"Just Be Strong, You Will Get through It" a Qualitative Study of Young Migrants' Experiences of Settling in New Zealand.
Migration, when it occurs during adolescence, is particularly challenging as it coincides with a myriad of other developmental and social changes. The present study set out to explore recent young migrants' experiences of settling in New Zealand. The qualitative study aimed to identify areas of particular challenge, examples of resilience and new insights into the acculturation process. Focus group interviews were conducted with migrant youth aged 16-19 from three urban secondary schools in Auckland The interviews were audio-recorded, transcribed and analyzed using a general inductive method. Key themes centered on new beginnings, confronting new realities, acceptance, support seeking and overcoming challenges. Young migrants in this study shared similar challenges during the early post-migration period. They were often faced with additional responsibility, being caught between two cultures while struggling with communication and language. However, they were able to draw on their own self-growth, gratitude, and social connections. This study provides an insight into experiences of young migrants in New Zealand, and offers suggestions for developing culturally relevant support to foster migrant youth wellbeing.


An abbreviated standard procedure for accurate tumor volume estimation in prostate cancer.
Quantitated tumor volume is reported to be the single most important morphologic predictor for lymph node metastasis and distant spread in the individual patient with adenocarcinoma of the prostate. There is a practical need for a system of tumor volume estimation that avoids the serial blocking of prostatectomy specimens required by standard techniques. Accordingly, in 145 prostatectomy specimens, cancer volumes obtained from computer planimetry of the full set of slides were compared with cancer volumes estimated visually in samples with fewer than half the standard number of slides selected according to three abbreviated protocols. Two of these abbreviated protocols gave cancer volume estimates that were within +/- 20% of the computer value on the full slide set in 96% and 89% of cases. These findings define a simple and relatively inexpensive procedure for deriving important prognostic information in a systematic fashion from the morphologic data obtained in prostatectomy specimens for adenocarcinoma of the prostate.


Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience.
Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.


Compartmentalized microfluidic culture platform to study mechanism of paclitaxel-induced axonal degeneration.
Chemotherapy induced peripheral neuropathy is a common and dose-limiting side effect of anticancer drugs. Studies aimed at understanding the underlying mechanism of neurotoxicity of chemotherapeutic drugs have been hampered by lack of suitable culture systems that can differentiate between neuronal cell body, axon or associated glial cells. Here, we have developed an in vitro compartmentalized microfluidic culture system to examine the site of toxicity of chemotherapeutic drugs. To test the culture platform, we used paclitaxel, a widely used anticancer drug for breast cancer, because it causes sensory polyneuropathy in a large proportion of patients and there is no effective treatment. In previous in vitro studies, paclitaxel induced distal axonal degeneration but it was unclear if this was due to direct toxicity on the axon or a consequence of toxicity on the neuronal cell body. Using microfluidic channels that allow compartmentalized culturing of neurons and axons, we demonstrate that the axons are much more susceptible to toxic effects of paclitaxel. When paclitaxel was applied to the axonal side, there was clear degeneration of axons; but when paclitaxel was applied to the soma side, there was no change in axon length. Furthermore, we show that recombinant human erythropoietin, which had been shown to be neuroprotective against paclitaxel neurotoxicity, provides neuroprotection whether it is applied to the cell body or the axons directly. This observation has implications for development of neuroprotective drugs for chemotherapy induced peripheral neuropathies as dorsal root ganglia do not possess blood-nerve-barrier, eliminating one of the cardinal requirements of drug development for the nervous system. This compartmentalized microfluidic culture system can be used for studies aimed at understanding axon degeneration, neuroprotection and development of the nervous system.


Bimodal control of a Ca(2+)-activated Cl(-) channel by different Ca(2+) signals.
Ca(2+)-activated Cl(-) channels play important roles in a variety of physiological processes, including epithelial secretion, maintenance of smooth muscle tone, and repolarization of the cardiac action potential. It remains unclear, however, exactly how these channels are controlled by Ca(2+) and voltage. Excised inside-out patches containing many Ca(2+)-activated Cl(-) channels from Xenopus oocytes were used to study channel regulation. The currents were mediated by a single type of Cl(-) channel that exhibited an anionic selectivity of I(-) > Br(-) > Cl(-) (3.6:1.9:1.0), irrespective of the direction of the current flow or [Ca(2+)]. However, depending on the amplitude of the Ca(2+) signal, this channel exhibited qualitatively different behaviors. At [Ca(2+)] < 1 microM, the currents activated slowly upon depolarization and deactivated upon hyperpolarization and the steady state current-voltage relationship was strongly outwardly rectifying. At higher [Ca(2+)], the currents did not rectify and were time independent. This difference in behavior at different [Ca(2+)] was explained by an apparent voltage-dependent Ca(2+) sensitivity of the channel. At +120 mV, the EC(50) for channel activation by Ca(2+) was approximately fourfold less than at -120 mV (0.9 vs. 4 microM). Thus, at [Ca(2+)] < 1 microM, inward current was smaller than outward current and the currents were time dependent as a consequence of voltage-dependent changes in Ca(2+) binding. The voltage-dependent Ca(2+) sensitivity was explained by a kinetic gating scheme in which channel activation was Ca(2+) dependent and channel closing was voltage sensitive. This scheme was supported by the observation that deactivation time constants of currents produced by rapid Ca(2+) concentration jumps were voltage sensitive, but that the activation time constants were Ca(2+) sensitive. The deactivation time constants increased linearly with the log of membrane potential. The qualitatively different behaviors of this channel in response to different Ca(2+) concentrations adds a new dimension to Ca(2+) signaling: the same channel can mediate either excitatory or inhibitory responses, depending on the amplitude of the cellular Ca(2+) signal.


Novel Photoinduced Squalene Cyclic Peroxide Identified, Detected, and Quantified in Human Skin Surface Lipids.
Skin surface lipids (SSLs) form the first barrier that protects the human organism from external stressors, disruption of the homeostasis of SSLs can result in severe skin abnormalities. One of the main causes of this disruption is oxidative stress that is primarily due to SSLs oxidation. Squalene (SQ), the most abundant lipid among SSLs, was shown to first undergo singlet molecular oxygen (1O2) oxidation to yield 6 SQ-monohydroperoxide (SQ-OOH) isomers as the primary oxidation products. However, due to the instability and lability of hydroperoxides, we found that when total SQ-OOH isomers are further photooxidized, they form a unique higher molecular weight secondary oxidation product. To generate the compound, we photooxidized total SQ-OOH isomers in the presence of ground state molecular oxygen (3O2), after its isolation and purification, we studied its structure using MS/MS, NMR, derivatization reactions, and chemical calculations. The compound was identified as 2-OOH-3-(1,2-dioxane)-SQ. Photooxidation of individual SQ-OOH isomers revealed that 6-OOH-SQ is the precursor of 2-OOH-3-(1,2-dioxane)-SQ and indicated the possibility of the formation of similar cyclic peroxides from each isomer following the same photoinduced chain reaction mechanism. An HPLC-MS/MS method was developed for the analysis of 2-OOH-3-(1,2-dioxane)-SQ and its presence on the skin was confirmed in SSLs of six healthy individuals. Its quantity on the skin correlated directly to that of SQ and was not inversely proportional to its precursor, indicating the possibility of its accumulation on the skin surface and the constant regeneration of 6-OOH-SQ from SQ's oxidation. In general, research on lipid cyclic peroxides in the human organism is very limited, and especially on the skin. This study shows for the first time the identification and presence of a novel SQ cyclic peroxide "2-OOH-3-(1,2-dioxane)-SQ" in SSLs, shedding light on the importance of further studying its effect and role on the skin.


Enhancement of Boiling with Scalable Sandblasted Surfaces.
Surface engineering has been leveraged by researchers to enhance boiling heat transfer performance, with benefits ranging from improved thermal management to more efficient power generation. While engineered surfaces fabricated using cleanroom processes have shown promising boiling results, scalable methods for surface engineering are still limited despite most real-world industry-scale applications involving large boiling areas. In this work, we investigate the use of sandblasting as a scalable surface engineering technique for the enhancement of pool boiling heat transfer. We vary the size of an abrasive Al2O3 sandblasting medium (25, 50, 100, and 150 μm) and quantify its effects on silicon surface conditions and boiling characteristics. The surface morphology and capillary wicking performance are characterized by optical profilometry and capillary rise tests, respectively. Pool boiling results and surface characterization reveal that surface roughness and volumetric wicking rate increase with the abrasive size, which results in improvements in the critical heat flux and the heat transfer coefficient of up to 192.6 and 434.3% compared to a smooth silicon surface, respectively. The significant enhancement achieved with sandblasted surfaces indicates that sandblasting is a promising option for improving boiling performance in industry-scale applications.


Towards a consensus on rheological models for elastography in soft tissues.
A rising wave of technologies and instruments are enabling more labs and clinics to make a variety of measurements related to tissue viscoelastic properties. These instruments include elastography imaging scanners, rheological shear viscometers, and a variety of calibrated stress-strain analyzers. From these many sources of disparate data, a common step in analyzing results is to fit the measurements of tissue response to some viscoelastic model. In the best scenario, this places the measurements within a theoretical framework and enables meaningful comparisons of the parameters against other types of tissues. However, there is a large set of established rheological models, even within the class of linear, causal, viscoelastic solid models, so which of these should be chosen? Is it simply a matter of best fit to a minimum mean squared error of the model to several data points? We argue that the long history of biomechanics, including the concept of the extended relaxation spectrum, along with data collected from viscoelastic soft tissues over an extended range of times and frequencies, and the theoretical framework of multiple relaxation models which model the multi-scale nature of physical tissues, all lead to the conclusion that fractional derivative models represent the most succinct and meaningful models of soft tissue viscoelastic behavior. These arguments are presented with the goal of clarifying some distinctions between, and consequences of, some of the most commonly used models, and with the longer term goal of reaching a consensus among different sub-fields in acoustics, biomechanics, and elastography that have common interests in comparing tissue measurements.


Single ion implantation for single donor devices using Geiger mode detectors.
Electronic devices that are designed to use the properties of single atoms such as donors or defects have become a reality with recent demonstrations of donor spectroscopy, single photon emission sources, and magnetic imaging using defect centers in diamond. Ion implantation, an industry standard for atom placement in materials, requires augmentation for single ion capability including a method for detecting a single ion arrival. Integrating single ion detection techniques with the single donor device construction region allows single ion arrival to be assured. Improving detector sensitivity is linked to improving control over the straggle of the ion as well as providing more flexibility in lay-out integration with the active region of the single donor device construction zone by allowing ion sensing at potentially greater distances. Using a remotely located passively gated single ion Geiger mode avalanche diode (SIGMA) detector we have demonstrated 100% detection efficiency at a distance of >75 microm from the center of the collecting junction. This detection efficiency is achieved with sensitivity to approximately 600 or fewer electron-hole pairs produced by the implanted ion. Ion detectors with this sensitivity and integrated with a thin dielectric, for example a 5 nm gate oxide, using low energy Sb implantation would have an end of range straggle of <2.5 nm. Significant reduction in false count probability is, furthermore, achieved by modifying the ion beam set-up to allow for cryogenic operation of the SIGMA detector. Using a detection window of 230 ns at 1 Hz, the probability of a false count was measured as approximately 10(-1) and 10(-4) for operation temperatures of approximately 300 K and approximately 77 K, respectively. Low temperature operation and reduced false, 'dark', counts are critical to achieving high confidence in single ion arrival. For the device performance in this work, the confidence is calculated as a probability of >98% for counting one and only one ion for a false count probability of 10(-4) at an average ion number per gated window of 0.015.


The Virtual Morris Water Task in 64 Patients With Bilateral Vestibulopathy and the Impact of Hearing Status.
Background: Previous studies have demonstrated spatial cognitive deficits in patients with bilateral vestibulopathy (BVP). However, BVP patients frequently present with a concomitant sensorineural hearing loss, which is a well-established risk factor of cognitive impairment and incident dementia. Nonetheless, previous research on spatial cognitive deficits in BVP patients have not taken hearing status into account. Objective: This study aims to compare spatial cognition of BVP patients with healthy controls, with analyses adjusting for hearing status. Methods: Spatial cognition was assessed in 64 BVP patients and 46 healthy controls (HC) by use of the Virtual Morris Water Task (VMWT). All statistical analyses were adjusted for hearing (dys)function, sex, age, education, and computer use. Results: Overall, patients with BVP performed worse on all outcome measures of the VMWT. However, these differences between BVP patients and healthy controls were not statistically significant. Nonetheless, a statistically significant link between sensorineural hearing loss and spatial cognition was observed. The worse the hearing, the longer subjects took to reach the hidden platform in the VMWT. Furthermore, the worse the hearing, the less time was spent by the subjects in the correct platform quadrant during the probe trial of the VMWT. Conclusion: In this study, no difference was found regarding spatial cognition between BVP patients and healthy controls. However, a statistically significant link was observed between sensorineural hearing loss and spatial cognition.


Benign solitary solid cold thyroid nodules: US-guided interstitial laser photocoagulation--initial experience.
To evaluate the effects of ultrasonography (US)-guided interstitial laser photocoagulation (ILP) on the volume of benign solitary solid cold thyroid nodules and any nodule-related symptoms. ILP was performed in 16 patients with normal thyroid function and a solid benign thyroid nodule. None of the patients had uptake on a radionuclide scan. Patients underwent one ILP session. A needle was positioned in the thyroid nodule with US guidance, and the laser fiber was placed in the lumen of the needle. Patients were treated for 287-1,200 seconds with an output power of 1-3 W. ILP was performed with continuous US guidance and terminated when the echogenic changes were stationary. Thyroid nodule volume and thyroid function were evaluated before and 1, 3, and 6 months after treatment. During the same period, 15 untreated patients (control group) were followed up to evaluate the size of the untreated thyroid nodule. In the 16 patients treated with ILP, the mean thyroid nodule volume decreased from 10 to 5.4 mL (P <.001) after 6 months. The median energy given was 761 J. There was no relationship between the dose of thermal energy given and nodule reduction. Pressure symptoms were significantly reduced (P =.0002) after 6 months. The treatment was well-tolerated in all patients. No significant change in thyroid nodule volume was seen in the control group. US-guided ILP could become a useful nonsurgical alternative in the treatment of the benign solitary solid cold thyroid nodule in patients who cannot or will not undergo surgery.


Thermographic assessment of neuropathic facial pain.
Ongoing pain, intermittent sharp pain, or intermittent dull aching pain around the teeth can evoke the suspicion of tooth pathology. However, when no dental cause can be found clinically or radiographically, the differential diagnosis involving neuropathic pain and pulpal pathology is still a challenge. Neuropathic facial pains are still too often misdiagnosed as tooth pain of dental origin, resulting in unnecessary dental extraction or endodontic therapy. The purpose of this study was to determine if electronic thermography was able to differentiate neuropathic facial pains presenting as toothache from pulpal pathology. Electronic thermography was used to compare asymptomatic subjects and subjects with neuropathic facial pains. Asymptomatic subjects and subjects with trigeminal neuralgia, pre-trigeminal neuralgia, and pulpal pain without periapical pathology showed no thermographic difference in the territory of the pain complaint when compared to the opposite nonpainful side. Patients with sympathetically maintained traumatic trigeminal neuralgia (atypical odontalgia) and half of the group with sympathetically independent traumatic trigeminal neuralgia presented with "hot" thermograms. The other half of the patients with sympathetically independent traumatic trigeminal neuralgia displayed "cold" thermograms in the area of their pain complaints. Electronic thermography was the least selective test for the group showing "cold" thermogram patterns (80% agreement with the thermographic characterization criteria). These data suggest that electronic thermography may be helpful in differentiating neuropathic pains from pulpal pathology.


[Effects of seed soaking with humic acid on wheat seedlings antioxidant system under salt-alkali stress].
The seeds of two spring wheat genotypes Longmai 26 and Kehan 16 were soaked with humic acid to study the effects of seed soaking with humic acid on the seedlings antioxidant system of the two genotypes under NaCl and Na2CO3 stresses. Under the salt and alkali stresses, the seedlings leaf proline (Pro) content increased, membrane permeability enhanced, and aboveground fresh mass decreased. Under NaCl stress, the leaf catalase (CAT) activity increased, peroxidase (POD) activity decreased, and superoxide dismutase (SOD) decreased after an initial increase; under Na2CO3 stress, the CAT and POD activities increased while the SOD activity was in adverse. The activities of the test antioxidant enzymes were higher under Na2CO3 than under NaCl stress. When the seeds were soaked with humic acid, the seedlings leaf glutathione (GSH) content increased, and the SOD and CAT activities improved, which effectively relieved the damage of salt-alkali stress on the seedlings growth. Some differences were observed in the resistance level and related mechanisms against the salt-alkali stress between the two wheat genotypes, possibly due to their different interactions with the salt ion components and concentrations and the ways of seed soaking.


Spatial mixed binary multiplication by photon echoes.
We demonstrate mixed binary multiplication of two or three numbers represented as spatial bit patterns by using a backward stimulated photon echo in a low-temperature solid activated by rare-earth ions. The photon-echo output image is the convolution-correlation of input images in a holographic arrangement, which can be interpreted as multiplication in a mixed binary format. The computation is extremely fast (~ 50 ns) and may be combined with temporal data processing for a versatile vector and matrix processor.


Graves' Disease Combined With Orthostatic Hypotension: A Two-Case Report.
Graves' disease (GD) is the most common cause of hyperthyroidism in the clinic, accounting for about 85% of all hyperthyroidisms. However, hyperthyroidism combined with OH has been rarely reported in the international community. We analyzed the clinical characteristics and pathogenesis of GD combined with orthostatic hypotension. We conducted a retrospective analysis of 2 GD combined with orthostatic hypotension cases diagnosed by Chinese and Western Medical Association Hospital of Southern Medical University from July to August 2018 and discussed their clinical characteristics, treatment methods, and pathogenesis. The main clinical manifestations of both two patients with hyperthyroidism were vertigo during postural changes or activities and relief from supine position and blood volume supplementation. Considering the lack of blood volume, the symptoms were alleviated after symptomatic treatment. The possibility of hyperthyroidism combined with orthostatic hypotension should be taken into consideration in clinical diagnosis and treatment.


Properties and Applications of the β Phase Poly(vinylidene fluoride).
Poly(vinylidene fluoride), PVDF, as one of important polymeric materials with extensively scientific interests and technological applications, shows five crystalline polymorphs with α, β, γ, δ and ε phases obtained by different processing methods. Among them, β phase PVDF presents outstanding electrical characteristics including piezo-, pyro-and ferroelectric properties. These electroactive properties are increasingly important in applications such as energy storage, spin valve devices, biomedicine, sensors and smart scaffolds. This article discusses the basic knowledge and character methods for PVDF fabrication and provides an overview of recent advances on the phase modification and recent applications of the β phase PVDF are reported. This study may provide an insight for the development and utilization for β phase PVDF nanofilms in future electronics.


Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol.
The role of glucagon-like peptide 1 (GLP-1) in insulin-dependent signaling is well-known; GLP-1 enhances glucose-dependent insulin secretion and lowers blood glucose in diabetes. GLP-1 receptors (GLP-1R) are also widely expressed in the brain, and in addition to its role in neuroprotection, it affects reward pathways. This systematic review aimed to analyze the studies on GLP-1 and reward pathways and its currently identified mechanisms. Methods: "Web of Science" and "Pubmed" were searched to identify relevant studies using GLP-1 as the keyword. Among the identified 26,539 studies, 30 clinical, and 71 preclinical studies were included. Data is presented by grouping rodent studies on palatable food intake, drugs of abuse, and studies on humans focusing on GLP-1 and reward systems. Results: GLP-1Rs are located in reward-related areas, and GLP-1, its agonists, and DPP-IV inhibitors are effective in decreasing palatable food intake, along with reducing cocaine, amphetamine, alcohol, and nicotine use in animals. GLP-1 modulates dopamine levels and glutamatergic neurotransmission, which results in observed behavioral changes. In humans, GLP-1 alters palatable food intake and improves activity deficits in the insula, hypothalamus, and orbitofrontal cortex (OFC). GLP-1 reduces food cravings partially by decreasing activity to the anticipation of food in the left insula of obese patients with diabetes and may inhibit overeating by increasing activity to the consumption of food in the right OFC of obese and left insula of obese with diabetes. Conclusion: Current preclinical studies support the view that GLP-1 can be a target for reward system related disorders. More translational research is needed to evaluate its efficacy on human reward system related disorders.


Second malignant neoplasms in lymphomas, secondary lymphomas and lymphomas in metabolic disorders/diseases.
With inconsistent findings, evidence has been obtained in recent years that metabolic disorders are closely associated with the development of lymphomas. Studies and multiple analyses have been published also indicating that some solid tumor survivors develop a secondary lymphoma, whereas some lymphoma survivors subsequently develop a second malignant neoplasm (SMN), particularly solid tumors. An interaction between the multiple etiologic factors such as genetic factors and late effects of cancer therapy may play an important role contributing to the carcinogenesis in patients with metabolic diseases or with a primary cancer. In this review, we summarize the current knowledge of the multiple etiologic factors for lymphomagenesis, focusing on the SMN in lymphoma, secondary lymphomas in primary cancers, and the lymphomas associated to metabolic disorders/diseases, which have been received less attention previously. Further, we also review the data of coexistence of lymphomas and hepatocellular carcinoma (HCC) in patients with infection of hepatitis C virus and hepatitis B virus.


Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways.
Osmotic stress activates MAPKs, including JNK and p38, which play important roles in cellular stress responses. Transforming growth factor-beta-activated kinase 1 (TAK1) is a member of the MAPK kinase kinase (MAPKKK) family and can activate JNK and p38. TAK1 can also activate IkappaB kinase (IKK) that leads to degradation of IkappaB and subsequent NF-kappaB activation. We found that TAK1 is essential for osmotic stress-induced activation of JNK but is not an exclusive mediator of p38 activation. Furthermore, we found that although TAK1 was highly activated upon osmotic stress, it could not induce degradation of IkappaB or activation of NF-kappaB. These results suggest that TAK1 activity is somehow modulated to function specifically in osmotic stress signaling, leading to the activation of JNK but not of IKK. To elucidate the mechanism underlying this modulation, we screened for potential TAK1-binding proteins. We found that TAO2 (thousand-and-one amino acid kinase 2) associates with TAK1 and can inhibit TAK1-mediated activation of NF-kappaB but not of JNK. We observed that TAO2 can interfere with the interaction between TAK1 and IKK and thus may regulate TAK1 function. TAK1 is activated by many distinct stimuli, including cytokines and stresses, and regulation by TAO2 may be important to activate specific intracellular signaling pathways that are unique to osmotic stress.


Cell Cycle Arrest in G2/M Phase Enhances Replication of Interferon-Sensitive Cytoplasmic RNA Viruses via Inhibition of Antiviral Gene Expression.
Vesicular stomatitis virus (VSV) (a rhabdovirus) and its variant VSV-ΔM51 are widely used model systems to study mechanisms of virus-host interactions. Here, we investigated how the cell cycle affects replication of these viruses using an array of cell lines with different levels of impairment of antiviral signaling and a panel of chemical compounds arresting the cell cycle at different phases. We observed that all compounds inducing cell cycle arrest in G2/M phase strongly enhanced the replication of VSV-ΔM51 in cells with functional antiviral signaling. G2/M arrest strongly inhibited type I and type III interferon (IFN) production as well as expression of IFN-stimulated genes in response to exogenously added IFN. Moreover, G2/M arrest enhanced the replication of Sendai virus (a paramyxovirus), which is also highly sensitive to the type I IFN response but did not stimulate the replication of a wild-type VSV that is more effective at evading antiviral responses. In contrast, the positive effect of G2/M arrest on virus replication was not observed in cells defective in IFN signaling. Altogether, our data show that replication of IFN-sensitive cytoplasmic viruses can be strongly stimulated during G2/M phase as a result of inhibition of antiviral gene expression, likely due to mitotic inhibition of transcription, a global repression of cellular transcription during G2/M phase. The G2/M phase thus could represent an "Achilles' heel" of the infected cell, a phase when the cell is inadequately protected. This model could explain at least one of the reasons why many viruses have been shown to induce G2/M arrest.IMPORTANCE Vesicular stomatitis virus (VSV) (a rhabdovirus) and its variant VSV-ΔM51 are widely used model systems to study mechanisms of virus-host interactions. Here, we investigated how the cell cycle affects replication of VSV and VSV-ΔM51. We show that G2/M cell cycle arrest strongly enhances the replication of VSV-ΔM51 (but not of wild-type VSV) and Sendai virus (a paramyxovirus) via inhibition of antiviral gene expression, likely due to mitotic inhibition of transcription, a global repression of cellular transcription during G2/M phase. Our data suggest that the G2/M phase could represent an "Achilles' heel" of the infected cell, a phase when the cell is inadequately protected. This model could explain at least one of the reasons why many viruses have been shown to induce G2/M arrest, and it has important implications for oncolytic virotherapy, suggesting that frequent cell cycle progression in cancer cells could make them more permissive to viruses.


Clinical electrophysiological effects of chronic administration of verapamil: the phenomenon of overdrive excitation of junctional pacemaker.
The electrophysiological effects of chronic administration of verapamil were studied in 10 patients with normal sinus node function, who received 160 mg of the drug every eight hours for at least two weeks. Uncorrected and corrected sinus node recovery time, sino-atrial conduction time, effective and functional refractory periods were normal in each case. In three patients, at the cessation of atrial pacing, an overdrive excitation of junctional pacemaker with short lasting A-V dissociation was observed.


Models of case management for working with young children: implications for mental health nurses.
The care of children with behavioural disorders/mental illnesses is an important and emerging role for mental health nurses. Unfortunately, there is little evidence on which to base their practice. Children, because of their rapid emotional, physical, and cognitive development, and their dependence on their families, need special consideration in their mental health care. The limited evidence available indicates that this special consideration should include a focus, not only on the child, but also on the parents and social and school networks of the child. Evidence from the adult literature indicates the most effective case management models are the ones in which the case manager offers as many services as possible, including talking therapies. This also seems to be true when working with children. Mental health nurses, because of their background and commitment to holistic care, are ideally suited to offer this type of service. However, mental health nurses have not been good at articulating what they do. This can limit the recognition of the contribution they make and their opportunities.


Reduction in adhesive small-bowel obstruction by Seprafilm adhesion barrier after intestinal resection.
Although Seprafilm has been demonstrated to reduce adhesion formation, it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction. This was a prospective, randomized, multicenter, multinational, single-blind, controlled study. This report focuses on those patients who underwent intestinal resection (n = 1,701). Before closure of the abdomen, patients were randomized to receive Seprafilm or no treatment. Seprafilm was applied to adhesiogenic tissues throughout the abdomen. The incidence and type of bowel obstruction was compared between the two groups. Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods. The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years. There was no difference between the treatment and control group in overall rate of bowel obstruction. The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm patients compared with no-treatment patients: 1.8 vs. 3.4 percent (P < 0.05). This finding represents an absolute reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent. In addition, a stepwise multivariate analysis indicated that the use of Seprafilm was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation. In both groups, 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days. Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up. The overall bowel obstruction rate was unchanged; however, adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm, which was the only factor that predicted this outcome.


Effect of aspirin and dipyridamole on the patency of lower extremity bypass grafts.
Recent clinical studies indicate that the use of aspirin and dipyridamole improves graft patency rates in patients with infrainguinal polytetrafluoroethylene (PTFE) grafts and aortocoronary vein grafts. We undertook a prospective, double-blind, randomized study to determine whether these drugs administered postoperatively to patients with PTFE or autologous vein infrainguinal bypasses would improve graft patency during the first 24 months after operation. Patients received either aspirin 325 mg and dipyridamole 75 mg or identical placebo tablets three times a day, taken orally. Patency rates were compared by computing standard life tables and comparing cumulative patency rates. One hundred patients with 102 grafts were studied. The cumulative patency rate at 24 months was not significantly different for the treatment (57%) versus control (67%) groups or for any subgroup. We conclude that aspirin and dipyridamole administered postoperatively in the doses used in this study do not improve the overall patency rates of vein or PTFE infrainguinal bypass grafts.


Gastroduodenal reflux induces group IIa secretory phospholipase A(2) expression and activity in murine esophagus.
Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A(2) (sPLA(2)) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA(2) protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA(2)(+/+)) mice (n= 28) underwent side-to-side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real-time RT PCR was used to quantitate the influence of GDR on group IIa sPLA(2) expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA(2) protein. A colorimetric assay was used to quantify total sPLA(2) activity after standardization of protein levels. Statistical analysis was conducted using Student's t-test. Group IIa sPLA(2) mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time-dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA(2) enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA(2) as well as sPLA(2) activity is induced by GDR. This novel finding indicates that sPLA(2) may play a role in the development of the histologic changes produced by GDR in esophageal mucosa.


Voltage gated potassium channel antibodies in amyotrophic lateral sclerosis.
Although overlap exists between the clinical manifestations in patients with acquired peripheral nerve hyperexcitibility and amyotrophic lateral sclerosis (ALS), the presence of VGKC antibodies has not been associated with the development or clinical manifestations of motor neuron disease. We present the finding of elevated potassium channel antibodies in a cohort of patients with ALS and demonstrate a higher number of abnormal titer levels and higher mean titer levels in ALS patients compared to a cohort of patients with peripheral nervous system disorders. These results suggest the possibility of a subset of ALS patients where autoimmunity could play a role in disease development and progression.


Incidence of occult papillary carcinoma of thyroid in Indian population: case series and review of literature.
To report the incidence of occult papillary carcinoma of thyroid in a tertiary care center in India in post-laryngectomy specimen of carcinoma of hypopharynx. Retrospective analysis. This is a retrospective analysis of incidentally detected papillary carcinoma of thyroid in 358 patients of carcinoma of hypopharynx treated with total/near total laryngectomy at our tertiary care institute from 2005 to 2011. Statistical analysis was performed using the software Statistical Package for the Social Sciences 20.0 (IBM, NY, USA). Percentages were calculated. Thyroid cancer was seen in 7/358 patients with incidence of 2%. Five patients had tumor localized to thyroid gland only. One patient had nodal metastasis with thyroid cancer and one had only metastatic cervical node with normal thyroid gland on final histopathology. Three of these patients (3/7) had a recurrence of carcinoma of hypopharynx within 1 year duration. The incidence of occult papillary carcinoma of thyroid varies from 0.25% to 7% in the Indian literature.


Decrease in serum asprosin levels following six weeks of spinning and stationary cycling training in overweight women.
Secreted by white adipose tissue, asprosin is a newly recognized adipokine whose physiological function is not well comprehended. This study intended to determine the effect of spinning and stationary cycling on serum asprosin levels in overweight women. Forty-five overweight women with BMI>25 kg/m2 in the age range of 30-40 years were assigned randomly to three groups of 15 participants: control, spinning (group cycling with music), and stationary bike (individual pedaling on a stationary bike). The participants performed the exercises three sessions per week for six weeks. Lipid profile and asprosin levels were measured by enzymatic and ELISA methods, respectively. Moreover, the paired t-test and one-way ANOVA were employed to make within-group and between-group comparisons, respectively. The stationary cycling and spinning exercise groups experienced significant reductions in weight, BMI, serum triglyceride, and asprosin levels from the pretest to the posttest. The control group showed no statistically significant differences. Serum concentrations of total cholesterol and low-density lipoprotein only declined in the spinning group. In this regard, neither the control group nor the stationary bicycle exhibited no significant change over time. The spinning group demonstrated a significant rise in high-density lipoprotein levels, which was not observed in the control group. In addition, there was no significant difference in WHR index between the intervention groups. By lowering the serum asprosin level, a spinning exercise program appears to be effective in reducing disorders linked to metabolic diseases in overweight women.


Clinicopathologic significance of ductal carcinoma in situ in breast core needle biopsies with invasive cancer.
To assess whether the presence and amount of intraductal component (IC) in diagnostic needle core biopsies (NCB) is predictive of an extensive IC (EIC), the authors evaluated 50 invasive ductal carcinomas diagnosed with NCB, and then excised via lumpectomy, with regard to the extent of IC in both the NCB and subsequent lumpectomy specimen. These parameters were compared with each other and with the lumpectomy margin status. Extent of IC in the NCB was evaluated by dividing the number of ducts that contained IC by the total number of tissue cores. A ratio of more than 0.5 was considered EIC (EICc). IC extent in the lumpectomy was established by estimating the percentage of the tumor corresponding to IC and was considered extensive (EIC(L)) if more than 25% and if there was presence of IC away from the invasive tumor. The mean size of resected tumors was 1.6 +/- 0.7 cm. In 29 cases (58%) there was no IC in the NCB (NegICc), 11 cases (22%) exhibited nonextensive IC (NEICc), and 10 cases (20%) demonstrated EICc. A total of 7%, 36%, and 70% of the NegICc, NEICc, and EICc cases respectively had EIC(L)(p < 0.0001). The presence of EIC(L) correlated significantly with close or positive margin status for in situ disease (EIC(L) positive, 12 of 13 [92%] vs EIC(L) negative, 11 of 37 [30%]; p = 0.004). None of the NegICc, 27% of NEICc, and 40% of EICc had a positive margin for in situ neoplasm in the lumpectomy specimen (p = 0.004), and 24%, 18%, and 50% had positive margins for invasive neoplasm (p = not significant). The authors conclude that EICc predicts EIC(L) and constitutes a risk factor for positive lumpectomy margin status-particularly for in situ tumor. EICc may thus be of clinical value in identifying a subset of patients that requires a wider local excision.


Protein histidine phosphatase: a novel enzyme with potency for neuronal signaling.
The importance of reversible phosphorylation for neuronal signaling and cell survival is well recognized. Knowledge in vertebrates, however, is so far limited to O-phosphates from serine, threonine, and tyrosine. The authors describe an enzyme acting on N-phosphates. It is the first protein histidine phosphatase identified in vertebrates. This histidine phosphatase is ubiquitously expressed in mammalian tissues including brain. Characterization and sequencing showed a yet unknown protein with no similarity to other phosphatases. In Caenorhabditis elegans, the homolog of this histidine phosphatase was exclusively expressed in neurons, suggesting a distinct role of reversible histidine phosphorylation in neuronal functions.


Maintenance of turgor by rapid sealing of puncture wounds in leaf epidermal cells.
When leaf epidermal cells are puncture wounded with a glass microcapillary tip, a small droplet of fluid is discharged and then evaporates, leaving a solid residue on the cell surface. For puncture wounds of about 3.5 micrometers in diameter, this process is complete within 2 to 3 seconds. A second puncture wound also exhibits a similar discharge, indicating the persistence of some turgor pressure within the cell, despite damage to the cell wall. Direct measurement of turgor on the large epidermal cells of Tradescantia virginiana L. demonstrated that turgor was substantially maintained (91-96%) after puncture wounding. Anatomical and histochemical evidence suggests that the damaged portion of the cell wall was sealed with an amorphous plug of material comprised of pectinaceous polysaccharides. Rapid sealing of puncture wounds and the maintenance of turgor in epidermal cells may be an important functional component of plant adaptation to physical damage such as that caused by insect feeding.


Horseradish Peroxidase-Crosslinked Calcium-Containing Silk Fibroin Hydrogels as Artificial Matrices for Bone Cancer Research.
Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer is reported. The proposed fast forming calcium-containing SF hydrogels spontaneously undergo SF conformational changes from random coil to β-sheet during time, exhibiting ionic, and pH stimuli responsiveness. In vitro response shows calcium-containing SF hydrogels' encapsulation properties and their ability to promote SaOs-2 tumor cells death after 10 days of culturing, upon complete β-sheet conformation transition. Calcium-containing SF hydrogels' angiogenic potential investigated in an in ovo chick chorioallantoic membrane (CAM) assay, show a high number of converging blood vessels as compared to the negative control, although no endothelial cells infiltration is observed. The in vivo response evaluated in subcutaneous implantation in CD1 and nude NCD1 mice shows that calcium-containing SF hydrogels are stable up to 6 weeks after implantation. However, an increased number of dead cells are also present in the surrounding tissue. The results suggest the potential of calcium-containing SF hydrogels to be used as novel in situ therapeutics for bone cancer treatment applications, particularly to osteosarcoma.


A Gaussian process regression model for walking speed estimation using a head-worn IMU.
Miniature inertial sensors mainly worn on waist, ankle and wrist have been widely used to measure walking speed of the individuals for lifestyle and/or health monitoring. Recent emergence of head-worn inertial sensors in the form of a smart eyewear (e.g. Recon Jet) or a smart ear-worn device (e.g. Sensixa e-AR) provides an opportunity to use these sensors for estimation of walking speed in real-world environment. This work studies the feasibility of using a head-worn inertial sensor for estimation of walking speed. A combination of time-domain and frequency-domain features of tri-axial acceleration norm signal were used in a Gaussian process regression model to estimate walking speed. An experimental evaluation was performed on 15 healthy subjects during free walking trials in an indoor environment. The results show that the proposed method can provide accuracies of better than around 10% for various walking speed regimes. Additionally, further evaluation of the model for long (15-minutes) outdoor walking trials reveals high correlation of the estimated walking speed values to the ones obtained from fusion of GPS with inertial sensors.


Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry.
A fundamental goal of protein biochemistry is to determine the sequence-function relationship, but the vastness of sequence space makes comprehensive evaluation of this landscape difficult. However, advances in DNA synthesis and sequencing now allow researchers to assess the functional impact of every single mutation in many proteins, but challenges remain in library construction and the development of general assays applicable to a diverse range of protein functions. This Perspective briefly outlines the technical innovations in DNA manipulation that allow massively parallel protein biochemistry and then summarizes the methods currently available for library construction and the functional assays of protein variants. Areas in need of future innovation are highlighted with a particular focus on assay development and the use of computational analysis with machine learning to effectively traverse the sequence-function landscape. Finally, applications in the fundamentals of protein biochemistry, disease prediction, and protein engineering are presented.


Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants.
The biophysical properties and physiologic effects of a series of clinical exogenous pulmonary surfactants was compared to determine the importance of the hydrophobic apoproteins (SP-B and C) as constituents of these preparations. The three exogenous surfactants studied, calf lung surfactant extract (CLSE), Survanta (Surfactant-TA), and Exosurf, all contain dipalmitoyl phosphatidylcholine (DPPC) as their major constituent. CLSE and Survanta also contain 1 to 2% of SP-B,C but Exosurf has the additives hexadecanol and tyloxapol instead to enhance the activity of DPPC. In adsorption experiments, CLSE reached a final surface tension of 22 mN/m, and Survanta and Exosurf reached 28 and 38 mN/m, respectively. Addition of 1% by weight of an apoprotein isolate containing both SP-B and C to Exosurf slightly improved its adsorption. In oscillating bubble studies, CLSE and Survanta decreased surface tension to low values of less than 1 and 2 mN/m, respectively, but Exosurf achieved a minimum value of only 29 mN/m. Addition of SP-B,C to Exosurf improved this minimum to 1 mN/m and approached the behavior of mixtures of synthetic DPPC with SP-B,C. In both adsorption and pulsating bubble experiments, the minimum surface tensions found for Exosurf were almost identical to those generated by tyloxapol alone. In studies of physiologic activity, 20 mg of CLSE or Survanta restored the pressure-volume mechanics of lavaged, surfactant-deficient excised rat lungs to 95 and 50%, respectively, of normal prelavage levels. Instillation of Exosurf (37.5 mg) produced a minimal improvement of only 10% compared to 70% for mixtures containing 1% SP-B,C with either Exosurf or DPPC.(ABSTRACT TRUNCATED AT 250 WORDS)


Experimental evaluation of mathematical models for predicting the thermal response of tissue to laser irradiation.
We investigated the ability of mathematical models to predict temperature rises in biological tissue duringlaser irradiation by comparing calculated values with experimental measurements. Samples of normal human aorta, beef myocardium, and polyacrylamide gel were irradiated in air with an argon laser beam, while surface temperatures were monitored with an IR camera. The effects of different surface boundary conditions in the model predictions were examined and compared with the experimental data. It was observed that, before a temperature of 60 degrees C was reached, the current mathematical models were capable of predicting tissue-surface temperature rises with an accuracy of 90% for a purely absorbing medium and with an accuracy of 75% for biological tissue (a scattering medium). Above 60 degrees C, however, the models greatly overestimated temperature rises in both cases. It was concluded that the discrepancieswere mainly a result of surface water vaporization, which was not considered in current models and which was by far the most significant surface-heat-loss mechanism for laser irradiation in air. The inclusion of surface water vaporization in the mathematical models provided a much better match between predicted temperatures and experimental results.


KDR stimulates endothelial cell migration through heterotrimeric G protein Gq/11-mediated activation of a small GTPase RhoA.
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) functions by activating two receptor tyrosine kinases, Flt-1 (VEGFR-1) and KDR (VEGFR-2), both of which are selectively expressed on the primary vascular endothelium. KDR is responsible for VPF/VEGF-stimulated endothelial cell (EC) proliferation and migration, whereas Flt-1 down-modulates KDR-mediated EC proliferation. Flt-1 mediates down-regulation of EC proliferation through pertussis toxin-sensitive G proteins, betagamma subunits, small GTPase CDC42, and partly by Rac-1. However, the molecular mechanism by which KDR mediates EC migration is not clear yet. Here we show for the first time that activation of RhoA and Rac1 is fully and partially required for KDR-mediated human umbilical vein endothelial cell (HUVEC) migration, respectively, and that CDC42, however, is not involved. Furthermore, overexpression of the RhoA dominant negative mutant RhoA-19N does not affect VPF/VEGF-stimulated KDR phosphorylation, intracellular Ca(2+) mobilization, and mitogen-activated protein kinase phosphorylation. Utilizing the receptor chimeras (EGDR and EGLT) in which the extracellular domain of the epidermal growth factor receptor (EGFR) was fused to the transmembrane domain and the intracellular domains of KDR and Flt-1, respectively, we demonstrate that RhoA activation is mediated by EGDR, not by EGLT, and that EGDR mediates activation of Rac1, not CDC42. Furthermore, the EGDR-mediated RhoA and Rac1 activation is regulated by G proteins Gq/11, Gbetagamma, and phospholipase C independent of phosphatidylinositol 3-kinase and intracellular Ca(2+) mobilization. Interestingly, the RhoA activation can be partially inhibited by overexpression of Rac1-17N, but overexpression of RhoA-19N has no effect on Rac1 activation. Finally, Gq/11 and Gbetagamma subunits are also required for VPF/VEGF-stimulated HUVEC migration. Taken together, our results indicate that KDR stimulates endothelial cell migration through a heterotrimeric G protein Gq/11 and Gbetagamma-mediated RhoA pathway.


bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin's lymphomas.
The authors investigated the structural organization of the bcl-1 locus, a putative oncogene associated with reciprocal chromosomal translocation t(11;14), by Southern blot hybridization analysis and its frequency, distribution, and prognostic significance in a panel of 156 clinically and pathologically well-defined B-cell chronic lymphocytic leukemias (CLLs) and non-Hodgkin's lymphomas (NHLs). The authors detected bcl-1 rearrangements in only 2 of 42 CLLs and 4 of 114 NHLs, specifically 3 of 29 diffuse small lymphocytic and 1 of 10 diffuse small cleaved cell and none of 5 diffuse intermediate lymphocytic, 13 follicular predominantly small cleaved, 17 follicular mixed small cleaved and large cell, 4 diffuse mixed small and large cell, 26 diffuse large cell, and 10 diffuse small noncleaved cell lymphomas. None of seven cases of Rai stage III or IV CLL or seven diffuse large cell lymphomas occurring as Richter's syndrome exhibited bcl-1 rearrangements. In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome). Therefore the demonstration of bcl-1 rearrangement does not appear to have clinically useful prognostic significance.


Design, synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7-arylaminopyrimido [4,5-d]pyrimidin-5(6H)-ones.
Synthesis and diuretic activity of some novel 2,4-diamino-6-aryl-7-arylaminopyrimidol4,5-d]pyrimidin-5(6H) -ones were described. The series was designed on the basis of structural similarity between pteridines and pyridopyrimidines. Designed molecules were synthesized by cyclo-condensation of 5-cyano-6-methylmercapto-3-aryl-2-arylaminopyrimidin-4(3H)-one with guanidine. All the compounds were screened for their diuretic activity using triamterene and furosemide as standard drugs. Compounds 2a, 2b, 2d, 2e and 2f were found more potent than triamterene. Compound 2e exhibited diuretic activity comparable to furosemide with greater natriuretic effect. It also exhibited significant antihypertensive activity.


Emotional reactivity across the adult life span: the cognitive pragmatics make a difference.
Previously, we found that during films about age-typical losses, older adults experienced greater sadness than young adults, whereas their physiological responses were just as large. In the present study, our goal was to replicate this finding and extend past work by examining the role of cognitive functioning in age differences in emotional reactivity. We measured the autonomic and subjective responses of 240 adults (age range=20 to 70) while they viewed films about age-typical losses from our previous work. Findings were fully supportive of our past work: The magnitude of subjective reactions to our films increased linearly over the adult years, whereas there were no age differences on the level of physiological reactivity. We also found that the subjective reactions of adults with high pragmatic intelligence were of moderate size independent of their own age or the age relevance of the emotion elicitor. In contrast, the subjective reactions of adults low on pragmatic intelligence were more variable. Together, this evidence suggests that research on age differences in emotional reactivity may benefit from a perspective that considers individual difference variables as well as contextual variations.


[Prevalence of cardiovascular risk factors in school-aged children].
This study was conducted to assess the distribution of cardiovascular risk factors (serum lipid profiles, BMI, blood pressure, fasting blood sugar) and evaluate the risk profile of CVD by the clustering of the cardiovascular risk factors in school-aged children in the Kyoung-Gi area. The study sample consists of 208 11 year-old children (51.4% boys, 48.6% girls) who participated in a cross-sectional screening of cardiovascular risk factors. We surveyed their socio-demographic characteristics, measured the anthropometric variables and analyzed the biochemical markers. Of the cardiovascular risk factors, the percentage risk of the BMI, dyslipidememia and hypertension were highest. The prevalence rates of total cholesterol and LDL-cholesterol in girls was higher than in boys. Also, the associations of the BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressures were highly significant. In addition, the proportion of subjects with 1, 2, 3 and 4 or more risk factors were 29.3, 12.5, 2.9 and 1.9%, respectively; therefore, a total of 97 subjects (46.6%) had at least one more risk factor. From these findings, we concluded that the rates of hypercholesterolemia, cardiovascular risk groups and obesity prevalence of these groups were relatively high. These data provide further evidence that the early intervention for cardiovascular health prevention and promotion in school-aged children is necessary at the population level.


Efficient Synthesis of Sugar Alcohols under Mild Conditions Using a Novel Sugar-Selective Hydrogenation Catalyst Based on Ruthenium Valence Regulation.
Sugar alcohols are the prominent alternatives of sugars in food, medical, and health industries. The ruthenium supported on multiwalled carbon nanotubes (Ru/MWCNTs) catalysts were prepared based on the Ru valence regulation strategy and applied for selective sugar hydrogenation to prepare various sugar alcohols including xylitol, arabinitol, sorbitol, mannitol, and galactitol for the first time, with high selectivity (>99.0%) and yield (>98.0%) under mild conditions (≤110 °C, 3.0 MPa H2 pressure). The hydrogenation reaction of xylose was further optimized and under mild conditions (100 °C, 3.0 MPa H2 pressure, and 500 rpm), which were lower than ever reported for high efficient synthesis of xylitol, 99.8% xylose conversion and 99.0% xylitol yield were achieved after 120 min of reaction.


Influence of Wrist Position on the Metacarpophalangeal Joint Motion of the Index Through Small Finger.
The metacarpophalangeal joints exhibit range of motion that is influenced by wrist position. Synergistic motion occurs between the wrist and the metacarpophalangeal joints with different static wrist positions affecting joints' motion capability. The aim of this study was to determine how different wrist positions influence the active range of motion of the index through small finger metacarpophalangeal joints. The active range of motion of the index through small finger metacarpophalangeal joints of 31 healthy subjects was measured in flexion/extension and radial/ulnar deviation in 5 different flexion/extension wrist positions, using biaxial electrogoniometers. There was a difference in range of motion of all fingers depending on the wrist position. The minimum metacarpophalangeal joint range of motion was found in 80° wrist extension, the maximum in neutral wrist position. For the index finger, flexion/extension was 84.7° (±8.6°) to 25.9° (±10.2°) and radial/ulnar deviation was 32.1° (±11.3°) to 22.6° (±12.8°). For the middle finger, flexion/extension was 84.8° (±8.5°) to 25.9° (±10.1°) and radial/ulnar deviation 28.8° (±11.1°) to 22.1° (±8.9). The fourth finger showed a range of motion for flexion/extension of 87.2° (±11.5°) to 22.8° (±11.6°) and radial/ulnar deviation of 8.1° (±5.8°) to 32.3° (±12.4°). The highest range of motion was measured at the fifth finger with flexion/extension of 84.0° (±8.6°) to 32.1°(±16.8°) and radial/ulnar deviation of 15.1° (±12.9°) up to 54.6° (±18.7°). The range of motion of the index through small finger metacarpophalangeal joints was significantly influenced by wrist position. The highest metacarpophalangeal joint range of motion of all fingers was conducted in neutral wrist positions. Apart from ergonomic implications, we conclude that metacarpophalangeal joint motion should be assessed under standardized wrist positions.


Absorption, distribution, metabolism and excretion of a new, 14C-labelled oxazolidinone MAO-A inhibitor in rat and dog.
1. After oral administration of 14C-labelled (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl -2-oxazolidinone (E2011) at a dose of 1 mg/kg, the blood level of radioactivity reached a maximum concentration (Cmax) of 0.545 microgram eq./ml after 0.25 h in the rat and of 0.900 microgram eq./ml after 0.5 h in the dog. In dog plasma, Cmax for radioactivity and unchanged E2011 were 0.862 microgram eq./ml and 0.650 microgram/ml respectively with corresponding Tmax (time at Cmax) of 0.75 and 0.25 h. The unchanged drug in dog plasma was below the detection limit (5 ng/ml plasma) after 24 h. 2. The tissue levels of radioactivity were measured at 0.25 (Tmax), 6, 24, and 168 h after administration to the rat and at 0.5 (Tmax), 24, and 168 h in the dog. The radioactivity was distributed in all tissues examined at Tmax in the rat and dog. The radioactivity levels of the cerebral cortex in the rat and dog were 26 and 36% of the plasma level at Tmax. The radioactivity in tissues decreased at almost the same rate as that in plasma. Plasma protein binding of the unchanged drug in the rat in vitro were about 70% in the range of 0.1-10 micrograms/ml, and those in the dog were about 45% in the same concentration range. 3. Cumulative excretion of radioactivity in the rat was 74.5% in urine and 22.5% in faeces after 7 days. In the dog, 55.5 and 36.5% of the radioactivity administered were excreted in urine and faeces respectively after 7 days. The biliary excretion of radioactivity in the cannulated rat was 23.0% within 48 h. 4. In tlc analysis of plasma and tissues of the rat and dog, the radioactivity for the unchanged drug was much higher than metabolites. In tlc analysis of urine, the same metabolites were detected in the rat and dog, and the radioactivity of a metabolite, IM1, was the highest in the both animals. Eight metabolites were detected in the plasma, tissues and excreta of the rat, and four metabolites in the dog. 5. In conclusion, the absorption, distribution, metabolism and excretion of 14C-labelled E2011 in the rat and dog have been established, and only minor differences were observed between these species.


Communication Assessment for Individuals With Minimal Verbal Skills: A Survey of Current Practices and Satisfaction.
Purpose There are few tools developed specifically to assess communication in people with minimal verbal skills. The literature suggests that "gold standard" assessment practice includes a combination of three components: observation, direct assessment, and indirect assessment. The purpose of this study was to describe the assessment methods practitioners and researchers currently use to measure communication skills in individuals with minimal verbal skills. We also wanted to gain information about professionals' satisfaction with their current assessment methods, as well as the factors they consider when selecting assessments for this population. Method A 24-question survey, composed of forced-choice, multiple-choice, Likert-type, and open-ended questions, was disseminated online using LimeSurvey. A total of 217 individuals responded to the survey. Results from the questionnaire were analyzed using qualitative and quantitative methods. Results The number and type of assessments used varied. Observation was the assessment method identified most frequently. Nineteen percent of the respondents reported using the gold standard approach (i.e., observation + direct + indirect). Many respondents were dissatisfied with some or many aspects of their current assessment method. Respondents who used the gold standard approach reported that their assessment method assisted in setting goals significantly better than those who did not use this approach. Comprehensiveness of skills assessed as well as ease and comfort level of the examinee were key factors in assessment selection. Conclusions Results from this survey suggest the need to continue to promote using multiple forms of assessment for individuals with minimal verbal skills. In addition, it points to the need to develop additional effective assessment methods for individuals with minimal verbal skills.


Electrochemistry and electrogenerated chemiluminescence of dithienylbenzothiadiazole derivative. Differential reactivity of donor and acceptor groups and simulations of radical cation-anion and dication-radical anion annihilations.
We report here the electrochemistry and electrogenerated chemiluminescence (ECL) of a red-emitting dithienylbenzothiadiazole-based molecular fluorophore (4,7-bis(4-(4-sec-butoxyphenyl)-5-(3,5-di(1-naphthyl)phenyl)thiophen-2-yl)-2,1,3-benzothiadiazole, 1b). 1b contains two substituted thiophene groups as strong electron donors at the ends connected directly to a strong electron acceptor, 2,1,3-benzothiadiazole, in the center. Each thiophene moiety is substituted in position 2 by 3,5-di(1-naphthyl)phenyl and in position 3 by 4-sec-butoxyphenyl. Cyclic voltammetry of 1b, with scan rate ranging from 0.05 to 0.75 V/s, shows a single one-electron reduction wave (E°(red) = -1.18 V vs SCE) and two nernstian one-electron oxidation waves (E°(1,ox) = 1.01 V, E°(2,ox) = 1.24 V vs SCE). Reduction of the unsubstituted 2,1,3-benzothiadiazole center shows nernstian behavior with E°(red) = -1.56 V vs SCE. By comparison to a digital simulation, the heterogeneous electron-transfer rate constant for reduction, k(r)° = 1.5 × 10(-3) cm/s, is significantly smaller than those for the oxidations, k(o)° > 0.1 cm/s, possibly indicating that the two substituted end groups have a blocking effect on the reduction of the benzothiadiazole center. The ECL spectrum, produced by electron-transfer annihilation of the reduced and oxidized forms, consists of a single peak with maximum emission at about 635 nm, consistent with the fluorescence of the parent molecule. Relative ECL intensities with respect to 9,10-diphenylanthracene are 330% and 470% for the radical anion-cation and radical anion-dication annihilation, respectively. Radical anion (A(-•))-cation (A(+•)) annihilation produced by potential steps shows symmetric ECL transients during anodic and cathodic pulses, while for anion (A(-•))-dication (A(2+•)) annihilation, transient ECL shows asymmetry in which the anodic pulse is narrower than the cathodic pulse. Digital simulation of the transient ECL experiments showed that the origin of the observed asymmetry is asymmetry in the amount of generated charges rather than instability of the electrogenerated species.


DNA Vaccine Delivery and Improved Immunogenicity.
The promise of DNA vaccines is as compelling today as it was more than a decade ago. Ease of manufacture, stability at ambient temperatures without the need for a cold chain and its ability to mimic natural infections and elicit appropriate immune responses makes this vaccine platform extremely attractive. Although, human clinical trials of DNA vaccines have yielded less than optimal results, the approval and licensing of a few veterinary vaccines is testimony to the proof-of-concept and the hope that licensed DNA vaccines for human use may not be too far away. Delivery and targeting of immunologically relevant cells appears to be the major hurdle in maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently pursued in achieving this objective are discussed.


Sinus pericranii: case report.
Sinus pericranii (SP) is an abnormal communication between the intracranial and extracranial venous drainage pathways. Treatment of this condition has mainly been recommended for aesthetic reasons and prevention of hemorrhage. The authors report a conservative treatment for the potentially lethal complications.


Cough in COPD: correlation of objective monitoring with cough challenge and subjective assessments.
The relationships between objective cough rates, cough reflex sensitivity, subjective estimates of cough frequency, and cough-related quality of life in patients with COPD are poorly understood. Twenty-six patients with stable COPD who complained of cough (76.9% men; mean +/- SD age, 68.7 +/- 6.9 years; mean FEV(1), 54.2 +/- 12.0% of predicted; median smoking history, 42.4 pack-years [range, 13 to 135 pack-years]). Subjects performed a cough challenge test, ambulatory daytime and overnight sound recordings, scored the severity of cough (0 to 5 score and visual analog scale) for each recording period, and completed a cough-specific quality of life questionnaire (CQLQ). Coughs were counted manually and quantified in terms of cough seconds per hour (cs/h): the number of seconds within the recording that contain cough. Overall median time spent coughing was 7.5 cs/h (range, 2.7 to 23.1 cs/h; daytime median, 12.4 cs/h [range, 3.3 to 40.4 cs/h]; overnight, 1.9 cs/h [0.0 to 19.0 cs/h]) [p = <0.01]. Median log concentration of citric acid eliciting five coughs (C5) was - 0.9 mol/L (range, - 1.5 to 0.0 mol/L). Day time but not overnight time spent coughing was significantly correlated with log C5 (log C5 r = - 0.49, p = 0.02, and r = - 0.20, p = 0.37, respectively). Subjective cough scores and visual analog scales were moderately associated with objective time spent coughing: daytime (r = 0.37, p = 0.03, and r = 0.41, p = 0.03) and overnight (r = 0.48, p = <0.01, and r = 0.5, p = 0.01), respectively. Subjective measures of cough and cough reflex sensitivity are statistically related to time spent coughing in patients with COPD, but with low-to-moderate levels of correlation. These measures have insufficient predictive value to substitute for objective time spent coughing; however, in conjunction with the CQLQ, they may provide a qualitative dimension to the assessment of cough.


The impact of modified instructions on ego-level scores: a psychometric hazard or indication of optimal ego level?
Various modified instructions have different effects on the Washington University Sentence Completion Test for Ego Development (Loevinger, 1985). These effects were reviewed and 2 alternative explanations were explored: The "measurement unreliability explanation" versus the "optimal level explanation." Both explanations were systematically studied in 2 test-retest experiments with the Sentence Completion Test for Children and Youths (Westenberg, Treffers, & Drewes, 1998). The modified instructions were to make a favorable impression on the tester ("fake good" condition) or to complete the sentences in as adult and mature a manner as one can ("be mature" condition). Both experiments were conducted with 9- to 15-year-old children and adolescents (N = 127, 128). As was anticipated, neither the fake good nor the be mature condition yielded higher (or lower) reliability indexes as compared to the standard instructions, hence discounting the measurement unreliability explanation. Also as expected, the fake good condition did not yield significantly higher ego-level scores, whereas the be mature condition did yield significantly higher ego-level scores. The former instructions did not convey information relevant to the construct or measure of ego development, whereas the latter instructions did convey information relevant for raising ego-level scores. It is argued that the higher scores under the be mature instructions might reflect the respondents' "optimal" ego level (best functioning), whereas the ego-level score under the standard instructions might reflect their "functional" level (normal functioning).


Chemical Fingerprinting of Seeds of Some Salvia Species in Turkey by Using GC-MS and FTIR.
Six species of Salvia seeds cultivated and grown in Cumra/Konya (Turkey) were evaluated using headspace gas chromatography mass spectroscopy (GC-MS) and Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) combined chemometrics of hierarchical cluster analysis (HCA) and principal component analysis (PCA). The major volatile compounds in the Salvia species are determined as n-hexanal (present in seven samples), sabinene (present in three samples), α-pinene (present in 13 samples), α-thujone (present in four samples), borneol (present in 11 samples), linalyl acetate (present in 10 samples), β-pinene (present in 13 samples), camphene (present in 13 samples), α-thujene (present in four samples), 2,4(10)-thujadien (present in two samples), β-myrcene (present in seven samples), limonen (present in 12 samples), 1,8-cineole (eucalyptol) (present in 13 samples) and camphor (present in nine samples). The most abundant (%) volatile compounds among all were detected as α-pinene, camphene, β-pinene and eucalyptol. For the first time, chemometrics of HCA and PCA is applied to FTIR and GC-MS data. The classification of all samples is performed on the basis of their chemical similarities and differences.


Peptides and their potential role in the treatment of diabetes and obesity.
It is estimated that 347 million people worldwide have diabetes and that over 1.5 billion adults worldwide are overweight. Predictions suggest these rates are increasing. Diabetes is a common complication in overweight and obese subjects, and in 2004, an estimated 3.4 million people died from consequences of high blood sugar. Thus, there is great interest in revealing the physiological systems that regulate body weight and blood sugar. Several peptidergic systems within the central nervous system and the periphery regulate energy homeostasis. A number of these systems have been investigated as potential treatments for obesity and the metabolic syndrome. However, manipulation of peptidergic systems poses many problems. This review discusses the peptidergic systems currently attracting research interest for their clinical potential to treat obesity. We consider first neuropeptides in the brain, including the orexigenic neuropeptide Y and melanin-concentrating hormone, and anorectic factors such as the melanocortins, ciliary neurotrophic factor, and neuromedin U. We subsequently discuss the utility of targeting peripheral gut peptides, including pancreatic polypeptide, peptide YY, amylin, and the gastric hormone ghrelin. Also, we analyze the evidence that these factors or drugs based on them may be therapeutically useful, while considering the disadvantages of using such peptides in a clinical context.


Risk Factors for Problematic Behaviors among Forensic Outpatients under the Medical Treatment and Supervision Act in Japan.
The Medical Treatment and Supervision Act (MTSA) was enacted in 2005 in Japan to promote the reintegration of clinical offenders with mental disorders into society. Under the MTSA, individuals who committed serious crimes in a state of insanity or diminished responsibility are diverted from the criminal justice system to the mental health system. Based on court decisions about MTSA-based treatment, clinical offenders have an obligation to engage in rehabilitation within their local community under the guidance of mental health professionals. However, patients under MTSA-based clinical treatments have faced various problems in the course of treatment, because of psychiatric as well as other static or dynamic factors, and sometimes have committed problematic behaviors, such as violence and medical non-compliance. Hence, this study aimed to clarify factors related to patients' inclusion in MTSA-based outpatient treatment and additionally, their commitment of problematic behaviors, based on confidential data acquired during a four-year government survey period (National Center of Neurology and Psychiatry) from MTSA enactment (July 15, 2005) to December 31, 2009. In total, we recruited 441 clinical offenders receiving MTSA-based outpatient treatment from 158 nationwide facilities. To evaluate related factors, we collected demographic, psychiatric, forensic, clinical treatment, and social service information. Statistical analyses demonstrated that predominant profiles of patients included male gender, younger age, low school history, psychiatric diagnoses (F1, F2, and F3), and no correctional or outpatient history before MTSA-based treatment. F1 or substance use diagnosis, in particular, was increasingly correlated with other factors, such as male gender, older age, and correctional history before MTSA treatment. Among the 441 patients, 189 (43%) committed problematic behaviors in the course of the MTSA-based outpatient treatment. Risk factors for patients' commitment of problematic behaviors comprised F1 diagnosis and inpatient history before MTSA-based treatment inclusion. In summary, reduction of overall problematic behaviors under the MTSA outpatient likely makes progress by focal attention to patients with psychiatric disorders caused by substance use and/or a past inpatient history for more severe psychiatric symptoms. This work is of ongoing and future importance in the domain of forensic community treatment, to connect risk-enhancing factors with risk management.


Telmisartan plus HCTZ vs. amlodipine plus HCTZ in older patients with systolic hypertension: results from a large ambulatory blood pressure monitoring study.
Systolic hypertension often requires combination therapy. Few data exist comparing angiotensin receptor blocker plus diuretic therapy with other combinations in older patients. In a prospective, randomized, open-label, blinded-end point trial, patients (> or =60 years of age) with predominantly systolic hypertension received telmisartan 40-80 mg or amlodipine 5-10 mg for 8 weeks, before the addition of hydrochlorothiazide (HCTZ) 12.5 mg for a further 6 weeks. Twenty-four-hour ambulatory blood pressure monitoring showed that telmisartan plus HCTZ (n=448) and amlodipine plus HCTZ (n=424) changed systolic blood pressure for the last 6 hours of the dosing interval by -18.3 and -17.4 mm Hg, respectively (p=0.2520). Over the 24-hour period, telmisartan plus HCTZ was superior (-19.3 and -17.2 mm Hg, respectively; p=0.001) and provided higher systolic control rates (65.9% and 58.3%, respectively; p=0.0175). Adverse events (41.2% and 53.7%, respectively) and discontinuations (5.0% and 11.3%, respectively) were lower (p<0.0001) with telmisartan than with amlodipine, mainly due to peripheral edema (1.2% and 24.3%, respectively).


[Influence of arachidonic acid metabolic inhibitors upon uterine contractions].
The stimulating action of uterine contractions of cyclooxygenase products and 5-lipoxygenase products in an arachidonic acid cascade and the role of the inhibitors of both pathways have recently been the subject of much attention. We studied the influences of these drugs using the myometriums of pregnant rats. The inhibitory effects on pregnant uterine contractions (in vitro) were in the order beta 2-stimulants (procaterol, pirbuterol) greater than AA-861 greater than flurbiprofen greater than indomethacin greater than BW-755C. The inhibitory potency was reinforced by concurrent administration of AA-861 and flurbiprofen. Stimulation of the uterine contractions by Leukotriene (LT) was LTD4 greater than LTC4, and also the inhibition of the LT strain was AA-861 greater than flurbiprofen. The stimulation of PGE1 analog (ONO-802) revealed the reaction of LT + AA-861 (-) and LT + flurbiprofen (+/-). As to the changes in c-AMP and c-GMP in the bath medium before and after the administration of each drug, the change in the administration of the LT strain was slight, and an increase in c-AMP and a decrease of c-GMP were noted following the administration of contraction inhibitory substances. Its variation ratios were noted, in the order: increase in c-AMP of AA-861 + flurbiprofen greater than pirbuterol AA-861 greater than BW-755C, and decrease in c-GMP of pirbuterol greater than AA-861 + flurbiprofen greater than A-861 greater than BW-755C.


Clinical features and diagnosis of 42 travellers with cutaneous leishmaniasis.
Leishmania species that occur within different geographical areas may cause different clinical manifestations, virulence and drug sensitivity. Patients/Methods. All patients with a clinical diagnosis of cutaneous leishmaniasis seen at the Hospital for Tropical Diseases from 1997 to 2000 were identified and clinical details recorded onto a database, with emphasis on clinical presentation, risk factors, travel history and laboratory diagnosis. Forty-two patients were identified, 23 of whom had travelled to New World and 19 to Old World countries. Clinical presentation typically consisted of a single nodule with ulceration. In 50% infection was caused by L. (Viannia) braziliensis. PCR was performed in specimens from 34 patients and species identification was possible in 32 cases (sensitivity 94%), the two PCR negative patients had amastigotes demonstrated by histology and culture. Patients were treated with established therapies. Seventy one percent were cured by treatment, 12% had a spontaneous cure, 7% were lost to follow-up and the remaining 10% required a second-line therapy. No relapses were reported during a mean follow-up period of 27 months. Our study highlights the need for comprehensive investigations and the advantages of PCR in the diagnosis of patients with suspected leishmaniasis in non-endemic regions of the world.


[Is it reasonable to perform any esthetic surgery in HIV positive patients?].
HIV seropositivity is becoming an increasingly frequent problem amongst candidates for aesthetic surgery. Although a routine screening test for HIV is not legally compulsory, it should nevertheless be requested prior to any aesthetic surgery. Is it reasonable to take the risk of aggravating the disease in order to perform purely elective aesthetic surgery? The answer to this question is not unequivocal, but must tend towards non-intervention, the reasons for which must be clearly explained to the patient in order to obtain his "informed consent".


Comprehensive Genomic Profiling of Upper-tract and Bladder Urothelial Carcinoma.
Characterization of the different genomic alterations (GAs) in urothelial carcinoma (UC), by site of origin, may identify contrasting therapeutic opportunities and inform distinct putative pathogenetic mechanisms. To describe the genomic landscape of UC based on the anatomic site of the primary tumor. In total, 479 upper tract UC (UTUC) and 1984 bladder UC (BUC) patients underwent comprehensive genomic profiling (CGP) to evaluate all classes of GAs, tumor mutational burden (TMB), and microsatellite instability (MSI) status. Targetable GAs and signatures were assessed according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT). Hybrid-capture-based CGP. Descriptive analyses and differences between anatomic subgroups were reported. In total, 39% of patients with UC harbored one or more tier 1-2 GAs, suggesting potential benefit from approved or investigational therapies. UTUC cases were enriched in FGFR3 short variant (SV) GA (20% vs 13%) and HRAS SV GA (7.3% vs 3%), the latter attributed specifically to enrichment in renal pelvis UC (9.5%) versus ureteral UC (1.8%, p=0.002). RB1 GAs were more frequent in BUC than in UTUC (21% vs 7.8% p<0.001). Non-FGFR3 kinase fusions were observed in 1% of patients, including BRAF/RAF1 fusions in 0.5%. BRAF mutations/fusions were observed in 2% of cases and were mutually exclusive with FGFR3 GA (p=0.002). There were no differences of TMB high/MSI high for primary tumor and metastatic sites, but UTUC was enriched for MSI high (3.4%) relative to BUC (0.8%, p<0.001). Differences in the genomic landscapes of UTUC and BUC were modest; however, patients with UTUC were enriched for FGFR3 and HRAS SV relative to BUC. Further investigation on UC, stratified by the site of origin, is warranted. In addition, these results suggest an opportunity for the routine incorporation of CGP prior to systemic therapy initiation in metastatic UC. Genomic profiling of advanced urothelial carcinoma can inform several therapeutic opportunities for patients, particularly those with upper tract urothelial carcinoma, an infrequent and generally aggressive tumor entity with nonoverlapping clinical features compared with its bladder counterpart, which is often treated based on the data extrapolated from bladder cancer.


The epidemiology of Salmonella infection of calves: the role of dealers.
Salmonellas were detected in the environment of 10 of the 12 calf dealers' premises studied. The cleaning and disinfection routines were often ineffective and salmonellas were isolated from 7.6% and 5.3% of the wall and floor samples before disinfection and 6.8% and 7.6% afterwards. Eight different salmonella serotypes were detected, of which the commonest were Salmonella typhimurium, predominantly phage type DT204C, and S. dublin. Plasmid profiles were used to fingerprint S. typhimurium DT204C and the results indicated that with the exception of one of the premises, prolonged salmonella-persistence in the environment was not occurring. Three separate epidemics of salmonellosis in calves were studied by use of plasmid profile analysis. The results illustrated the role of delers, and their subcontractors, in the dissemination of salmonellas. The study concludes with suggestions for methods to reduce the spread of salmonellas in the calf marketing chain.


Transplantation of Human Adipose Stem Cells Using Acellular Human Amniotic Membrane Improves Angiogenesis in Injured Endometrial Tissue in a Rat Intrauterine Adhesion Model.
Endometrial injury resulting in intrauterine adhesion is associated with extensive damage to the regenerative basal layer of the endometrium and represents a major therapeutic challenge. Human adipose stem cells (hASCs) hold promise for future clinical use in the individualized therapy of injured endometrial tissue. Here, we observed that the use of the acellular human amniotic membrane (AHAM) significantly increased the expression of angiogenic factors, including angiogenin (ANG) and vascular endothelial growth factor (VEGF), in hASCs in vitro. The three-dimensional engineered hASC-AHAM grafts significantly increased the endometrial receptivity, as increased endometrial thickness, greater numbers of endometrial glands, and higher protein levels of leukemia inhibitory factor were observed in injured endometrial tissue that was treated with these grafts compared to those detected in injured endometrial tissue that was treated with AHAM alone. In addition, the hASC-AHAM grafts significantly increased the vascular density in the injured endometrial tissue in rats, when transplanted into an injured uterine cavity. Using the EGFP+-hASC-AHAM grafts for transplantation, we confirmed that the hASCs maintained higher protein levels of ANG and VEGF in the injured uterine cavity in vivo. The results of this study suggest that the ability of the engineered hASC-AHAM grafts to repair injured endometrial tissue may be associated with their ability to promote angiogenesis through the upregulated expression of angiogenic factors in hASCs. These findings may support individualized stem cell-based therapy for endometrial disease using bioartificial grafts.


Proficiency Based Progression (PBP) training- the future model for dental operative skills training?: A systematic review and meta-analysis of existing literature.
To evaluate the effectiveness of Proficiency-Based Progression (PBP) operative training using validated performance metrics, by comparing this to standard, conventional training methods. This systematic review was conducted in accordance with the guidelines of the Transparent Reporting of Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the MERSQI tool and the Cochrane Risk of Bias tool. Results were pooled using biased corrected standardized mean difference and ratio-of-means (ROM). Summary effects were evaluated using a series of fixed and random effects models. The primary outcome was the number of procedural errors performed comparing PBP and non-PBP-based training pathways. In quantitative synthesis testing for procedural errors, a pooled meta-analysis on 87 trainees was conducted using random-effects models. In a ROM analysis, PBP was estimated to reduce the mean rate of errors by 62%, when compared to standard training (ROM 0.38, 95% CI: 0.25; 0.58; p < 0.001) Sources: The electronic databases of PubMed, Embase, Web of Science, MEDLINE and Cochrane library's CENTRAL were searched from inception to 8/11/2021. Filters activated were Randomized Controlled trials, clinical trial. 13 studies were included for review with 11 included in the quantitative synthesis from 174 potentially relevant publications identified by the search strategy. Main inclusion criteria were studies comparing standard surgical/operative training with proficiency-based simulation training using validated metrics based on expert performance. Our meta-analysis found that PBP training improved trainees' performances, by decreasing procedural errors. There is sufficient evidence to explore PBP training for use in dental skills training. PBP training was estimated to reduce the mean rate of operative errors by 62%, when compared to standard training. Given that there is a direct correlation between operative skill and patient outcomes, these data suggest that there is sufficient evidence to explore PBP training for use in dental skills training.


The Context of Caring and Concern for Falling Differentiate Which Mobile Fall Technology Features Chinese Family Caregivers Find Most Important.
Falls are not only a leading cause of death and disability, but also a strain on the capacity for caregivers to provide care. This study examined how the context of caregiving relates to the importance of caregiver-defined mobile fall prevention feature sets. A sample of 266 family caregivers, recruited from a Chinese social media platform, reported care for an older adult and interest in mobile fall prevention technology features. Factor analysis identified three caregiver-defined feature sets: automatic fall response, digitized fall prevention tools, and social features. Multiple regression showed caregivers' concern about falling was the most robust predictor of a feature set's importance. Poisson regression revealed that caregiver concern and assistance with instrumental activities of daily living were associated with rating more features as important. Our findings suggest that caregivers are interested in mobile fall prevention technologies that support older adults' independence while also alleviating concerns about falling.


Mismatch negativity and personality traits in chronic primary insomniacs.
The thalamo-(fronto)cortical circuit is involved in sleep regulation, and its dysfunction might contribute to the pathophysiology of chronic primary insomnia. To obtain more evidence of the involvement of the circuit, we studied 23 patients with chronic primary insomnia and 28 healthy volunteers via the assessment of mismatch negativity (MMN) elicited by tone intensity deviance, and of personality traits measured by Zuckerman's Sensation Seeking Scales, and Zuckerman-Kuhlman's Personality Questionnaire. In insomniacs, MMN amplitude at Fz was significantly larger; Depression, which was measured by Plutchik-van Praag's Depression Inventory, and Neuroticism-anxiety and Impulsivity scores were higher, while the Thrill and adventure seeking score was lower; MMN amplitude was positively correlated with Depression and with Impulsivity. In healthy subjects, MMN amplitude at Fz was positively correlated with Neuroticism-anxiety, but negatively with Experience seeking. The larger MMN and distinct personality traits suggest a hyperactivity in the thalamo-(fronto)cortical neuronal circuit in insomniacs, which is probably the result of weak thalamic gating mechanisms, or an imbalance of several neurotransmitter systems.


A wooden orbital foreign body.
A case is reported in which a patient presented, 18 months after initial injury, with a progressive proptosis of the left eye. X-rays did not reveal a foreign body but a fracture of the lateral orbital wall and an area of soft tissue density were seen on the CT scan. Exploration of the orbit revealed a 2 cm wooden fragment in the floor of the orbit.


Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene.
Heme oxygenase-1 (HO-1) protects cells from various insults including oxidative stress. Transcriptional activators, including the Nrf2/Maf heterodimer, have been the focus of studies on the inducible expression of ho-1. Here we show that a heme-binding factor, Bach1, is a critical physiological repressor of ho-1. Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo, while heme abrogated this repressor function of Bach1 by inhibiting its binding to the ho-1 enhancers. Gene targeting experiments in mice revealed that, in the absence of Bach1, ho-1 became expressed constitutively at high levels in various tissues under normal physiological conditions. By analyzing bach1/nrf2 compound-deficient mice, we documented antagonistic activities of Bach1 and Nrf2 in several tissues. Chromatin immunoprecipitation revealed that small Maf proteins participate in both repression and activation of ho-1. Thus, regulation of ho-1 involves a direct sensing of heme levels by Bach1 (by analogy to lac repressor sensitivity to lactose), generating a simple feedback loop whereby the substrate effects repressor-activator antagonism.


[Expression of occludin and zona occluden-1 and their morphologic changes in vagina mucosal cells in patients undergoing vaginal construction by using sigmoid colon].
In order to evaluate the changes of neovaginal defense function in the sight of physical barrier by investigating the changes in the histological morphology and expression of occludin, zona occluden-1 (ZO-1) in mucosal cells of the neovagina in patients undergoing vaginal construction by sigmoid colon. Fifteen cases with neovagina constructed by sigmoid colon matched with 15 cases' vaginal mocusa as control specimens were observed with light microscopic and electron microscopic methods. At the same time, the expression of occludin and ZO-1 were semiquantitatively measured by streptavidin-perosidase (SP) immunohistochemical method. (1) Squamous metaplasia was observed in colonic mucosa from lower one-third of the artificial vagina in 10 cases (67%, 10/15). (2) The intercellular tight junctions of neovaginal mucosa became shorter and wider, the number of them were decreased or disappeared by electron microscopic study. (3) In upper neovagina, the positive rates of occludin and ZO-1 expression in mucosal cells were 80% (12/15) and 73% (11/15), respectively. In lower neovaginal mucosa where squamous metaplasia occurred, the positive rates of two protein expression in cells were both 100% (10/10) and also was 100% (15/15) in control group, which showed significant difference (P < 0.05, P < 0.01). In lower neovaginal mucosa where squamous metaplasia hadn't occurred, the positive expression of two protein in cells (4/5, 2/5) were significantly lower than those in lower neovaginal mucosa where squamous metaplasia had happened 100% (10/10), 100% (10/10) and in control group [100% (15/15), 100% (15/15)] (P < 0.05), while there were no significantly difference in positive expression of two protein in cells between this group and upper neovagina (P > 0.05). The squamous metaplasia had occurred in lower neovaginal mucosa. The decreased expression of occludin and ZO-1 in upper and lower neovaginal mucosa where squamous metaplasia didn't occurred. However, In lower neovaginal mucosa where squamous metaplasia occurred, the expression of occludin and ZO-1 in cells were similar to those in control group, which might play a role in the defense function of neovaginal mucosa.