Observation of ultralong-range Rydberg molecules.
Rydberg atoms have an electron in a state with a very high principal quantum number, and as a result can exhibit unusually long-range interactions. One example is the bonding of two such atoms by multipole forces to form Rydberg-Rydberg molecules with very large internuclear distances. Notably, bonding interactions can also arise from the low-energy scattering of a Rydberg electron with negative scattering length from a ground-state atom. In this case, the scattering-induced attractive interaction binds the ground-state atom to the Rydberg atom at a well-localized position within the Rydberg electron wavefunction and thereby yields giant molecules that can have internuclear separations of several thousand Bohr radii. Here we report the spectroscopic characterization of such exotic molecular states formed by rubidium Rydberg atoms that are in the spherically symmetric s state and have principal quantum numbers, n, between 34 and 40. We find that the spectra of the vibrational ground state and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)-Rb(ns), agree well with simple model predictions. The data allow us to extract the s-wave scattering length for scattering between the Rydberg electron and the ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100 meV), and to determine the lifetimes and the polarizabilities of the Rydberg molecules. Given our successful characterization of s-wave bound Rydberg states, we anticipate that p-wave bound states, trimer states and bound states involving a Rydberg electron with large angular momentum-so-called trilobite molecules-will also be realized and directly probed in the near future.


The leptin receptor mediates apparent autocrine regulation of leptin gene expression.
The possibility that the leptin receptor (LEPR) mediates autocrine regulation of leptin expression in adipose tissue was examined in 10-day-old Zucker rat pups with different copy numbers of the leptin receptor mutation (Lepr(fa)). Plasma leptin concentrations and adipose tissue mRNA levels for leptin were related to copy number of the mutation (fa/fa > fa/+ > +/+). These relationships were independent of plasma insulin concentration. Reduced copy number for the functional leptin receptor apparently results in a diminished negative feedback signal to the leptin gene in adipose tissue. Thus, leptin appears to close a short regulatory loop controlling its own synthesis in adipose tissue.


Recurrent carotid disease: will stents be an alternative to surgery?
To report the results of balloon angioplasty in recurrent carotid occlusive disease and evaluate the potential for stent implantation. Between April 1991 and September 1995, 15 patients with carotid restenosis underwent 17 endoluminal procedures in 3 common carotid and 14 internal carotid arteries. Two postdilation complications (dissection and acute occlusion) required prompt stenting; one common carotid artery was stented for postdilation residual stenosis. One recurrent lesion was also stented 6 months after initial angioplasty. One stroke, 1 silent cerebral infarction, and 3 transient ischemic attacks occurred in the balloon angioplasty patients (33% neurological complication rate). The common carotid stent patient died 3 days postoperatively due to hyperperfusion syndrome. Long-term follow-up in two stent patients showed no restenosis at 18 and 48 months, respectively. The 11 balloon angioplasty patients likewise have not demonstrated restenosis. Balloon angioplasty alone appears too risky for treating recurrent carotid disease. Stents may offer a safer alternative, particularly when implanted primarily.


Human T lymphotropic virus type II (HTLV-II): epidemiology, molecular properties, and clinical features of infection.
Human T lymphotropic virus, type II (HTLV-II), infection has been shown to be endemic in a number of American Indian populations, and high rates of infection have also been documented in intravenous drug abusers in urban areas throughout the world. Although the role of HTLV-II in human disease has yet to be clearly defined, there is accumulating evidence that like HTLV-I, infection may also be associated with rare lymphoproliferative and neurological disorders. In this article we review and summarize the epidemiology, molecular properties and clinical features of HTLV-II infection.


Non-invasive breath collection in murine models using a newly developed sampling device.
Volatile organic compounds (VOCs) in exhaled breath have the potential to be used as biomarkers for screening and diagnosis of diseases. Clinical studies are often complicated by both modifiable and non-modifiable factors influencing the composition of VOCs in exhaled breath. Small laboratory animal studies contribute in obtaining fundamental insight in alterations in VOC composition in exhaled breath and thereby facilitate the design and analysis of clinical research. However, long term animal experiments are often limited by invasive breath collection methods and terminal experiments. To overcome this problem, a novel device was developed for non-invasive breath collection in mice using glass nose-only restrainers thereby omitting the need of anesthetics. C57Bl/6 J mice were used to test reproducibility and different air sampling settings for air-flow (ml min-1) and time (minutes). Exhaled air was collected on desorption tubes and analysed for VOCs by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). In total 27 compounds were putatively identified and used to assess the variability of the VOC measurements in the breath collections. Best reproducibility is obtained when using an air flow of 185 ml min-1and a collection time of 20 min. Due to the non-invasive nature of breath collections in murine models, this device has the potential to facilitate VOC research in relation to disturbed metabolism and or disease pathways.


van't Hoff and calorimetric enthalpies II: effects of linked equilibria.
The complexity of binding reactions, including the linkage with other equilibria, is becoming increasingly apparent in biological processes such as signal transduction. Understanding these interactions requires obtaining thermodynamic profiles for each of the equilibria that occur in a binding event. Concern has been raised as to whether linked equilibria contribute differently to thermodynamics, such as DeltaH degrees and DeltaC(p), obtained from calorimetric and van't Hoff methods. We have previously shown that linked equilibria do not contribute differently to the van't Hoff and calorimetrically determined DeltaH degrees for processes such as linked folding or hydration. Here, examples of proton and ion linkage are examined. We show that there is no reason to expect the calorimetric and van't Hoff DeltaH degrees to be different, even without prior knowledge of the presence or absence of linked equilibria, as long as the system is permitted to equilibrate. However, it is possible to create experimental scenarios that result in and discrepancies. Furthermore, it is found that the presence of linked equilibria in all cases can result in "nonconventional" DeltaH degrees and DeltaC(p) profiles, making data analysis nontrivial.


Oenothein B suppresses lipopolysaccharide (LPS)-induced inflammation in the mouse brain.
Oenothein B has been recently evaluated for its ability to affect inflammatory responses in peripheral tissues. In this study, we examined its effect on the damage to the central nervous system due to systemic inflammation. For this purpose, ICR mice were injected with an intraperitoneal (i.p.) dose of lipopolysaccharide (LPS; 1 mg/kg mouse). When oenothein B was administered per os (p.o.), it suppressed (1) LPS-induced abnormal behavior in open field; (2) LPS-induced microglial activation in the hippocampus and striatum; and (3) LPS-induced cyclooxygenase (COX)-2 production in the hippocampus and striatum of these mice. These results suggest that oenothein B had the ability to reduce neuroinflammation in the brain during systemic inflammation.


Scientific Meetings.
In the issue of 16 Sept., page 526, the American Mathematical Society which will hold its 62nd annual meeting in Houston, Tex., on 27-29 Dec. was incorrectly listed as the American Meteorological Society.


Inhibition of pear fruit ripening by mannose.
Softening of the flesh and the rise in ethylene evolution and respiration associated with ripening in pear (Pyrus communis L.) fruit was delayed when mannose was vacuum infiltrated into intact fruit. The extent of delay could be modified by altering the concentration or the volume of mannose applied to the fruit. Inhibition of ripening was associated with phosphorylation of mannose to mannose 6-phosphate (M6P), and accumulation of M6P was associated with lowered levels of inorganic phosphate (Pi), glucose 6-phosphate (G6P), and ATP in the fruit tissue. Subsequently, however, as the M6P was metabolized, the levels of Pi, G6P, and ATP increased and ripening processes were concomitantly released from inhibition. Hence, the degree of inhibition by mannose or the release from inhibition was related to the level of M6P in the fruit and its rate of metabolism. The data provide correlative evidence to support a view that one inhibitory effect of mannose is depletion of Pi in the cell as a result of phosphorylation of mannose to M6P. Inhibition of ripening by mannose was not alleviated by co-application of glucose as a competitive substrate for the hexokinase(s), or by Pi, presumably the depleted metabolite. Also, incubation of tissue disks with M6P resulted in inhibition of ethylene production and respiration. The structural analogs of mannose, glucosamine, and 2-deoxyglucose, which have been shown to mimic mannose action in several plant tissues, did not cause inhibition of ripening of pear fruit comparable with that associated with mannose. Both analogs stimulated respiration, and glucosamine caused only a small inhibition of softening and ethylene evolution. Another mannose analog, alpha-methylmannoside, did inhibit fruit ripening though to a lesser extent than mannose. Its influence was also associated with accumulation of M6P and a decrease of Pi levels. We conclude that the mannose effect may, in part, be due to M6P toxicity, as well as by depletion of Pi.


Central projections of primary sensory neurons innervating different parts of the vibrissae follicles and intervibrissal skin on the mystacial pad of the rat.
The cell bodies and central projections of neurons innervating the vibrissae follicles and adjacent skin in the rat were investigated by retrograde and transganglionic transport of HRP. The cell bodies of neurons innervating the vibrissa follicle via the deep vibrissa nerve (DVN) were the largest, followed by those innervating the follicle via the superficial vibrissa nerve (SVN). The smallest cell bodies were those innervating the intervibrissal skin. The DVN neurons terminated centrally as an almost uninterrupted column through the trigeminal sensory nuclear complex. The DVN projections to nucleus caudalis and C1 dorsal horn were entirely restricted to laminae III, IV, and V. Besides the projections to lamina V, the DVN projections were strictly localized somatotopically at all levels replicating the peripheral organization of the vibrissae. The SVNs projected sparsely to midlevels of the main sensory nucleus but not to nuclei oralis and interpolaris. The main SVN projections appeared in laminae I-III of nucleus caudalis. In addition, a small projection to lamina V was observed. The projections to laminae II and III were organized mediolaterally in a similar way as the DVN projections; those to laminae I and V were less restricted. The intervibrissal skin neurons projected sparsely to the caudal main sensory nucleus and to the border between nuclei oralis and interpolaris. The projections to nucleus caudalis were restricted to laminae I-III and V and were organized in a similar way as the SVN projections.


Referral patterns of patients with liver metastases due to colorectal cancer for resection.
Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. Retrospective review of patient's charts diagnosed with colorectal liver metastases over a 10-year period. One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.


The grief process for patient, family, and physician.
In the grieving process, patient, family, and health professionals have the same needs-rest, relaxation, nourishment, a sense of security, trust, hope in the future, and humor among them. Grief, defined as a shared, universal, and natural neuropsychobiologic expression in response to loss, is distinct from mourning, a practice that varies in expression across diverse cultures. To aid in an understanding of grief and its effects, the author looks at the models for grief proposed by Kubler-Ross, Bowlby, Parkes, Worden, and Wolfelt. Addressing patients' concerns requires physicians be empathic, attentive, and respective and have willingness to take time, be present, and listen.


Radiation Recall Dermatitis in Patients Treated With Immune Checkpoint Inhibitors: A Case Report and Literature Review.
Radiation recall dermatitis (RRD) is defined as a skin reaction in the previously irradiated area triggered by a systemic agent's administration. The use of immune checkpoint inhibitors (ICI) alone and in combination with other treatments is increasing in many cancers. ICI-associated radiation recall reactions such as dermatitis, pneumonia, and myelitis have been reported so far. We report a case of nivolumab (anti-programmed cell death protein-1 antibody) induced RRD in a patient with head and neck cancer and review the publications reporting RRD associated with other ICI in the literature. The patient was diagnosed with neck metastasis of unknown primary origin and underwent surgery followed by adjuvant chemoradiotherapy (CRT). During the follow-up, radiotherapy (RT) was performed to the left parotid region, right neck level 1b, and the left neck skin due to recurrence. After three months of the last RT session, she was started on nivolumab due to the metastatic disease. Four weeks later, she was represented with erythematous squamous plaque-like lesions starting from the left temporomandibular region and spreading to the anterior chest, which corresponded to the previously irradiated area. A biopsy was performed with the differential diagnosis of skin metastases which revealed subacute spongiotic dermatitis. The lesions completely regressed in two weeks with the use of topical steroids and antihistamine tablets. Nivolumab treatment was not interrupted, and no reaction was observed during or after the next cycle. Although RRD is rarely encountered clinically, it is a diagnosis that should be kept in mind while continuing treatment with systemic agents in patients with a history of RT. With the widespread use of ICI, RRD associated with these treatments could be better defined and appropriately managed.


Treatment of patients with HIV in state of flux.
Protection of patients' privacy is important professionally, legally, and personally. Nurses must use discretion when discussing the HIV status of a patient with others. Treating patients with HIV or AIDS involves protection of staff as well as the patient.


Built environment and early infection of COVID-19 in urban districts: A case study of Huangzhou.
Since COVID-19 spread rapidly worldwide, many countries have experienced significant growth in the number of confirmed cases and deaths. Earlier studies have examined various factors that may contribute to the contagion rate of COVID-19, such as air pollution, smoking, humidity, and temperature. As there is a lack of studies at the neighborhood-level detailing the spatial settings of built environment attributes, this study explored the variations in the size of the COVID-19 confirmed case clusters across the urban district Huangzhou in the city of Huanggang. Clusters of infectious cases in the initial outbreak of COVID-19 were identified geographically through GIS methods. The hypothetic relationships between built environment attributes and clusters of COVID-19 cases have been investigated with the structural equation model. The results show the statistically significant direct and indirect influences of commercial vitality and transportation infrastructure on the number of confirmed cases in an infectious cluster. The clues ch inducing a high risk of contagions have been evidenced and provided for the decision-making practice responding to the initial stage of possible severe epidemics, indicating that the local public health authorities should implement sufficient measures and adopt effective interventions in the areas and places with a high probability of crowded residents.


Correlation of reaction time and EEG log bandpower from dry frontal electrodes in a passive fatigue driving simulation experiment.
Fatigue is one of the causes of falling asleep at the wheel, which can result in fatal accidents. Thus, it is necessary to have practical fatigue detection solutions for drivers. In literature, electroencephalography (EEG) along with the surrogate measure of reaction time (RT) has been used to develop fatigue detection algorithms. However, these solutions are often based upon wet multi-channel EEG electrodes which are not feasible or practical for drivers. Using dry electrodes and headband like designs would be better. Hence, this study aims to investigate the correlation of EEG log bandpower against RT via a Muse headband which has dry frontal EEG electrodes. 31 subjects underwent an hour-long driving simulation experiment with car deviation events. Based on the video and EEG data, 5 `Sleepy' and 5 `Alert' subjects are identified and analyzed. A differential signal between Fp1 and Fp2 is computed so as to remove the effects of eye blinks, and is analyzed for correlation with RT. Significant positive correlation is found for log delta (1-4 Hz) bandpower, and significant negative correlations for log theta (4-8 Hz) and alpha (8-12 Hz) bandpowers, but the positive correlation of log beta (12-30 Hz) bandpower with RT is not significant. This is a good first step towards building a practical fatigue detection solution for drivers in the future.


Surgical microwave ablation for multifocal non-resectable liver metastases: a single institution experience treating five or more liver lesions.
Thermal ablation is an effective treatment for patients with metastatic colon and rectal cancer and allows surgeons to offer curative intent therapy to patients who are otherwise not candidates for resection. We aimed to report outcomes of a single institution experience using microwave ablation (MWA) with or without resection to treat five or more liver metastases. In this retrospective cohort study, the University of Minnesota Division of Surgical Oncology liver surgery database was queried to identify all patients who underwent thermal ablation of five or more colorectal liver metastases (CRLM) between 2012-2018. We reviewed patient, disease, and tumor characteristics and measured local, intrahepatic, and extrahepatic recurrence (EHR) rates. We also calculated median overall survival (OS) and disease-free survival (DFS). Ten patients identified had five or more (range, 5-18) tumors ablated with or without combined liver and bowel resection. Median age was 50, and most patients were male (70%) and Caucasian (90%). Four patients received ablation alone (5-12 lesions), while six had combined resection and ablation (5-18 lesions). Ablation was performed laparoscopically in six patients, and four had ablations without resection. All patients received pre- and post-operative chemotherapy. A median of 7 tumors were ablated per patient. Median follow-up was 2.3 years. Among 75 tumors ablated, ablation site recurrence (ASR) (within 1 cm of ablation site) was seen in three with a per-lesion recurrence rate of 4%. Intrahepatic recurrence (IHR) occurred in 6 (60%) patients and EHR in 1 (10%). Five patients underwent retreatment of IHR during follow-up. Median OS was 3 years and DFS was 7.1 months. At the time of last follow up, 6 patients were disease-free. Thermal ablation can provide acceptable DFS and OS, even with high volume metastatic colorectal cancers. Future efforts should be focused on defining selection criteria for those most likely to benefit from this aggressive approach.


Space Charge Effects on Ion Mobility Spectrometry.
We study the space charge limited maximal current density j″ of mobility-selected ions that can be transmitted in ion mobility spectrometry (IMS). Theory and experiments focus on differential mobility analyzers (DMAs), but are readily generalizable to other IMS devices. Repulsion between the ions in the cloud leads to beam spreading, with significant broadening once the ion number density n becomes comparable to the space charge saturation limit nsat = εoEo/(eΔ). Δ is the distance traversed by the ions in the direction of an externally imposed electric field Eo, and e is the charge on each ion. For ions of electrical mobility Z, j″ is then limited below j″sat = ZEoensat = ZεoEo2/Δ. A theory including diffusion and space charge effects is developed that reduces to Burgers' exactly solvable equation. The theory is tested in experiments with room temperature electrosprays (ES) of 100 mM [ethyl3N+-formate-] in methanol. This spray produces primarily a single ionic species at very high initial concentration n, which may be tuned above or below nsat by varying the distance from the ES emitter to the inlet slit of the DMA. Mobility-selected ion densities n > 3.108 ions/cm3 are achieved, with n~nsat, and with drastically broadened mobility peak shapes having the approximate top hat-predicted shapes. However, the largest n values approaching nsat are not quantitatively measurable because the densest sprays do not fill the outlet slit length. Graphical Abstract .


Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation.
Ion homeostasis in the inner ear is essential for proper hearing. Anion exchangers are one of the transporters responsible for the maintenance of homeostasis, but their expression profile in the primate cochlea has not been fully characterized. However, species-specific overlapping expression patterns and functional compensation in other organs, such as the kidney, pancreas and small intestine, have been reported. Here, we determined the expression patterns of the anion exchangers SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A11, SLC4A2 and SLC4A3 in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). Although the pattern of expression of SLC26A4 and SLC26A5 was similar to that in rodents, SLC26A7, SLC4A2, SLC4A3 exhibited different distributions. Notably, five transporters, SLC26A4, SLC26A6, SLC26A11 SLC4A2 and SLC4A3, were expressed in the cells of the outer sulcus. Our results reveal a species-specific distribution pattern of anion exchangers in the cochlea, particularly in the outer sulcus cells, suggesting functional compensation among these exchangers. This "primate-specific" pattern may be related to the human-specific hearing loss phenotypes of channelopathy disorders, including the SLC26A4-related diseases Pendred syndrome/DFNB4.


[Is "involuntary childlessness" within the realm of family medicine responsibility of the general practitioner?].
The aim of the study was to assess whether or not management of infertility is within the domain of the general practitioner in his capacity as a family physician. All accredited family physicians in the wider area of Goettingen were invited to take part in our survey. A total of 57 doctors (84%) participated. In personal interviews the family physicians were encouraged to frankly discuss the following main topics: the frequency of infertility in their own practice as well as their care for and attitudes towards infertile patients. Many family physicians interviewed were reluctant to address involuntary childlessness and underestimated its frequency. According to their patients' needs and demands, however, family doctors--above all in rural practices--have been participating in the screening and counseling of, and providing emotional support for, involuntarily childless patients. A qualitative analysis of the interview data revealed that many family physicians regarded infertility as the patients' private matter and placed it within the domain of specialists. About one-third of the physicians expressed negative attitudes towards infertile patients. Moreover, assisted reproduction techniques were sometimes rejected as "unnatural" methods. If a family-oriented approach should be amplified in family practice by offering supportive counseling for infertile patients, continuing medical education will have to take these attitudes into account.


Dual anti-angiogenic and cytotoxic properties of ruthenium(III) complexes containing pyrazolato and/or pyrazole ligands.
An oxo-bridged diruthenium(III) complex containing pyrazolato and pyrazole ligands is stable against ascorbic-acid reduction, induces apoptosis (60%, 48 h) against HeLa cells at 10 microM level and exhibits promising anti-angiogenic activity at its sub-cytotoxic concentrations. Other mononuclear ruthenium(III) complexes containing pyrazole ligands [Ru(pz)(4)X(2)](+) exhibit dual anti-angiogenic and cytotoxic properties.


Age-related Activation of Cyclic GMP-AMP synthase-Stimulator of Interferon Genes Signaling in the Auditory System is Associated with Presbycusis in C57BL/6J Male Mice.
Presbycusis, or age-related hearing loss (ARHL), is primarily associated with sensory or transduction nerve cell degeneration in the peripheral and/or central auditory systems. During aging, the auditory system shows mitochondrial dysfunction and increased inflammatory responses. Mitochondrial dysfunction promotes leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to induce type I interferon and inflammatory responses. However, whether this pathway is involved in the occurrence and development of ARHL is unknown. This study aimed to determine whether there are age-related changes in the levels of cytosolic mtDNA and cGAS-STING pathway activation in the auditory pathway and to explore their relationship with ARHL. The results showed that cGAS-positive immunoreactive cells were observed in the cochlea, inferior colliculus, and auditory cortex. Levels of cytosolic mtDNA, cGAS, STING, phosphorylated interferon regulatory factor 3, and cytokines were significantly increased in the cochlea, inferior colliculus, and auditory cortex of 6-, 9-, and 12-month-old mice compared with 3-month-old mice. These findings suggested that cytosolic mtDNA may play an important role in the pathogenesis of ARHL by activating cGAS-STING-mediated type I interferon and inflammatory responses.


Immunodistribution of amyloid beta protein (Aβ) and advanced glycation end-product receptors (RAGE) in choroid plexus and ependyma of resuscitated patients.
RAGE (receptor for advanced glycation end-products) participates in the influx transport of glycated Aβ (amyloid beta) from the blood to the brain. Because little is known of the RAGE operating in brain barriers such as those in the choroid plexus and ependyma, the aim of the present study was to examine the immunodistributions of RAGE and Aβ peptides in the choroid plexus where the blood-cerebrospinal fluid barrier (B-CSF) is located, and in ependyma of the brain ventricles associated with functions of the cerebrospinal fluid-brain barrier (CSF-B). The study was performed on patients over 65 years successfully resuscitated after cardiac arrest with survival a few weeks. The control group consisted of age-matched individuals who were not resuscitated and died immediately after cardiac arrest. In resuscitated patients, but not in controls, RAGE receptors were localized in choroid plexus (CP) epithelial cells and in ependymal cells bordering the brain ventricles. These cells form the B-CSF and CSF-B barriers. The presence of Aβ was detected within the CP blood vessels and in the basement membrane of the CP epithelium. In numerous cytoplasmic vacuoles of CP epithelial and ependymal cells Aβ protein was found and our observations suggest that the contents of those vacuoles were undergoing progressive digestion. The results demonstrated that CP epithelium and ependymal cells, equipped with RAGE receptors, not only play an important role in the creation of amyloid deposits in the brain but are also places where Aβ may be utilized. The RAGE transportation system should be a main target in the therapy of brain amyloidosis, a well-known risk factor of Alzheimer disease.


Characterization of a gE/gI/TK gene-deleted pseudorabies virus variant expressing the Cap protein of porcine circovirus type 2d.
Porcine circovirus type 2 (PCV2) plays a key role in the etiology of PCV2-associated disease (PCVAD), and its predominant strain is PCV2d which is not completely controlled by most commercially available vaccines against PCV2a strains. Pseudorabies (PR) caused by pseudorabies virus (PRV) variants re-emerged in Bartha-K61 vaccine-immunized swine herds in late 2011, which brought considerable losses to the global pig husbandry. Therefore, it is significantly important to develop a safe and effective vaccine against both PCV2d and PRV infection. In the present study, the PCV2d ORF2 gene was amplified by PCR, and cloned into the BamHI site of PRV transfer plasmid pG vector to obtain the recombinant transfer plasmid pG-PCV2dCap-EGFP. Subsequently, it was transfected into ST cells infected with the three gene deleted PRV variant strain NY-gE-/gI-/TK- to generate a recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+/EGFP+, and then the EGFP gene was knocked out to harvest the rPRV NY-gE-/gI-/TK-/PCV2dCap+ using gene-editing technology termed CRISPR/Cas9 system. The recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ had similar genetic stability and proliferation characteristics to the parental PRV as indicated by PCR and one-step growth curve test, and the expression of Cap was validated by Western blot. In animal experiment, higher PCV2-specific ELISA antibodies and detectable PCV2-specific neutralizing antibodies could be elicited in mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ compared to commercial PCV2 inactivated vaccine. Moreover, the recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ significantly reduced the viral loads in the hearts, livers, spleens, lungs, and kidneys in mice following a virulent PCV2d challenge. Mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ developed comparable PRV-specific humoral immune responses and provided complete protection against a lethal PRV challenge. Together, the rPRV NY-gE-/gI-/TK-/PCV2dCap+ recombinant strain has strong immunogenicity.


Acne Severity and Sleep Quality in Adults.
Poor sleep quality is extremely prevalent, with about one third of adults in the USA obtaining less than the recommended amount of sleep. In addition, poor sleep quality has been linked to an increased risk of many conditions, including diabetes, hypertension, psychiatric conditions, and overall all-cause mortality. Research has shown that sleep disturbance does impact skin disease, although many details of this relationship are still unclear. The goal of this study is to determine if there is a relationship between acne severity and sleep quality in adults. Forty subjects with acne were recruited from dermatology clinics in Cleveland, OH, to participate in this study. Acne severity was assessed using the Global Acne Grading Scale (GAGS). To assess sleep quality, subjects completed the Pittsburgh Sleep Quality Index (PSQI) and completed a seven-day sleep journal. Subjects also completed the Dermatology Life Quality Index (DLQI), the Patient Health Questionnaire-2 (PHQ-2), and provided information about current and past acne treatments as well as their opinion regarding their own acne severity and exacerbating factors. Our findings support the hypothesis that there is a potential relationship between sleep quality and acne.


The effect of transcutaneous auricular vagus nerve stimulation on HRV in healthy young people.
Transcutaneous auricular vagus nerve stimulation (taVNS) has shown positive effects on a variety of diseases. Considering that decreased heart rate variability (HRV) is closely associated with morbidity and mortality for a variety of diseases, it is important to investigate the effect of taVNS on HRV. In Study 1, we conducted a two-stage cross-over trial to compare the effects of taVNS and sham taVNS (staVNS) on HRV. In Study 2, we systematically tested the effects of different taVNS parameters on high frequency (HF) component of HRV. The results showed that taVNS significantly increased measurements of root mean square of the difference between successive RR intervals (RMSSD), percentage of number of pairs of adjacent RR intervals differing greater than 50ms (pRR50), standard deviation of all RR intervals (SDRR), HF. Significantly, enhancement of HF and pRR50 persisted into recovery period. In addition, higher baseline LF/HF ratio was associated with greater LF/HF ratio decrease. Findings also showed that there was no significant difference in measurements of HF between different taVNS parameters. These studies suggest that taVNS could increase HRV, it may help taVNS in the treatment of low HRV related diseases. However, taVNS may not have parameter-specific effects on HRV.


Characteristics of abnormal menstrual cycle and polycystic ovary syndrome in community and hospital populations.
Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age. The involvement of an abnormal menstrual cycle in the etiology of PCOS remains unclear. We aimed to analyze the characteristics of abnormal menstrual cycles and their association with PCOS in community and hospital patient populations. Women with PCOS identified from 2111 permanent female residents in the community of Beijing and 506 outpatients obtained from the reproductive clinic of Peking University Third Hospital were recruited for this study, comprising the PCOS community group and the PCOS hospital group, respectively. Each group was further divided into four subgroups according to the length of menstrual cycles: <21 days; 21-34 days; 35-60 days; and >60 days. Women in each group were interviewed using a questionnaire to assess factors including age, age of menarche, menstrual cycle history, related family history, and modified Ferriman-Gallwey (mF-G) score. All women received transvaginal ultrasound scan and had fasting blood samples taken for endocrine evaluation. A two-tailed P value of <0.05 was considered significant. In the community population, the prevalence of abnormal menstrual cycle was 27.19% (574/2111). The prevalence of PCOS in the community was 6.11% (129/2111) according to Rotterdam criteria. In the community group, the most common menstrual cycle length was 35-60 days, whereas for the hospital group, it was >60 days. In both the community and hospital groups, the most common phenotype of PCOS was that of Oligo/amenorrhea+PCO+ hyperandrogenism (HA) (O+P+H) (P=0.000). With increasing cycle length of 35-60 days to >60 days, the percentages of Oligo/amenorrhea+PCO (O+P) and O+P+H were found to significantly decrease in the community group and significantly increase in the hospital group (P=0.000 for each). In the hospital group, as the menstrual cycle length increased from 35-60 days to >60 days, the rate of spontaneous abortion increased significantly (P=0.000), meanwhile the rate of poorly-secreted endometrium and abnormal endometrial hyperplasia increased significantly (P=0.000). The prevalence of PCOS in the Beijing community of women was 6.11%. Oligo/amenorrhea was the most common type of abnormal menstrual cycle and may be an indicator for PCOS and endometrial lesions. Gynecologists should seek relevant medical information from women in the community to promptly diagnose PCOS and then follow up patients for potential development of subsequent complications.


Gut mucosal-arterial Pco2 gradient as an indicator of splanchnic perfusion during systemic hypo- and hypercapnia.
By accounting for influences of systemic acid-base disturbances, gut mucosal-arterial Pco2 gradient (Pico2 - Paco2) has been increasingly advocated as a more specific marker of splanchnic perfusion than Pico2 alone. We examined the stability of the Pico2 - Paco2 gradient compared with raw Pico2 measurements during induced systemic hypo- and hypercapnia. A prospective animal study. A university research laboratory. Twenty anesthetized, paralyzed, and mechanically ventilated mongrel dogs. After a baseline period during which Paco2 was maintained near 40 torr, the animals were divided into four groups. Minute ventilation was then altered by adjusting tidal volume, frequency, or both to achieve group Paco2 values of 15, 20, 60, and 80 torr for groups 1 through 4, respectively. Portal blood flow was monitored and maintained near baseline levels by infusion of intravenous fluids. Intestinal Pico2 was measured continuously by using capnometric recirculating gas tonometry. Mean (+/- SE) aggregate baseline Pico2 - Paco2 was 16.9+/-3.3 torr. After 60 mins of hypoventilation, Pico2 - Paco2 decreased to 14.2+/-1.1 and to 13.7+/-2.7 torr in groups 3 and 4, respectively (p = NS, compared with baseline for both). On the other hand, after 60 mins of hyperventilation, Pico2 - Paco2 increased to 37.9+/-3.6 and 28.0+/-6.3 torr in groups 1 and 2, respectively (p < .0001, compared with baseline for both). In this model of maintained portal blood flow, Pico2 - Paco2 remained essentially stable after hypoventilation but increased significantly after inducing hyperventilation. Our findings warrant cautious interpretation of Pico2 - Paco2 as an indicator of splanchnic perfusion during systemic hypocapnia.


Catalyst-free synthesis of 3,1-benzoxathiin-4-ones/1,3-benzodioxin-4-ones.
An unambiguous and precise method for the synthesis of 3,1-benzoxathiin-4-ones/1,3-benzodioxin-4-ones by the reaction of propargylic alcohols and salicylic/thiosalicylic acids under a catalyst-free and open-air atmosphere is described. This strategy is found to be quite general using various 2-mercapto and 2-hydroxybenzoic acids providing benzoxathiinones/benzodioxinones in good yields.


Complications of glaucoma drainage device surgery: a review.
To review current literature on the complications of the use of glaucoma drainage device surgery. The use of glaucoma drainage devices has increased significantly in recent years for both primary treatment of glaucoma and refractory glaucoma. The efficacy and safety of glaucoma drainage devices has been well established, so they are a viable surgical option in patients who fail medical therapy. With the increased use of these devices, understanding their complications is essential in managing these patients. The prevention and management of complications associated with glaucoma drainage device insertion has some similarities to that of a trabeculectomy. The glaucoma drainage devices have additional complications associated with the fact that hardware is left within the eye. There have been no definitive answers as to the perfect surgical technique to prevent complications but careful surgical performance, tube placement and use of a double-layered graft over the tube are likely to lead to a better outcome. The rate of complications also dictates careful follow up to identify these complications early in their process as early intervention will likely lead to better outcomes.


Diamine Oxidase from Cultured Roots of Hyoscyamus niger: Its Function in Tropane Alkaloid Biosynthesis.
Diamine oxidase was partially purified from cultured roots of Hyoscyamus niger L. that produce considerable amounts of tropane alkaloids, and then characterized. N-Methylated amines inhibited the activity of the enzyme more strongly than the corresponding primary amines. N-Methylputrescine was the best substrate of those studied, the respective K(m) values for it and for putrescine and cadaverine being 0.33, 2.85, and 6.25 millimolar. The specificity constants V(max)/K(m) for putrescine and cadaverine were 11 and 1% of the constant for N-methylputrescine. Marked specificity for the N-methylated diamine would enable the Hyoscyamus enzyme to function specifically in tropane alkaloid biosynthesis.


Recent trends of age-specific pneumoconiosis mortality rates in the United States, 1985-1996: coal workers' pneumoconiosis, asbestosis, and silicosis.
The authors examined the temporal trends of age-specific pneumoconiosis mortality from coal worker's pneumoconiosis (CWP), asbestosis, and silicosis in the United States in 1985-1996. Mortality data were derived from the National Center for Health Statistics multiple causes of death files for the period. Age-specific mortality rates were computed for three age groups (15-44, 45-64, and > or = 65 years) among decedents with mention of CWP, asbestosis, or silicosis. Linear regression analysis was performed to examine the annual changes in age-specific mortality rates, by age group, with each specific condition. The CWP mortality rates declined significantly (p = 0.0001) in the groups 45 years old and older, but not in the age group 15-44. Asbestosis mortality rates declined significantly (p = 0.005) for the age group 45-64, while increasing (p = 0.0001) for those aged 65 years and older. However, in the younger age group 15-44, the rates showed no significant trend. Silicosis mortality rates declined significantly (p = 0.0001) for all groups. The continued occurrence of deaths from CWP, asbestosis, and silicosis among young adults may be the result of high levels of exposure to occupational risks. These results suggest that pneumoconiosis surveillance may help to evaluate the temporal pneumoconiosis mortality patterns in the United States.


Molecular density functional theory of water describing hydrophobicity at short and long length scales.
We present an extension of our recently introduced molecular density functional theory of water [G. Jeanmairet et al., J. Phys. Chem. Lett. 4, 619 (2013)] to the solvation of hydrophobic solutes of various sizes, going from angstroms to nanometers. The theory is based on the quadratic expansion of the excess free energy in terms of two classical density fields: the particle density and the multipolar polarization density. Its implementation requires as input a molecular model of water and three measurable bulk properties, namely, the structure factor and the k-dependent longitudinal and transverse dielectric susceptibilities. The fine three-dimensional water structure around small hydrophobic molecules is found to be well reproduced. In contrast, the computed solvation free-energies appear overestimated and do not exhibit the correct qualitative behavior when the hydrophobic solute is grown in size. These shortcomings are corrected, in the spirit of the Lum-Chandler-Weeks theory, by complementing the functional with a truncated hard-sphere functional acting beyond quadratic order in density, and making the resulting functional compatible with the Van-der-Waals theory of liquid-vapor coexistence at long range. Compared to available molecular simulations, the approach yields reasonable solvation structure and free energy of hard or soft spheres of increasing size, with a correct qualitative transition from a volume-driven to a surface-driven regime at the nanometer scale.


Migrants and allergy: a new view of the atopic march.
Atopy is the result of the influence of environmental factors on genetically predisposed individuals. Migration flows represent an interesting model to study the possible reciprocal roles of genes and environment. In this review the following issues influencing the development of allergic sensitization and/or atopic disorders in migrants will be rooted out: 1) ethnicity, genetic polymorphisms and risk of atopy; 2) double faceted effects of parasitic infestations; 3) biodiversity loss and industrial progress. Moreover, an extensive revision of the literature about the relationship between the migratory status and allergy development is provided.


[Chewing lice (Phthiraptera: Ischnocera, Amblycera) of starlings (Sturnus vulgaris, L.) in Turkey].
This study was carried out in order to detect chewing lice species occurring on starlings (Sturnus vulgaris, L). For this purpose, 27 starlings which were shot and sent in nylon bags to our laboratory by hunters were inspected for lice. Nine lice specimens were collected from the starlings and they were preserved in vials separately in 70% alcohol. They were cleared in 10% KOH for one or two days and mounted on slides in Canada balsam. They were examined by light microscope and identified to species. Four (14.81%) of 27 starlings were found to be infested with lice. Four species were identified as Myrsidea cucullaris (Nitzsch, 1818), Brueelia nebulosa (Burmeister, 1838), Sturnidoecus sturni (Schrank, 1766) and Brueelia sp. All of them have been reported for the first time from starlings in Turkey.


The impact of structured blood glucose testing on attitudes toward self-management among poorly controlled, insulin-naïve patients with type 2 diabetes.
Patients with T2DM often view self-monitoring of blood glucose (SMBG) as burdensome and pointless, which may affect their broader attitudes toward diabetes management. We examined how a structured SMBG protocol influenced diabetes self-efficacy and autonomous motivation over time, and linked these to changes in glycemic control. The Structured Testing Program (STeP) is a 12-month, two-arm, cluster-randomized trial that assessed the efficacy of structured SMBG in 483 insulin-naïve T2DM patients. Measures included: Confidence in Diabetes Self-Care for Type 2 patients (CIDS-T2), Diabetes-related Autonomous Motivation (DRAM), self-management behaviors and HbA1c. Intent-to-treat (ITT) and per-protocol (PP) analyses showed significant increases in CIDS-T2 scores over time (main effects p<0.0001). PP analysis showed significant between-group differences (p<0.05), with adherent STG patients displaying greater CIDS-T2 improvement than ACG patients. PP analyses showed main and between-group effects in DRAM with similar findings. Changes in CIDS-T2 were related to HbA1c changes over time; no self-management variable mediated this relationship. CIDS-T2 and HbA1c displayed a significant time-concordant relationship. Structured SMBG leads to significant increases in self-confidence and autonomous motivation associated with diabetes self-management. Changes in self-confidence are linked to changes in glycemic control and share a time-concordant relationship.


The doctor-patient relationship and prescribing patterns. A view from primary care.
The doctor-patient relationship has been described in economic terms as an 'agency relationship' where informed agents make decisions for uninformed clients. However, the decision to prescribe and the decision to accept the prescription by the patient are more complex in nature and involve many variables. Other factors, such as the 'need' for the prescription and the disease state (acute or chronic) also influence prescribing practice. Communication between the physician and patient was found to be important for rational and effective prescribing. The client can make better decisions with the relevant information, thus breaking down the agency relationship that once existed.


Regulation of the angiotensin AT1 receptor expression by hypercholesterolemia.
The AT1 receptor mediates most of the biological effects of angiotensin II and has therefore been implicated in the pathogenesis of hypertension as well as arteriosclerosis. Hypercholesterolemia is a prominent risk factor for the development of these cardiovascular diseases. Since experimental results from hyperlipidemic animal models suggested an interaction of the renin-angiotensin system and hypercholesterolemia, the effects of low-density lipoprotein (LDL) and hypercholesterolemia has recently been investigated in vitro and in vivo. LDL causes in cultured vascular smooth muscle cells an up-regulation of AT1 receptor gene expression which is followed by an enhanced functional response upon stimulation with angiotensin II. This effect is also evident in vivo, as assessed in hypercholesterolemic rabbits. The vascular AT1 receptor expression is increased approximately twofold in hypercholesterolemic rabbits in comparison to normocholesterolemic animals. This leads ultimately to an enhanced angiotensin II-induced vasoconstriction. Thus, hypercholesterolemia and elevated concentrations of LDL enhance AT1 receptor expression in the vasculature causing an enhanced biological effectiveness of the renin-angiotensin system. This interaction may explain that blockade of the renin-angiotensin system attenuates the progress of arteriosclerosis in the hypercholesterolemic organismen and indicates a pathophysiologically important role for the lipid-induced AT1 receptor up-regulation.


Investigation of the binding geometry of a peripheral membrane protein.
A growing number of modules including FYVE domains target key signaling proteins to membranes through specific recognition of lipid headgroups and hydrophobic insertion into bilayers. Despite the critical role of membrane insertion in the function of these modules, the structural mechanism of membrane docking and penetration remains unclear. In particular, the three-dimensional orientation of the inserted proteins with respect to the membrane surface is difficult to define quantitatively. Here, we determined the geometry of the micelle penetration of the early endosome antigen 1 (EEA1) FYVE domain by obtaining NMR-derived restraints that correlate with the distances between protein backbone amides and spin-labeled probes. The 5- and 14-doxyl-phosphatidylcholine spin-labels were incorporated into dodecylphosphocholine (DPC) micelles, and the reduction of amide signal intensities of the FYVE domain due to paramagnetic relaxation enhancement was measured. The vector of the FYVE domain insertion was estimated relative to the molecular axis by minimizing the paramagnetic restraints obtained in phosphatidylinositol 3-phosphate (PI3P)-enriched micelles containing only DPC or mixed with phosphatidylserine (PS). Additional distance restraints were obtained using a novel spin-label mimetic of PI(3)P that contains a nitroxyl radical near the threitol group of the lipid. Conformational changes indicative of elongation of the membrane insertion loop (MIL) were detected upon micelle interaction, in which the hydrophobic residues of the loop tend to move deeper into the nonpolar core of micelles. The micelle insertion mechanism of the FYVE domain defined in this study is consistent with mutagenesis data and chemical shift perturbations and demonstrates the advantage of using the spin-label NMR approach for investigating the binding geometry by peripheral membrane proteins.


[Peculiarities of the investigation, clinics and treatment of stylohyoid syndrome and glossopharyngeal neuropathy].
The aim of the study was to investigate the causes and the clinics of stylohyoid syndrome and its tendency to convert into glossopharyngeal nerve neuropathy; to investigate clinical peculiarities of glossopharyngeal neuropathy; to estimate differential diagnosis criteria for the glossopharyngeal neuropathy and stylohyoid syndrome; as well as to propose optimal treatment of the neuropathy. Sixty-five patients with stylohyoid syndrome and 53 patients with glossopharyngeal neuropathy have been treated on. The diagnosis was estimated according to the data of clinical and X-ray investigation. For the localization of affected zone we performed modified facial straight plain radiograms of the patients in open bite position, facial oblique contact radiograms, orthopantomograms and cervical spondylograms. The majority of the patients were females; they comprised 61.5% of patients with stylohyoid syndrome and 56.6% of glossopharyngeal neuropathy sufferers. Older persons had neuropathy, younger--stylohyoid syndrome. The mean age of neuropathy patients was 63.8 years, and of stylohyoid syndrome--57.1 years. Seven years and longer duration of disease was observed in 73.3% of glossopharyngeal neuropathy patients, while duration of 7 and more years was observed in only 3.1% of stylohyoid syndrome patients. The mean duration of glossopharyngeal neuropathy was 10.9 years, and of stylohyoid syndrome--2.6 years. The analysis of etiological factors showed they are the same for both diseases. The core of the glossopharyngeal neuropathy pathogenesis is destruction at the glossopharyngeal nerve or at the perivascular plexus of carotid artery, because of elongation or dislocation of styloid processus in case of neck osteochondrosis and compression by ossified styloid ligament. In case of stylohyoid syndrome, inflammatory processes occur at the above-mentioned nervous elements.


Quality of life after stroke: a longitudinal analysis of a cluster randomized trial.
Health-related quality of life (QoL) is poor after stroke, but may be improved with comprehensive care plans. We aimed to determine the effects of an individualized management program on QoL in people with stroke or transient ischemic attack (TIA), describe changes in QoL over time, and identify variables associated with QoL. This was a multicenter, cluster randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients with stroke or TIA aged ≥ 18 years were randomized by general practice to receive usual care or an intervention comprising a tailored chronic disease management plan and education. QoL was assessed at baseline and 3, 12, and 24 months after baseline using the Assessment of Quality of Life instrument. Patient responses were converted to utility scores ranging from - 0.04 (worse than death) to 1.00 (good health). Mixed-effects models were used for analyses. Among 563 participants recruited (mean age 68.4 years, 64.5% male), median utility scores ranged from 0.700 to 0.772 at different time points, with no difference observed between intervention and usual care groups. QoL improved significantly from baseline to 3 months (ß = 0.019; P = 0.015) and 12 months (ß = 0.033; P < 0.001), but not from baseline to 24 months (ß = 0.013; P = 0.140) in both groups combined. Older age, females, lower educational attainment, greater handicap, anxiety and depression were longitudinally associated with poor QoL. An individualized management program did not improve QoL over 24 months. Those who are older, female, with lower educational attainment, greater anxiety, depression and handicap may require greater support. https://www.anzctr.org.au . Unique identifier: ACTRN12608000166370.


Modifications in the phosphorylation of cell proteins related to the expression of src gene in chicken embryo fibroblasts.
The possible physiological targets of pp60src in chicken embryo fibroblasts transformed by Rous sarcoma virus were looked for by a general screening of the modifications of phosphorylation of the major cell phosphoproteins. These modifications were analyzed quantitatively by SDS-PAGE of total cell proteins on gradient gels, combined with a computerized densitometric evaluation of gel autoradiographies, using cells labeled with either [14C]-amino acids or with [32P]-phosphate. A large numbers of proteins, 37 out of the 68 studied, were found to be more phosphorylated in virally transformed cells. The determination of the phosphoamino acid content of proteins which were more phosphorylated in transformed cells and the study of the kinetics of protein phosphorylation in cells infected by a ts mutant, after a shift from the nonpermissive to the permissive temperature, showed that, among these proteins, five displayed a large increase in phosphotyrosine content and an early increase in phosphorylation after the temperature shift. These proteins of 36 K, 41 K, 46 K, 65 K and 280-300 K doublet are therefore good candidates for being physiological targets of pp60src in the cell.


Elevation in plasma catecholamines in response to insulin stress is under both neuronal and nonneuronal control.
We have examined the contribution of neurogenic and nonneurogenic influences to the secretion of adrenal catecholamines (CA) in adult rats after iv administration of insulin. Plasma CA levels were measured in control rats and in rats after surgical or pharmacological adrenal denervation or adrenalectomy. Insulin-induced CA secretion was biphasic and proportional to the insulin dose used. The first phase was neurogenic in origin and produced a moderate increase in plasma adrenaline (A) levels, with little or no change in noradrenaline (NA) levels. This neurogenic increase in plasma A was reduced by partial denervation and abolished by surgical complete adrenal denervation, adrenalectomy, or administration of hexamethonium and atropine. The second phase occurred later and produced a dramatic increase in both plasma A and NA. This phase was initiated when the plasma glucose level fell below 75 mg/100 ml. This late release of A and NA was not altered by surgical or pharmacological adrenal denervation, showing that it was nonneuronal in origin. However, both the early and late phases were abolished by adrenalectomy, showing that adrenal secretion of CA was the origin of the increased plasma levels of NA and A. The late rise in plasma CA was also abolished by iv administration of glucose. These data suggest that the mechanism responsible for the nonneurogenic secretion of adrenal CA in response to insulin stress was sensitive to the level of hypoglycemia.


Sample stacking capillary electrophoretic microdevice for highly sensitive mini Y short tandem repeat genotyping.
Lab-on-a-chip provides an ideal platform for short tandem repeat (STR) genotyping due to its intrinsic low sample consumption, rapid analysis, and high-throughput capability. One of the challenges, however, in the forensic human identification on the microdevice is the detection sensitivity derived from the nanoliter volume sample handling. To overcome such a sensitivity issue, here we developed a sample stacking CE microdevice for mini Y STR genotyping. The mini Y STR includes redesigned primer sequences to generate smaller-sized PCR amplicons to enhance the PCR efficiency and the success rate for a low copy number and degraded DNA. The mini Y STR amplicons occupied in the 5- and 10-mm stacking microchannels are preconcentrated efficiently in a defined narrow region through the optimized sample stacking CE scheme, resulting in more than tenfold improved fluorescence peak intensities compared with that of a conventional cross-injection microcapillary electrophoresis method. Such signal enhancement allows us to successfully analyze the Y STR typing with only 25 pg of male genomic DNA, with high background of female genomic DNA, and with highly degraded male genomic DNA. The combination of the mini Y STR system with the novel sample stacking CE microdevice provides the highly sensitive Y STR typing on a chip, making it promising to perform high-performance on-site forensic human identification.


Critical appraisal of the DRG system. Problem areas for DRG reimbursement in the U.S.A.
This Prospective Payment System (PPS) utilising Diagnosis Related Groups (DRGs) which was introduced for the reimbursement of acute care hospitals for Medicare patients in the U.S., was adopted primarily to control the rapidly rising costs of health care and, as an initial effort to retain the solvency of the Nation's Medicare Hospital Insurance Trust Fund. It is this factor, an overall decrease of health care dollars to health care providers and not the DRG system, which has generated the most criticism and concern. The DRG system, as a method to accomplish control of the expenditure of health care dollars and the method of implementation of this system in the United States, also generates criticism and concern from health care providers. One thing is certain, health care providers in the United States have seen just the beginning of what promises to be a rapidly changing environment driven by the need to control costs. The challenge will be to provide quality health care in a price competitive environment. This paper attempts to explore some of the criticisms and concerns of health care providers that result from the threat to reduce health care dollars and the methodology implemented to accomplish that objective.


Phakomatous choristoma of the orbit.
Phakomatous choristoma is a rare adnexal congenital tumor of lenticular anlage. The authors performed a standard orbital tomography of the orbits for the evaluation of a mass that was palpable in the left lower eyelid of a 3-month-old boy. Hematoxylin-eosin, special stainings and immunohistochemistry were performed on the excised mass. The histopathological and immunohistochemical findings confirmed the diagnosis of phakomatous choristoma. The CT scans showed that the mass was located in the orbit. Even though phakomatous choristoma is usually reported as a lower eyelid lesion, the orbital localization offers a better explanation for the chronological embryonic origin of this rare pediatric tumor.


The dolognawmeter: a novel instrument and assay to quantify nociception in rodent models of orofacial pain.
Rodent pain models play an important role in understanding the mechanisms of nociception and have accelerated the search for new treatment approaches for pain. Creating an objective metric for orofacial nociception in these models presents significant technical obstacles. No animal assay accurately measures pain-induced orofacial dysfunction that is directly comparable to human orofacial dysfunction. We developed and validated a high throughput, objective, operant, nociceptive animal assay, and an instrument to perform the assay termed the dolognawmeter, for evaluation of conditions known to elicit orofacial pain in humans. Using the device our assay quantifies gnawing function in the mouse. We quantified a behavioral index of nociception and demonstrated blockade of nociception in three models of orofacial pain: (1) TMJ inflammation, (2) masticatory myositis, and (3) head and neck cancer. This assay will be useful in the study of nociceptive mediators involved in the development and progression of orofacial pain conditions and it will also provide a unique tool for development and assessment of new therapeutic approaches.


Speed of saccade execution and inhibition associated with fractional anisotropy in distinct fronto-frontal and fronto-striatal white matter pathways.
Fast cancellation or switching of action plans is a critical cognitive function. Rapid signal transmission is key for quickly executing and inhibiting responses, and the structural integrity of connections between brain regions plays a crucial role in signal transmission speed. In this study, we used the search-step task, which has been used in nonhuman primates to measure dynamic alteration of saccade plans, in combination with functional and diffusion-weighted MRI. Functional MRI results were used to identify brain regions involved in the reactive control of gaze. Probabilistic tractography was used to identify white matter pathways connecting these structures, and the integrity of these connections, as indicated by fractional anisotropy (FA), was correlated with search-step task performance. Average FA from tracts between the right frontal eye field (FEF) and both right supplementary eye field (SEF) and the dorsal striatum were associated with faster saccade execution. Average FA of connections between the dorsal striatum and both right SEF and right inferior frontal cortex (IFC) as well as between SEF and IFC predicted the speed of inhibition. These relationships were largely behaviorally specific, despite the correlation between saccade execution and inhibition. Average FA of connections between the IFC and both SEF and the dorsal striatum specifically predicted the speed of inhibition, and connections between the FEF and SEF specifically predicted the speed of execution. In addition, these relationships were anatomically specific; correlations were observed after controlling for global FA. These data suggest that networks supporting saccade initiation and inhibition are at least partly dissociable. Hum Brain Mapp 37:2811-2822, 2016. © 2016 Wiley Periodicals, Inc.


Deep-learning-based approach for strain estimation in phase-sensitive optical coherence elastography.
In this Letter, a deep-learning-based approach is proposed for estimating the strain field distributions in phase-sensitive optical coherence elastography. The method first uses the simulated wrapped phase maps and corresponding phase-gradient maps to train the strain estimation convolution neural network (CNN) and then employs the trained CNN to calculate the strain fields from measured phase-difference maps. Two specimens with different deformations, one with homogeneous and the other with heterogeneous, were measured for validation. The strain field distributions of the specimens estimated by different approaches were compared. The results indicate that the proposed deep-learning-based approach features much better performance than the popular vector method, enhancing the SNR of the strain results by 21.6 dB.


Plant-based vaccines against respiratory diseases: current status and future prospects.
Respiratory infections have an enormous, worldwide epidemiologic impact on humans and animals. Among the prophylactic measures, vaccination has the potential to neutralize this impact. New technologies for vaccine production and delivery are of importance in this field since they offer the potential to develop new immunization approaches overriding the current limitations that comprise high cost, safety issues, and limited efficacy. Areas covered: In the present review, the state of the art in developing plant-based vaccines against respiratory diseases is presented. The review was based on the analysis of current biomedical literature. Expert commentary: Preclinical and clinical evaluations of several vaccine candidates against influenza, tuberculosis, respiratory syncytial virus, pneumonia, anthrax and asthma are discussed and placed in perspective.


Dissociable neural routes to successful prospective memory.
Identifying the processes by which people remember to execute an intention at an appropriate moment (prospective memory) remains a fundamental theoretical challenge. According to one account, top-down attentional control is required to maintain activation of the intention, initiate intention retrieval, or support monitoring. A diverging account suggests that bottom-up, spontaneous retrieval can be triggered by cues that have been associated with the intention and that sustained attentional processes are not required. We used a specialized experimental design and functional MRI methods to selectively marshal and identify each process. Results revealed a clear dissociation. One prospective-memory task recruited sustained activity in attentional-control areas, such as the anterior prefrontal cortex; the other engaged purely transient activity in parietal and ventral brain regions associated with attentional capture, target detection, and episodic retrieval. These patterns provide critical evidence that there are two neural routes to prospective memory, with each route emerging under different circumstances.


Novel transcription factors in human CD34 antigen-positive hematopoietic cells.
Transcription factors (TFs) and the regulatory proteins that control them play key roles in hematopoiesis, controlling basic processes of cell growth and differentiation; disruption of these processes may lead to leukemogenesis. Here we attempt to identify functionally novel and partially characterized TFs/regulatory proteins that are expressed in undifferentiated hematopoietic tissue. We surveyed our database of 15 970 genes/expressed sequence tags (ESTs) representing the normal human CD34(+) cells transcriptosome (http://westsun.hema.uic.edu/cd34.html), using the UniGene annotation text descriptor, to identify genes with motifs consistent with transcriptional regulators; 285 genes were identified. We also extracted the human homologues of the TFs reported in the murine stem cell database (SCdb; http://stemcell.princeton.edu/), selecting an additional 45 genes/ESTs. An exhaustive literature search of each of these 330 unique genes was performed to determine if any had been previously reported and to obtain additional characterizing information. Of the resulting gene list, 106 were considered to be potential TFs. Overall, the transcriptional regulator dataset consists of 165 novel or poorly characterized genes, including 25 that appeared to be TFs. Among these novel and poorly characterized genes are a cell growth regulatory with ring finger domain protein (CGR19, Hs.59106), an RB-associated CRAB repressor (RBAK, Hs.7222), a death-associated transcription factor 1 (DATF1, Hs.155313), and a p38-interacting protein (P38IP, Hs. 171185). The identification of these novel and partially characterized potential transcriptional regulators adds a wealth of information to understanding the molecular aspects of hematopoiesis and hematopoietic disorders.


Untargeted Metabolomic Analysis Combined With Multivariate Statistics Reveal Distinct Metabolic Changes in GPR40 Agonist-Treated Animals Related to Bile Acid Metabolism.
Metabolomics has been increasingly applied to biomarker discovery, as untargeted metabolic profiling represents a powerful exploratory tool for identifying causal links between biomarkers and disease phenotypes. In the present work, we used untargeted metabolomics to investigate plasma specimens of rats, dogs, and mice treated with small-molecule drugs designed for improved glycemic control of type 2 diabetes mellitus patients via activation of GPR40. The in vivo pharmacology of GPR40 is not yet fully understood. Compounds targeting this receptor have been found to induce drug-induced liver injury (DILI). Metabolomic analysis facilitating an integrated UPLC-TWIMS-HRMS platform was used to detect metabolic differences between treated and non-treated animals within two 4-week toxicity studies in rat and dog, and one 2-week toxicity study in mouse. Multivariate statistics of untargeted metabolomics data subsequently revealed the presence of several significantly upregulated endogenous compounds in the treated animals whose plasma level is known to be affected during DILI. A specific bile acid metabolite useful as endogenous probe for drug-drug interaction studies was identified (chenodeoxycholic acid-24 glucuronide), as well as a metabolic precursor indicative of acidic bile acid biosynthesis (7α-hydroxy-3-oxo-4-cholestenoic acid). These results correlate with typical liver toxicity parameters on the individual level.


Identification of catabolite control protein A from Staphylococcus aureus as a target of silver ions.
Staphylococcus aureus is one of the most common pathogenic bacteria that causes human infectious diseases. The emergence of antibiotic-resistant strains of S. aureus promotes the development of new anti-bacterial strategies. Silver ions (Ag+) have attracted profound attention due to their broad-spectrum antimicrobial activities. Although the antibacterial properties of silver have been well known for many centuries, its mechanism of action remains unclear and its protein targets are rarely reported. Herein, we identify the catabolite control protein A (CcpA) of S. aureus as a putative target for Ag+. CcpA binds 2 molar equivalents of Ag+via its two cysteine residues (Cys216 and Cys242). Importantly, Ag+ binding induces CcpA oligomerization and abolishes its DNA binding capability, which further attenuates S. aureus growth and suppresses α-hemolysin toxicity. This study extends our understanding of the bactericidal effects of silver.


The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants.
Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.


Mayflies of the genus Nonnullidens Grant & Peters 1993 (Ephemeroptera: Leptophlebiidae) from New Guinea.
In light of the discovery of four new species of Leptophlebiidae (Ephemeroptera) from the Indonesian part ofNew Guinea, the generic name Barba Grant & Peters 1993 syn.n. is regarded here to be a junior synonym of Nonnullidens Grant & Peters 1993. Nonnullidens variegatus sp. n., N. niger sp. n. and N. reductus sp. n. are described from larvae, subimagoes and imagoes, with the stages associated by rearing. Nonnullidens depapricus sp. n. is described from an immature male larva of the last instar. Nonnullidens mariae comb.n. formerly known only from eastern New Guinea, is reported from the Baliem Valley.


New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and outcome study.
Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis. We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations. Phenotype was characterized by a comprehensive echocardiography focusing on mitral valve apparatus in comparison with control relatives. In this X-linked disease valves lesions were severe in men and moderate in women. Most men had classical features of mitral valve prolapse (MVP), but without chordal rupture. By contrast to regular MVP, mitral leaflet motion was clearly restricted in diastole and papillary muscles position was closer to mitral annulus. Valvular abnormalities were similar in the four families, in adults and young patients from early childhood suggestive of a developmental disease. In addition, mitral valve lesions worsened over time as encountered in degenerative conditions. Polyvalvular involvement was frequent in males and non-diagnostic forms frequent in females. Overall survival was moderately impaired in men (P = 0.011). Cardiac surgery rate (mainly valvular) was increased (33.3 ± 9.8 vs. 5.0 ± 4.9%, P < 0.0001; hazard ratio 10.5 [95% confidence interval: 2.9-37.9]) owing mainly to a lifetime increased risk in men (76.8 ± 14.1 vs. 9.1 ± 8.7%, P < 0.0001). FLNA-MVD is a developmental and degenerative disease with complex phenotypic expression which can influence patient management. FLNA-MVD has unique features with both MVP and paradoxical restricted motion in diastole, sub-valvular mitral apparatus impairment and polyvalvular lesions in males. FLNA-MVD conveys a substantial lifetime risk of valve surgery in men.


Smoking may increase the risk of influenza hospitalization and reduce influenza vaccine effectiveness in the elderly.
Through its effects on the immune system, smoking may facilitate influenza virus infection, its severity and its most frequent complications. The objective was to investigate the smoking history as a risk factor for influenza hospitalization and influenza vaccine effectiveness in elderly smokers/ex-smokers and non-smokers. We carried out a multicenter case-control study in the 2013-2014 and 2014-2015 influenza seasons. Cases aged ≥65 years and age-, sex-matched controls were selected from 20 Spanish hospitals. We collected epidemiological variables, comorbidities, vaccination history and the smoking history. The risk of hospitalization due to smoking (current smokers and ex-smokers) was determined using the adjusted odds ratio (aOR) with conditional logistic regression models. Vaccine effectiveness (VE) was calculated using the formula: VE = (1 - aOR) × 100. We studied 728 cases and 1826 controls. Cases had a higher frequency of smoking (47.4% vs 42.1%). Smoking was associated with an increased risk of influenza hospitalization (aOR = 1.32, 95% CI: 1.04-1.68). Influenza vaccine effectiveness in preventing hospitalization was 21% (95% CI: -2 to 39) in current/ex-smokers and 39% in non-smokers (95% CI: 22-52). A history of smoking may increase the risk of hospitalization in smokers and ex-smokers. Preventing smoking could reduce hospitalizations due to influenza. Smokers and ex-smokers should be informed of the risk of hospitalization due to influenza infection, and encouraged to stop smoking. Smokers should be considered an at-risk group to be aggressively targeted for routine influenza vaccination.


[Family structure, parental support, and leaving home among young Americans in the twentieth century].
"This paper examines the effects of childhood family structure on patterns of home leaving (route and timing). The analysis uses data from the [U.S.] National Survey of Families and Households.... Family disruption is linked with leaving home via all routes except college attendance.... We interpret the results as indicating the ways the parental home provides the resources needed for a successful launching into adult independence or prompts leaving home either too early, or to new living arrangements likely to make establishing a stable independent adult role set more difficult." (SUMMARY IN ENG AND SPA)


Personal, situational and organizational aspects that influence the impact of patient safety incidents: A qualitative study.
When a patient safety incident (PSI) occurs, not only the patient, but also the involved health professional can suffer. This study focused on this so-called "second victim" of a patient safety incident and aimed to examine: (1) experienced symptoms in the aftermath of a patient safety incident; (2) applied coping strategies; (3) the received versus needed support and (4) the aspects that influenced whether one becomes a second victim. Thirty-one in-depth interviews were performed with physicians, nurses and midwives who have been involved in a patient safety incident. The symptoms were categorized under personal and professional impact. Both problem focused and emotion focused coping strategies were used in the aftermath of a PSI. Problem focused strategies such as performing a root cause analysis and the opportunity to learn from what happened were the most appreciated, but negative emotional responses such as repression and flight were common. Support from colleagues and supervisors who were involved in the same event, peer supporters or professional experts were the most needed. A few individuals described emotional support from the healthcare institution as unwanted. Rendered support was largely dependent on the organizational culture, a stigma remained among healthcare professionals to openly discuss patient safety incidents. Three aspects influenced the extent to which a healthcare professional became a second victim: personal, situational and organizational aspects. These findings indicated that a multifactorial approach including individual and emotional support to second victims is crucial.


The Utility of Flexion-Extension Radiographs in Degenerative Cervical Spondylolisthesis.
Retrospective radiologic analysis. The aim was to investigate if lateral flexion-extension radiographs identify additional cases of degenerative cervical spondylolisthesis (DCS) that would be missed by obtaining solely neutral upright radiographs, and determine the reliability of magnetic resonance imaging (MRI) in diagnosis. DCS and instability can be a cause of neck pain, radiculopathy, and even myelopathy. Standard anteroposterior and lateral radiographs and MRI of the cervical spine will identify most cervical spine pathology, but spondylolisthesis and instability are dynamic issues. Standard imaging may also miss DCS in some cases. We compared the number of patients who demonstrated cervical spondylolisthesis on lateral neutral and flexion-extension radiographs in addition to MRI. We used established criteria to define instability as ≥2 mm of listhesis on neutral imaging, and ≥1 mm of motion between flexion-extension radiographs. A total of 111 patients (555 cervical levels) were analyzed. In all, 41 patients (36.9%) demonstrated cervical spondylolisthesis on neutral and/or flexion-extension radiographs. Of the 77 levels of spondylolisthesis, 17 (22.1%) were missed on neutral radiographs ( P ,0.05). Twenty levels (26.0%) were missed when flexion-extension radiographs were used alone ( P =0.02). Twenty-nine levels (37.7%) of DCS identified on radiograph were missed by MRI ( P =0.004). Lateral flexion-extension views can be useful in the diagnosis of DCS. These views provide value by identifying a significant cohort of patients that would be undiagnosed based on neutral radiographs alone. Moreover, MRI missed 38% of DCS cases identified by radiographs. Therefore, lateral radiographs can be a useful adjunct to neutral radiographs and MRI when instability is suspected or if these imaging modalities are unable to identify the source of a patient's neck or arm pain.


Saturation of enzyme kinetics in circadian clock models.
From the mathematical study of simple models for circadian rhythm, the authors identified a clear effect of saturation in the enzyme kinetics on the promotion or suppression of a sustained oscillation. In the models, a clock gene (per gene) is transcribed to produce mRNAs, which are translated to produce proteins in the cytosol which are then transported to the nucleus and suppress the transcription of the gene. The negative feedback loop with a long time delay creates sustained oscillation. All the enzymatic reactions (e.g., degradation, translation, and modification) are assumed to be of Michaelis-Menten type. The reaction rate increases with the amount of substrate but saturates when it is very large. The authors prove mathematically that the saturation in any of the reactions included in the feedback loop (in-loop reaction steps) suppresses the oscillation, whereas the saturation of both degradation steps and the back transport of the protein to cytosol (branch reaction steps) makes the oscillation more likely to occur. In the experimental measurements of enzyme kinetics and in published circadian clock simulators, in-loop reaction steps have a small saturation index whereas branch reaction steps have a large saturation index.


Peripheral Ossifying Fibroma Evolved From Pyogenic Granuloma.
The aim of the present article is to present the clinical case of a large peripheral ossifying fibroma that evolved from a previously diagnosed pyogenic granuloma in a 50-year-old woman. The patient was referred for treatment of a lesion over the buccal and palatal gingiva close to the left upper first molar. It was purplish-red in color, approximately 3 cm in diameter, having a smooth surface, a pedicled and bleeding base, with seven years of evolution, and diagnosed as pyogenic granuloma. After three years of evasion, the patient returned reporting an increase in the lesion and difficulty in eating. Clinically the nodule was lobular in appearance, pink in color and smooth, pediculated, firm in consistency, non-bleeding, about 5 cm in its greatest extension, extending to the maxillary tuberosity. The lesion was excised and referred for histopathological examination, which led to the diagnosis of peripheral ossifying fibroma. The patient was followed for approximately 18 months, prosthetically rehabilitated, with satisfactory healing and no clinical signs of recurrence. The possible evolution of a pyogenic granuloma to a peripheral ossifying fibroma was observed in this case, based on the histopathological changes that occurred, with the development of calcified material, fibrous maturation, and decreased vascular content of the initial lesion after three years.


[CD137 signaling promotes angiogenesis through regulating macrophage M1/M2 polarization].
Objective: To investigate whether CD137 signaling can promote angiogenesis via regulating macrophage M1/M2 polarization. Methods: (1) The primary peritoneal macrophages in mice induced by 3% thiglycollate broth were divided into three groups: control group, CD137 signaling activated group and CD137 signaling inhibited group. Various specific markers of M1 and M2 macrophages were detected to observe the phenotype change of macrophages, and the macrophages protein expression of CD137, CD86 and CD206 was detected by flow cytometry (FCM). The protein and mRNA expression of induced nitric oxide synthase (iNOS), arginase Ⅰ(Arg-1) was determined by Western blot and RT-PCR, respectively. The secretion levels of IL-12 and IL-10 in culture supernatant of macrophages were detected by ELISA. (2) Macrophages were co-cultured with the endothelial cells (bEnd.3), and macrophages were implanted in the upper chamber, endothelial cells were implanted in stromal glue of the lower chamber. The experiment was divided into three groups: the control group, CD137 signaling activated group and peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibited group, and tube formation ability of endothelial cells in each group was determined. Results: (1) The purity of primary peritoneal macrophages in mice was (97.93±1.31)%. The expression of CD137 on the surface of macrophages was (97.40±2.70)%. (2) Compared with control group, the mRNA and protein expression levels of Arg-1 were significantly increased and the mRNA and protein expression of iNOS were significantly decreased in CD137 signaling activated group (all P<0.05). Compared with CD137 signaling activated group, the mRNA and protein expression of Arg-1 were significantly lower and the mRNA and protein expression levels of iNOS were significantly higher in CD137 signaling inhibited group (all P<0.05). FCM results showed that the average fluorescence intensity of CD206 was higher, while the average fluorescence intensity of CD86 was lower in CD137 signaling activated group than in control group (P<0.05, P<0.01, respectively); the expression of CD206 was significantly lower, while the expression of CD86 was higher, in the CD137 signaling inhibited group than in CD137 signaling activated group (P<0.05, P<0.01, respectively). ELISA results showed that the secretion of IL-10 was higher, and the secretion level of IL-12 was significantly lower in CD137 signaling activated group than in control group (both P<0.01); the secretion of IL-10 was significantly lower and the secretion of IL-12 was significantly higher in CD137 signaling inhibited group than in CD137 signaling activated group (both P<0.05). (3) Values of the formation of tube length and branch number were both longer in CD137 signaling activated group than control group (P<0.05). The formation of the tube length and branch number were less in PPAR-γ inhibited group than in CD137 signaling activated group (P<0.05). Conclusion: CD137 signaling can promote angiogenesis by regulating macrophage M1/M2 polarization.


Exposure to a Multilevel, Multicomponent Obesity Prevention Intervention (OPREVENT2) in Rural Native American Communities: Variability and Association with Change in Diet Quality.
The OPREVENT2 obesity prevention trial was a multilevel multicomponent (MLMC) intervention implemented in rural Native American communities in the Midwest and Southwest U.S. Intervention components were delivered through local food stores, worksites, schools, community action coalitions, and by social and community media. Due to the complex nature of MLMC intervention trials, it is useful to assess participants' exposure to each component of the intervention in order to assess impact. In this paper, we present a detailed methodology for evaluating participant exposure to MLMC intervention, and we explore how exposure to the OPREVENT2 trial impacted participant diet quality. There were no significant differences in total exposure score by age group, sex, or geographic region, but exposure to sub-components of the intervention differed significantly by age group, sex, and geographical region. Participants with the highest overall exposure scores showed significantly more improvement in diet quality from baseline to follow up compared to those who were least exposed to the intervention. Improved diet quality was also significantly positively associated with several exposure sub-components. While evaluating exposure to an entire MLMC intervention is complex and imperfect, it can provide useful insight into an intervention's impact on key outcome measures, and it can help identify which components of the intervention were most effective.


[Melanoma in xeroderma pigmentosum: 12 cases].
Xeroderma pigmentosum is a rare genodermatosis, with a defect affecting recovery of ultraviolet-induced damages and characterized by a high rate of malignancies of the exposed skin areas. We studied melanoma features of patients with xeroderma pigmentosum. A retrospective study of xeroderma pigmentosum patients admitted to the Charles Nicolle Hospital of Tunis between 1973 and 1998. Two hundred sixteen patients with xeroderma pigmentosum were registered. Melanoma was present in 12 patients, 7 females and 5 males. Two patients were sisters. Cutaneous melanoma was found in 8 patients. Four patients presented with metastatic melanoma. The median age for development of the first melanoma was 17.5 years. All of the cutaneous melanomas were found on the face. Lentigo malignant melanoma was reported in 3 cases. The tumors were treated with surgical excision. Except for a melanoma affecting the orbit, characterized by a fatal outcome, no metastases were detected at the different investigations. Melanoma occurs frequently in patients with xeroderma pigmentosum, it has been reported in 5.5 p. 100 of cases and 11.3 p. 100 of patients with cutaneous carcinoma. The age of onset was low: 17.5 years. It appeared later than the carcinoma. The location of cutaneous melanoma in face in xeroderma pigmentosum patients indicates that they were caused mainly by sunlight exposure. Lentigo malignant melanoma was the most frequent type. Prognosis is difficult to define owing to the large number of other cutaneous malignancies. Apart from one case of rapidly fatal orbital melanoma, we recorded long survivals even in cases of melanoma revealed by metastases.


Divergent transport mechanisms for pyrimidine nucleosides in petunia pollen.
Petunia hybrida pollen exhibits divergent transport mechanisms for pyrimidine nucleosides. Uridine and cytidine show all the properties of being actively transported, a nucleoside transport mechanism not hitherto reported in plant cells. Contrasting with this, thymidine transport has the properties of a nonactive, carrier-mediated system. Reasons for these different mechanisms are considered to lie in the high demand for uridine and cytidine, obtained perhaps from stylar tissue, for the biosynthetic reactions of the pollen tube, while thymidine demand is lower due to the absence of DNA replication in germinating Petunia pollen.


Patient-centred care, diabetes self-management and glycaemic control among Omani patients with type-2 diabetes.
This study examined the relationships between patient-centred care, diabetes self-management and selected health outcomes for Omani patients with type-2 diabetes. Cross-sectional surveys were administered for 237 patients with type-2 diabetes. Hierarchical regression analyses examined the relationships between the selected study variables. The sample was middle-aged (M = 48, SD = 11.0 years) with nearly a decade (M = 9.68, SD = 6.11) since being diagnosed with type-2 diabetes, with higher than ideal glycaemic control measures (M = 8.8%, SD = 2.4%). In bivariate analyses, patient-centred care was positively associated with diabetes self-management but not with glycaemic control or quality of life. However, after controlling demographic and clinical characteristics, patient-centred care was positively associated with both physical and mental aspects of health-related quality of life. In the final regression model, controlling for demographic and clinical characteristics and patient-centred care, diabetes self-management significantly predicted both glycaemic control and both physical and mental aspects of health-related quality of life. The findings support that providing individualized care may contribute to the self-management of chronic conditions. For achieving optimal outcomes, it may be necessary for providers to effectively assess patients' unique challenges and motivations. Increasing diabetes self-management may improve quality of life and reduce diabetes complications.


Variability in techniques and patient safety protocols in discography: a national multispecialty survey of International Spine Intervention Society members.
National survey. (1) Characterize the way discography is being carried out and by which specialties. (2) Quantify adherence to the International Spine Intervention Society (ISIS) guidelines. (3) To see if there is experience or specialty differences in technique. Discography is a controversial diagnostic tool that attempts to correlate disc morphology to concordant pain. It is increasingly performed by different specialties as a prelude to fusion, disc replacement, and percutaneous intradiscal procedures. A consensus committee of the ISIS has published guidelines for performing discography to increase diagnostic accuracy, standardize technique, and improve patient safety. This survey wishes to see how closely these guidelines are followed. In all, 500 members of the ISIS were randomly selected to receive a 13-item questionnaire. The questions included the following demographic information: specialty, number of discograms in 1 year (<15, 15-50, >50). Patient safety questions included the following: use of preoperative antibiotics, intradiscal antibiotics, postoperative antibiotics, and use of double needle technique. Technical questions included the following: needle entry on the opposite site of symptoms, injecting the control disc first, using manometry to record opening pressure, using manometry to record pressure on pain reproduction, injecting discs adjacent to the painful disc, and using pain assessment forms. Comparison of responses was made between specialties. Responses to the questions were also compared based on the number of procedures performed per year. The response rate to the questionnaire was 34.6%. Of the 173 respondents, the following specialties were represented: 100 (57.8%) Anesthesiology, 53 (30.6%) Physical Medicine and Rehabilitation (PMR), 16 (9.2%) Radiology, 4 (2.3%) Other. Number of procedures carried out was as follows: <15 (22.54%), 15 to 50 (50.86%), >50 (26.58%). The adherence to patient safety guidelines were as follows: preoperative antibiotics (83.81%), intradiscal antibiotics (84.97%), postprocedure antibiotics (9.82%), use of double needle technique (64.16%). The adherence to technical guidelines were as follows: optional use of computed tomography scan (64.78%), pain assessment sheet (66.47%), entering on the side opposite symptoms (48.55%), manometry for opening pressure (65.31%), manometry of pain reproduction pressure (72.25%), injecting a control disc first (78.61%), injecting discs adjacent to the painful disc (56.64%). Significant differences across Anesthesiology, PMR, and Radiology were detected for computed tomography, intradiscal antibiotics, opening pressure, pain assessment form, and pain pressure measurement. There was no effect of volume of procedures done on overall adherence to guidelines. A significant interaction between specialty and number of procedures performed was detected for compliance with intradiscal antibiotics (P=0.092), opening pressure (P=0.027), and pain pressure (P=0.029) for respondents with >50 procedures. Respondents in Radiology were approximately 98% less likely to use intradiscal antibiotics compared with those in Anesthesiology (odds ratio, 0.019; 95% confidence interval, 0.001-0.264). PMR respondents were approximately 83% less likely than Anesthesiologists to use opening pressure (odds ratio, 0.168; 95% confidence interval, 0.035-0.82) when procedures were <15 per year. Discography is being performed by multiple different specialties: Anesthesiology, PMR, Radiology (highest to lowest in number, respectively). Overall adherence to guidelines pertaining to infection control was fair except for double needle technique which was poor. Adherence to guidelines that affect the diagnostic value was poor. There is specialty variation in adherence to guidelines and to a lesser extent volume based effect on compliance.