Detection and quantification of calcium fluoride using micro-Raman spectroscopy.
Investigations on the caries-preventive effect of calcium fluoride have been seriously hampered by the lack of adequate detection techniques. In this paper, the micro-Raman technique is introduced as a suitable method for CaF2 quantification with a spot size typically 5 microns. Advantages of this measuring technique and associated problems are described for CaF2 determination in the presence of large amounts of hydroxyapatite. The data show that a comparative analysis of Raman intensities of calcium fluoride and phosphate ions of hydroxyapatite can be used for quantification of CaF2 concentrations. The intensity behaviour of the CaF2 and hydroxyapatite Raman lines is explained considering the absorption-scattering cross-sections of the two components. The ratio of the Raman intensity (322 cm-1) of CaF2 to the phosphate Raman intensity (432/447 cm-1) of hydroxyapatite was found to be related linearly to the ratio of the concentration of CaF2 to that of hydroxyapatite. At present, the lower limit of CaF2 quantification is approximately 3 wt%. The technique has already been applied on fluoridated bovine enamel, and Raman emissions due to CaF2 or CaF2-like material formed on/in enamel have been detected for the first time.


[Lactoferrin and transferrin--iron-binding proteins in physiological and pathological vitreous bodies].
Having demonstrated transferrin (TF) and the TF receptor in periretinal membranes, we now present results of quantitative studies of TF and lactoferrin (LF), another protein with iron-binding properties. Normal human vitreous contains 74 +/- 7 mg/l TF, but less than 50 micrograms/l LF (ELISA). The TF levels determined in vitreous aspirates from patients with proliferative intraocular diseases [traumatic proliferative vitreoretinopathy (PVR), idiopathic PVR, and proliferative diabetic retinopathy (PDR)] were higher. A statistically significant difference between the levels in the vitreous in the three types of proliferative intraocular disease and in physiological vitreous was not observed. In contrary to TF, LF could not be labeled in surgically obtained membrane specimens using immunochemistry. Apparently LF does not have the same importance for cell proliferation in proliferative intraocular diseases as is suggested for TF.


Achronal generalized synchronization in mutually coupled semiconductor lasers.
Heil et al. [Phys. Rev. Lett. 86, 795 (2001)] recently discovered achronal synchronization of chaos in mutually coupled semiconductor lasers. This paper offers an analytic interpretation of their experiment using a simple rate equation model. Local eigenvalue analysis shows that isochronal synchronization is unstable; achronal synchronization, on the other hand, is stable if a generalized synchronization function is introduced. Single- and multimode simulations have substantiated this rate equation interpretation. Finally, there is a brief examination of "chaos pass filtering."


Structural and functional properties of the TRK family of neurotrophin receptors.
The Trk family of tyrosine-protein kinases, TrkA, TrkB, and TrkC, are the signaling receptors that mediate the biological properties of the NGF family of neurotrophins. This family of growth factors includes in addition to NGF, BDNF, NT-3, and NT-4. TrkA is the NGF receptor. TrkB serves as a receptor for both BDNF and NT-4, and TrkC is the primary receptor for NT-3. NT-3 is a somewhat promiscuous ligand that can also activate TrkA and TrkB receptors at high concentrations. The trkB and trkC genes also encode noncatalytic receptor isoforms of an, as yet, unknown function. In addition to the Trk receptors, the NGF family of neurotrophins also binds with low affinity to an unrelated molecule, designated p75, a member of the TNF-receptor superfamily. Recently, we have generated strains of mice lacking each of these tyrosine-kinase receptors by gene targeting in embryonic stem cells. Characterization of these mutant mice is providing relevant information regarding the critical role that these receptors play in the ontogeny of the mammalian nervous system.


Integration of piezo-capacitive and piezo-electric nanoweb based pressure sensors for imaging of static and dynamic pressure distribution.
Recently, highly flexible and soft pressure distribution imaging sensor is in great demand for tactile sensing, gait analysis, ubiquitous life-care based on activity recognition, and therapeutics. In this study, we integrate the piezo-capacitive and piezo-electric nanowebs with the conductive fabric sheets for detecting static and dynamic pressure distributions on a large sensing area. Electrical impedance tomography (EIT) and electric source imaging are applied for reconstructing pressure distribution images from measured current-voltage data on the boundary of the hybrid fabric sensor. We evaluated the piezo-capacitive nanoweb sensor, piezo-electric nanoweb sensor, and hybrid fabric sensor. The results show the feasibility of static and dynamic pressure distribution imaging from the boundary measurements of the fabric sensors.


Antipsychotic effects of verapamil in schizophrenia.
The antipsychotic effects of verapamil were tested in a double-blind, placebo-controlled, randomized study in 18 patients who met Research Diagnostic Criteria for acute schizophrenia. The antipsychotic effect of verapamil as measured by the Bunney-Hamburg Global Rating Scale were equal to those of haloperidol. Both verapamil and haloperidol were superior to placebo in decreasing psychotic symptoms. The results indicate that verapamil may have clinical utility in the treatment of schizophrenia.


Weight gain with olanzapine: Drug, gender or age?
The introduction of atypical antipsychotics was a big step forward in the treatment of schizophrenia and other psychoses. Their limitations, however, became evident over time. To study the causes of weight gain associated with the use of olanzapine-an atypical antipsychotic drug. Eighty patients fulfilling the ICD-10 criteria for schizophrenia, predominantly with negative symptoms, were included in this study to evaluate weight gain as an adverse effect of treatment with olanzapine in relation to age, gender, dose and body mass index (BMI). Sociodemographic data and baseline weight along with height (to calculate the BMI) were recorded before the initiation of treatment. The patients were administered a flexible dose of olanzapine (5-15 mg) as monotherapy. Pregnant patients, smokers and those with endocrine disorders, cardiac problems and organic brain dysfunction were excluded from the study. The increase in weight as a neuroleptic side-effect of olanzapine was recorded and analysed in relation to age, gender, dose and BMI. Of the patients receiving olanzapine, 66.6% had a weight gain of 1-5 kg over a period of 4 weeks. The weight gain was not related to the dose of the drug or BMI. The interesting finding was that the increase in weight was significantly related to age >/=40 years and female sex, indicating that women >/=40 years of age are more prone to gain weight with olanzapine therapy in comparison with women <40 years and men of any age group. The potential for weight gain associated with the use of atypical antipsychotics to cause long-term complications will need further study. Clinicians are encouraged to monitor weight, plasma glucose and leptin levels, and lipid parameters in patients receiving olanzapine.


Analysis of hydration and subchondral bone density on the viscoelastic properties of bovine articular cartilage.
Articular cartilage is known to be a viscoelastic material, however little research has explored the impact of cartilage water content and bone density on its viscoelasticity. This study aimed to isolate subchondral bone density and hydration of articular cartilage and analyse their effects on the viscoelastic properties of articular cartilage. Dynamic mechanical analysis was used to test samples at frequencies of 1, 8, 12, 29, 49, 71, and 88 Hz. Synthetic bone material with densities of 663.7 kg/m3 and 156.8 kg/m3 were used to mimic the bone mineral density (BMD). Dehydration occurred in a stepwise manner at relative humidity (RH) levels of 100%, 30%, and 1%. These relative humidity levels led to water contents of approximately 76%, 8.5%, and ≈ 0% by mass, respectively. Samples from eight bovine femoral heads were tested under a sinusoidal load. Storage stiffness was lower on the lower substrate density. Storage stiffness, though, increased as cartilage samples were dehydrated from a water content of 76% to 8.5%; decreasing again as the water content was further reduced. Loss stiffness was lower on a lower density substrate and decreased as the water content decreased. In conclusions, a decrease in hydration decreases the loss stiffness, but a non-linear relationship between hydration and storage stiffness may exist. Additionally, higher BMD values led to greater storage and loss stiffnesses.


Sex-related differences in outcome after endovascular revascularization for lower extremity artery disease.
Background: Sex-related differences may influence the outcome of endovascular revascularization (EVR) in patients with lower extremity arterial disease (LEAD) even under optimized healthcare supply. Patients and methods: LEAD patients who underwent EVR at the Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Germany between 2014 and 2016 were included into the retrospective study. Detailed information on risk factors and co-morbidities, medication, LEAD related measures, and interventional parameters were assessed. Outcome defined as technical success rate, complications, and mortality was analyzed up to 12 months follow-up. Results: In total, 165 female and 437 male LEAD patients were included. Women and men presented with comparable severity of LEAD in terms of critical limb threatening ischemia (46.2%), wound status (34.9%), and amputation rate (9.6%, all n.s.) at index. Intake of platelet inhibitors (65.8% female vs. 70.0% male), oral anticoagulants (21.3% vs. 25.4%), and statins (65.6% vs. 76.0%) was observed less frequently in female patients. Against the background of high technical success (85%), in-hospital death (0.8%), severe adverse cardiac (MCE; 1.7%), and limb events (MALE; 6.1%) occurred at low rates in either sex. Adjusted long-term mortality was not affected by patients' sex (female HR 0.755; p=0.312). Conclusions: Despite critical LEAD stages in every second patient, EVR was performed safe with high technical success rates in female and male patients. Long-term outcomes were observed at comparatively low rates in both sexes at the specialized vascular center. During aftercare, supply with statin therapy turned out improvable particularly in female LEAD patients.


[Analysis of clinical costs for inpatients with the urologic diseases in 1997].
Because of recent increases in health care costs, reformation care cost system similar to the disease related group/prospective payment system (DRG/PPS) was attracted attention in Japan. We analyzed the costs for inpatients with urologic diseases in our institution and compared them with the costs reported in Japanese trials of DRG/PPS. Subject consisted of 363 consecutive urologic diseases inpatients treated in our hospital in the period between April 1 1997 and March 31 1998. Of these 107 had bladder tumor, 79 BPH (benign prostatic hyperplasia), 34 prostate tumor, 32 renal tumor, 17 in urinary stone (excluding cases with bladder stones) and 94 cases in others. The total hospital charge for each case was calculated, and the averages and standard deviations for each disease were analyzed. We analyzed the relationship between hospital charges for each disease, and complications, the degree of disease, age and length of stay (LOS). Health care costs are assessed in unit, each of which is the equivalent of 10 yen. The average of total hospital charges was 108,841.6 points for bladder tumor, 61,692.2 points for BPH, 96,825.3 points for prostate tumor, 188,459.0 points for renal tumor, and 66,052.2 points for urinary stones. The standard deviation was 99,611.3 points for bladder tumors, 16,712.9 points for BPH, 65,419.3 points for prostate tumor, 204,389.6 points for renal tumor and 30,081.7 points for urinary stone. There was a positive correlation between hospital charge and LOS in most diseases. The average hospital charges for each disease were much higher than the reimbursement charges of the trial Japanese DRG/PPS. Shortening of LOS using established clinical pathways reduces health care costs. However, in Japan, the wide range of preliminary results suggests that it may be too early to introduce the DRG/PPS system for health care cost. Furthermore nationwide investigations are needed before the introduction of the DRG/PPS system into Japanese health care reimbursement system.


Exploring the role and capacity of school teachers in Zambia to support orphans and vulnerable children: considerations for educational resource allocation in Lusaka, Zambia.
This study investigated teachers' perceptions of their role as HIV/AIDS educators and also their role in providing care for orphans and vulnerable children (OVC) across the different school systems in Lusaka, Zambia. Researchers used a combined quantitative and qualitative narrative approach. Original cross-sectional data were collected through face-to-face survey and in-depth interviews with school teachers in the Lusaka. A sample of 720 teachers from 123 schools completed surveys in 2008, with a 91% response rate for teachers, and 100% for schools sampled. Teachers for all school types reported that schools and teachers are the appropriate community resource for HIV-prevention education for youth and support for OVC. This study suggests that schools could serve as a source and alternative mechanism of support for vulnerable children.


A simple way to plan implant positioning: the "S-technique".
This study presents a technique for improving implant placements. As is widely known, a correct positioning is essential in restoration-driven implants, as well as in tilted implants in order to obtain satisfactory final functional and esthetic results. To this end, some authors have emphasized the importance of using a diagnostic and/or surgical guide to plan the exact implant position. In practice, one of the clinical problems faced is how to check the accuracy of the template prior to initiating the surgical phase. A simple method called the "S-Technique" is proposed in order to evaluate and to change, if necessary, the projected position of the implants by way of metal rods as radiopaque markers. This device is easy to produce and is cost-saving to the clinician and, therefore, to the patient. Furthermore, in specific patients, this method could also decrease the need for computerized tomography scans and/or radiographs, thus reducing health risks for the patient.


Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis.
Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.


Corticotropin-releasing hormone directly activates noradrenergic neurons of the locus ceruleus recorded in vitro.
The neuropeptide corticotropin-releasing hormone (CRH) activates locus ceruleus (LC) neurons, thereby increasing norepinephrine levels throughout the CNS. Despite anatomical and physiological evidence for CRH innervation of the LC, the mechanism of CRH-evoked activation of LC neurons is unknown. Moreover, given the apparent absence of mRNA for CRH receptors in LC neurons, the exact location of action of CRH within the cerulear region is debated. Using in vitro intracellular recordings from rat brainstem, we examined whether CRH exerts a direct effect on LC neurons and which ionic currents are likely affected by CRH. We demonstrate that CRH dose-dependently increases the firing rate of LC neurons through a direct (TTX- and cadmium-insensitive) mechanism by decreasing a potassium conductance. The CRH-evoked activation of LC neurons is, at least in part, mediated by CRH1 receptors and a cAMP-dependent second messenger system. These data provide additional support that CRH functions as an excitatory neurotransmitter in the LC and the hypothesis that dysfunction of the CRH peptidergic and noradrenergic systems observed in patients with mood and anxiety disorders are functionally related.


Protein kinase Cδ inactivation inhibits cellular proliferation and decreases survival in human neuroendocrine tumors.
The concept of targeting cancer therapeutics toward specific mutations or abnormalities in tumor cells, which are not found in normal tissues, has the potential advantages of high selectivity for the tumor and correspondingly low secondary toxicities. Many human malignancies display activating mutations in the Ras family of signal-transducing genes or over-activity of p21(Ras)-signaling pathways. Carcinoid and other neuroendocrine tumors have been similarly demonstrated to have activation of Ras signaling directly by mutations in Ras, indirectly by loss of Ras-regulatory proteins, or via constitutive activation of upstream or downstream effector pathways of Ras, such as growth factor receptors or PI(3)-kinase and Raf/mitogen-activated protein kinases. We previously reported that aberrant activation of Ras signaling sensitizes cells to apoptosis when the activity of the PKCδ isozyme is suppressed and that PKCδ suppression is not toxic to cells with normal levels of p21(Ras) signaling. We demonstrate here that inhibition of PKCδ by a number of independent means, including genetic mechanisms (shRNA) or small-molecule inhibitors, is able to efficiently and selectively repress the growth of human neuroendocrine cell lines derived from bronchopulmonary, foregut, or hindgut tumors. PKCδ inhibition in these tumors also efficiently induced apoptosis. Exposure to small-molecule inhibitors of PKCδ over a period of 24 h is sufficient to significantly suppress cell growth and clonogenic capacity of these tumor cell lines. Neuroendocrine tumors are typically refractory to conventional therapeutic approaches. This Ras-targeted therapeutic approach, mediated through PKCδ suppression, which selectively takes advantage of the very oncogenic mutations that contribute to the malignancy of the tumor, may hold potential as a novel therapeutic modality.


A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study.
Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63.98%) and 191 patients (66.8%) had a thrombophilia marker. Eighty nine (46.6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61.8% of patients with high risk of VTE. Among them, 37.7% were treated in the third trimester only and 24.1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0.35%) and two postpartum-related VTE (0.7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0.35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.


Mechanisms of protective immunity against S. mansoni infection in mice vaccinated with irradiated cercariae. VI. Influence of the major histocompatibility complex.
Inbred mouse strains develop different levels of resistance to challenge infection with Schistosoma mansoni in response to vaccination with irradiated cercariae. The role of the major histocompatibility complex (MHC) in determining this genetic polymorphism in acquired resistance was investigated. Previous studies suggested that inbred mice bearing either the b or d MHC haplotypes develop a higher level of vaccine induced resistance than do mice with other MHC haplotypes. An analysis of an F1 cross between an H-2b strain (C57BL/6) and an H-2k strain (C3H/HeJ) indicated that the ability to develop high levels of immunity is inherited in a dominant fashion. In order to confirm that the development of high resistance is an MHC associated trait, B10, C3H, BALB and B6 congenic mice bearing different H-2 haplotypes were compared. On either the B10, B6, or BALB background, substitution of b or d with k or a MHC alleles resulted in a decreased level of vaccine induced immunity. The observed decreases were more pronounced in BALB and B6 than in B10 congenics suggesting an influence of background (non-MHC linked) genes on protective immunity. Similarly, C3H.SW (H-2b) mice developed a significantly higher level of acquired resistance than C3H/HeSn (H-2k) mice. Cross and backcross experiments between H-2b and H-2k B6 congenic mice confirmed the dominant inheritance of high resistance as well as the MHC linkage of the trait. These data indicate that the MHC locus exerts a quantitative influence on vaccine induced resistance in certain inbred mouse strains and provide further support for the concept that the protection elicited by irradiated cercariae is the manifestation of a specific host immune response.


Comparing staple fixation to buttress plate fixation in high tibial osteotomy.
A retrospective study was made between July 1988 and March 1992, of 171 patients (223 knees) who had high tibial osteotomy at the Singapore General Hospital. Seventy-four cases (97 knees) had buttress plate fixation and 97 cases (126 knees) had staple fixation. The mean postoperative Hospital for Special Surgery Knee Score was 87.0 for the buttress plate group and 87.4 for the staple group. The difference was statistically not significant (P > 0.05). The hospitalisation stay was shorter in the staple fixation group as compared to the buttress plate group (P < 0.05). However, the mean rehabilitation time was shorter in the buttress plate group as compared to the staple fixation group (P < 0.05). The incidence of wound infection was higher among those fixed with buttress plate (9 cases) as compared to those fixed with staple (1 case). The difference was statistically significant (P < 0.05). Buttress plate fixation did not seem to eliminate the risk of non-union of the osteotomy (4 out of 126 osteotomies compared to 3 out of 97 in the staple group), neither did it prevent recurrence of varus deformity (2 out of 126 osteotomies). Overall it would appear that buttress plating did not have any significant advantage over staple fixation for high tibial osteotomy.


Provider-controlled or user-dependent contraceptive methods: Levels and pattern among married women of reproductive age in China, 1988-2006.
To explore levels and patterns in contraceptive use since the introduction of informed choice in reproductive health services in China since 1994, and to assess the implications of reproductive health service needs among married women of reproductive age in China. Data from Chinese nationwide surveys of family planning and reproductive health undertaken in 1988, 1997, 2001, and 2006 were analyzed to assess levels and trends in patterns of contraceptive use among married women by age, residence, and number of children. Contraceptive methods were classified into two categories: provider-controlled and user-dependent methods. The provider-controlled pattern for contraceptive use was predominant regardless of whether women were free to choose their own contraceptives. Older, rural women, and those with more than one child preferred provider-controlled contraceptive methods; this trend has changed little after 1997. In contrast, the user-controlled methods were preferred by young, urban women, strikingly with no or only one child, and geographically in more affluent areas in north or southwest China. A preference for user-dependent methods is noted in the urban areas but inclination towards provider-controlled contraceptive methods is still prevalent in rural areas in China.


Hospital quality improvement activities and the effects of interventions on pneumonia: a multistate study of Medicare beneficiaries.
This article evaluates the relative effectiveness of quality improvement interventions on increasing the time to antibiotic administration after a diagnosis of pneumonia. Clinical data were abstracted from the medical records of 17,040 Medicare beneficiaries discharged from one of 215 acute-care hospitals across 15 states. Thirteen Quality Improvement Organizations collected data on hospital quality improvement interventions from each hospital in this study. Medicare discharges between January 1997 and January 2002 define the study period. Most hospitals implemented multiple interventions to improve pneumonia care. Only 3 individual interventions were found to be effective in increasing time to antibiotic administration. Data feedback and benchmarking and medical records checklists had a positive effect on time to antibiotic administration. Administrative support by itself had a negative effect on the quality indicator. Although several combinations of interventions were also found effective, generalizations about the use of multiple interventions in quality improvement are difficult to make from retrospective studies.


Protective Behavioral Strategies and Alcohol Use While Pregaming: The Moderating Role of Depression and Anxiety Symptoms.
The study evaluated the moderating role of anxiety and depression symptoms on the association between subscales on the Protective Behavioral Strategies for Pregaming (PBSP) scale (safety and familiarity, setting drink limits, pacing drinking, and minimizing intoxication) and alcohol consumption during pregaming. Methods: Participants were 359 traditional age undergraduate college students (M = 20, SD = 1.37; 61.7% female; 61.2% White) who reported pregaming in the past year. All participants completed measures through an online survey which evaluated PBSP, depression and anxiety symptoms, and alcohol use during pregame events in the past month. Results: Among students with high depression symptoms, the more frequent use of PBSP to minimize intoxication was not associated with alcohol consumption levels, whereas among those with low depression symptoms, higher use of PBSP to minimize intoxication was associated with higher alcohol consumption. Among those with high anxiety symptoms, the more frequent use of PBSP to minimize intoxication was associated with lower alcohol consumption at pregaming events, whereas among those with low anxiety symptoms, the use of this PBSP was associated with higher alcohol consumption. The more frequent use of PBSP related to safety and familiarity among those with high anxiety symptoms was unrelated to alcohol consumption during pregaming, whereas among those low in anxiety symptoms, the more frequent use of this PBSP was associated with lower alcohol consumption. Conclusion: The findings begin to inform clinical care and intervention techniques aimed at reducing harm associated with risky drinking practices among a vulnerable subset of college students.


Attentional load classification in multiple object tracking task using optimized support vector machine classifier: a step towards cognitive brain-computer interface.
Cognitive brain-computer interface (cBCI) is an emerging area with applications in neurorehabilitation and performance monitoring. cBCI works on the cognitive brain signal that does not require a person to pay much effort unlike the motor brain-computer interface (BCI) however existing cBCI systems currently offer lower accuracy than the motor BCI. Since attention is one of the cognitive signals that can be used to realise the cBCI, this work uses the multiple object tracking (MOT) task to acquire the desired electroencephalograph (EEG) signal from healthy subjects. The main objective of the paper is to explore the preliminary applications of support vector machine (SVM) classifier to classify the attentional load in multiple object tracking task. Results show that the attentional load can be classified using SVM with sensitivity, specificity, and accuracy of 94.03%, 92.50%, and 93.28%, respectively using the spectral entropy EEG feature. The classification performance promises the potential application of the current approach in the cognitive brain-computer interface for neurorehabilitation.


Possible involvement of protein-tyrosine kinases such as p72syk in the disc-sphere change response of porcine platelets.
We previously reported that p72syk, a non-receptor tyrosine kinase, was activated maximally at 10 s after thrombin or thromboxane A2 stimulation, even in platelets that were not allowed to aggregate [Taniguchi et al. (1993) J. Biol. Chem. 268, 2277-2279; Maeda et al. (1993) Biochem. Biophys. Res. Commun. 197, 62-67]. Then, the change in the shape of porcine platelets induced by the thromboxane A2 analogue, STA2, and the role of protein-tyrosine kinases including p72syk in this response were evaluated, using the shape-change parameter. We show that p72syk activation is correlated with the disc-sphere change in a time- and dose-dependent manner following stimulation by STA2. Tyrphostin B44, a potent protein-tyrosine kinase inhibitor, reduced the thromboxane A2-evoked p72syk activation and the disc-sphere change in a dose-dependent manner. Furthermore, the translocation of p72syk to the cytoskeleton-rich fraction and an increase in the tyrosine phosphorylation of an about 120 kDa protein were observed during the disc-sphere change induced by STA2. These lines of evidence suggest that the activation of protein-tyrosine kinases such as p72syk may be involved in the disc-sphere change response in thromboxane A2-stimulated porcine platelets.


Smoking, antihypertensive treatment benefit, and comprehensive antihypertensive treatment approach: some thoughts on the results of the International Prospective Primary Prevention Study in Hypertension.
Several major studies investigated the possibility of a primary preventive effect of beta-blockers. The International Prospective Primary Prevention Study in Hypertension (IPPPSH) compared a beta-blocker-containing vs. a non-beta-blocker-containing antihypertensive regimen in 6,357 moderate-severe hypertensive men and women treated over 3-5 years. Blood pressure (BP) control was comparable with either regimen. beta-Blocker treatment was associated with less hypokalemia, earlier electrocardiogram normalization, and fewer withdrawals for uncontrolled hypertension. In agreement with the Medical Research Council (MRC) trial on mild hypertension and the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial, but at variance with the Primary Prevention Metoprolol in Patients with Hypertension (MAPHY) study, cardiac event rates were similar in beta-blocker- and non-beta-blocker-treated patients. With either regimen, in-study BP reduction was associated with a lower rate of stroke as well as of cardiac events. In a subgroup analysis, nonsmokers appeared to derive beta-blocker benefit, the results being similar to those of the MRC. Smokers required higher doses of drugs to achieve diastolic target pressure, had a higher heart rate and hematocrit, and a higher cardiac event rate than nonsmokers at any given level of diastolic pressure. Except for the MAPHY trial, these primary prevention studies do not support the concept of a cardiac primary preventive effect of antihypertensive beta-blockade but stress the importance of good BP control and a comprehensive risk factor prevention approach in the management of hypertensive patients.


The electrophysiological correlates of recent and remote recollection.
Research using event related potentials (ERPs) to explore recognition memory has linked late parietal old/new effects to the recollection of episodic information. In the vast majority of these studies, the retrieval phase immediately follows encoding and consequently, very little is known about the ERP correlates of long term recollection. This is despite the fact that in other areas of the memory literature there is considerable interest in consolidation theories and the way episodic memory changes over time. The present study explored the idea that consolidation and forgetting processes operating over a moderate retention interval can alter the ERP markers of recollection memory. A remember/know test probed memory for stimuli studied either 15 minutes (recent memory) or 1 week (remote memory) prior to the test phase. Results revealed an attenuated late parietal effect for remote compared to recent remember responses, a finding that remained significant even when these recognition judgments were matched for reaction time. Experiments 2a and 2b identified characteristic differences between recent and remote recognition at the behavioural level. The 1 week delay produced an overall decline in recognition confidence and a dramatic loss of episodic detail. These behavioural changes are thought to underlie the ERP effects reported in the first experiment. The results highlight that although the neural basis of memory may exhibit significant changes as the length of the retention interval increases, it is important to consider the extent to which this is a direct effect of time or an indirect effect due to changes in memory quality, such as the amount of detail that can be recollected.


Impact of cyclosporine A on magnesium homeostasis: clinical observation in lung transplant recipients and experimental study in mice.
Hypomagnesemia is a common finding in patients receiving cyclosporine A (CsA) therapy. The relationship between CsA-induced hypomagnesemia and nephrotoxicity and the effects of oral magnesium (Mg) supplementation remain unclear. After a retrospective analysis of the time-course of plasma Mg and creatinine levels in lung allograft recipients treated with both CsA and oral Mg supplementation, we investigated the effects of CsA treatment on Mg homeostasis in mice with normal or Mg-deficient diet and the effects of oral Mg supplementation on plasma Mg levels. Thirty lung-allograft recipients entered the retrospective study. One thousand two hundred twenty-eight blood samples were analyzed for blood and creatinine levels. Cyclosporine A (50 mg/kg/day by intraperitoneal injection) was administered to mice maintained on normal diet (1400 ppm) or Mg-deficient (50 ppm) diet. Magnesium levels were determined in plasma, urine, feces and femur, and creatinine levels were determined in plasma and urine. Plasma Mg concentration declines from the day of transplantation in 36.7% of the patients despite Mg supplementation, without correlation with creatinine changes. In mice, CsA induced an early moderate hypomagnesemia, which could not be ameliorated by oral Mg supplementation and was aggravated by low-Mg dietary, late increase in plasma creatinine and decrease in urine creatinine without histological signs of renal injury, decrease in intestinal Mg absorption and Mg mobilization from bone. Cyclosporine A treatment may induce moderate hypomagnesemia that is aggravated by inadequate Mg intake and is not ameliorated by Mg supplementation. Because of the clinical complications of hypomagnesemia, Mg should be monitored regularly in allograft recipients receiving CsA.


Transformation of methylotrophic yeast Hansenula polymorpha: cloning and expression of genes.
We developed a host-vector system for transformation and gene cloning experiments using the methylotrophic yeast Hansenula polymorpha. Regeneration of protoplasts in a medium containing polyethylene glycol before plating made transformation more efficient and reproducible (2 to 3 x 10(4) micrograms DNA). The frequency of transformation was significantly lower when dominant resistance marker Cup1r was used for transformant selection. The transformation system developed was used to clone the DNA fragment which complements functionally the defect in the dihydroxyacetone kinase (DHAK*) activity of a H. polymorpha mutant strain. The DNA insert isolated was shown to increase by up to ten times the activity of DHAK in transformants carrying recombinant plasmids. When recombinant plasmids were introduced into S. cerevisiae, the transformants obtained acquired the ability to grow on the medium with dihydroxyacetone as a sole carbon source and the activity of DHAK was observed.


Histamine H-2 receptor stimulation and inhibition of pepsin secretion in the dog.
Although low doses of histamine (less than 150 nM/kg.hr) stimulate pepsin secretion, higher doses inhibit pepsin secretion in a dose-dependent manner. To better histamine stimulation of pepsin, histamine was used at doses at the lower end of the dose-response scale in five dogs with gastric fistula. Five doses of histamine below the ED50 for acid, viz, 9, 22.5, 67.5, 90 and 112 nM/kg.hr in 45-min steps, provided values for pepsin secretion from which Ed50 = 11.4 nmol/kg.hr (i.e., about 1/12 the ED50 for acid) and calculated maximum 22,600 peptic U/30 min were calculated. To document the inhibition, pepsin secretion was first stimulated by an infusion of bethanechol (0.4 mumol/kg.hr). A super-added injection of the histamine H-2 agonist 4-methylhistamine (0.4 or 0.8 mumol/kg) produced strong additional acid stimulation and immediate 40% suppression of pepsin secretion. The ratio pepsin/acid was reduced to one-third of control for the 90 min after 4-methylhistamine. The most specific H-2 agonist impromidine had the same effects, whereas pentagastrin (1.95 nmol/kg) inhibited both acid and pepsin secretion stimulated by bethanechol. The specificity of H-2 effect of impromidine was confirmed by simultaneous tachycardia and hypotension; pentagastrin did not produce cardiovascular effects. These studies confirm the unique effect of histamine on the peptic cell of the dog in which both stimulation and inhibition are H-2 receptor-mediated effects.


Ubiquitin fusion expression and tissue-dependent targeting of hG-CSF in transgenic tobacco.
Human granulocyte colony-stimulating factor (hG-CSF) is an important human cytokine which has been widely used in oncology and infection protection. To satisfy clinical needs, expression of recombinant hG-CSF has been studied in several organisms, including rice cell suspension culture and transient expression in tobacco leaves, but there was no published report on its expression in stably transformed plants which can serve as a more economical expression platform with potential industrial application. In this study, hG-CSF expression was investigated in transgenic tobacco leaves and seeds in which the accumulation of hG-CSF could be enhanced through fusion with ubiquitin by up to 7 fold in leaves and 2 fold in seeds, leading to an accumulation level of 2.5 mg/g total soluble protein (TSP) in leaves and 1.3 mg/g TSP in seeds, relative to hG-CSF expressed without a fusion partner. Immunoblot analysis showed that ubiquitin was processed from the final protein product, and ubiquitination was up-regulated in all transgenic plants analyzed. Driven by CaMV 35S promoter and phaseolin signal peptide, hG-CSF was observed to be secreted into apoplast in leaves but deposited in protein storage vacuole (PSV) in seeds, indicating that targeting of the hG-CSF was tissue-dependent in transgenic tobacco. Bioactivity assay showed that hG-CSF expressed in both seeds and leaves was bioactive to support the proliferation of NFS-60 cells. In this study, the expression of bioactive hG-CSF in transgenic plants was improved through ubiquitin fusion strategy, demonstrating that protein expression can be enhanced in both plant leaves and seeds through fusion with ubiquitin and providing a typical case of tissue-dependent expression of recombinant protein in transgenic plants.


cAMP-induced switching in turning direction of nerve growth cones.
Development of the nervous system depends on the correct pathfinding and target recognition by the growing tip of an axon, the growth cone. Diffusible or substrate-bound molecules present in the environment may serve as either attractants or repellents to influence the direction of growth-cone extension. Here we report that differences in cyclic-AMP-dependent activity in a neuron may result in opposite turning of the growth cone in response to the same guidance cue. A gradient of brain-derived neurotrophic factor normally triggers an attractive turning response of the growth cone of Xenopus spinal neurons in culture, but the same gradient induces repulsive turning of these growth cones in the presence of a competitive analogue of cAMP or of a specific inhibitor of protein kinase A. This cAMP-dependent switch of the turning response was also found for turning induced by acetylcholine, but not for the turning induced by neurotrophin-3 (NT-3). Thus, in the presence of other factors that modulate neuronal cAMP-dependent activity, the same guidance cue may trigger opposite turning behaviours of the growth cone during its pathfinding in the nervous system.


The clinical and financial impact of non-invasive vascular testing in the USA.
Health care costs in the USA have increased dramatically during the past 10 years, and it is widely believed that they have reached crisis dimensions. Vascular laboratories are a segment of the USA health care industry that has experienced particularly rapid growth in the last decade. In 1992, USA Medicare payments (for patients > or = 65 years) totalled US$304,492,588 for 3,673,695 non-invasive vascular studies. This figure represents only one segment of USA health care costs and, if all segments were considered, the 1992 total for vascular laboratory services would probably approach one billion USA dollars. The expansion of vascular laboratory utilization is attributed to a number of factors: (i) increased recognition of the clinical value of non-invasive vascular studies; (ii) replacement of invasive (angiographic) procedures; (iii) expanded surveillance application; (iv) the verification of carotid endarterectomy for treatment of carotid stenosis; (v) widespread, unlimited access; (vi) over-utilization; (vii) greed. Widespread awareness of the crisis in USA health care funding has imposed cost-containment pressure where virtually none existed previously. The vascular laboratory is no exception to this trend, and the following measures have been suggested for controlling vascular laboratory costs: (i) demonstration of the clinical and cost effectiveness of non-invasive vascular studies; (ii) utilization review; (iii) pre-approval of requests for vascular studies; (iv) linkage of vascular study reimbursement with clinical diagnosis; (v) limitations on self-referral; (vi) reduced reimbursement; (vii) capitation; (viii) diagnosis-related reimbursement; (ix) accreditation. This article summarizes the factors that have led to increased utilization of vascular laboratory services, and discusses methods proposed for containing vascular laboratory expenditure.


Risk factors for perioperative acute kidney injury after adult cardiac surgery: role of perioperative management.
The development of acute kidney injury (AKI) after adult cardiac surgery is associated with increased morbidity and mortality. Our aim was to assess the risk factors for postoperative AKI and whether the addition of perioperative management variables can improve AKI prediction. We studied 3,219 patients operated from January 2006 to December 2009. The AKI was defined as proposed by the Acute Kidney Injury Network. Patient preoperative characteristics, as well as intraoperative, cardiopulmonary bypass (CPB), and postoperative management variables, were evaluated for association with AKI with logistic regression analysis. The model including all variables was assessed first, then separate models including only preoperative variables followed by the sequential addition of intraoperative, CPB, and postoperative management variables were tested; receiver operating characteristic analysis was used to evaluate and compare models' discriminatory power. The AKI occurred in 288 of 3,219 patients (8.9%). Logistic regression analysis identified 15 predictors of AKI; 4 were preoperative (age, diabetes, smoking, and serum creatinine), 4 intraoperative (inotropes, erythrocytes transfusion, cross-clamp time, and need of a new pump run), 2 CPB-related (urine output and furosemide administration during CPB), and 5 postoperative (erythrocytes transfusion, administration of vasoconstrictors, inotropes, diuretics, and antiarrhythmics). Model-discrimination performance improved from an area under the curve of 0.830 (95% confidence interval 0.807 to 0.854) for the model including only preoperative variables to an area under the curve of 0.904 (95% confidence interval 0.886 to 0.921) for the model including all variables (p<0.001). Several factors influence AKI development after cardiac surgery and perioperative patient management significantly affects AKI occurrence. Predictive models can be sensibly improved by the addition of these variables.


Percutaneous management of ureteral injuries that are diagnosed late after cesarean section.
We wanted to present the results of percutaneous management of ureteral injuries that were diagnosed late after cesarean sections (CS). Twenty-two cases with 24 ureteral injuries that were diagnosed late after CS underwent percutaneous nephrostomy (PN), antegrade double J (DJ) catheter placement and balloon dilatation or a combination of these. The time for making the diagnosis was 21 +/- 50.1 days. The injury site was the distal ureter in all cases (the left ureter: 13, the right ureter: 7 and bilateral: 2). Fifteen complete ureteral obstructions were detected in 13 cases. Ureteral leakage due to partial (n = 4) or complete (n = 3) rupture was noted in seven cases. Two cases had ureterovaginal fistula. All the cases were initially confirmed with antegrade pyelography and afterwards they underwent percutaneous nephrostomy. Balloon dilatation was needed in three cases. Antegrade DJ stents were placed in 10 cases, including the three cases with balloon dilatation. Repetition of percutaneous nephrostomy with balloon dilatation and DJ stent placement was needed in one case with complete obstruction. All the cases were followed-up with US in their first week and then monthly thereafter for up to two years. Eighteen ureters (75%) were managed by percutaneous procedures alone. A total of six ureter injuries had to undergo surgery (25%). Percutaneous management is a good alternative for the treatment of post-CS ureteral injuries that are diagnosed late after CS. Percutaneous management is at least preparatory for a quarter of the cases where surgery is unavoidable.


The Ca-Transport ATPase of Plant Plasma Membrane Catalyzes a nH/Ca Exchange.
Microsomal vesicles from 24-hour-old radish (Raphanus sativus L.) seedlings accumulate Ca(2+) upon addition of MgATP. MgATP-dependent Ca(2+) uptake co-migrates with the plasma membrane H(+)-ATPase on a sucrose gradient. Ca(2+) uptake is insensitive to oligomycin, inhibited by vanadate (IC(50) 40 micromolar) and erythrosin B (IC(50) 0.2 micromolar) and displays a pH optimum between pH 6.6 and 6.9. MgATP-dependent Ca(2+) uptake is insensitive to protonophores. These results indicate that Ca(2+) transport in these microsomal vesicles is catalyzed by a Mg(2+)-dependent ATPase localized on the plasma membrane. Ca(2+) strongly reduces DeltapH generation by the plasma membrane H(+)-ATPase and increases MgATP-dependent membrane potential difference (Deltapsi) generation. These effects of Ca(2+) on DeltapH and Deltapsi generation are drastically reduced by micromolar erythrosin B, indicating that they are primarily a consequence of Ca(2+) uptake into plasma membrane vesicles. The Ca(2+)-induced increase of Deltapsi is collapsed by permeant anions, which do not affect Ca(2+)-induced decrease of DeltapH generation by the plasma membrane H(+)-ATPase. The rate of decay of MgATP-dependent DeltapH, upon inhibition of the plasma membrane H(+)-ATPase, is accelerated by MgATP-dependent Ca(2+) uptake, indicating that the decrease of DeltapH generation induced by Ca(2+) reflects the efflux of H(+) coupled to Ca(2+) uptake into plasma membrane vesicles. It is therefore proposed that Ca(2+) transport at the plasma membrane is mediated by a Mg(2+)-dependent ATPase which catalyzes a nH(+)/Ca(2+) exchange.


COVID-19 Vaccine Willingness and Hesitancy Among Marshallese Pacific Islanders.
COVID-19 has disproportionally burdened racial and ethnic minorities. Minority populations report greater COVID-19 vaccine hesitancy; however, no studies document COVID-19 vaccine willingness among Marshallese or any Pacific Islander group, who are often underrepresented in research. This study documents United States (US) Marshallese Pacific Islanders': willingness to get the COVID-19 vaccine, willingness to participate in vaccine trials, and sociodemographic factors associated with willingness. From July 27, 2020-November 22, 2020, a convenience sample of US Marshallese adults were recruited through e-mail, phone calls, and a Marshallese community Facebook page to participate in an online survey. Of those surveyed (n = 120), 32.5% were extremely likely to get the COVID-19 vaccine; 20.8% were somewhat likely; 14.2% were unlikely or very unlikely; and 26.7% stated they did not know or were not sure. Only 16.7% stated they were willing to participate in a COVID-19 vaccine trial. Vaccine willingness was positively associated with older age, higher income, and longer US residence. Health insurance status and having a primary care provider were positively associated with vaccine willingness. Findings demonstrate within-group variation in COVID-19 vaccine willingness.


Retronychia: A Paradigm Shift?
Retronychia is an increasingly known cause of paronychia. It was classically regarded as an indication for total nail plate avulsion, but recent case series have questioned the real need for this approach. In order to establish a proper recommendation for patients presenting with retronychia, we retrospectively reviewed all articles with retronychia case reports. Total nail plate avulsion is still the most efficient treatment option. Topical steroids and other noninvasive approaches can be useful in some early, mild cases, but further prospective studies are needed in order to access their efficacy.


Insect rearing protocols in forensic entomology: Benefits from collective rearing of larvae in a carrion beetle Necrodes littoralis L. (Silphidae).
Forensic entomologists frequently use a developmental method to estimate a post-mortem interval (PMI). Such estimates are based usually on the blow fly larvae or puparia. Data on their development is obtained by rearing them in colonies. In the case of beetles, which can be also useful for PMI estimation, development data is frequently collected by rearing them individually. However, some carrion beetles are gregarious, for instance, Necrodes littoralis (Linnaeus, 1758) (Silphidae). We compared mortality, rate of development and body size of emerged adult beetles reared individually and in aggregations. Mortality was much higher for beetles reared individually, particularly at low temperatures. The rearing protocol affected the time of immature development and the size of adult insects. Individually reared specimens developed much longer at 16°C, whereas at 20°C and 26°C development times of individually reared beetles were slightly shorter. Significant differences in the body size were observed only at 16°C; beetles that developed in aggregations were larger at this temperature. These findings demonstrate that aggregating is particularly beneficial for larvae of N. littoralis at low temperatures, where it largely reduces mortality and facilitates growth. Moreover, these results indicate that in forensic entomology the protocol of individual rearing is unsuitable for gregarious beetles, as it produces reference developmental data of low quality.


Is chemical antithrombotic prophylaxis effective in elective thoracolumbar spine surgery? Results of a systematic review.
Systematic review Study rationale and context: There is controversy regarding the efficacy and safety of chemical prophylaxis to prevent deep venous thrombosis (DVT) and pulmonary embolism (PE) in elective spinal procedures.Commonly performed elective spine surgeries done through a posterior approach have a very low associated risk of DVT/PE. The lack of consensus is due in part to a limited amount of quality evidence based literature dealing with this issue. To compare chemical prophylaxis with no chemical prophylaxis in preventing venous thromboembolism in elective thoracolumbar spine surgery. We undertook a systematic review of the literature to assess the efficacy and safety of chemical prophylaxis in preventing venous thromboembolism in elective thoracolumbar spine surgery. Pubmed, EMBASE, Cochrane, National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Articles were reviewed by two independently working reviewers. Inclusion and exclusion criteria were set and each article was subject to a predefined quality rating scheme. We identified only two articles meeting our inclusion criteria. Neither study demonstrated a significant difference between chemical prophylaxis versus no prophylaxis in preventing thromboembolic events. There was an increased incidence of perioperative bleeding with low dose Coumadin in one of the studies. The incidence of DVT and PE in commonly performed elective posterior spinal procedures is very low. While there is a limited amount of randomized literature looking at this issue, the current literature does not support the routine use of chemical prophylaxis for low risk patients undergoing these procedures.


Metabolic control by dehydroascorbic acid: Questions and controversies in cancer cells.
For a long time, the effect of vitamin C on cancer cells has been a controversial concept. From Linus Pauling's studies in 1976, it was proposed that ascorbic acid (AA) could selectively kill tumor cells. However, further research suggested that vitamin C has no effect on tumor survival. In the last decade, new and emerging functions for vitamin C have been discovered using the reduced form, AA, and the oxidized form, dehydroascorbic acid (DHA), independently. In this review, we summarized the latest findings related to the effects of DHA on the survival and metabolism of tumor cells. At the same time, we put special emphasis on the bystander effect and the recycling capacity of vitamin C in various cellular models, and how these concepts can affect the experimentation with vitamin C and its therapeutic application in the treatment against cancer.


Congenitally corrected transposition of the great arteries plus dextrocardia operated with an unusual operative technique.
We describe a case of congenitally corrected transposition of the great arteries plus dextrocardia and normal anatomical abdominal viscera. Systemic (tricuspid) valve replacement was performed due to moderately severe valve regurgitation. An unusual operative technique was used because of the patient's rare morphology. On cardiopulmonary bypass, the systemic valve was approached via a left atriotomy anterior to the left pulmonary veins, whereby the surgeon was positioned on the patient's left side. As the surgeon had excellent exposure from the opposite side of the table, he was able to perform a tricuspid valve replacement through the left atrium. Our aim is to share our limited experience of such cardiac morphology, which may oblige the surgeon to be positioned on the left side of the table to perform systemic valve surgery.


Spatial patterns of diabetes related health problems for vulnerable populations in Los Angeles.
Rates for Diabetes Mellitus continue to rise in most urban areas of the United States, with a disproportionate burden suffered by minorities and low income populations. This paper presents an approach that utilizes address level data to understand the geography of this disease by analyzing patients seeking diabetes care through an emergency department in a Los Angeles County hospital. The most vulnerable frequently use an emergency room as a common care access point, and such care is especially costly. A fine scale GIS analysis reveals hotspots of diabetes related health problems and provides output useful in a clinic setting. Indeed these results were used to support the work of a progressive diabetes clinic to guide management and intervention strategies. Hotspots of diabetes related health problems, including neurological and kidney issues were mapped for vulnerable populations in a central section of Los Angeles County. The resulting spatial grid of rates and significance were overlaid with new patient residential addresses attending an area clinic. In this way neighbourhood diabetes health characteristics are added to each patient's individual health record. Of the 29 patients, 4 were within statistically significant hotspots for at least one of the conditions being investigated. Although exploratory in nature, this approach demonstrates a novel method to conduct GIS based investigations of urban diabetes while providing support to a progressive diabetes clinic looking for novel means of managing and intervention. In so doing, this analysis adds to a relatively small literature on fine scale GIS facilitated diabetes research. Similar data should be available for most hospitals, and with due consideration for preserving spatial confidentiality, analysis outputs such as those presented here should become more commonly employed in other investigations of chronic diseases.


Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.
Bloom's syndrome (BS) is a rare autosomal recessive disorder of humans characterized by severe pre- and postnatal growth deficiency, immunodeficiency, genomic instability, and a predisposition to a wide variety of neoplasms. The genomic instability is evidenced in BS somatic cells as a high incidence of gaps and breaks, chromatid exchanges, chromosome rearrangements, and locus-specific mutations. BS arises from a mutation in BLM, a gene encoding a protein with homology to the RecQ helicase family. Men with BS are sterile; women have reduced fertility and a shortened reproductive span. The current immunocytological study on mouse spermatocytes shows that the BLM protein is first evident as discrete foci along the synaptonemal complexes (SCs) of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociate from the synapsed autosomal axes during early pachynema and are no longer seen in mid-pachynema. BLM colocalizes with the single-stranded DNA binding replication protein A, which has been shown to be involved in meiotic synapsis. However, there is a temporal delay in the appearance of BLM protein along the SCs relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomologue interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the SCs, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I.


Occult hepatitis B virus infection: a covert operation.
Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus-specific nucleic acid does not always translate into infectivity, and the occurrence of primer-generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti-HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti-HBc) positive (+/-anti-HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16-guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti-HBc reaction or a detectable HBV DNA.


Maternal-fetal T4 transfer does not suffice to prevent the effects of in utero hypothyroidism.
It has been suggested recently that in congenitally hypothyroid infants with organification defect there is a maternal-fetal transfer of thyroxine (T4). The present study was conducted to evaluate how effective the maternal-fetal transfer is and whether the maternal T4 can prevent intrauterine hypothyroidism. The clinical, laboratory and radiological data on 271 full-term infants with persistent primary congenital hypothyroidism, detected by the national screening program, were used to assess the degree of in utero hypothyroidism. For 6 out of 50 athyroid infants, two pretreatment blood samples spotted on filter paper were available for calculating the T4 disappearance rate. Most infants with agenesis of the thyroid had very low T4 and very high levels of thyroid-stimulating hormone compared to infants with ectopic thyroid. In the athyroid infants the initial T4 declined to low and undetectable levels. Bone maturation was significantly delayed while the clinical symptomatology was more prominent in the athyroid congenital hypothyroid infants, as compared with the ectopic thyroid infants. In conclusion, there is some maternal-fetal transfer of T4. However, this transfer is insufficient to suppress the fetal levels of thyroid-stimulating hormone and prevent intrauterine hypothyroidism.


Responses of leaf respiration to temperature and leaf characteristics in three deciduous tree species vary with site water availability.
We measured responses of leaf respiration to temperature and leaf characteristics in three deciduous tree species (Quercus rubra L., Quercus prinus L. and Acer rubrum L.) at two sites differing in water availability within a single catchment in the Black Rock Forest, New York. The response of respiration to temperature differed significantly among the species. Acer rubrum displayed the smallest increase in respiration with increasing temperature. Corresponding Q(10) values ranged from 1.5 in A. rubrum to 2.1 in Q. prinus. Dark respiration at ambient air temperatures, expressed on a leaf area basis (Rarea), did not differ significantly between species, but it was significantly lower (P < 0.01) in trees at the wetter (lower) site than at the drier (upper) site (Q. rubra: 0.8 versus 1.1 micromol m(-2) s(-1); Q. prinus: 0.95 versus 1.2 micromol m(-2) s(-1)). In contrast, when expressed on a leaf mass basis (R(mass)), respiration rates were significantly higher (P < 0.01) in A. rubrum (12.5-14.6 micromol CO(2) kg(-1) s(-1)) than in Q. rubra (8.6-9.9 micromol CO(2) kg(-1) s(-1)) and Q. prinus (9.2-10.6 micromol CO(2) kg(-1) s(-1)) at both the lower and upper sites. Respiration on a nitrogen basis (R(N)) displayed a similar response to R(mass). The consistency in R(mass) and R(N) between sites indicates a strong coupling between factors influencing respiration and those affecting leaf characteristics. Finally, the relationships between dark respiration and A(max) differed between sites. Trees at the upper site had higher rates of leaf respiration and lower A(max) than trees at the lower site. This shift in the balance of carbon gain and loss clearly limits carbon acquisition by trees at sites of low water availability, particularly in the case of A. rubrum.


Blood pressure-independent effect of candesartan on cardio-ankle vascular index in hypertensive patients with metabolic syndrome.
Angiotensin receptor blockers (ARBs) are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI) in comparison with calcium channel blockers (CCBs) alone in hypertensive patients with metabolic syndrome (MetS). A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP) significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to improve subclinical atherosclerosis of patients with MetS.


Suicides and ambient temperature in Switzerland: A nationwide time-series analysis.
Previous literature suggests that ambient temperature may play a role in increasing the risk of suicide. Although in Switzerland suicides are an important cause of death, limited research exists on risk factors for suicidal behaviour, including ambient temperature. We aimed to assess the short-term association between ambient temperature and suicide risk in Switzerland between 1995 and 2016, and the differences by region, individual characteristics and method of suicide. We collected daily data on suicides and mean temperatures in each canton of Switzerland. We used a two-stage approach, consisting of a case time series analysis using conditional quasi-Poisson and distributed lag non-linear models followed by a multivariate meta-regression analysis. We conducted subgroup analyses by sex, age (<35, 35-65 and >65 years) and method of suicide (violent or nonviolent). Between 1995 and 2016, there were a total of 24,067 suicides in Switzerland. Overall, we found a positive and non-linear temperature-suicide association in all regions. On average, the risk of suicide increased by 34% (1.34 relative risk [95% confidence interval: 1.19-1.52]) from the 10th to the 99th temperature percentile in Switzerland (lag period of 0-2 days). Indications of larger risks were mostly found in females, younger individuals (<35 years) and with nonviolent methods. Regional risks ranged from 24% (East region) to 55% (North-West region). Our findings suggest that increasing temperatures could be considered a risk factor for suicidal behaviour in Switzerland. Knowledge of the profile of people committing suicide could help us to understand the mechanisms behind this association and thus support policymakers in suicide prevention.


Effects of reinforcement value on instruction following under schedules of negative reinforcement.
The effects of reinforcement value and social control on instruction following under a negative-reinforcement (escape) schedule were studied. Initially, responding produced timeouts from pressing a force cell under a low and a high force requirement on a fixed-ratio 1 schedule of reinforcement. Next, participants were reexposed to the low and high force requirements, but were instructed that the experimenter expected them to decrease the number of timeouts relative to the previous exposures to the procedure. Even though following the instruction led to a decrease in number of timeouts and to an increase in effort (i.e., was non-efficient), instruction following occurred consistently for each participant and was modulated by reinforcement value. That is, the decrease in the number of timeouts (i.e., instruction following) was lower under the high force requirement than under the low force requirement. These results replicate and extend previous findings that instructions interact with social and nonsocial contingencies in controlling human behavior.


Th17 response and inflammatory autoimmune diseases.
The proinflammatory activity of T helper 17 (Th17) cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17) pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD). Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.


A high risk study of young children of parents with panic disorder and agoraphobia with and without comorbid major depression.
Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders.


The evolving role and care management approaches of safety-net Medicaid managed care plans.
This article provides new empirical data about the viability and the care management activities of Medicaid managed-care plans sponsored by provider organizations that serve Medicaid and other low-income populations. Using survey and case study methods, we studied these "safety-net" health plans in 1998 and 2000. Although the number of safety-net plans declined over this period, the surviving plans were larger and enjoying greater financial success than the plans we surveyed in 1998. We also found that, based on a partnership with providers, safety-net plans are moving toward more sophisticated efforts to manage the care of their enrollees. Our study suggests that, with supportive state policies, safety-net plans are capable of remaining viable. Contracting with safety-net plans may not be an efficient mechanism for enabling Medicaid recipients to "enter the mainstream of American health care," but it may provide states with an effective way to manage and coordinate the care of Medicaid recipients, while helping to maintain the health care safety-net for the uninsured.


Evaluation of Crestal Bone Loss Around Straight and Tilted Implants in Patients Rehabilitated by Immediate-Loaded Full-Arch All-on-4 or All-on-6: A Prospective Study.
The aim of this prospective study was to compare implant success rate and crestal bone loss around tilted and straight implants supporting immediate-loading full-arch rehabilitations. Twenty consecutive patients with edentulous jaws treated between June 2013 and July 2015 who satisfied all inclusion and exclusion criteria were included in the study. All patients were rehabilitated through a full-arch restoration supported by 4 or 6 immediately loaded implants. Clinical and radiographic examinations were scheduled every 12 months to evaluate implant success rates and crestal bone levels. Significant differences in crestal bone levels and success rates between straight and tilted implants were investigated by means of independent statistical analysis; differences were regarded as significant if P < .05. Seventy straight and 50 tilted implants were placed to rehabilitate 14 mandibles and 12 maxillae in 20 patients. After a follow-up of 12 to 36 months, survival rate was 97.1% for straight implants and 96.0% for tilted implants; while success rates were 94.3% and 94.0%, respectively. Success and survival rates were not significantly different (P > .05). Change in crestal bone level was 0.5 ± 0.4 mm for straight implants and 0.6 ± 0.4 mm for tilted implants (P > .05). Straight and tilted implants seemed to have similar behavior after immediate loading rehabilitations. After functional loading, straight and tilted implants did not differ significantly in clinical outcome.


Apparatus and method to measure dielectric properties (epsilon(') and epsilon(")) of ionic liquids.
Conventional techniques for measurement of dielectric properties of ionic liquids or electrolyte solutions fail because the samples are largely short circuited by the high electrical conductance. The object of the author's research activity was to elaborate an apparatus (microwave dielectrometer) and method suitable to measure the dielectric constant (epsilon(')) and loss factor (epsilon(")) of well conducting ionic liquids and other solvents. This process is based on a revised waveguide method completed with an automatic calibration possibility. Contrary to conventional measuring methods this technique uses about 20 W/g power density. The measurements were carried out at 2.45 GHz frequency in the temperature range from 10 up to 100 degrees C. The obtained (epsilon(')) and (epsilon(")) values of different solvents were compared with several published (calculated and measured) data. Statistical analysis was used to determine the error of measurements and distilled water was chosen as a standard for study of data dispersion. To accomplish statistical analysis, namely, the dielectric characteristics have to be determined at the same temperature. The values of variances were less or equal 1 in case of epsilon(') and decrease with increasing temperature. In case of epsilon(") the variance data were much smaller.


Reviewers' Identity Cues in Online Product Reviews and Consumers' Purchase Intention.
This research performs three experiments to investigate the influence mechanisms of identity cues in product reviews on consumers' purchase intention, and to examine the effects of reference groups. The results indicate that: (1) identity cues in positive reviews have a significant positive impact on consumers' purchase intention, while identity cues in negative reviews have a significant negative impact on consumers' purchase intention; in addition, identity cues play a greater role in amplifying the impact of negative reviews on purchase intention; (2) emotional social support has a mediating role in the relationship between reviewers' identity cues and purchase intention, while informational social support and review credibility only play significant mediating roles under all positive reviews scenario; and (3) identity cues of dissociative groups have a negative impact on purchase intention, whereas identity cues of in-groups or aspirational groups have a positive impact on the purchase intention. These findings complement existing research on online reviews and offer insights into the management and strategic oversight of product reviews for e-commerce platforms and merchants.


Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.
The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice. First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida. The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.


Cystic mature teratoma of the thoracic region in a child: An unusual case.
Cystic mature teratomas of the spinal cord are rare lesions. Teratomas account for up to 0.1% of all spinal cord tumors. Teratomas include tissues that originate from the three germ layers. Several congenital disorders may accompany the teratoma. Teratomas are classified as mature, immature or malignant type according to their histological characteristics. Thoracic spinal teratomas are uncommon in the pediatric age group. More than half of the patients are adults. We present herein a five-year-old male patient who was referred to our clinic with cystic mature teratoma at the T12 level.


The role of different methanogen groups evaluated by Real-Time qPCR as high-efficiency bioindicators of wet anaerobic co-digestion of organic waste.
Methanogen populations and their domains are poorly understood; however, in recent years, research on this topic has emerged. The relevance of this field has also been enhanced by the growing economic interest in methanogen skills, particularly the production of methane from organic substrates. Management attention turned to anaerobic wastes digestion because the volume and environmental impact reductions. Methanogenesis is the biochemically limiting step of the process and the industrially interesting phase because it connects to the amount of biogas production. For this reason, several studies have evaluated the structure of methanogen communities during this process. Currently, it is clear that the methanogen load and diversity depend on the feeding characteristics and the process conditions, but not much data is available. In this study, we apply a Real-Time Polymerase Chain Reaction (RT-PCR) method based on mcrA target to evaluate, by specific probes, some subgroups of methanogens during the mesophilic anaerobic digestion process fed wastewater sludge and organic fraction of the municipal solid waste with two different pre-treatments. The obtained data showed the prevalence of Methanomicrobiales and significantly positive correlation between Methanosarcina and Methanosaetae and the biogas production rate (0.744 p < 0.01 and 0.641 p < 0.05). Methanosarcina detected levels are different during the process after the two pre-treatment of the input materials (T-test p < 0.05). Moreover, a role as diagnostic tool could be suggested in digestion optimisation.


Breast Cancer among Women Living in Poverty: Better Care in Canada than in the United States.
This historical study estimated the protective effects of a universally accessible, single-payer health care system versus a multi-payer system that leaves many uninsured or underinsured by comparing breast cancer care of women living in high poverty neighborhoods in Ontario or California between 1996 and 2011. Women in Canada experienced better care particularly as compared to women who were inadequately insured in the United States. Women in Canada were diagnosed earlier (rate ratio [RR] = 1.12) and enjoyed better access to breast conserving surgery (RR = 1.48), radiation (RR = 1.60) and hormone therapies (RR = 1.78). Women living in high poverty Canadian neighborhoods even experienced shorter waits for surgery (RR = 0.58) and radiation therapy (RR = 0.44) than did such women in the US. Consequently, women in Canada were much more likely to survive longer. Regression analyses indicated that health insurance could explain most of the better care and better outcomes in Canada. Over this study's 15-year timeframe 31,500 late diagnoses, 94,500 sub-optimum treatment plans and 103,500 early deaths were estimated in high poverty US neighborhoods due to relatively inadequate health insurance coverage. Implications for social work practice, including advocacy for future reforms of US health care are discussed.


Scaling of the metrics of visually-guided arm movements during motor learning in primates.
Hand trajectory, tangential velocity and acceleration, time and distance until peak velocity and reaction time were analyzed during the process of learning a skilled, visually-guided arm movement. Primates were trained to move a cursor with a manipulandum from a start box to target boxes displayed on a horizontal video screen during control conditions and when the relationship (gain) between the cursor and manipulandum was altered. The animals adapted to the altered feedback over 100-200 trials. A subsequent testing phase with randomly interspersed trials using the control gain demonstrated that the animals had modified their movements appropriately for the novel gain. Examination of the kinematics revealed that in adapting to a novel gain, primates scaled movement amplitude, tangential velocity, acceleration, and duration appropriately for the distance the hand needed to travel. Yet time to peak velocity was kept constant. Reaction time also remained unchanged for three of the four animals. Movements were performed in two phases, the first from movement onset to peak velocity and the second from peak velocity until the end of the movement. During the first phase the shape of the trajectory and velocity profile were stereotypic and without evidence of any corrections, consistent with this phase being essentially open loop. However, corrections occurred in the second phase and we propose visual feedback was used to correct for the difference in hand/cursor position. Learning appeared to involve utilizing the errors from previous trials to modify the early feedforward phase of subsequent trials. Peak tangential velocity, total movement duration and distance reached at peak tangential velocity all scaled linearly with the total movement distance required at each gain. Based on regression analyses, for none of these variables were the changes in learning completely adequate to compensate for total distance required. However, distance to peak velocity scaled with peak velocity in relation to the control gain. The results show that non-human primates adopt a consistent strategy when learning to scale a multi-joint movement. The metrics of the movement scaled yet the time to peak velocity remained constant, suggesting independent control of time and amplitude. Keeping time to peak velocity constant as well as the scaling of peak velocity with distance to peak velocity are viewed as ways to simplify the learning process.


Patterns of healthcare seeking behavior among persons with diabetes in Central India: A mixed method study.
Management of diabetes is complex and requires multiple lifestyle modifications, drug therapy, and a sustained regular follow-up. Complexities of health-seeking pattern in individuals with diabetes have been poorly characterized. To understand the health-seeking patterns, and reasons of provider preference and switching among persons with diabetes. We performed a mixed methods study in an urban slum setting of Bhopal. This urban slum was chosen as being a field practice area of the institute, a complete sampling frame with listing of households, and individuals with chronic disease conditions (including diabetes) was available. To be included in the study, the individual should have been an adult, aged ≥20 years, and diagnosed as type 2 diabetes mellitus. Descriptive statistical analysis of sociodemographic and disease management variables was performed. For qualitative component, interviews were transcribed and primary coding was done by two investigators followed by condensation of codes into themes or categories. The frequency of these content categories was presented with count and proportions. In total, 60 individuals with diabetes were interviewed. Of all individuals, 36 (60%) were asymptomatic at the time of the first diagnosis, and 57 (95%) were currently under treatment from some healthcare provider. About 25 (41.6%) switched their first provider and remaining continued with the same provider. Second provider was sought by 9 (36%) of 25 patients. Reasons for switching were perceived nonrelief, cost of care, distance of facility, and behavior of care provider. Healthcare provider switching is common among persons with diabetes which has implications on continuity of care.


Certain vitamin D metabolites potentiate the expression of parathyroid hormone bioactivity.
With the development of a sensitive bioassay for the skeletal effects of parathyroid hormone (PTH), it has become possible to investigate the possible interaction between PTH and vitamin D3 metabolites. This assay is based on the stimulation of glucose-6-phosphate dehydrogenase (G6PD) activity in either the hypertrophic chondrocytes of the growth plate or the osteoblasts lining the metaphyseal trabeculae of rat metatarsals. The response to PTH is paralleled by the activity of dibutyryl cAMP. None of the vitamin D3 metabolites tested had any effect on enzyme activity when tested by themselves. However, both 1,25(OH)2D3 and 25(OH)D3 caused a dose-related potentiation of the response to PTH. Neither 1,24,25(OH)3D3 nor 1,25(OH)2D3 26,23-lactone potentiated the response to PTH. Because this potentiation of the response to PTH occurs after only 8 minutes, it is suggested that it represents a nongenomic response to the vitamin D3 metabolites.


Nucleotide sequence of the gene encoding the two-subunit pilin of Bacteroides nodosus 265.
The nucleotide sequence of the gene encoding pilin from Bacteroides nodosus 265 has been determined. The pilin is encoded by a single-copy gene, from which can be predicted a prepilin comprising a single protein chain of Mr 16,637. The prepilin sequence differs in several respects from the mature protein sequence. Seven additional N-terminal amino acid residues are present in prepilin, whereas residue 8, phenylalanine, undergoes posttranslational modification to become the N-methylated amino-terminal residue of mature pilin. In addition, further processing occurs through internal cleavage to produce two noncovalently linked subunits characteristic of pilins from serogroup H of B. nodosus, of which strain 265 is a member. The position of cleavage has been identified between alanine residues at positions 72 and 73 of the mature 149-residue pilin protein. The predicted pilin sequence of B. nodosus 265 shows extensive N-terminal amino acid sequence homology with other pilins of the N-methylphenylalanine type. In addition this sequence also shows homology with these N-methylphenylalanine-type pilins in the C-terminal region of the molecule, especially with pilin from Pseudomonas aeruginosa PAK.


Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004.
The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 x 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.


Evidence that cyclosporine treatment during pregnancy predisposes offspring to develop autoantibodies.
Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases.


Comparison of Fentanyl-Propofol and Ketamine-Propofol Combination in Induction and Maintenance with Intravenous Anesthesia for Short Surgical Procedures at Moderate Elevations.
The aim of the study is to evaluate the efficacy of Ketamine-Propofol compared to Fentanyl-Propofol combination during induction and maintenance of total intravenous anesthesia for short surgical procedures at moderate elevation. A prospective pilot study was done comparing between Fentanyl (1.2 mcg/kg)- Propofol and Ketamine (0.5mg/kg)-Propofol with 30 in each group at moderate altitude of approximately 2514 meters for the requirement of positive pressure ventilation, changes in heart rate and mean arterial pressure intraoperatively, total Propofol consumption and time to attain Modified Steward Score of 6. Requirement for positive pressure ventilation was significantly high in Fentanyl-Propofol group 18 (60%) compared to Ketamine-Propofol 1 (0.03%) [P = 0.00]. Fall in oxygen saturation was significant at 2 minute of Ketamine or Fentanyl [95% CI, 3.10-5.76, P = 0.00], after induction with Propofol [95% CI, 2.30-4.03, P = 0.00], 5 minute [95% CI, 1.66-3.54, P = 0.00], 10 minutes [95% CI, 0.55-2.32, P = 0.02], 15 minutes [95% CI, 0.50-2.09, P = 0.00] and 20 minutes [95% CI, 0.43-2.23, P = 0.00] respectively after study drug between the groups. Total Propofol consumption was significantly higher [95% CI, 0.19-0.43, P = 0.00] in KP (1.55±0.27mg/kg) compared to FP (1.23±0.16 mg/kg). At moderate elevations of 2514 meters, during the induction and maintenance of intravenous anesthesia, Ketamine-Propofol causes significantly less fall in oxygen saturation in the first 20 minutes requiring lesser need of positive pressure ventilation with comparable least fall in heart rate and mean arterial pressure with higher total Propofol consumption when compared to Fentanyl-Propofol. It took a significantly longer time to recovery with Modified steward score of maximum 6 with Ketamine-Propofol.


Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells.
The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H2O2 enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H2O2 level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC.