, 0.38 for respiratory rate, 0.31 for wheeze, and 0.25 for retractions. All values were statistically significantly greater than 0 at p less than 0.01. Correlations for total score and for oximetry were 0.68 and 0.88, respectively. The median difference between oximetry readings was 1. The correlation coefficient between total score and oximetry was -0.04. The limited agreement for clinical signs makes comparison of patient illness severity between studies difficult.(ABSTRACT TRUNCATED AT 250 WORDS)


Nanomaterial-based Microfluidic Chips for the Capture and Detection of Circulating Tumor Cells.
Circulating tumor cells (CTCs), a type of cancer cells that spreads from primary or metastatic tumors into the bloodstream, can lead to a new fatal metastasis. As a new type of liquid biopsy, CTCs have become a hot pursuit and detection of CTCs offers the possibility for early diagnosis of cancers, earlier evaluation of chemotherapeutic efficacy and cancer recurrence, and choice of individual sensitive anti-cancer drugs. The fundamental challenges of capturing and characterizing CTCs are the extremely low number of CTCs in the blood and the intrinsic heterogeneity of CTCs. A series of microfluidic devices have been proposed for the analysis of CTCs with automation capability, precise flow behaviors, and significant advantages over the conventional larger scale systems. This review aims to provide in-depth insights into CTCs analysis, including various nanomaterial-based microfluidic chips for the capture and detection of CTCs based on the specific biochemical and physical properties of CTCs. The current developmental trends and promising research directions in the establishment of microfluidic chips for the capture and detection of CTCs are also discussed.


[Effects of GDP on the activity and expression of mitochondrial uncoupling proteins in rat brain in vitro].
To investigate the regulatory role of purine nucleotide on uncoupling proteins (UCPs), the activity of UCPs and the expressions of UCP4 and UCP5 in mitochondria of rat brain tissues incubated with GDP were observed in vitro. The cerebral hemispheres of adult male Sprague-Dawley rats were removed and clipped into 8-10 mm3 tissue mass which incubated with 1 mmol/L GDP (GDP group), or only incubation medium (control group), for 30 min in vitro. The mitochondria from incubated tissue mass of rat brain were isolated by centrifugation. The activity of UCPs was detected by the method of [3H]-GTP binding with UCPs specifically. The maximal binding content (Bmax) and the dissociation constant (Kd) were determined from Scatchard plot. The mRNA and protein expressions of UCP4 and UCP5 were measured by RT-PCR and Western blot, respectively. The results showed that Bmax was increased and Kd was decreased in rat brain mitochondria in GDP group compared with that in control group. But the mRNA and protein expressions of UCP4 and UCP5 exhibited no statistically significant changes. It is thus suggested that GDP inhibits the activity of mitochondrial UCPs in rat brain in vitro, but exhibits no effect on the expressions of UCP4 and UCP5.


A Simple, Rapid Method for Determination of Melatonin in Plant Tissues by UPLC Coupled with High Resolution Orbitrap Mass Spectrometry.
Melatonin (MLT) was involved in regulating various stages of plant growth and development. However, due to the low concentration and complex matrixes of plant, the analysis of MLT is a challenging task. In this study, we developed a rapid and efficient method with simplified sample preparation by employing UPLC coupled with a high resolution Orbitrap mass spectrometry, and stable isotope-labeled MLT (MLT-d4) was first used as internal standard in the developed analytical method. In the developed method, we used one-step liquid-liquid extraction to purify the crude extracts both from shoot and root of rice for the analysis, which remarkably simplify the sample preparation process. The method exhibits high specificity and recovery yield (>96.4%). Good linearities were obtained for MLT ranging from 0.01 to 20 ng/ mL with determination coefficient (R2) of 0.9991. The limit of detection for MLT was 0.03 pg. Reproducibility of the method was evaluated by intra-day and inter-day measurements and the results showed that relative standard deviations were less than 7.2%. Moreover, MLT quantification was accomplished by using only 100 mg fresh plant tissues. Additionally, the established method was successfully applied to investigate the spatiotemporal distributions of MLT in rice under cadmium (Cd) stress condition. We found that the content of MLT in shoot and root of rice increased under Cd stress, suggesting that MLT would play a crucial role in modulating the responses to Cd stress in different plant tissues.


Rates of personality disorders in substance abusers: a comparison between DSM-III-R and DSM-IV.
The publication of the DSM-IV represents the first revision in 7 years to the DSM-III-R diagnostic criteria. The purpose of the current study is to evaluate the impact of changes to the Axis II criteria on diagnostic rates in a substance abusing population. We interviewed 370 patients entering treatment using a modified version of the SCID-II, which allowed for the diagnosis of both DSM-III-R and DSM-IV Axis II diagnoses. Prevalence rates for each Axis II disorder are given, as well as kappa statistics showing diagnostic agreement between the two systems. The results of this study indicate good rates of diagnostic agreement between the two systems with a few notable exceptions. Poor rates of diagnostic agreement were obtained for the histrionic and dependent diagnostic categories. No single diagnostic change appears to be responsible for the prevalence rate differences between the two systems.


Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model.
Magnetic resonance imaging (MRI) is widely employed for the diagnosis of multiple sclerosis (MS). However, sometimes, the lesions found by MRI do not correlate with the neurological impairments observed in MS patients. We recently showed autoreactive T cells accumulate in the fifth lumbar cord (L5) to pass the blood-brain barrier and cause inflammation in the central nervous system of experimental autoimmune encephalomyelitis (EAE) mice, an MS model. We here investigated this early event using ultrahigh-field MRI. T2-weighted image signals, which conform to the water content, increased in L4 and L5 during the development of EAE. At the same time, the sizes of L4 and L5 changed. Moreover, angiographic images of MRI showed branch positions of the blood vessels in the lower lumbar cords were significantly altered. Interestingly, EAE mice showed occluded and thickened vessels, particularly during the peak phase, followed by reperfusion in the remission phase. Additionally, demyelination regions of some MS patients had increased lactic acid content, suggesting the presence of ischemic events. These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.


[Organ and Effective Doses Using Automation Organ Dose Estimation Software for Lung Cancer Screening Using Low-dose Computed Tomography].
The purpose of this study was to evaluate the differences in the organ doses and the effective doses using three types of automated organ dose estimation software for low-dose computed tomography (CT) screening for lung cancer and to evaluate the correlations between each dose and size-specific dose estimates (SSDEs). Seventy-two adults who underwent low-dose CT screening for lung cancer were included, and the organ doses and the effective doses were calculated using each of automated organ dose estimation software. We evaluated differences between software for the organ doses and the effective doses and the correlations between each dose and SSDEs. Differences in organ doses and effective doses were observed among the software. The organ doses showed a strong correlation (r=0.833-0.995) with SSDEs for organs within the scan range. The effective doses showed a strong correlation (r=0.830-0.970) with SSDEs, although there were significant differences among the software. Although the organ doses and the effective doses differed between software, it may be possible to estimate them from SSDEs by using linear regression equations.


Neuropsychiatric symptoms in Alzheimer disease and cognitively impaired, nondemented elderly from a community-based sample in Brazil: prevalence and relationship with dementia severity.
The objectives of this study were to describe the prevalence of neuropsychiatric symptoms of dementia in Alzheimer disease (AD) and cognitively impaired nondemented (CIND) subjects from a community-based Brazilian sample and to correlate these symptoms with severity of cognitive deficits. A total of 1,563 randomly selected subjects were evaluated with the following screening tests: Mini-Mental Status Examination, Fuld Object Memory Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly, and Activities of Daily Living-International Scale. Screen positives were submitted to a workup for dementia, physical and neurologic examination, cranial computed tomography or cerebral magnetic resonance imaging, the Cambridge Examination for Mental Disorders, Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Sixty patients with AD, 25 CIND, and 78 healthy elderly subjects were evaluated. Informants reported that 78.33% of patients with AD had one or more neuropsychiatric symptoms. Apathy (53.33%), depression (38.33%), sleep alterations (38.33%), and anxiety (25%) were the most prevalent disturbances in AD subjects. These disturbances were more prevalent in patients with AD than in the comparison group and CIND individuals. In the CIND group, the most frequent neuropsychiatric symptoms were anxiety and sleep alterations (both with 24%) followed by depression (16%). Total NPI scores were significantly different between AD and CIND groups, AD and comparison groups, and CIND and the comparison group. Apathy was the only neuropsychiatric symptom that was significantly different between the groups divided according to the CDR being more frequent in subjects with moderate to severe dementia. Neuropsychiatric symptoms seem to be as common in patients living in a developing country as they are in demented patients from the developed world. Indeed, the fact that some of our results are similar to other population-based studies may suggest that cultural factors play a minor role in the emergence of these symptoms, at least in a Latin American country like Brazil.


Effect of thinning on density of Pinus nigra tree using X-ray computed tomography.
This study was carried out to determine the effect of thinning on density, extractives and lignin content of Pinus nigra Amold tree. Wood density was measured with computed tomography and 540+/-20 kg m(-3) were determined on control samples. Density of samples from thinning applied plot was 520+/-20 kg m(-3). The results showed that thinning slightly changes the density of wood and this change is caused by springwood content. In contrast, extractives and lignin content were not changed with thinning.


Complete tomography of a high-fidelity solid-state entangled spin-photon qubit pair.
Entanglement between stationary quantum memories and photonic qubits is crucial for future quantum communication networks. Although high-fidelity spin-photon entanglement was demonstrated in well-isolated atomic and ionic systems, in the solid-state, where massively parallel, scalable networks are most realistically conceivable, entanglement fidelities are typically limited due to intrinsic environmental interactions. Distilling high-fidelity entangled pairs from lower-fidelity precursors can act as a remedy, but the required overhead scales unfavourably with the initial entanglement fidelity. With spin-photon entanglement as a crucial building block for entangling quantum network nodes, obtaining high-fidelity entangled pairs becomes imperative for practical realization of such networks. Here we report the first results of complete state tomography of a solid-state spin-photon-polarization-entangled qubit pair, using a single electron-charged indium arsenide quantum dot. We demonstrate record-high fidelity in the solid-state of well over 90%, and the first (99.9%-confidence) achievement of a fidelity that will unambiguously allow for entanglement distribution in solid-state quantum repeater networks.


Implementing the new guidelines for hypertension: JNC 7, ADA, WHO-ISH.
The new guidelines issued by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) emphasize that aggressive blood pressure (BP) control is essential to reducing morbidity and mortality. Additionally, guidelines issued by the American Diabetes Association (ADA) and the World Health Organization-International Society of Hypertension (WHO-ISH) emphasize the critical need for lowering BP levels. Achieving BP goals is a challenge for patients and their physicians, and most patients are not at goal. Poor BP control is even more of a challenge for patients with diabetes and chronic kidney disease since their goals are even lower. The strategies for lowering BP levels include patient lifestyle changes, adherence to therapy, and regular monitoring of BP levels. To summarize the antihypertension guidelines recommended by WHO-ISH, JNC 7, the ADA, and the Hypertension in African Americans Working Group (HAAW Group) of the International Society on Hypertension in Blacks and evaluate the pharmacist.s collaborative role in the management of hypertension by examining the results of programs designed to include pharmacist counseling. The relevant literature was evaluated and reviewed. Emphasis was placed on literature that evaluated strategies to improve BP control. Results from several programs and studies showed positive effects of pharmacist collaboration. A program that provided pharmacist academic detailing to physicians at 5 Veterans Affairs facilities resulted in significant increases in patients receiving beta-blocker therapy or thiazide diuretics and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy. Another study in which hypertensive patients received clinical services from pharmacists showed significant improvement in patients. knowledge of hypertension and its management and in patient adherence, and also showed a significant increase in the number of patients whose BP stayed in the normal range. A 6-month, controlled, single-blind, parallel-group study of 51 hypertensive patients showed significant improvements in BP control, quality of life, and overall patient satisfaction in the study group that received treatment through a primary care team that included pharmacists. Among patients at a Veterans Administration medical center, results suggested that the intervention of a clinical pharmacist improved documentation of drug therapy and estimated patient compliance. A study of the effectiveness of comanagement in 197 hypertensive patients with physician-pharmacist collaboration using an evidence-based, systematic approach showed that a significantly larger number of patients in the study group achieved BP control than in the control group. The expanded role of clinical pharmacists in programs for evaluating, monitoring, and treating patients with hypertension can result in improved adherence to therapy and established guidelines. As members of interdisciplinary health care teams, pharmacists should utilize the JNC 7 guidelines and scientific evidence to consult with physicians about medications, design effective formularies, and collaborate with physicians in evaluating and comanaging patients with hypertension.


Oral bacteria inhibit Helicobacter pylori growth.
Various oral bacterial species were found to inhibit the growth of Helicobacter pylori strains. The growth inhibitory activities of most of these oral bacteria were adversely affected by heating at 80 degrees C for 60 min or by protease treatment, indicating that these bacteria produce bacteriocin-like inhibitory proteins against H. pylori strains. The antagonistic effects of oral bacteria against H. pylori may restrain colonization by this organism in the oral cavity.


A New Semiparametric Approach to Finite Mixture of Regressions using Penalized Regression via Fusion.
For some modeling problems a population may be better assessed as an aggregate of unknown subpopulations, each with a distinct relationship between a response and associated variables. The finite mixture of regressions (FMR) model, in which an outcome is derived from one of a finite number of linear regression models, is a natural tool in this setting. In this article, we first propose a new penalized regression approach. Then, we demonstrate how the proposed approach better identifies subpopulations and their corresponding models than a semiparametric FMR method does. Our new method fits models for each person via grouping pursuit, utilizing a new group-truncated L 1 penalty that shrinks the differences between estimated parameter vectors. The methodology causes the individuals' models to cluster into a few common models, in turn revealing previously unknown subpopulations. In fact, by varying the penalty strength, the new method can reveal a hierarchical structure among the subpopulations that can be useful in exploratory analyses. Simulations using FMR models and a real-data analysis show that the method performs promisingly well.


Pharmacological actions of tetrandrine in inflammatory pulmonary diseases.
Tetrandrine is a principle from a traditional Chinese medicine of the root of Stephania tetrandra S Moore approved by State Drugs Administration of China as a new drug for the treatment of silicosis. Except for its antiinflammatory, antifibrogenetic, immunomodulating effects and antioxidant effects, tetrandrine presents antiallergic effects, inhibitory effects on pulmonary vessels and airway smooth muscle contraction, and platelet aggregation via its nonspecific calcium channel antagonism that suggested its potential in the treatment of asthma, pulmonary hypertension and chronic obstructive pulmonary disease (COPD). In general, the clinical results to date with tetrandrine in asthma and pulmonary hypertension have been exciting. The last 10 years have witnessed great leaps forward in our understanding of the molecular biology and biochemistry of chronic inflammatory diseases as well as the treatment drugs, which may create opportunities for future therapeutic innovation, development of tetrandrine derivatives or new extracts from other Chinese medicine. The current article briefly reviews the basic and clinical pharmacology of tetrandrine as well as the in vitro and in vivo data supporting the view that tetrandrine is as a novel drug for the treatment of silicosis, asthma and pulmonary hypertension.


Literacy in the time of Coronavirus: an Italian perspective: Value of literacy in the context of a pandemic.
COVID-19 pandemic, with its dramatic impact on society, poses a challenge to Health Pro-motion and to its principles of empowerment, social cohesion and citizens' democratic participation in health policies. In this pressing emergency, public health strategies aimed at preventing the spread of the pandemic have been primarily oriented towards restrictive measures (travel restrictions, use of PPE) in absence of an adequate educational communication, aimed at increasing citizens' knowledge and skills in regard to the emergency context. To offer a perspective on the Italian situation, in terms of health literacy and life skills in the context of COVID-19 pandemic, aimed not only at identifying deficits, but particularly at determining opportuni-ties and resources (assets) - offered by the peculiar context of crisis - useful to provide citizens with the necessary tools to comprehend the criticalities linked with the emergency and to shape their behaviour to new requirements, in absence of external obligations, as well as to promote future participation of the population - both effective and informed - in a social and political context. A non-systematic review of literature on the subject of health literacy and social cohesion in emergency contexts has been supported by a qualitative assessment, based on the model of assets and on the Italian condition in the last trimester of 2020. The scarce ability of the population to independently adequate habits and behaviour to new criti-calities required by the risk of infection - as well as the necessity to suspend their empowerment and capa-bility from government authorities to protect public health - has been firstly traced back to a widespread lack of literacy and life skills at a general population level. The current situation of crisis offers a peculiar opportunity of tools, circumstances and receptiveness to highlight such deficits, as well as an intervention on multiple fronts, in order to increase literacy and capability, both on an individual and on a community level, through inclusive and sustainable initiatives. A prevention strategy based on the critical understanding of risk and risk-related criticalities is the only one which can aspire to last over time, while offering an effective tool for the safeguarding of public health, along with an opportunity of being prepared to contrast future emergencies more effectively. The development of such strategies represents one of the most significant contributions Health Promotion can offer in the time of Coronavirus.


DNA adducts in marine and freshwater fish as biomarkers of environmental contamination.
The analysis of DNA modifications in aquatic animals may serve as a sensitive marker of exposure to genotoxic contaminants. This is of importance in assessing water quality regarding pollution with genotoxic compounds, food safety analysing edible aquatic animals and in terms of ecotoxicology. Covalent modification of DNA is considered a crucial event in chemical carcinogenesis and thus may be considered a biomarker of an early genotoxic effect. Measuring DNA adducts is unique in that these lesions may be considered a biomarker of both exposure and effect. A number of studies have described the analysis of the DNA isolated from the liver of both freshwater and marine fish. Considerable levels of DNA adducts have been observed in some animals from contaminated lakes or rivers. Low levels were observed in DNA from the liver of marine fish. The background levels of DNA adducts have to be determined in animals from appropriate uncontaminated control sites that are matched for species, gender, age and season of the year. It is of crucial importance to consider the species analysed since there have been reports of the non responsiveness of some species.


Role of IgM and angiotensin II Type I receptor autoantibodies in local complement activation in placental ischemia-induced hypertension in the rat.
Preeclampsia is characterized by development of hypertension during pregnancy and reduced placental perfusion. Previous studies in a rat model of placental ischemia-induced hypertension demonstrated that inhibiting complement activation attenuated increased maternal blood pressure with C3a and C5a identified as the important products of complement activation. Given that in other forms of ischemia both natural IgM and antigen antibody complexes initiate complement activation, we hypothesized that placental ischemia exposes neoepitopes recognized by IgM to cause local complement activation and hypertension. Alternatively, we postulated that autoantibody to angiotensin II Type 1 receptor (AT1-AA) interacts with AT1 receptors to cause complement activation. Since complement activation occurs in kidney and placenta in preeclampsia, we used immunohistochemistry to determine IgM deposition and local complement activation in each organ (C3 deposition), and quantitative real-time polymerase chain reaction (qRT-PCR) to quantitate mRNA for endogenous regulators of complement activation CD55, CD59 and Complement receptor 1-related gene/protein y (Crry). On gestation day (GD)14.5, timed pregnant Sprague Dawley rats underwent Sham surgery or placement of clips on inferior abdominal aorta and ovarian arteries to create placental ischemia using the reduced utero-placental perfusion pressure (RUPP) model. As previously reported, RUPP surgery increased mean arterial pressure and circulating C3a on GD19.5. In placenta, IgM and C3 deposition increased, whereas mRNA for complement regulators Crry and CD59 decreased along with Crry protein in RUPP compared to Sham treated animals. In kidney, IgM deposition increased in animals subjected to RUPP vs Sham surgery without a significant change in C3 deposition and coincident with an increase in mRNA for CD55 and CD59. The AT1 receptor antagonist losartan prevents placental ischemia-induced hypertension as well as AT1-AA interaction with AT1 receptors. However, losartan did not attenuate complement activation as measured by circulating C3a or placental C3 deposition. Importantly, our studies indicate that following placental ischemia, complement activation is not due to AT1-AA but is associated with IgM deposition. These studies suggest a role for natural antibodies interacting with placental ischemia-induced neoepitopes to activate complement and contribute to hypertension.


Antifungal activity and mode of action of saponins from Madhuca butyracea Macb.
The antifungal activity of saponins isolated as a byproduct from the defatted cake of M. butyracea oil seed is reported. The inhibitory concentrations against plant pathogenic fungi ranged from 500 to 2000 ppm. Maximum sensitivity to saponins was shown by Penicillium expansum. Cephalosporium acrimonium, Helminthosporium oryzae and Trichoderma viride. The saponins caused leakage of cell components and underwent degradation by fungus, Trichoderma viride. The usefulness of saponins as antimycotic agents is discussed.


Prediction of regulatory networks in mouse abdominal wall.
Sequence specific transcription factors are essential for pattern formation and cell differentiation processes in mammals. The formation of the abdominal wall depends on a flawless merge of several developmental fields in time and space. The absence of Pitx2 leads to an open abdominal wall in mice, while mutations in humans result in umbilical defects, suggesting that a single homeobox transcription factor coordinates the formation and patterning of this anatomical structure. Gene expression analysis from abdominal tissue including the abdominal wall after removal of the major organs, of wild type, Pitx2 heterozygote and mutant mice, at embryonic day 10.5, identified 275 genes with altered expression levels. Pitx2 target genes were clustered using the "David Bioinformatics Functional Annotation Tool" web application, which bins genes according to gene ontology (GO) key word enrichment. This provided a way to both narrow the target gene list and to start identifying potential gene families regulated by Pitx2. Target genes in the most enriched bins were further analyzed for the presence and the evolutionary conservation of Pitx2 consensus binding sequence, TAATCY, on the -20 kb, intronic and coding gene sequences. Twenty Pitx2 target genes that passed all the above criteria were classified as genes involved in cell transport and growth. Data from these studies suggest that Pitx2 acts as an inhibitor of protein transport and cell apoptosis contributing to the open body wall phenotype. This work provides the framework to which the developmental network leading to abdominal wall syndromes can be built.


The use of plant extracts and their phytochemicals for control of toxigenic fungi and mycotoxins.
Mycotoxins present a great concern to food safety and security due to their adverse health and socio-economic impacts. The necessity to formulate novel strategies that can mitigate the economic and health effects associated with mycotoxin contamination of food and feed commodities without any impact on public health, quality and nutritional value of food and feed, economy and trade industry become imperative. Various strategies have been adopted to mitigate mycotoxin contamination but often fall short of the required efficacy. One of the promising approaches is the use of bioactive plant components/metabolites synergistically with mycotoxin-absorbing components in order to limit exposure to these toxins and associated negative health effects. In particular, is the fabrication of β-cyclodextrin-based nanosponges encapsulated with bioactive compounds of plant origin to inhibit toxigenic fungi and decontaminate mycotoxins in food and feed without leaving any health and environmental hazard to the consumers. The present paper reviews the use of botanicals extracts and their phytochemicals coupled with β-cyclodextrin-based nanosponge technology to inhibit toxigenic fungal invasion and detoxify mycotoxins.


Young Africans' representations of the origins of same-sex attraction and implications for sexual and mental health.
Sexual minorities are stigmatised in much of sub-Saharan Africa, restricting their access to sexual health services and undermining their mental health. Although public attitudes and social representations inform the experience of sexual stigma, little is known about how young Africans make sense of sexual diversity. We conducted a thematic analysis of 56 texts contributed by young people from 10 countries in response to a prompt in a scriptwriting competition inviting participants to 'tell a story about someone who is attracted to people of the same sex'. We analysed accounts of the origins of same-sex attraction, a prominent theme in the narratives. Two-thirds of the texts provide an explicit or implicit explanation, presenting same-sex attraction as innate (15/38) and/or the consequence of environmental influences (32/38), including parental behaviour, gender separation, trauma, foreign influences and evil spirits. Expressions of the potential to avert or cure same-sex attraction are common. Young people's sense-making around sexual diversity draws on available sociocultural and symbolic resources, some of which may be highly stigmatising, and reflects local, national and transnational influences. The need to explain same-sex attraction and the preponderance of harmful explanatory frameworks compounds sexual minority youth's vulnerability to sexual stigma, harmful coping strategies and mental health challenges.


Increment of late sodium currents in the left atrial myocytes and its potential contribution to increased susceptibility of atrial fibrillation in castrated male mice.
The incidence of atrial fibrillation (AF) is correlated with decreased levels of testosterone in elderly men. Late sodium current may exert a role in AF pathogenesis. The purpose of this study was to explore the effect of testosterone deficiency on AF susceptibility and the therapeutic effect of late sodium current inhibitors in mice. Male ICR mice (5 weeks old) were castrated to establish a testosterone deficiency model. One month after castration, dihydrotestosterone 5 mg/kg was administered subcutaneously for 2 months. Serum total testosterone level was assessed by enzyme-linked immunosorbent assay. High-frequency electrical stimulation was used to induce atrial arrhythmias. Whole-cell patch-clamp technique was used to for single-cell electrophysiologic study. Serum dihydrotestosterone levels of castration mice declined significantly but recovered with administration of exogenous dihydrotestosterone. In comparison with sham mice, the number of AF episodes significantly increased by 13.5-fold, AF rate increased by 3.75-fold, and AF duration prolonged in castrated mice. Dihydrotestosterone administration alleviated the occurrence of AF. Action potential duration at both 50% and 90% repolarization were markedly increased in castrated mice compared to sham controls. The late sodium current was enhanced in castrated male mice. These alterations were alleviated by treatment with dihydrotestosterone. Systemic application of the INa-L inhibitors ranolazine, eleclazine, and GS967 inhibited the occurrence of AF in castrated mice. Testosterone deficiency contributed to the increased late sodium current, prolonged action potential repolarization, and increased susceptibility to AF. Blocking of late sodium current is beneficial against the occurrence of AF in castrated mice.


Extending health care to AFDC recipients who obtain jobs: results of a demonstration.
This study investigated the outcomes of a demonstration project that provided free medical coverage to former Aid to Families with Dependent Children (AFDC) recipients who were holding jobs with limited or no health benefits. Data were collected on the Medicaid expenditures of 54 eligible participants and their dependents for up to two years before they exited welfare; the expenditures averaged 56 percent less for adults and 45 percent less for children than the respective AFDC averages for the county. Because only 22 percent of the eligible participants took advantage of the program, telephone interviews also were conducted with 24 people who did not participate in or dropped out of the health plan. The main reasons cited for not enrolling were a misunderstanding of the program, a claim that no notification of the program was received, and a lack of interest. These results and their policy implications are presented in the context of the Family Support Act's mandate that states extend medical assistance coverage to AFDC recipients whose cases are closed because of employment.


ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma.
5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.


[Outcomes of secondary implantation of posterior-chamber intraocular lenses in children with capsular and scleral sutural fixation].
The functional results and postoperative complications of secondary implantation of posterior-chamber artificial lenses (AL) in 122 children (165 eyes) aged 2 to 7 years. The specific feature of this operation in children is the high frequency of postoperative complications: 48 and 60% after capsular fixation and scleral sutural fixation, respectively. In most cases, they appear as a second-grade inflammatory reaction in the early postoperative period and as slowly progressive iridocyclitis in the late postoperative period. Secondary implantation of posterior-camber ALs with capsular fixation is an effective and safe technique for correcting aphakia in children, by yielding good functional results. Postoperative complications are treatable and fail to lower visual acuity. Secondary implantation of ALs with scleral fixation in children is associated with a relatively high risk of intractable complications that decrease visual results and it should be performed in single cases if there are strict indications.


[Survey of Arsenic/Heavy Metals and Pesticide Residues in Edible Insects for Human Consumption or Supplied in Japan].
Arsenic (As) and heavy metals (Cd, Hg, Pb, and Cu) and pesticide residues in 14 edible insects were investigated. The maximum levels of elements were 6.15 for As, 0.82 for Cd, 0.50 for Hg, 0.67 for Pb, and 297.7 ppm for Cu. Fenobucarb (or BPMC) has been quantified through GC- and LC-MS/MS analysis at a concentration of approximately 3 ppm. Further studies of the contaminants may help ensure the safety of edible insect consumption.


High-grade non-Hodgkin's lymphoma stage I. A retrospective study of treatment, outcome and prognostic factors in 213 patients.
In a retrospective study of 213 patients with high-grade non-Hodgkin's lymphomas clinical stage I, diagnosed 1985-1990, pretreatment prognostic variables and result of treatment were analysed. The median age of the patients was 67 years. Treatment consisted of radiotherapy in 61%, chemotherapy (10%) chemotherapy followed by radiotherapy (23%) and surgery alone (5%) of the patients. Complete response was achieved in 89% of the patients with estimated relapse-free survival at 5 years of 73%. Relative 5-year survival of all patients was 73%. After chemotherapy followed by radiotherapy the relapse rate was 15% compared with 29% after radiotherapy only. The 5-year relative survival differed between 58% and 74% in the treatment groups. Age, sex, nodal versus extranodal lymphoma, systemic symptoms, bulk of tumor and level of serum lactic dehydrogenase (s-LDH) were analysed as prognostic factors. In multivariate variate analysis, only age 65 years or older and elevated s-LDH were significant independent adverse prognostic factors.


Comparative study of planned and unplanned excisions for the treatment of soft tissue sarcoma of the extremities.
Unplanned excision of soft tissue sarcomas is common because benign soft tissue lesions are very frequent. This study evaluated the impact of unplanned resections on overall survival, local recurrence and distant metastasis in patients with soft tissue sarcomas of the extremities. In total, 52 patients who were diagnosed with soft tissue sarcomas between May 2001 and March 2011 were analyzed in a retrospective study. Of these patients, 29 (55.8%) had not undergone previous treatment and the remaining 23 (44.2%) patients had undergone prior resection of the tumor without oncological planning. All subsequent surgical procedures were performed at the same cancer referral center. The follow-up ranged from 6 to 122 months, with a mean of 39.89 months. Age, lesion size and depth, histological grade, surgical margins, overall survival, local and distant recurrence and adjuvant therapies were compared. Residual disease was observed in 91.3% of the re-resected specimens in the unplanned excision group, which exhibited greater numbers of superficial lesions, low histological grades and contaminated surgical margins compared with the re-resected specimens in the planned excision group. No differences were observed in local recurrence and 5-year overall survival between the groups, but distant metastases were significantly associated with planned excision after adjustment for the variables. There was no difference between patients undergoing unplanned excision and planned excision regarding local recurrence and overall survival. The planned excision group had a higher risk of distant metastasis, whereas there was a high rate of residual cancer in the unplanned excision group.


Kiloniella spongiae sp. nov., isolated from a marine sponge and emended description of the genus Kiloniella Wiese et al. 2009 and Kiloniella laminariae.
A Gram-reaction-negative, aerobic, rod-shaped and non-motile marine bacterium, designated MEBiC09566(T) was isolated from a sponge collected at Uljin County in the coastal area of the East Sea (36° 55' N, 129° 25' E), Korea. The 16S rRNA gene sequence analysis revealed that strain MEBiC09566(T) showed the highest similarity with the Kiloniella laminariae LD81(T) (96.7%). Growth was observed at 11-31 °C (optimum 25 °C), at pH 6.0-8.5 (optimum pH 7.0) and with 0-6% (optimum 2.5%) NaCl. The predominant cellular fatty acids were summed feature 8 (comprised of C18:1ω7c/C18:1ω6c) and summed feature 3 (comprised of C16:1ω7c and/or C16:1ω6c). The DNA G+C content is 44.6 mol%. The major respiratory quinone is Q-9. Phosphatidylethanolamine, phosphatidylglycerol, an unidentified lipid, two unidentified aminophospholipids and one unidentified aminolipid were detected as major polar lipids. On the basis of this polyphasic taxonomic data, it is concluded that strain MEBiC09566(T) should be classified as representing a novel species in the genus Kiloniella and the name proposed is Kiloniella spongiae sp. nov. The type strain is MEBiC09566(T) ( = KCCM 43040(T) = JCM 19930(T)). Emended descriptions of the genus Kiloniella Wiese et al. 2009 and Kiloniella laminariae are also given.


Enzymatic degradation of the polymer capsules with a hydrophobic core in the presence of Langmuir lipid monolayer as a model of the cellular membrane.
Submicrocapsules were prepared from diethylaminoethyl dextran (DEAE-D), xanthan gum (XG) and bovine serum albumin (BSA) on oil cores by ultrasonic treatment. These capsules were modified with poly-L-lysine (PLL) via electrostatic adsorption. The behavior of the capsules was investigated at an air-water interface after their introduction into an aqueous subphase. The interaction of the capsules with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer formed on the water surface (model cellular membrane) was studied both upon their introduction under the condensed monolayer and with the use of a dilute colloidal solution of the capsules as a subphase. Biodegradation of the proteinaceous capsules with subsequent oil-core release was demonstrated by influence of pronase. The Langmuir lipid monolayer was found to be a good model for investigation of drug release from the capsules in the presence of the cellular membrane.


[Non-penetrating deep sclerectomy in the treatment of advanced cases of open angle glaucoma].
The purpose of the paper was to examine the efficacy of non-penetrating deep sclerectomy (NPDS) with sodium hyaluronate implants and mitomycin C in the treatment of advanced cases of open angle glaucoma. Thirty-five eyes of 35 patients with medically uncontrolled advanced open angle glaucoma were retrospectively analyzed. Visual acuity and intraocular pressure measurement were performed before and after surgery at 1 and 7 days and 1, 6 and 12 months. Visual field was analyzed before and 12 months after surgery. The mean preoperative intraocular pressure was 27+/-3.1 mm Hg and 18.1+/-1.5 at 12 month after surgery (p<0.05). Visual acuity decreased more than two rows on Snellen chart in 4 patients. Visual field analysis shows mean defect MD--17+/-5.2 before surgery and 20.1+/-6.2 after 12 month of follow up (p>0.05). Complete success rate defined as an IOP lower than 21 mmHg without medications was 51%. In 3 eyes we performed needling and in 8 goniopuncture. Postoperative complications included hyphaema in 3 eyes, choroidal detachment in 1 eye, bleb fibrosis in 2 eyes. 1. Deep sclerectomy with SK-GEL implant and antimetabolites provided good reasonable control of intraocular pressure. 2. In uncomplicated cases it let us achieve stabilization of the visual field.


Transport in tight-binding bond percolation models.
Most of the investigations to date on tight-binding, quantum percolation models focused on the quantum percolation threshold, i.e., the analog to the Anderson transition. It appears to occur if roughly 30% of the hopping terms are actually present. Thus, models in the delocalized regime may still be substantially disordered, hence analyzing their transport properties is a nontrivial task which we pursue in the paper at hand. Using a method based on quantum typicality to numerically perform linear response theory we find that conductivity and mean free paths are in good accord with results from very simple heuristic considerations. Furthermore we find that depending on the percentage of actually present hopping terms, the transport properties may or may not be described by a Drude model. An investigation of the Einstein relation is also presented.


A Randomized Controlled Trial: The Effect of Own Mother's Breast Milk Odor and Another Mother's Breast Milk Odor on Pain Level of Newborn Infants.
Objective: Our research was conducted empirically to determine whether another mother's breast milk could be used to reduce the pain of newborns who were not able to access their own mother's milk for any reason. Materials and Methods: The sample group of the research included 90 newborns [smell of own mother's milk (30), smell of another mother's milk (30), and the control group (30)] hospitalized in the unit. A neonatal information form was used as the data collection tool, the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) was used to assess the newborn's pain, and an evaluation form prepared by the researcher was used to record the findings. Results: The group which was exposed to their own mother's milk had a significantly lower N-PASS mean score compared to other groups and the group which was exposed to another mother's milk was observed to have a significantly lower N-PASS mean score compared to the control group (p < 0.05). While the median values for the total time spent crying of the "own mother's milk" group and the "another mother's milk" group were similar; the total time spent crying of the control group had a significantly higher median value. Conclusion: Our research determined that, while the most effective method for reducing pain in newborns was the smell of their own mother's breast milk, for newborns who were not able to access their own mother's breast milk, the smell of breast milk from a different mother could also be used.


[The role of occupational context factors in medication administration errors].
The incidence of medication administration errors (MAE) is high and costly for patients and health institutions. Human factors and factors relating to the work context intervene in their occurrence. The aim of this article is to identify the role of factors in the work setting related to occurrence of MAEs in the hospital field. A narrative review of the literature. Eight articles were included following a review of MEDLINE, CINAHL and COCHRANE LIBRARY databases for the 2002-2012 period. Distractions and interruptions, work overload, design of units and characteristics of the material stood out amongst the work context factors intervening in the occurrence of medication administration errors. The creation of organizational artefacts to reduce interruptions; patient involvement in medication administration; the introduction of new technologies and improving the labelling of medications can help reduce the incidence of medication administration errors. To advance in identifying and managing factors that are precursors of medication administration errors, we recommend the carrying out of studies or reviews of prospective cohorts.


Antioxidant activity of milk protein hydrolysate in alloxan-induced diabetic rats.
We investigated the effects of milk protein concentrate (MPC) and milk protein concentrate hydrolysate (MPCH) as antioxidant agents in rats. Six groups of healthy (non-diabetic) and type-II diabetic rats were used: (1) healthy rats (control), (2) alloxan-induced rats (diabetic control group), (3) healthy rats treated orally with MPC, (4) diabetic rats treated orally with MPC, (5) healthy rats treated orally with MPCH, and (6) diabetic rats treated orally with MPCH. We concluded that treatment with MPC or MPCH reduced the level of thiobarbituric acid reactive substances in healthy and diabetic rats. Treatment with MPC or MPCH improved activities of antioxidant enzymes (catalase, superoxide dismutase, reduced glutathione, glutathione-S-transferase, and glutathione peroxidase) in healthy and diabetic rats. From the present data, we concluded that both MPC and MPCH contain potent antioxidants and could improve the health of rats or other animals with diabetes mellitus.


What influences the home range size of free-roaming domestic dogs?
In many regions of the world domestic dogs are free roaming and live in close relationship with humans. These free-roaming domestic dogs (FRDD) can cause public health problems such as dog bites and transmission of infectious diseases. To effectively control diseases transmitted by FRDD, knowledge on the dogs' behaviour is required. To identify predictors of home range (HR) size, we collected global positioning system data from 135 FRDD living in eight Aboriginal and Torres Strait Islander communities in Northern Australia. The core HR size ranged from 0·17 to 2·33 ha and the extended HR size from 0·86 to 40·46 ha. Using a linear mixed effect model with a Restricted Maximum Likelihood approach, the dog's sex and reproductive status were identified as predictors of roaming. Non-castrated males had the largest HRs, followed by neutered females. Also, FRDDs were found to roam further during the pre- than the post-wet season. These findings have implications for infectious disease spread. Identification of risk groups for disease spread within a population allows for more targeted disease response and surveillance. Further investigation of predictors of roaming in other FRDD populations worldwide would increase the external validity of such studies.


Fever and rash in a 3-year-old girl: Rocky Mountain spotted fever.
Initial symptoms of Rocky Mountain spotted fever (RMSF), a tick-borne illness caused by Rickettsia rickettsii, are nonspecific and include headache, gastrointestinal disturbances, malaise, and myalgias, followed by fever and rash. The classic triad of fever, rash, and history of tick exposure is uncommon at presentation. Clinical manifestations of RMSF range from virtually asymptomatic to severe. Because of the potentially fatal outcome of RMSF, presumptive clinical diagnosis and empiric antimicrobial therapy can be critical. We present the case of a 3-year-old girl from New York State who presented with fever and rash.


Engineering artificial small RNAs for conditional gene silencing in Escherichia coli.
It has become increasingly evident that noncoding small RNAs (sRNAs) play a significant and global role in bacterial gene regulation. A majority of the trans-acting sRNAs in bacteria interact with the 5' untranslated region (UTR) and/or the translation initiation region of the targeted mRNAs via imperfect base pairing, resulting in reduced translation efficiency and/or mRNA stability. Additionally, bacterial sRNAs often contain distinct scaffolds that recruit RNA chaperones such as Hfq to facilitate gene regulation. In this study, we describe a strategy to engineer artificial sRNAs that can regulate desired endogenous genes in Escherichia coli. Using a fluorescent reporter gene that was translationally fused to a native 5' mRNA leader sequence, active artificial sRNAs were screened from libraries in which natural sRNA scaffolds were fused to a randomized antisense domain. Artificial sRNAs that posttranscriptionally repress two endogenous genes ompF and fliC were isolated and characterized. We anticipate that the artificial sRNAs will be useful for dynamic control and fine-tuning of endogenous gene expression in bacteria for applications in synthetic biology.


Transient phase retardation in single and double pass traveling wave electrooptic light modulators.
The transient response of the phase retardation for electrical and optical signals traveling in the same and opposite directions along an electrooptic modulator crystal is calculated. Using these results, the transient response of the phase retardation for single and double pass traveling wave optical modulators is calculated.


[Preparation and modification of polyhedral oligomeric silsesquioxane-containing hybrid monolithic capillary columns].
Two kinds of hybrid monolithic capillary columns were prepared via free radical polymerization. First, the hybrid monolithic column was in situ fabricated by using two polyhedral oligomeric silsesquioxanes (POSS), POSS-methacryl substituted (cage mixture, n = 8, 10, 12) (POSS-MA) and POSS-(1-propylmethacrylate)-heptaisobutyl substituted (Bu-POSS), as crosslinker and monomer, respectively, in the presence of porogenic solvents (propanol/ PEG400) and initiator (azodisobutyronitrile). Second, the hybrid monolithic column was similarly prepared by using POSS-MA, as sole monomer under the same conditions. The resulting two kinds of hybrid monolithic columns, poly (Bu-POSS-co-POSS-MA) and poly (POSS-MA), were characterized and applied for the separation of alkylbenzenes by capillary liquid chromatography (cLC), showing good mechanical stability and reproducibility. Additionally, the poly (POSS-MA) monolith could be easily modified with other organic monomers, such as stearyl methacrylate (SMA) and benzyl metacrylate (BeMA), with the presence of methacryl groups on the surface of the poly(POSS-MA) monolith. Compared with the raw poly(POSS-MA) monolith, the post-modified poly(POSS-MA) monolith exhibited higher column efficiency and better selectivity. This simple process of using POSS reagents via free radical polymerization is providing a novel way for the preparation of the organic-silica hybrid monolithic columns.


Interactions of mammalian proteins with cisplatin-damaged DNA.
We have undertaken the systematic isolation and characterization of mammalian proteins which display an affinity for cisplatin-damaged DNA. Fractionation of human cell extracts has led to the identification of two classes of proteins. The first includes proteins that bind duplex DNA in the absence of cisplatin damage and retain their affinity for DNA in the presence of cisplatin-DNA adducts. The DNA-dependent protein kinase (DNA-PK) falls into this class. The inhibition of DNA-PK phosphorylation activity by cisplatin-damaged DNA has led to the hypothesis that cisplatin sensitization of mammalian cells to ionizing radiation may be mediated by DNA-PK. The second class of proteins identified are those which display a high relative affinity for cisplatin-damaged DNA and a low affinity for undamaged duplex DNA. Proteins that fall into this class include high mobility group 1 protein (HMG-1), replication protein A (RPA) and xeroderma pigmentosum group A protein (XPA). Each protein has been isolated and purified in the lab. The interaction of each protein with cisplatin-damaged DNA has been assessed in electrophoretic mobility shift assays. A series of DNA binding experiments suggests that RPA binds duplex DNA via denaturation and subsequent preferential binding to the undamaged DNA strand of the partial duplex. DNA substrates prepared with photo-reactive base analogs on either the damaged or undamaged DNA strand have also been employed to investigate the mechanism and specific protein-DNA interactions that occur as each protein binds to cisplatin-damaged DNA. Results suggest both damage and strand specificity for RPA and XPA binding cisplatin-damaged DNA.


Suppression of microtubule dynamics by benomyl decreases tension across kinetochore pairs and induces apoptosis in cancer cells.
We found that benomyl, a benzimidazole fungicide, strongly suppressed the reassembly of cold-depolymerized spindle microtubules in HeLa cells. Benomyl perturbed microtubule-kinetochore attachment and chromosome alignment at the metaphase plate. Benomyl also significantly decreased the distance between the sister kinetochore pairs in metaphase cells and increased the level of the checkpoint protein BubR1 at the kinetochore region, indicating that benomyl caused loss of tension across the kinetochores. In addition, benomyl decreased the intercentrosomal distance in mitotic HeLa cells and blocked the cells at mitosis. Further, we analyzed the effects of benomyl on the signal transduction pathways in relation to mitotic block, bcl2 phosphorylation and induction of apoptosis. The results suggest that benomyl causes loss of tension across the kinetochores, blocks the cell cycle progression at mitosis and subsequently, induces apoptosis through the bcl2-bax pathway in a manner qualitatively similar to the powerful microtubule targeted anticancer drugs like the vinca alkaloids and paclitaxel. Considering the very high toxicity of the potent anticancer drugs and the low toxicity of benomyl in humans, we suggest that benomyl could be useful as an adjuvant in combination with the powerful anticancer drugs in cancer therapy.


[Clinical evaluation of antimalarial drugs].
We have analyzed the clinical data of 189 patients with malaria to establish antimalarial regimens in Japan. The causative parasite species were Plasmodium falciparum in 56 cases (30%), P. vivax in 132 (70%) and P. malariae in 1 (1%). The outcomes f malaria cases are as follows: Cure rats in falciparum and vivax malaria are 86% and 91%, respectively. Two patients died of falciparum malaria and recurrence occurred in 6 cases (11%) of falciparum malaria. Relapse was seen in 12 (9%) of vivax malaria. Chloroquine was most frequently used among antimalarial agents (in 123 cases, 65% of the total) for suppressing acute attacks. The efficacy of chloroquine was evaluated by classifying each case into three groups: chloroquine alone in group one, chloroquine in combination with other antimalarials in group two and other antimalarials except chloroquine in group three. The cure rate among each group is about 80% and there is no difference among them. However, it is noticeable that recurrence occurred when patients were treated with a combination of chloroquine and quinine. We have found a similar result as this in another old report in Japan. Primaquine is effective for eliminating hepatic tissue schizonts but in this study, relapse occurred in 12 cases of vivax, although primaquine had been used in 10 out of 12 cases. In primaquine group, relapse occurred at a similar rate between chloroquine and Fansidar cases. Further studies are needed to decide whether a larger dose of primaquine is appropriate for treatment of vivax malaria. Recovery periods from fever and parasitemia were compared between chloroquine and Fansidar cases.(ABSTRACT TRUNCATED AT 250 WORDS)


[Prediction of etiology based on the clinical type of convulsion in the neonatal period].
To determine whether the seizure clinical type is predictive of etiology. This is a prospective study from 9 neonatal and pediatric intensive care units. Neonatal seizures were defined clinically as described by Volpe. The seizures etiology was defined by positive clinical date, cranial sonogram and laboratory investigation routinely obtained in all neonates with seizures. Correlation between seizures type and etiologies was determined by Odds ration (OR). During one year 89 neonates develop neonatal seizures and the etiologies were determined. The mains seizures types were: subtle (n = 59; 66.3%), tonic (n = 27; 30.4%), clonic (n = 20; 22.4%), myoclonic (n = 4; 4.5%). The most frequent etiologies determined were: asphyxia (n = 60; 67.4%), hypocalcemia (n = 19; 21.3%), hypoglicemia (n = 14; 15.7%), peri-intraventricular hemorrhage (n = 13; 14%). The OR estimate that clonic seizures (OR 5.65 - 1.34 < OR < 23.61%) is predictive to peri-intraventricular hemorrhage. The OR estimate high risk to periventricular hemorrhage when the seizure is the clonic type. When the seizure is subtle type the risk is low to this etiology.


NuMA: a bipartite nuclear location signal and other functional properties of the tail domain.
Nuclear Mitotic Apparatus protein (NuMA) is a 238-kDa protein of the nuclear matrix in interphase that relocates to the spindle poles in mitosis. The globular tail domain (residues 1701 to 2115) contains the nuclear targeting sequence, the site for binding to the mitotic spindle as well as a site responsible for nuclear reformation. To more precisely map these sites, we inserted full-length human NuMA and 16 derivatives with increasing truncations of the tail domain into the pCMV5 vector and induced transient expression. NuMA was found in the interphase nucleus of all transfected BHK cells expressing either full-length NuMA or NuMA mutant proteins ending at or after residue 2005. In contrast, mutants ending at or before residue 2003 remained in the cytoplasm. In the full-length NuMA molecule, point mutations at position 1988 or 1989 or a double mutation at residues 2004 and 2005 cause NuMA to accumulate in the cytoplasm of both BHK and HeLa cells. The combined results indicate a bipartite nuclear location signal involving the sequences RKR (1987-1989) and KK (2004-2005) which are separated by 14 amino acid residues. In 30% of BHK cells transfected by the full-length clone, cytoplasmic aggregates of NuMA that colocalize with the centrosomes were documented in addition to the nuclear staining. In cells with large aggregates the cytoplasmic microtubular profile was disturbed. Observation of micronuclei formation suggests that a region important for normal nuclear reformation lies in the C-terminal 130 residues. Finally, NuMA mutant proteins ending at or after residue 1800 bound to the spindle poles of mitotic cells, while NuMA proteins ending at or before residue 1750 did not.


The Influence of Situational Cues on Children's Creativity in an Alternative Uses Task and the Moderating Effect of Selective Attention.
Taking a perception-action perspective, we investigated how the presence of different real objects in children's immediate situation affected their creativity and whether this effect was moderated by their selective attention. Seventy children between ages 9 and 12 years old participated. Verbal responses on a visual Alternative Uses Task with a low stimulus and high stimulus condition were coded on fluency, flexibility, and originality. Selective attention was measured with a visual search task. Results showed that fluency was not affected by stimulus condition and was unrelated to selective attention. Flexibility was positively associated with selective attention. Originality, net of fluency and flexibility, showed a main effect of stimulus condition in an unexpected direction, as children gave more original responses in the low stimulus condition compared to the high stimulus condition. A significant moderation effect revealed that children with better selective attention skills benefitted from a low stimulus environment, whereas children with weaker selective attention performed better in a high stimulus environment. The findings demonstrate differential effects of the immediate situation and selective attention, and support the hypothesis that creativity is impacted by immediate situation and selective attention, yet in unexpected ways.


[Status asthmaticus treated with inhaled isoflurane and intravenous isoproterenol].
We report the case of an 18-year-old man with status asthmaticus who was treated with inhaled isoflurane and intravenous isoproterenol. The patient was intubated and mechanical ventilation was began immediately after admission to the hospital. He received intravenous methylprednisolone and aminophyline, and frequent inhalation of isoproterenol aerosol. However, his respiratory status deteriorated: peak inspiratory pressure increased markedly, and right pneumothorax, right lower lobe atelectasis, and hypotension developed. He was then given isoflurane by inhalation and a continuous intravenous infusion of isoproterenol, which was followed by marked improvement in his respiratory and hemodynamic status. Isoflurane can be effective in patients with status asthmaticus, and it does not increase the arrhythmogenicity of catecholamines. Intravenous administration of isoproterenol can also be useful in the treatment of patients with status asthamticus. The combination of isoflurane with intravenous isoproterenol may be useful when status asthmaticus is hard to control with conventional therapy.