Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus.
Experimental infection of Lewis rats with Borna disease virus (BDV) causes an immune-mediated nonpurulent meningoencephalitis. Viral persistence in the central nervous system is accompanied by mononuclear infiltrates, activated monocytic/microglial cells and reactive astrocytes. The immune-mediated process was further characterized by expression analysis of allograft inflammatory factor-1 (AIF-1), a novel marker of monocyte/microglial activation and of glial fibrillary acid protein (GFAP) between day 3 and day 50 post infection (p.i.). Potential neuroprotective effects of these cells were studied by the induction of haeme oxygenase-1 (HO-1), a defensive molecule against oxidative stress in various brain insults. In BDV-infected rat brains, mononuclear infiltrates and AIF-1 expression increased up to day 28 p.i. During early time points p.i., AIF-1 expression was mainly found in inflammatory lesions and adjacent brain parenchyma. Already 24 days p.i., a widespread upregulation of AIF-1 was observed which declined only moderately beyond day 28 p.i. HO-1 induction was maximal between days 18 and 28 p.i. Increased amounts of GFAP-positive astrocytes were present beyond 24 days p.i. Viral antigen expression increased simultaneously to the inflammatory reaction and persisted up to 50 days p.i. Widespread upregulation of AIF-1 indicates an early, long-lasting microglial activation, which might be involved in the immunesurveillance of the immune-mediated inflammatory events. The early peak of HO-1 most likely represents a neuroprotective, anti-inflammatory response by invading monocytes, microglial cells and astrocytes during the formation of encephalitic lesions and acute viral replication.


Cholecystectomy in pregnancy.
During the 17 years 1955 through 1971, 20 gravid patients underwent cholecystectomy. This represented 1 case for every 1259 deliveries (0.079% of 25,189 deliveries). The primary indication for surgery was repeated attacks of gallbladder colic. Generally, surgery was performed between the 10th and the 20th week of gestation. There was one spontaneous abortion; this occurred at 10 weeks of gestation, 42 days after surgery.


A study of the enquiry workload in a regional drug information centre.
In a study of the workload in a regional drug information centre, 65% of enquiries received were classed as urgent and required an answer on the day of receipt. The number varied considerably from day to day but no discernible pattern of either urgent or non-urgent enquiries was found. Manpower requirements are discussed on the basis of workload on the busiest days for urgent enquiries. It is calculated that with an annual workload of 1,106 enquiries the mean utilization of a full-time pharmacist on this work is 64% rising to 93% on the busiest days.


Functional analysis of the metallothionein gene cgMT1 isolated from the actinorhizal tree Casuarina glauca.
cgMT1 is a metallothionein (MT)-like gene that was isolated from a cDNA library of young nitrogen-fixing nodules resulting from the symbiotic interaction between Frankia spp. and the actinorhizal tree Casuarina glauca. cgMT1 is highly transcribed in the lateral roots and nitrogen-fixing cells of actinorhizal nodules; it encodes a class I type 1 MT. To obtain insight into the function of cgMT1, we studied factors regulating the expression of the MT promoter region (PcgMT1) using a beta-glucuronidase (gus) fusion approach in transgenic plants of Arabidopsis thaliana. We found that copper, zinc, and cadmium ions had no significant effect on the regulation of PcgMT1-gus expression whereas wounding and H2O2 treatments led to an increase in reporter gene activity in transgenic leaves. Strong PcgMT1-gus expression also was observed when transgenic plants were inoculated with a virulent strain of the bacterial pathogen Xanthomonas campestris pv. campestris. Transgenic Arabidopsis plants expressing cgMT1 under the control of the constitutive 35S promoter were characterized by reduced accumulation of H2O2 when leaves were wounded and by increased susceptibility to the bacterial pathogen X. campestris. These results suggest that cgMT1 could play a role during the oxidative response linked to biotic and abiotic stresses.


Reply to comment on "Are body mass index and performance status enough to assess the nutritional and functional status of elderly patients undergoing gastric cancer surgery?"


Chondrectomy--Review of Surgical Instrumentation and its Effectiveness.
ΒACKGROUND: To present surgical instrumentation used in knee chondrectomy and evaluate its effectiveness - a review of the literature. Surgical removal of joint cartilage, or chondrectomy, has been performed by orthopedists since the 1950s. Initially carried out as an open surgery, it has generally come to be performed arthroscopically. Its aim is to create even and stable cartilaginous edges perpendicular to the joint surface and a suitably prepared bottom of the defect for optimum integration of the cartilaginous regenerate. In order to present surgical instrumentation used in knee chondrectomy, English-language journals from the years 2010-2013 with an Impact Factor (2013) of at least 2.0 were analyzed. Papers concerning effectiveness and precision of knee chondrectomy according to the instrument used were also analyzed. According to the articles the most popular instruments used to debride chondral defects are open bone curettes (67% of the surgeries), scalpels (35%) and shavers (21%). Open bone curettes were used most frequently in open surgeries (78%), often along with scalpels (49% of the surgeries). In arthroscopic procedures, the most common instruments were shavers (50% of the surgeries) and open bone curettes (49%). 1. In open chondrectomies, the most frequently used instruments are open bone curettes and scalpels. 2. Of all instrumentation presented in this review, this combination ensures the highest precision, as required by Steadman's criteria, of debriding the edges and bottom of a chondral defect. 3. In arthroscopic procedure, a shaver and an open bone curette is the most frequently used combination. 4. None of the instruments and their combinations used in arthroscopic procedure ensures debridement of the defect in compliance with Steadman's recommendations.


Energetics of ventricular contraction as traced in the pressure-volume diagram.
The pressure-volume (P-V) relationship of the canine left ventricle can reasonably be simulated by a time-varying elastance model. In this model the total mechanical energy generated by a contraction can be determined theoretically from the change in the elastance. Applying this theory to the actual left ventricle, we have found that the area in the P-V diagram circumscribed by the end-systolic P-V relation line, the end-diastolic P-V relation curve, and the systolic segment of the P-V trajectory is equivalent to the total mechanical energy generated by ventricular contraction. We call this area the systolic P-V area (PVA). We have studied experimentally the correlation between the PVA and myocardial oxygen consumption (VO2) in the canine left ventricle. VO2 was linearly correlated with PVA regardless of the contraction mode and loading conditions in a given left ventricle. The VO2-PVA relation parallel shifted upward with positive inotropic agents. This shift comprised a significant increase in VO2 component for the unloaded contraction. We therefore consider that further analyses of the VO2-PVA relationship will greatly promote our understanding of cardiac energetics.


Simulation of flow in the silk gland.
Spiders and silkworms employ the complex flow of highly concentrated silk solution as part of silk fiber spinning. To understand the role of fluidic forces in this process, the flow of silk solution in the spider major ampullate and silkworm silk glands was investigated using numerical simulation. Our simulations demonstrate significant differences between flow in the spider and silkworm silk glands. In particular, shear flow effects are shown to be much greater in the spider than the silkworm, the silkworm gland exhibits a much different flow extension profile than the spider gland, and the residence time within the spider gland is eight times greater than in the silkworm gland. Lastly, simulations on the effect of spinning speed on the flow of silk solution suggest that a critical extension rate is the initiating factor for fiber formation from silk solution. These results provide new insight into silk spinning processes and will guide the future development of novel fiber spinning technologies.


Impact of antinucleants on transdermal delivery of testosterone from a spray.
The goal was to explore whether the incorporation of antinucleant polymers into a testosterone spray formulation could stabilize a putative supersaturated state and improve the delivery of the drug across the skin. Several antinucleants were screened using differential scanning calorimetry (DSC) and two candidates showed particular promise: a cyclodextrin derivative (RAMEB) and a vinylpyrrolidone/vinyl acetate copolymer (Kollidon VA64). These agents also improved significantly the long-term stability of saturated solutions of the drug. Further, using the method of mixed cosolvents, it was possible to create, in the presence of 5% w/v antinucleant polymer, supersaturated ethanol/propylene glycol/water (4:1:1 v/v) solutions of the drug with degrees of saturation between 1.4 and 2.6; however, these metastable systems existed only transiently under carefully controlled conditions and had reverted back to equilibrium solubilities of the drug within 6 h. When the same solutions were administered to hairless rat skin in vitro from mechanical sprays, no improvement in testosterone delivery, relative to a nonstabilized control, was observed. It appears, therefore, that the in situ crystallization process of the drug is more complex and incompletely understood (and cannot be predicted from DSC experiments). The complicated evaporation/volatilization process, which takes place when a spray is pulverized, requires better characterization before the use of supersaturation for testosterone delivery can be optimized.


Combination of Near Infrared Light-Activated Photodynamic Therapy Mediated by Indocyanine Green with Etoposide to Treat Non-Small-Cell Lung Cancer.
Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer.


Contrast adaptation in cat lateral geniculate nucleus and influence of corticothalamic feedback.
Contrast adaptation is a basic property of visual information processing. However, important questions about contrast adaptation in the lateral geniculate nucleus (LGN) remain. For example, it is unclear whether the different information channels have the same or distinct contrast adaptation properties and mechanisms. It has been recognized that the visual system is not a one-way ascending pathway, but also contains descending feedback projections. Although studies have explored the role of this feedback system, it is unclear whether corticothalamic feedback contributes to adaptation in the LGN. To investigate these questions, we studied contrast adaptation of LGN neurons in anesthetized and paralysed cats by measuring electrophysiological responses to visual test stimuli before and after adaptation induced by prolonged visual stimulation. After adaptation, contrast response functions were usually shifted towards higher contrasts, indicating decreased contrast gain, and the maximum response decreased. Also, contrast adaptation effects were stronger in Y-cells than in X-cells. Furthermore, adaptation effects were still observed in the LGN when the corticothalamic feedback was inactivated. Changes in the contrast gain of Y-cells were diminished in the absence of feedback, while contrast gain was largely unchanged in X-cells. Our observations confirm that contrast adaptation occurs in LGN neurons and furthermore demonstrate that Y-cells show stronger adaptation effects than X-cells. These results also provide an example of how corticothalamic feedback modulates contrast information processing distinctly in different information channels.


Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form (Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities.
This study sought to investigate the anticholinesterase and antioxidative properties of quercetin and its glycosylated conjugate, rutin. The in vitro inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, inhibition of Fe(2+)-induced lipid peroxidation in rat's brain homogenates, radicals scavenging, and Fe(2+)-chelating abilities of the flavonoids were investigated in vitro with concentrations of the samples ranging from 0.06 to 0.6 mM. Quercetin had significantly higher AChE and BChE inhibitory abilities than rutin. Quercetin also had stronger inhibition of Fe(2+)-induced lipid peroxidation in rat's brain homogenates. Similarly, quercetin had higher radical scavenging abilities than rutin. Quercetin also had stronger Fe(2+)-chelating ability than rutin. The inhibition of cholinesterases and antioxidative properties are possible mechanisms by which the flavonoids can be used in the management of oxidative stress-induced neurodegeneration.


CXCR4-Targeted Necrosis-Inducing Peptidomimetic for Treating Breast Cancer.
Triple-negative breast cancer is an aggressive subtype with a high recurrence rate, potential for metastasis, and a poor prognosis. The chemokine receptor, CXCR4, is a promising molecular target in breast cancer therapy. Here, we have developed a CXCR4-targeted antitumor peptidomimetic (named CTCE-KLAK), which is a fusion of the CXCR4 receptor antagonist CTCE-9908 and the D-form of proapoptotic peptide (KLAKLAK)2, for the treatment of breast cancer. First, we investigated the in vitro antitumor activity of CTCE-KLAK against various breast cancer cells and noncancerous mammary epithelial cells. CTCE-KLAK showed cell-selective cytotoxicity and induced rapid necrotic cell death in breast cancer cells but not in normal cells. In contrast, unconjugated peptides such as the carboxylate analogues of CTCE-9908 and D(KLAKLAK)2 were not cytotoxic to these cells. The tumor selectivity of CTCE-KLAK for cytotoxic activity depends on its internalization into tumor cells. There was no cleavage of caspase-3, caspase-7, or PARP1 in CTCE-KLAK-treated cells. In addition, cell death by CTCE-KLAK was not prevented by z-VAD-fmk, a pan-caspase inhibitor that inhibits cisplatin-induced cell death. These data indicate that the CTCE-KLAK conjugate is a cell-selective inducer of necrosis. Furthermore, we evaluated the in vivo antitumor activity of CTCE-KLAK in the 4T1 mouse metastatic breast cancer model. Intravenous administration of CTCE-KLAK significantly inhibited tumor growth and lung metastasis. Together, these findings suggest that the necrosis-inducing peptidomimetic CTCE-KLAK is a promising CXCR4-targeted agent for treating triple-negative breast cancer.


The neural correlates of attention orienting in visuospatial working memory for detecting feature and conjunction changes.
The neural mechanisms of attentional orienting in visuospatial working memory for change detection were investigated. A spatial cue was provided with the onset time manipulated to allow more effective top-down control with an early cue than with a late cue. The change type was also manipulated so that accurate detection depended on color or the binding of color and location. The results showed that both the frontal and parietal regions subserved the change detection task without cueing. When data were collapsed over the two change types, early cueing increased activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) while late cueing increased activation in the right inferior parietal lobule (IPL) and temporoparietal junction (TPJ) as compared with the no-cue condition. The cue onset time led to different levels of enhancement in the frontal and posterior cortices related to top-down control and stimulus-driven orienting. For feature detection, early cueing increased activation in the right MFG and late cueing increased activation in the bilateral precuneus (PCu), right TPJ, and right cuneus. The neural correlates of conjunction detection involved the right PCu and cerebellum without cueing, were associated with the anterior MFG, left IFG, and the left STG with early cueing, and involved the right MFG, left IFG, and right IPL with late cueing. The left IFG was correlated with memory retrieval of the cued representation for conjunction detection, and the right posterior PCu was associated with maintenance and memory retrieval among competing stimuli.


A compact, high-voltage pulsed charging system based on an air-core pulse transformer.
Charging systems of pulsed power generators on mobile platforms are expected to be compact and provide high pulsed power, high voltage output, and high repetition rate. In this paper, a high-voltage pulsed charging system with the aforementioned characteristics is introduced, which can be applied to charge a high-voltage load capacitor. The operating principle of the system and the technical details of the components in the system are described in this paper. The experimental results show that a 600 nF load capacitor can be charged to 60 kV at 10 Hz by the high-voltage pulsed charging system for a burst of 0.5 s. The weight and volume of the system are 60 kg and 600 × 500 × 380 mm(3), respectively.


[Solitary adrenal metastasis of pulmonary cancer].
We describe the case of a 46-year-old man with lung cancer and simultaneous solitary adrenal metastases. Adrenalectomy was performed 12 weeks after lung resection through a right subcostal laparotomy. Treatment was complemented with chemotherapy. Twelve months after adrenalectomy the patient was found free of signs of disease and was in satisfactory condition. The advantages of and indications for surgical resection of suprarenal metastasis are discussed in the light of published literature. In some cases, survival may improve with exeresis and chemotherapy.


Thinking about your running movement makes you less efficient: attentional focus effects on running economy and kinematics.
A number of studies have shown that attentional focus instructions can effect running economy. This study assessed spiroergometry, as well as running kinematics as a possible mechanism to explain these effects. Twelve runners had to focus their attention on either their running movement, their breathing or on a video while running on a treadmill at a set, submaximum speed. Spiroergometry and running kinematics were measured. Results revealed worse running economy in both internal focus conditions (breathing and movement) compared to the external focus condition (video), replicating previous findings. In addition, vertical oscillation during the running movement was elevated in the movement compared to the video condition, indicating a less efficient running style. No changes in kinematics were found for the breathing compared to the video condition. Therefore, consciously focusing on the running movement moves runners away from their optimised running pattern and leads to detriments in economy. The decreases in running economy in the breathing condition can be better explained by changes in breathing patterns.


Ubiquitin Chains Bearing Genetically Encoded Photo-Cross-Linkers Enable Efficient Covalent Capture of (Poly)ubiquitin-Binding Domains.
Ubiquitin-mediated signaling pathways regulate essentially every aspect of cell biology in eukaryotes. Ubiquitin receptors typically contain ubiquitin-binding domains (UBDs) that have the ability to recognize monomeric ubiquitin (Ub) and polymeric Ub (polyUb) chains. However, how signaling specificity is achieved remains poorly understood, and many of the UBDs that selectively recognize polyUb chains of particular linkages still need to be identified and characterized. Here we report the incorporation of a genetically encoded photo-cross-linker, p-benzoyl-l-phenylalanine (Bpa), into recombinant Ub and enzymatically synthesized polyUb chains. This allows photo-cross-linking (covalent bond formation) of monoUb and K48- and K63-linked diUb chains to UBDs. This approach provides a framework for understanding Ub cellular signaling through the capture and identification of (poly)Ub-binding proteins.


Formal Total Synthesis of Actinoranone and Asymmetric Synthesis of Labda-7,13-(E)-dien-15-ol.
The syntheses of the polyketide and terpenoid fragments of actinoranone are reported in a concise fashion, relying on catalytic methods. Minimization on the use of protecting groups and redox reactions allowed the synthesis of the carbon backbone of actinoranone in 20 steps (11 steps for LLS). The asymmetric synthesis of labda-7,13-(E)-dien-15-ol is also disclosed.


In defense of the internet: the relationship between Internet communication and depression, loneliness, self-esteem, and perceived social support.
As more people connect to the Internet, researchers are beginning to examine the effects of Internet use on users' psychological health. Due in part to a study released by Kraut and colleagues in 1998, which concluded that Internet use is positively correlated with depression, loneliness, and stress, public opinion about the Internet has been decidedly negative. In contrast, the present study was designed to test the hypothesis that Internet usage can affect users beneficially. Participants engaged in five chat sessions with an anonymous partner. At three different intervals they were administered scales measuring depression, loneliness, self-esteem, and social support. Changes in their scores were tracked over time. Internet use was found to decrease loneliness and depression significantly, while perceived social support and self-esteem increased significantly.


Pure-strain and genetically mosaic liver tumors histochemically identified with the -glucuronidase marker in allophenic mice.
A histochemical procedure for beta-glucuronidase has been used to make visible the cellular genotypes of liver tumors and of surrounding normal liver clones in allophenic mice. The animals had lifelong genetic mosaicism for cells with the allele for low beta-glucuronidase activity (g/g genotype, C3H strain) and cells with the allele for high activity (G/G genotype, C57BL/6 or BALB/c strain). The former strain is also hepatoma-susceptible; both the latter are nonsusceptible. Of 12 "spontaneous" hepatomas examined, nine were entirely of susceptible-strain hepatic cells and one was of the nonsusceptible strain; the pure-strain tumors usually arose in a liver environment containing clones of each genotype. The cells therefore behave largely autonomously with respect to gene control of tumor susceptibility. However, two tumors with malignant cells of both genotypes were formed, which suggests some measure of intercellular transmission of tumor information. Alternatively, transformation might have occurred in two or more cells concurrently. Mosaic tumors in either case imply that even a hepatoma of one inbred strain, whether in a single-genotype animal or an allophenic mouse, may comprise diverse clones of transformed cells. Possibly many or all hepatomas may therefore be genetically complex entities.


[Preoperative Embolization for Solid Cerebellar Hemangioblastoma on the Day of Surgery:Two Case Reports].
Surgical resection of solid cerebellar hemangioblastomas can be challenging because of the profuse blood supply and tight space. We report two cases of solid cerebellar hemangioblastomas treated via surgical resection with the aid of preoperative endovascular embolization on the day of surgery. Case 1: A 36-year-old woman presented with a two-month history of headache and vomiting. Magnetic resonance imaging(MRI)revealed a right cerebellar solid mass, mild hydrocephalus, and apparent peritumoral edema. Angiogram showed a highly vascularized mass, three feeding arteries from the superior cerebellar artery(SCA), and a dilated vein draining into the confluence. We performed preoperative embolization of the three feeders with 15% n-butyl-2-cyanoacrylate(NBCA). Final angiogram showed an absence of tumor staining. Tumor resection was performed on the same day, and gross total resection was achieved with no complications. Case 2: A 36-year-old man presented with a four-month history of headache and numbness in the left upper extremity. MRI revealed a right cerebellar solid mass with peritumoral edema. Angiogram showed a highly vascularized mass with two feeding arteries from the right SCA, one from the left posterior inferior cerebellar artery(PICA), and a dilated vein draining into the confluence. Preoperative embolization was performed with 15% NBCA, and complete devascularization was achieved. Tumor resection was performed on the same day, and gross total resection was achieved with no complications. In conclusion, preoperative embolization with NBCA on the day of surgery is a safe and effective adjunctive treatment for solid cerebellar hemangioblastoma.


ASB clinical biomechanics award winner 2016: Assessment of gaze stability within 24-48hours post-concussion.
Approximately 90% of athletes with concussion experience a certain degree of visual system dysfunction immediately post-concussion. Of these abnormalities, gaze stability deficits are denoted as among the most common. Little research quantitatively explores these variables post-concussion. As such, the purpose of this study was to investigate and compare gaze stability between a control group of healthy non-injured athletes and a group of athletes with concussions 24-48hours post-injury. Ten collegiate NCAA Division I athletes with concussions and ten healthy control collegiate athletes completed two trials of a sport-like antisaccade postural control task, the Wii Fit Soccer Heading Game. During play all participants were instructed to minimize gaze deviations away from a central fixed area. Athletes with concussions were assessed within 24-48 post-concussion while healthy control data were collected during pre-season athletic screening. Raw ocular point of gaze coordinates were tracked with a monocular eye tracking device (240Hz) and motion capture during the postural task to determine the instantaneous gaze coordinates. This data was exported and analyzed using a custom algorithm. Independent t-tests analyzed gaze resultant distance, prosaccade errors, mean vertical velocity, and mean horizontal velocity. Athletes with concussions had significantly greater gaze resultant distance (p=0.006), prosaccade errors (p<0.001), and horizontal velocity (p=0.029) when compared to healthy controls. These data suggest that athletes with concussions had less control of gaze during play of the Wii Fit Soccer Heading Game. This could indicate a gaze stability deficit via potentially reduced cortical inhibition that is present within 24-48hours post-concussion.


Involvement of ORL1 receptor and ERK kinase in the orphanin FQ-induced nociception in the nucleus accumbens of rats.
Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide, which has been identified as an endogenous ligand of the opioid receptor-like (ORL1) receptor. The present study investigated the nociceptive effect of intra-nucleus accumbens (intra-NAc) injection of OFQ, and the involvement of ERK pathway in such effect. Intra-NAc injection of OFQ (0.1, 0.5, 1 nmol) dose-dependently decreased the nociceptive thresholds on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. Moreover, the intra-NAc injection of OFQ-induced decreases in HWLs were antagonized by intra-NAc injection of (Nphe(1))nociceptin(1-13)NH(2), an antagonist of ORL1 receptor, in a dose-dependent way. Furthermore, the OFQ-induced nociception could be attenuated by pretreatment with the mitogen-activated protein kinase/ERK kinase (MEK) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126). Our results demonstrate that OFQ induces nociceptive effects in NAc. The effect was blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) and attenuated by U0126, suggesting that the activation of ERK pathways is involved in the OFQ-induced nociceptive effect in the NAc of rats.


Teaching Tradition: Diverse Perspectives on the Pilot Urban American Indian Traditional Spirituality Program.
Many urban American Indian community members lack access to knowledgeable participation in indigenous spiritual practices. And yet, these sacred traditional activities remain vitally important to their reservation-based kin. In response, our research team partnered with an urban American Indian health center in Detroit for purposes of developing a structured program to facilitate more ready access to participation in indigenous spiritual knowledge and practices centered on the sweat lodge ceremony. Following years of preparation and consultation, we implemented a pilot version of the Urban American Indian Traditional Spirituality Program in the spring of 2016 for 10 urban AI community participants. Drawing on six first-person accounts about this program, we reflect on its success as a function of participant meaningfulness, staff support, mitigated sensitivities, and program structure. We believe that these observations will enable other community psychologists to undertake similar program development in service to innovative and beneficial impacts on behalf of their community partners.


Colesevelam hydrochloride.
The pharmacology, pharmacodynamics, clinical efficacy, drug interactions, adverse effects, and dosage and administration of colesevelam hydrochloride are reviewed. Colesevelam hydrochloride is a nonabsorbed lipid-lowering agent approved for use alone or in combination with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors for the reduction of low-density-lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia. Colesevelam forms nonabsorbable complexes with bile acids in the gastrointestinal (GI) tract, resulting in changes in plasma lipid levels, including total, LDL, and high-density-lipoprotein cholesterol and triglycerides. Colesevelam has been reported to be four to six times as potent as traditional bile acid sequestrants (BASs), perhaps because of its greater binding affinity for glycocholic acid. Unlike cholestyramine and colestipol, colesevelam appears to reduce LDL cholesterol in a dose-dependent manner. In clinical trials, colesevelam demonstrated efficacy either alone or in combination with HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia. Combination therapy appeared to be more effective than monotherapy. Although infection, headache, and GI adverse effects have been reported for colesevelam, the rates do not differ significantly from those occurring with placebo. The constipation that typically hinders compliance with traditional BASs is minimal. In one study, the rate of compliance with colesevelam was 93%. There is little evidence of clinically significant interactions involving colesevelam. The maintenance dosage is three 625-mg tablets twice daily or six tablets once daily, taken with meals. Colesevelam provides an effective alternative to cholestyramine and colestipol while offering the potential for fewer adverse effects and better compliance. Studies are needed to directly compare colesevelam with traditional BASs.


Chemical vapor synthesis of size-selected zinc oxide nanoparticles.
ZnO can be regarded as one of the most important metal oxide semiconductors for future applications. Similar to silicon in microelectronics, it is not only important to obtain nanoscale building blocks of ZnO, but also extraordinary purity has to be ensured. A new gas-phase approach to obtain size-selected, nanocrystalline ZnO particles is presented. The tetrameric alkyl-alkoxy zinc compound [CH(3)ZnOCH(CH(3))(2)](4) is chemically transformed into ZnO, and the mechanism of gas-phase transformation is studied in detail. Furthermore, the morphological genesis of particles via gas-phase sintering is investigated, and for the first time a detailed model of the gas-phase sintering processes of ZnO is presented. Various analytical techniques (powder XRD, TEM/energy-dispersive X-ray spectroscopy, magic-angle spinning NMR spectroscopy, FTIR spectroscopy, etc.) are used to investigate the structure and purity of the samples. In particular, the defect structure of the ZnO was studied by photoluminescence spectroscopy.


[Molecular evolution and geographic origins of type 1 human lymphotrophic virus in Colombia detected by RFLP polymorphism].
The human T-lymphotropic virus type I (HTLV-I) infection is a public health problem in many endemic areas of Colombia. The subtyping of HTLV-I was based on the analysis of restriction fragment length polymorphisms (RFLP) in 3'LTR proviral DNA. From 31 HTLV-I isolates collected throughout Colombia, a RFLP analysis in a 737 bp 3'LTR fragment was performed. Fifty-eight percent (18/31) were identified as the Cosmopolitan subtype a, 19.4% (6/31) in the West African subtype b, 12.9% (4/31) in the Cosmopolitan subtype b and 9.6% (3/31) in the West African subtype c. The phylogenetic analysis of 3'LTR nucleotide sequences indicated that all the isolates in the current study were in the subgroup B or Japanese, in contrast with the highly divergent isolates from native Amerindians grouped in subgroup a or Transcontinental. The supported hypothesis was that of a post-Columbus introduction of virus represented in the African-American communities of the Colombian South Pacific. Some viral isolates from Colombian native Amerindians exhibited a nucleotide variation compatible with a Paleolithic introduction of the virus. The genetic diversity of HTLV-I in Colombia is complex and probably represents several independent introductions of lymphotropic virus.


Epidemiology and clinical relevance of Staphylococcus aureus intestinal carriage: a systematic review and meta-analysis.
Recent data highlight the importance of screening more than one site for improving the detection of S. aureus colonization. Intestinal carriage is frequently under-investigated and its clinical impact ought to be defined a better way. Areas covered: This review and meta-analysis provide an updated overview of prevalence, characteristics and clinical significance of S. aureus intestinal carriage in different populations, both for methicillin-susceptible and -resistant S. aureus strains. Expert commentary: Intestinal S. aureus carriage is documented with higher prevalence in children and in patients with S. aureus skin and soft tissue infections. This site of colonization was shown to be associated with a high risk of dissemination in the environment and with S. aureus infection. Intestinal carriage is frequently retrieved in nasal carriers, reflecting probably an association with a high bacterial load. Exclusive intestinal carriage present in one third of intestinal carriers can be associated with infection. Comparative genotyping analysis of different strains from nasal and extra-nasal sites of carriage, including the intestinal ones, in the same individuals, would allow a better comprehension of the pathophysiology of S. aureus endogenous infection. It could also permit to improve the prevention of these infections by decolonization of sites implicated in infection genesis.


Investigation of the hair follicle inner root sheath in scarring and non-scarring alopecia.
Premature desquamation of the inner root sheath (IRS) is described as a defining histologic feature of follicular degeneration syndrome/central centrifugal cicatricial alopecia (CCCA). However, IRS abnormalities have been noted in other types of alopecia. We evaluated the IRS in terminal hair follicles with transverse sections stained with hematoxylin-eosin and Ziehl-Neelsen stains in 22 non-scarring (7 areata and 15 androgenetic) and 21 scarring (13 CCCA, 2 lichen planopilaris, 2 lupus erythematosus, 1 folliculitis decalvans and 3 end stage) alopecia cases. In addition, we evaluated 15 normal controls with longitudinal sections to establish the level of IRS desquamation. The IRS was present in 99.5 +/- 0.01% (mean +/- standard error) of normal follicles at the level of the arrector pili muscle/sebaceous gland/sweat gland coil (L2) and variably present at higher levels. The IRS was present at L2 in 97.9 +/- 1.5% of alopecia areata, 87.4 +/- 5.3% of androgenetic alopecia, 59.3 +/- 7.0% of CCCA and 49.4 +/- 11.3% of other scarring alopecia follicles. Premature desquamation of the IRS was identified in CCCA; however, it was also noted in other scarring alopecia cases. IRS premature desquamation is a non-specific histologic feature in scarring alopecia and cannot be used alone as a defining feature of CCCA.


Intermedin promotes hepatocellular carcinoma cell proliferation through the classical Wnt signaling pathway.
The proliferative activity of hepatic carcinoma cells is directly associated with tumorigenesis, tumor development, metastasis and invasion. A variety of cytokines and peptides serve important roles in the development of hepatic carcinoma. The aim of the present study was to examine the effect of intermedin (IMD) on hepatic carcinoma cell proliferation and its mechanism of action. HepG2 hepatic carcinoma cell lines were treated with human recombinant IMD1-53 and its receptor antagonist IMD17-47. Cell proliferation was detected using a Cell Counting kit-8. The activation of the classical Wnt signaling pathway was demonstrated by the ratio of TOPflash:FOPflash luciferase activity. The expression of c-Myc and cyclin D1 downstream of the Wnt signaling pathway were detected using reverse transcription-quantitative polymerase chain reaction analysis. It was demonstrated that IMD may promote the proliferation of HepG2 cells in a time-dependent manner, and that the IMD receptor antagonist IMD17-47 could eliminate this promotion. IMD may activate classical Wnt signaling pathway transcriptional activity and the mRNA levels of certain downstream target genes. Furthermore, blocking of the Wnt signaling pathway may inhibit IMD-induced HepG2 cell proliferation to a certain extent. IMD may promote hepatic carcinoma cell proliferation by binding with receptor antagonist IMD17-47 and activating the Wnt signaling cascade, thus providing a novel avenue for the treatment of hepatic carcinoma.


Solitary Benign Schwannoma of the Foot Presenting Clinically as a Ganglion Cyst A Case Study.
An unusual case of solitary benign schwannoma of the foot is presented. Clinical examination, magnetic resonance imaging, and intraoperative findings all confirm the suspicion of a ganglion cyst. After attempted aspiration failed to produce any aspirate, excisional biopsy was performed. The pathology report confirms schwannoma with hematoxylin and eosin stain and subsequently reaffirmed with positive S100 protein stain. Even though schwannoma of the foot had been reported in the literature, this was an unusual case, as the lesion was presented as a superficial, ganglion cyst-like lesion on the bottom of the foot.


Spatially Selective Solvation Structure by Electronegative Micro-Arrays for Stable Lithium-Metal Anode Interface.
For electrolytes with conventional lithium salt concentration, it is not easy to generate sufficient anion-derived beneficial inorganic components to stabilize the electrolyte-lithium metal anode interface due to the repulsion of the free-state anions by the anode. In this study, the above issues are solved through the strong interaction between electronegative materials and lithium ions (Li+ ). A locally high Li+ concentration strategy is proposed by preparing micro-arrays of electronegative nano-hydroxyapatite (nHA) on the Cu foil. It is found that the oxygen atoms in the phosphate group (-PO4 ) of the nHA can strongly adsorb Li+ to form a locally Li+ -rich region, which increases the probability of anions interacting with Li+ . The formation of more Li+ -coordinated anions at the electrolyte-anode interface can reduce the Li+ de-solvation energy barrier, and enable the anions to completely decompose into lithium fluoride (LiF) and lithium nitride (Li3 N) on the Li metal anode. The interfacial transfer dynamics is accelerated and the Li dendrites are effectively suppressed. Under high current density, the anode exhibits a long lifespan with high Coulombic efficiency and small polarization voltage. The nHA micro-arrays achieve the targeted solvation structure at the electrolyte-anode interface while ensuring conventional lithium salt concentration in the bulk electrolyte.


Comparison of Glucose Tolerance between Kidney Transplant Recipients and Healthy Controls.
Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly unknown. Enrolled in this study were 94 kidney transplant recipients and 134 kidney transplant donors, as the healthy controls, who were treated at our institution. The 75 g-oral glucose tolerance test (OGTT) was performed in the recipients, and the healthy controls received an OGTT before donor nephrectomy. We assessed the prevalence of glucose intolerance including impaired fasting glucose and/or impaired glucose tolerance, as well as insulin secretion and insulin resistance using the homeostasis model assessment, and compared the results between the two groups. Multivariate analysis after adjustment for age, gender, body mass index, estimated glomerular filtration rate, and systolic blood pressure showed that the prevalence of glucose intolerance, insulin resistance, insulin secretion, and 2 h plasma glucose levels were significantly higher in the kidney transplant recipients compared to the healthy controls. Elevation of insulin secretion in kidney transplant recipients may be compensatory for increase of insulin resistance. Impaired compensatory pancreas β cell function may lead to glucose intolerance and NODAT in the future.


Is management of complex abdominal aortic aneurysms consistent? A questionnaire-based survey.
Complex abdominal aortic aneurysm (AAA) is a relatively common presentation to the vascular specialist. Despite this there is little consensus on how to manage the often comorbid group of patients. Recent advances in endovascular technology have led to the availability of multiple devices, many of which could be used to treat the same aneurysm. The aim of this study was to quantify this potential variability across vascular specialists from multiple countries. An online survey was emailed to members of the Vascular Society for Great Britain and Ireland (VSGBI), the Canadian Society for Vascular Surgery (CSVS) and the Australian and New Zealand Society for Vascular Surgery (ANZSVS). The survey presented a vignette of a 63-year-old woman with significant respiratory comorbidity and a 54 mm juxtarenal AAA (7 mm neck). There were no other adverse morphological features for endovascular repair. The survey included images and questions related to management of the aneurysm. The survey received 238 responses; 61 from ANZSVS, 65 from CSVS and 112 from VSGBI. VSGBI specialists were significantly more likely to continue surveillance than both ANZSVS (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.61-7.65; P<0.001) and CSVS counterparts (OR 2.61, 95% CI: 1.29-5.47; P<0.01). ANZSVS specialists were significantly more likely to perform an endovascular repair than those from CSVS (OR 3.28, 95% CI: 1.50-7.40; P<0.01) and VSGBI (OR 3.65, 95% CI: 1.81-7.59; P<0.001). CSVS specialists were significantly more likely to manage the aneurysm with open surgery than colleagues from the VSGBI (OR 6.57, 95% CI: 2.58-18.46; P<0.001) and ANZSVS (OR 7.18, 95% CI: 2.22-30.79; P<0.001). Significant variation in the management of a juxtarenal AAA between countries was observed. The same patient would be more likely to have an endovascular repair in Australia and New Zealand, open surgery in Canada and continuing surveillance in the UK and Ireland. This variation reflects the lack of long-term evidence and international consensus on the optimal management of complex AAA.


Molecular polymorphism of strains within Paramecium septaurelia (Ciliophora, Oligohymenophorea).
RAPD-PCR fingerprinting and ARDRA riboprinting revealed polymorphism within P. septaurelia strains from Russia (4 strains from Lower Volga Basin), and one strain from USA, Florida. However, the first method showed the existence of four RAPD genotypes while the second revealed only two groups of strains with different band patterns. All studied strains had a high percentage of surviving hybrid clones in the inter-strain crosses, with little differentiation of strains within species. Intra-species differentiation of strains in RAPD band patterns may be connected with the degree of inbreeding for the studied species. Species of the P. aurelia complex can be arranged according to the degree of inbreeding characteristic for each, which is correlated with the degree of DNA polymorphism revealed by the RAPD method from extreme inbreeders (e.g. P. sexaurelia), moderate inbreeders (e.g. P. triaurelia) to weak inbreeders (e.g. P. pentaurelia). P. septaurelia of the P. aurelia complex should be included in the group of extreme inbreeder.


Epidural catheter placement in neonates: sonoanatomy and feasibility of ultrasonographic guidance in term and preterm neonates.
We report the first prospective sonoanatomic study in neonates with the aim to perform ultrasonographic-guided epidural catheter placement in this age group. One hundred forty-five neonates with a body weight < or =4 kg (0.53-4 kg) were included in this prospective study. The study was divided into 3 consecutive parts. In the first part, the neuraxial sonoanatomy of 60 neonates was evaluated. In the second part, 50 neonates scheduled for major abdominal surgery were enrolled. In this part, the depth of the ligamentum flavum measured with ultrasound was matched up to the depth evaluated clinically with the loss-of-resistance technique. In the third part, ultrasonographic epidural catheter placement was performed in 35 neonates weighing between 620 g and 4 kg. The ligamentum flavum, the dura mater, and the termination of the spinal cord could be identified in all patients. The first part showed a good correlation between body weight and depth of the ligamentum flavum. The median termination of the spinal cord corresponded to vertebral level L2. The second part confirmed a good correlation between depth of the ligamentum flavum evaluated clinically and the depth predicted with ultrasound. Finally, real-time ultrasound-guided epidural placement was possible in all 35 neonates. Ultrasound examination of the spinal cord anatomy provides valuable information for epidural catheter placement in neonates. Ultrasonography enables a real-time identification of the tip of the needle within the epidural space and a visualization of the spread of local anesthetic in these patients.


Methylprednisolone aceponate for atopic dermatitis.
The 4th generation topical corticosteroids (TCS) have demonstrated a most favorablerisk-benefit ratio. Methylprednisolone aceponate (MPA) is a non-halogenated corticosteroid with a methyl group at C6, which confers higher intrinsic activity. MPA is included in the group of potent TCS (category III/IV). A literature review is carried out of the clinical efficacy, pharmacokinetics, and adverse effects of MPA, especially for the treatment of atopic dermatitis (AD). Several clinical studies support the use of MPA in infants and children, with minimal local or systemic adverse effects reported. The pharmacokinetic profile and the low rate of adverse effects of MPA are most suitable for the treatment of atopic dermatitis (AD), a chronic disease with frequent flaring that can involve extensive areas of the skin. Most patients with AD can be easily brought into control with the use of only TCS. Achieving a complete healing of eczema is key in AD, and once the skin is clinically healthy, emollients can be used according to the physician and patient preferences. Physicians should be trained in the recognition of early or subtle manifestations of active eczema that are most suitably treated with topical TCS to achieve a most rapid and satisfactory control of the disease. If the whole area with eczema is not treated, active eczema will remain and treatment will be ineffective. Insufficient use of TCS will lead to inefficiency and frustration.


Acoustic neuroma presenting as sudden hearing loss with recovery.
In our series of patients operated on for acoustic neuromas at New York University Medical Center between 1974 and 1983, 13% (17 of 133) had sudden hearing loss. Of these, approximately 23% (four of 17) had recovered auditory function before acoustic neuroma extirpation. Three patients spontaneously recovered, while one improved with steroid therapy. Contrast computerized tomography demonstrated a widened internal auditory canal and evidence of cerebellopontine angle tumor, respectively, in 88% and 59% of patients with sudden hearing loss and acoustic neuroma. Clinical characteristics suggesting acoustic neuroma as the cause of sudden hearing loss with or without auditory recovery could not be identified in our series. Our data support the rationale that patients with unilateral sudden hearing loss, even with recovery, must be evaluated for a possible cerebellopontine lesion.


About half of the noninferiority trials tested superior treatments: a trial-register based study.
A concern that noninferiority (NI) trials pose a risk of degradation of the treatment effects is prevalent. Thus, we aimed to determine the fraction of positive true effects (superiority rate) and the average true effect of current NI trials based on data from registered NI trials. All NI trials carried out between 2000 and 2007 analyzing the NI of efficacy as the primary objective and registered in one of the two major clinical trials registers were studied. Having retrieved results from these trials, random effects modeling of the effect estimates was performed to determine the distribution of true effects. Effect estimates were available for 79 of 99 eligible trials identified. For trials with binary outcome, we estimated a superiority rate of 49% (95% confidence interval = 27-70%) and a mean true log odds ratio of -0.005 (-0.112, 0.102). For trials with continuous outcome, the superiority rate was 58% (41-74%) and the mean true effect as Cohen's d of 0.06 (-0.064, 0.192). The unanticipated finding of a positive average true effect and superiority of the new treatment in most NI trials suggest that the current practice of choosing NI designs in clinical trials makes degradation on average unlikely. However, the distribution of true treatment effects demonstrates that, in some NI trials, the new treatment is distinctly inferior.


Instantaneous fMRI based cerebral parameters for automatic Alzheimer, mild cognitive impairment and healthy subject classification.
Automatic identification and categorization of Alzheimer's patients and the ability to distinguish between different levels of this disease would be very helpful to the research community studying this disease since non-automatic approaches are both very time-consuming and highly dependent upon the experience of experts. Here, it is proposed that instantaneous cerebral phase and envelope information from functional magnetic resonance imaging data is of use to discriminate between Alzheimer's patients, mild cognitively impaired subjects and healthy individuals. Following a region-of-interest analysis of functional magnetic resonance imaging data, different features including power, entropy, and coherency features are derived from the instantaneous phase and envelope signal sequences. Various sets of features are calculated and fed to a sequential forward floating feature selection algorithm to identify the most discriminative and informative feature sets. A Student's t-test was employed to select the most relevant features from the sets. Finally, a K-nearest neighbor classifier is used to distinguish between classes in a three-class categorization problem. The reported performance in overall accuracy using functional magnetic resonance imaging data of 111 combined participants is 80.1% with 80.0% sensitivity for the distinction of both Alzheimer's and healthy categories. This is comparable to the state-of-the-art approaches recently proposed for this task. The significance of obtained results was statistically confirmed by the evaluation of standard classification performance indicators. Results illustrate that the analytic phase and envelope feature indices derived from the region of interest signals described here are significant discriminators suited to distinguish between Alzheimer patients and healthy subjects.


Arterial wall tethering as a distant boundary condition.
A standing difficulty in the problem of blood vessel tethering has been that only one of the two required boundary conditions can be fully specified, namely, that at the inner (endothelial) wall surface. The other, at the outer layer of the vessel wall, is not known except in the limiting case where the wall is fully tethered such that its outer layer is prevented from any displacement. In all other cases, where the wall is either free or partially tethered, a direct boundary condition is not available. We present a method of determining this missing boundary condition by considering the limiting case of a semi-infinite wall. The result makes it possible to define the degree of tethering imposed by surrounding tissue more accurately in terms of the displacement of the outer layer of the vessel wall, rather than in terms of equivalent added mass which has been done in the past. This new approach makes it possible for the first time to describe the effect of partial tethering in its full range, from zero to full tethering. The results indicate that high tethering leads to high stresses and low displacements within the vessel wall, while low tethering leads to low stresses and high displacements. Since both extremes would be damaging to wall tissue, particularly elastin, this suggest that moderate tethering would be optimum in the physiological setting.


Comparison of the Efficacy Between Two Micro-Operative Therapies of Old Patients With Osteoporotic Vertebral Compression Fracture: A Network Meta-Analysis.
Osteoporotic vertebral compression fracture (OVCF) afflicts most aged people. Except for conservative therapy (CT), percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are another two the common choices, but current evaluation of their efficacy is not performed. All the trial data were originated from electronic database including PubMed, Embase, and Cochrane Library. Four indicators with mean difference (MD) or odd ratio (OR) with their 95% credible interval (95% CrI) were analyzed to evaluate the efficacy, including the value of visual analog scale (VAS), Oswestry disability index (ODI), relieving kyphotic angle (KA), and rate of fracture. Besides, the results were demonstrated in the forest plots and slash tables. Furthermore, the surface under the cumulative ranking curve (SUCRA) was calculated. A total of 32 trials among 2,852 patients are included. Using network comparison, we found that PKP and PVP both have good performance as OVCF treatments. However, in different aspects, PKP seemed to be the best to eliminate pain with high value of SUCRA on ODI and VAS (0.624 and 0.588, respectively), and PVP had better performance in KA and decreasing incidence of fracture. The micro-operative therapy, both PKP and PVP, had better efficacy than CT in four aspects. And PKP was better in pain alleviating, according to VAS and ODI results, while PVP had the superiority in KA and reducing the incidence of fracture. J. Cell. Biochem. 118: 3205-3212, 2017. © 2017 Wiley Periodicals, Inc.


Direct demonstration that receptor crosslinking or aggregation is important in insulin action.
Exposure of adipocytes to antibodies to the insulin receptor results in a blockade of (125)I-labeled insulin binding, stimulation of glucose oxidation, and many more insulin-like effects. Allowing for differences in purity, antireceptor antibody is equipotent with insulin on a molar basis. Both the bivalent F(ab')(2) and monovalent Fab' fragments of the antireceptor antibody are fully active in inhibiting (125)I-labeled insulin binding. Bivalent F(ab')(2) also retains its insulin-like effects. In contrast, the monovalent Fab' loses almost all ability to stimulate glucose oxidation and acts as a competitive antagonist of insulin-stimulated glucose oxidation. Addition of anti-F(ab')(2) antisera, which crosslink the Fab'-receptor complexes, results in a restoration of the insulin-like activity of the antibody. Similarly, when cells are exposed to submaximal doses of insulin, addition of anti-insulin antibodies at low concentration enhances the biological activity of insulin. These data suggest that receptor occupancy by ligand is not sufficient for signal generation and that the insulin-like effects of antireceptor antibody (and perhaps insulin itself) require receptor aggregation or clustering. This aggregation, however, appears to be independent of microfilaments or microtubules because the insulin-like effects of antireceptor antibody, and in fact, of insulin itself, are unaffected by agents that are known to disrupt these structures.


Hypoglycemic activity and mechanisms of myricetin.
Myricetin has been reported to have a wide variety of beneficial physiological functions. The present study was designed to investigate the mechanism of high purity myricetin, as a hypoglycemic functional component on high fat diet (HFD) fed streptozotocin (STZ) induced diabetic rats. Four-week antihyperglycemic effects of myricetin were assayed. The results showed that continuous administration of myricetin (50 and 200 mg/kg body weight) in HFD/STZ induced diabetic rats dose-dependently reduced the body serum glucose and insulin. Furthermore, administrations of myricetin significantly increased the expression of insulin receptor (InsR) and glucose transporter 4 (GLUT4) gene and increased the expression of glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK) gene. Moreover, myricetin protected pancreatic tissue from HFD fed STZ induced apoptosis through regulation of Bcl-2 associated X (Bax) gene and B-cell lymphoma-2 (Bcl-2) gene. The experimental results show that myricetin has significant health benefits and can be explored as a potentially promising dietary supplement for auxiliary hypoglycemic.


2 cases of HLA-B27-positive seronegative spondylarthritides in pediatric age treated with adalimumab.
Seronegative spondyloarthritis is strongly correlated to HLA-B27, and in the long term, it causes limitations to the movements of vertebral joints. In recent years, the numbers of patients diagnosed with axial spondyloarthritis have increased due to the widespread use of magnetic resonance imaging (MRI) for diagnostic imaging. We report the cases of 2 pediatric patients diagnosed with axial spondyloarthritis, and whose disease activity was successfully controlled using adalimumab. In case 1, the patient was a 15-year-old boy. The onset of the disease was marked by neck pain ; HLA-B27 was positive, and the MRI revealed sacroiliac arthritis. After being diagnosed with axial spondyloarthritis, he began receiving oral steroid therapy. Gradual recurrence was observed, and adalimumab treatment was initiated. In case 2, the patient was a 9-year-old boy. Bilateral pain was present in the shoulder joints, ankles, and knee joints. The patient was diagnosed with polyarticular juvenile idiopathic arthritis, and treatment using oral steroids, immunosuppressants and tocilizumab. The arthralgia disappeared, but at the age of 12 years, pain recurred in the sacroiliac joint and the Achilles tendon, the HLA-B27 was positive, and the MRI revealed sacroiliac arthritis. The condition was diagnosed as axial spondyloarthritis; adalimumab treatment was initiated. Adalimumab was effective in the treatment of axial spondylitis occurring in childhood.


Enhanced Cerebral Blood Volume under Normobaric Hyperoxia in the J20-hAPP Mouse Model of Alzheimer's Disease.
Early impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer's disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy.


Expression of FOXM1 and PLK1 predicts prognosis of patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most frequently encountered malignant tumor types and to improve its treatment, effective prognostic biomarkers are urgently required. Cell cycle dysregulation is a significant feature of cancer progression. The aim of the present study was to estimate the expression levels of forkhead box protein M1 (FOXM1) and polo-like kinase 1 (PLK1), both of which have essential roles in cell cycle regulation, and determine their prognostic value in HCC. To this end, FOXM1 and PLK1 expression levels were assessed in The Cancer Genome Atlas and International Cancer Genome Consortium Japan HCC cohorts, and the associations between their co-expression were determined via Pearson's correlation analysis. Furthermore, the overall survival and disease-free survival in these cohorts for different FOXM1 and PLK1 expression statuses were analyzed. In vitro knockdown experiments were also performed using Huh7 cells. The results obtained indicated overexpression of FOXM1 and PLK1 in HCC tumor tissues as well as a positive correlation between FOXM1 and PLK1 expression. The results also suggested that both FOXM1 and PLK1 are required for HCC cell proliferation. In addition, upregulation of FOXM1 and PLK1 was indicated to be associated with poor prognosis of patients with HCC. However, only their coordinated overexpression was identified as an independent prognostic factor for HCC.


[Dehiscence of the Pericardial Patch, after Surgical Treatment of Active Infective Aortic Valve Endocarditis with Reconstruction of the Aortic Annulus Using a Glutaraldehyde-treated Autologous Pericardium].
A 50-year-old man was admitted with fever and chill sensation 6 months ago. Transthoracic echocardiography (TTE) showed left and right coronary cusp prolapses and a thickened tissue of the aortic curtain. Congestive heart failure due to active infective aortic valve endocarditis was diagnosed, and he underwent aortic valve replacement. The aortic annulus was reconstructed using a glutaraldehydetreated autologous pericardium. Six months after surgery, TTE showed severe aortic regurgitation and saccular change in the aortic annulus. Transesophageal echocargiography showed some echo free space from left to noncoronary cusp and abnormal movement of the prosthetic valve annulus. Intraoperative examination showed dehiscence of the pericardial patch from the aortic wall, but no finding of infection. Aortic valve rereplacement was performed with reconstruction of the aortic annulus using a bovine pericardium. To prevent the dehiscence of the pericardial patch from the aortic wall, sutures fixing the prosthetic valve were passed from outside of the aortic wall.


The binding sites for tRNA on eukaryotic ribosomes.
We have studied the non-enzymic binding of phe-tRNA to ribosomes from rat liver using deacylated tRNA to inhibit binding to the P-site and puromycin (5 x 10-minus3M) to inhibit binding to the A-site. We conclude that at a low concentration of magnesium ions (10mM) phe-tRNA is bound only at the A-site of 80S irbosomes, whereas at a high concentration of magnesium ions (40mM) phe-tRNA is also bound at the P-site. Studies with edeine indicate that, during non-enzymic binding of phe-tRNA, eukaryotic ribosomes (in contrast to prokarotic ribosomes) have the A-site of the 60S subunit and the initiation site of the 40S subunit juxtaposed. This may account for the differences observed, in formation of diphenylalanyl-tRNA and phenylalanyl-puromycin, between phe-tRNA bound non-enzymically to the P-sites of eukaryotic and prokaryotic ribosomes.


Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies.
Systemic adenoviral readministration appears to be limited by immunogenicity. We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. Recombinant adenoviruses carrying a reporter lacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the lacZ gene was estimated histochemically and quantitatively. Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutralising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific T cells in response to adenoviral readministration was suppressed significantly by immunosuppressive FK506 treatment, levels of transgene expression in the liver achieved by intrabiliary adenoviral readministration were not significantly different between animals treated with and without FK506. Furthermore, third adenoviral administration into the common bile duct also induced successful transgene expression in the liver. These results suggest that adenovirus mediated gene transfer into the liver may be repeatable without immunosuppressive strategies in clinical settings by means of endoscopic retrograde cholangiography.


Safety of mesenchymal stem cells for clinical application.
Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-term in vitro expansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.


The Quantitative Measurements of Vascular Density and Flow Area of Optic Nerve Head Using Optical Coherence Tomography Angiography.
The purpose of this study was to evaluate the vascular density (VD) and the flow area on optic nerve head (ONH) and peripapillary area, and the impact of age and sex using optical coherence tomography angiography (OCTA) in healthy human subjects. Both eyes of each volunteer were scanned by an RTVue XR Avanti; Optovue with OCTA using the split-spectrum amplitude-decorrelation angiography algorithm technique. Masked graders evaluated enface angiodisc OCTA data. The flow area of ONH and the VD were automatically calculated. A total of 79 eyes of patients with a mean age of 37.03±11.27 were examined. The total ONH (papillary and peripapillary) area VD was 56.03%±4.55%. The flow area of the ONH was 1.74±0.10 mm/1.34 mm. The temporal and inferotemporal peripapillary VD was different between male and female patients. Increasing age causes some changes in the flow area of the ONH and the papillary VD from the third to the fourth decade (analysis of variance test; P<0.05). A normal quantitative database of the flow area and VD of the papillary and peripapillary area, obtained by RTVue XR with OCT angiography technique, is presented here.


Toward quantitative "in vivo biochemistry" with fluorescence fluctuation spectroscopy.
Quantitative description of protein dynamics and interactions in vivo with temporal and spatial resolution is a key step in dissecting molecular mechanisms in cell biology. Fluorescence fluctuation spectroscopy (FFS) has recently emerged as a powerful in vivo tool for assessing molecular concentration and movement and formation of hetero- and homo-oligomeric complexes. This article discusses point FFS-based analysis methods that have proven useful to cell biologists, focusing on the kinds of information they provide, their pros and cons, and the basic instrumentation required. Along the way, we describe briefly a few recent examples where these analyses have helped address important biological questions.


Biological characterization of prasinomycin, a phosphorus-containing antibiotic.
Prasinomycin, a new antibiotic from the green spore streptomycete, Streptomyces prasinus, primarily inhibits the growth of gram-positive microorganisms. Like penicillin, it is effective only against growing cells. Though primarily bacteriostatic at levels about the minimal inhibitory concentration, it is bactericidal at higher levels. Neither synergism nor antagonism could be demonstrated for prasinomycin with a variety of other antibiotics. It is highly active upon subcutaneous administration to mice infected with Staphylococcus aureus, Streptococcus pyogenes C203, or Diplococcus pneumoniae. Prasinomycin has a unique prophylactic action whereby one dose protects mice against experimental infections for as long as 2 months. It is more effective against S. aureus infections in mice when administered subcutaneously 20 hr prior to infection than when given in divided doses 1 hr before and 4 hr after infection.


Non-fluent progressive aphasia, depression, and OCD in a woman with progressive supranuclear palsy: neuroanatomical and neuropathological correlations.
This paper details the case of a 64-year-old woman who presented to the psychiatry service with worsening mood in the context of a diagnosis of obsessive-compulsive disorder (OCD). On further examination she was found to have clinical findings consistent with frontotemporal lobar degeneration of the non-fluent progressive aphasia subtype. At post-mortem she was found to have progressive supranuclear palsy. We argue, in retrospect, that her OCD was likely prodromal to the development of her dementia. This case highlights the fact that frontotemporal lobar degeneration/progressive supranuclear palsy (FTLD/PSP) and other "tauopathies" represent a complex group of neurodegenerative disorders that may masquerade for many years as refractory psychiatric disorders.


Combined renovascular hypertension and diabetes in rats: a new preparation of congestive cardiomyopathy.
Myocardial function, electrophysiologic characteristics, and structure were studied in rats with both renovascular hypertension and streptozotocin-induced diabetes (HD). Ventricular papillary muscles from untreated rats with HD showed a marked slowing of isometric and isotonic contractions. Peak developed tension and peak shortening were preserved, except in one animal with findings of congestive heart failure. Transmembrane action potentials increased fivefold in duration. Myocardial interstitial fibrosis was frequently observed. Physiologic parameters of rats with HD treated by left nephrectomy, captopril, and insulin were very similar to those of age-matched controls. The mortality rate of rats with HD was 43% over 5 to 6 months in the first study. In a second study, spontaneously dying rats with HD were compared with those deliberately killed. A 55% mortality was observed over 7 months. Myocardial structural damage and histologic evidence of congestive heart failure were more frequent in spontaneously dying rats with HD. Combined renovascular hypertension and diabetes in rats appears to be a new preparation of congestive cardiomyopathy.


Verifying the Relative Efficacy between Continuous Positive Airway Pressure Therapy and Its Alternatives for Obstructive Sleep Apnea: A Network Meta-analysis.
Obstructive sleep apnea (OSA) is a common breathing disorder, and continuous positive airway pressure (CPAP) therapy together with its alternatives has been developed to treat this disease. This network meta-analysis (NMA) was aimed to compare the efficacy of treatments for OSA. Cochrane Library, MEDLINE, and Embase were searched for eligible studies. A conventional and NMA was carried out to compare all therapies. Sleeping characteristics, including Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), arterial oxygen saturation, and arousal index (AI), and changes of blood pressure were selected as outcomes. A total of 84 studies were finally included after rigorous screenings. For the primary outcomes of AHI and ESS, the value of auto-adjusting positive airway pressure (APAP), CPAP, and oral appliance (OA) all showed statistically reduction compared with inactive control (IC). Similar observation was obtained in AI, with treatments of the three active interventions. A lower effect of IC in SaO2 was exhibited when compared with APAP, CPAP, and OA. Similar statistically significant results were presented in 24 h systolic blood pressure and 24 h DBP when comparing with CPAP. Our NMA identified CPAP as the most efficacious treatment for OSA patients after the evaluation of sleeping characteristics and blood pressures. In addition, more clinical trials are needed for further investigation due to the existence of inconsistency observed in this study.


Lung perfusion changes in COVID-19 pneumonia: a dual energy computerized tomography study.
There is limited and contradictory information about pulmonary perfusion changes detected with dual energy computed tomography (DECT) in COVID-19 cases. The purpose of this study was to define lung perfusion changes in COVID-19 cases with DECT, as well as to reveal any possible links between perfusion changes and laboratory findings. Patients who had a positive RT-PCR for SARS-CoV-2 and a contrast-enhanced chest DECT examination were included in the study. The pattern and severity of perfusion deficits were evaluated, as well as the relationships between perfusion deficit severity and laboratory results and CT severity ratings. The paired t-test, Wilcoxon test, and Student's t-test were used to examine the changes in variables and perfusion deficits. p < 0.05 was regarded as statistically significant. Study population consisted of 40 patients. Mean age was 60.73 ± 14.73 years. All of the patients had perfusion deficits at DECT images. Mean perfusion deficit severity score of the population was 8.45 ± 4.66 (min.-max, 1-19). In 24 patients (60%), perfusion deficits and parenchymal lesions matched completely. In 15 patients (37.5%), there was partial match. D dimer, CRP levels, CT severity score, and perfusion deficit severity score all had a positive correlation. Perfusion deficits are seen not only in opacification areas but also in parenchyma of normal appearance. The CT severity score, CRP, D-dimer, and SpO2 levels of the patients were determined to be related with perfusion deficit severity. Findings of the current study may confirm the presence of micro-thrombosis in COVID-19 pneumonia.


Dexmedetomidine for acute baclofen withdrawal.
Intrathecal baclofen is widely accepted as a treatment option for severe spasticity through its γ-Aminobutyric acid-B (GABAB ) agonist properties. Abrupt cessation can lead to severe and life-threatening withdrawal characterized by altered mental status, autonomic dysreflexia, rigidity, and seizures. This symptomatic presentation is similar to alcohol withdrawal, which is mediated by modification of GABAA expression. Use of the α2-adrenergic agonist dexmedetomidine for the treatment of ethanol withdrawal has been widely reported, raising the question of its potential role in baclofen withdrawal. We present a case of the successful treatment of acute severe baclofen withdrawal with a dexmedetomidine infusion. A 15-year-old patient with spastic quadriparesis and cerebral palsy underwent unexpected removal of his baclofen pump due to an infection that was encountered during a planned pump revision. Following removal, he was placed on high dose enteral baclofen every 6 h. Despite further benzodiazepine supplementation, he had progressive hemodynamic instability, severe rebound spasticity, and intermittent spontaneous clonus consistent with baclofen withdrawal. A dexmedetomidine infusion was titrated to a peak dose of 16 mcg per hour with successful treatment of withdrawal symptoms. The patient became normotensive without tachycardia. Tone and agitation improved. Dexmedetomidine is to our knowledge a previously unreported option for treatment of acute severe baclofen withdrawal. We report a case of safe and efficacious use in a patient with spastic quadriparesis on chronic intrathecal baclofen. Scientifically rigorous comparison with other options remains to be performed.


Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases.
Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients. We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry. IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA). The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies.


Vasal reanastomosis using fibrin glue combined with sutures: which combination of sutures in a delayed protocol? Experimental study in rats.
The actual number of transmural sutures needed to ensure a successful fibrin-glued vasovasostomy is a key study parameter of the few experimental works already published. The present work was done to evaluate fibrin-glued vasovasostomy in rats in combination with only 2 transmural sutures. We compared the results to our previous study in which we demonstrated the efficiency of a combination of the use of fibrin glue with 3 sutures in comparison with a conventional microsurgical technique. Twenty Sprague-Dawley rats underwent bilateral vasectomy followed 2 weeks later by bilateral vasovasostomy using fibrin glue combined with 2 transmural sutures. Each animal was sacrificed 7 weeks postoperatively after a 3-week mating period with a Sprague-Dawley female rat, the vasal specimens were evaluated for sperm granuloma formation. Mean operative time and fertility rates were recorded. The combination of fibrin glue with 2 transmural sutures gave evidence of less successful performances than the combination with 3 transmural sutures and the conventional microsurgical technique for all parameters evaluated but the mean operative time. Our study underlines the need for a third transmural suture placed 120 degrees apart from the others when performing a fibrin glue delayed vasovasostomy. This allows a better vas lumen opening at the anastomotic site and therefore a more efficient vasal anastomosis in a delayed protocol.


DNA metabarcoding assessment of Neotropical ichthyoplankton communities is marker-dependent.
The study of ichthyoplankton is paramount to understanding fish assemblages' reproductive dynamics. DNA metabarcoding has been applied as a rapid, cost-effective, and accurate taxonomy tool, allowing the identification of multiple individuals simultaneously. However, there remain significant challenges when using DNA metabarcoding, such as molecular marker choice according to the taxonomic resolution and length of the fragment to be sequenced, primer bias, incomplete reference databases, and qualitative inference incongruences. Here, 30 ichthyoplankton pools collected from a Neotropical river were identified at a molecular level using DNA metabarcoding to compare the resolution, sensibility, specificity, and relative read abundance (RRA) recovery of three molecular markers: the standard COI fragment (650 pb, with each end analyzed individually) and two short 12S rRNA genes markers (≅200 bp - NeoFish and MiFish markers). The combined use of the three markers increased the genera detection rates by 25%-87.5%, allowing an increased taxonomic coverage and robust taxonomic identification of complex Neotropical ichthyoplankton communities. RRA is marker-dependent, indicating caution is still needed while inferring species abundance based on DNA metabarcoding data when using PCR-dependent protocols.


Effectiveness of gait training with lower limb orthosis for a patient with severe Guillain-Barré syndrome at a Kaifukuki rehabilitation ward.
Tanaka M, Wada Y, Kawate N. Effectiveness of gait training with lower limb orthosis for a patient with severe Guillain-Barré syndrome at a Kaifukuki rehabilitation ward. Jpn J Compr Rehabil Sci 2021; 12: 48-52. We report the case of a patient with severe Guillain-Barré syndrome (GBS), whose ambulation recovered despite requiring total assistance on admission to a Kaifukuki rehabilitation ward. Gait training using knee-ankle-foot and ankle-foot orthoses was highly effective, based on the improvement in lower extremity muscle strength. A female in her 20s was previously diagnosed with GBS and was transferred to a Kaifukuki rehabilitation ward on hospitalization day 57. On admission, the lower extremities had a manual muscle test grade of 1, and the functional independence measure motor score (mFIM) was 13. She began training to stand upright using a tilt table and a knee-ankle-foot orthosis. Gait training with an adjustable posterior strut ankle-foot orthosis was initiated from 9 weeks after admission, with the fixed, brake, resistance, and freedom settings of the orthosis for the ankle joint adjusted according to the improvement in lower extremity muscle strength. At discharge, she was ambulatory without assistive devices and foot orthoses, and her mFIM had improved to 91. She returned to work 2 months later. This report describes the effectiveness of standing and gait training with a foot orthosis in improving ambulation in a severe GBS patient admitted to a Kaifukuki rehabilitation ward. Medical management and high-intensity rehabilitation are essential for patients with severe GBS during Kaifukuki rehabilitation.


Ultra-rapid Electrophilic Cysteine Arylation.
Rapid bond-forming reactions are crucial for efficient bioconjugation. We describe a simple and practical strategy for facilitating ultra-rapid electrophilic cysteine arylation. Using a variety of sulfone-activated pyridinium salts, this uncatalyzed reaction proceeds with exceptionally high rate constants, ranging from 9800 to 320,000 M-1·s-1, in pH 7.0 aqueous buffer at 25 °C. Such reactions allow for stoichiometric bioconjugation of micromolar cysteine within minutes or even seconds. Even though the arylation is extremely fast, the chemistry exhibits excellent selectivity, thus furnishing functionalized peptides and proteins with both high conversion and purity.


Role of Minerals and Trace Elements in Diabetes and Insulin Resistance.
Minerals and trace elements are micronutrients that are essential to the human body but present only in traceable amounts. Nonetheless, they exhibit well-defined biochemical functions. Deficiencies in these micronutrients are related to widespread human health problems. This review article is focused on some of these minerals and trace element deficiencies and their consequences in diabetes and insulin resistance. The levels of trace elements vary considerably among different populations, contingent on the composition of the diet. In several Asian countries, large proportions of the population are affected by a number of micronutrient deficiencies. Local differences in selenium, zinc, copper, iron, chromium and iodine in the diet occur in both developed and developing countries, largely due to malnutrition and dependence on indigenous nutrition. These overall deficiencies and, in a few cases, excess of essential trace elements may lead to imbalances in glucose homeostasis and insulin resistance. The most extensive problems affecting one billion people or more worldwide are associated with inadequate supply of a number of minerals and trace elements including iodine, selenium, zinc, calcium, chromium, cobalt, iron, boron and magnesium. This review comprises various randomized controlled trials, cohort and case-controlled studies, and observational and laboratory-based studies with substantial outcomes of micronutrient deficiencies on diabetes and insulin resistance in diverse racial inhabitants from parts of Asia, Africa, and North America. Changes in these micronutrient levels in the serum and urine of subjects may indicate the trajectory toward metabolic changes, oxidative stress and provide disease-relevant information.


[Schizophrenia and violence].
As compared to the general population schizophrenic patients are at increased risk of becoming delinquent. The majority of schizophrenic patients do not commit any crime, and the risk of the general population to be a target of a violent act by a person with schizophrenia is low. The causes of delinquency in schizophrenia are complex, but certain risk characteristics (e. g. an accompanying substance abuse) have been identified. The treatability and legal prognosis of schizophrenic offenders are good, which suggests that establishing a suitable helpers network could also be used for violence prevention in patients at risk.


Comparison of "Live High-Train Low" in normobaric versus hypobaric hypoxia.
We investigated the changes in both performance and selected physiological parameters following a Live High-Train Low (LHTL) altitude camp in either normobaric hypoxia (NH) or hypobaric hypoxia (HH) replicating current "real" practices of endurance athletes. Well-trained triathletes were split into two groups (NH, n = 14 and HH, n = 13) and completed an 18-d LHTL camp during which they trained at 1100-1200 m and resided at an altitude of 2250 m (PiO2 = 121.7±1.2 vs. 121.4±0.9 mmHg) under either NH (hypoxic chamber; FiO2 15.8±0.8%) or HH (real altitude; barometric pressure 580±23 mmHg) conditions. Oxygen saturations (SpO2) were recorded continuously daily overnight. PiO2 and training loads were matched daily. Before (Pre-) and 1 day after (Post-) LHTL, blood samples, VO2max, and total haemoglobin mass (Hb(mass)) were measured. A 3-km running test was performed near sea level twice before, and 1, 7, and 21 days following LHTL. During LHTL, hypoxic exposure was lower for the NH group than for the HH group (220 vs. 300 h; P<0.001). Night SpO2 was higher (92.1±0.3 vs. 90.9±0.3%, P<0.001), and breathing frequency was lower in the NH group compared with the HH group (13.9±2.1 vs. 15.5±1.5 breath.min(-1), P<0.05). Immediately following LHTL, similar increases in VO2max (6.1±6.8 vs. 5.2±4.8%) and Hb(mass) (2.6±1.9 vs. 3.4±2.1%) were observed in NH and HH groups, respectively, while 3-km performance was not improved. However, 21 days following the LHTL intervention, 3-km run time was significantly faster in the HH (3.3±3.6%; P<0.05) versus the NH (1.2±2.9%; ns) group. In conclusion, the greater degree of race performance enhancement by day 21 after an 18-d LHTL camp in the HH group was likely induced by a larger hypoxic dose. However, one cannot rule out other factors including differences in sleeping desaturations and breathing patterns, thus suggesting higher hypoxic stimuli in the HH group.


Estradiol induces cell proliferation in MCF‑7 mammospheres through HER2/COX‑2.
Cluster of differentiation (CD)44+/CD24- breast cancer cells have stem cell‑like characteristics and are potent initiators of tumorigenesis. Mammosphere cells can partially initiate breast tumorigenesis by inducing estradiol (E2)‑dependent breast cancer cells. However, the mechanisms by which E2 mediates cancer formation in MCF‑7 mammosphere (MS) cells have remained elusive. In the present study, MS cells were isolated by sphere culture. It was possible to maintain these MS cells in culture for long periods of time, while retaining the CD44+/CD24- stem cell marker status. The CD44+/CD24- status was confirmed by flow cytometry. Furthermore, the stem‑cell markers Musashi‑1, cytokeratin (CK)7 and CK19 were identified by immunofluorescence microscopy. It was revealed that treatment of MS cells with E2 increased the expression of CD44, whereas decreased the expression of CD24 on MS cells. In addition, treatment with E2 increased colony formation by MS cells. E2 also induced cyclooxygenase‑2 (COX‑2) expression in MS cells, which promoted their proliferation through the estrogen receptor/human epidermal growth factor receptor 2 (HER2)/mitogen‑activated protein kinase/phosphoinositide‑3 kinase signaling pathway. The results suggested a tumorigenic mechanism by which E2 promotes tumor cell proliferation via HER2/COX‑2 signaling. The present study provided evidence for the molecular impact of E2 on breast tumorigenesis, and suggested possible strategies for preventing and treating human breast cancer.


Biodegradation and product identification of [14C]hexabromocyclododecane in wastewater sludge and freshwater aquatic sediment.
In a previous study the biodegradation of hexabromocyclododecane (HBCD) was reported to occur under realistic environmental concentrations in soils and freshwater aquatic sediments with biotransformation half-lives ranging from approximately 2 days to 2 months. In this study we extend our knowledge as to the environmental behavior of HBCD with respect to the fate of the three major diastereomers of HBCD (alpha, beta, and gamma) as well as to the identification of major intermediate metabolites formed during degradation. Substantial biological transformation of the alpha-, beta-, and gamma-[14C]HBCD diastereomers was observed in wastewater (i.e., digester) sludge and in freshwater aquatic sediment microcosms prepared under aerobic and anaerobic conditions. Concomitant with the loss of [14C]HBCD in these matrixes there was a concurrent production of three [14C]products. Using a combination of high performance liquid chromatography atmospheric pressure photoionization mass spectrometry and gas chromatography electron impact ionization mass spectrometry these metabolites were identified as tetrabromocyclododecene, dibromocyclododecadiene, and cyclododecatriene. We propose that HBCD is sequentially debrominated via dihaloelimination where at each step there is the loss of two bromines from vicinal carbons with the subsequent formation of a double bond between the adjacent carbon atoms. These results demonstrate that microorganisms naturally occurring in aquatic sediments and anaerobic digester sludge mediate complete debromination of HBCD.


Evidence for Luttinger-liquid behavior in crossed metallic single-wall nanotubes.
Transport measurements through crossed metallic single-wall nanotubes are presented. We observe a zero-bias anomaly in one tube which is suppressed by a current flowing through the other nanotube. These results are compared with a Luttinger-liquid model which takes into account electrostatic tube-tube coupling together with crossing-induced backscattering processes. Explicit solution of a simplified model is able to describe qualitatively the observed experimental data with only one adjustable parameter.


Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor.
The purpose of this study was to characterize enzyme, receptor, and signaling involved in the synthesis and the activity of cysteinyl leukotrienes (cys-LTs) in human umbilical vein endothelial cells (HUVECs). We used primary cultures of HUVECs and evaluated the formation of cys-LTs by RP-HPLC. Suicide inactivation and subcellular localization of the enzyme responsible for the conversion of leukotriene (LT) A(4) into LTC(4) were studied by repeated incubations with LTA(4) and immunogold electron microscopy. The CysLT(2) receptor in HUVECs was characterized by equilibrium binding studies, Western blot analysis, and immunohistochemistry. Concentration-response curves in HUVECs and in transfected COS-7 cells were used to characterize a novel specific CysLT(2) receptor antagonist (pA(2) of 8.33 and 6.79 against CysLT(2) and CysLT(1) receptors, respectively). The results obtained provide evidence that the mGST-II synthesizing LTC(4) in HUVECs is pharmacologically distinguishable from the LTC(4)-synthase (IC(50) of MK886 <5 μM for LTC(4)-synthase and >30 μM for mGST-II), is not suicide-inactivated and is strategically located on endothelial transport vesicles. The CysLT(2) receptor is responsible for the increase in intracellular Ca(2+) following exposure of HUVECs to cys-LTs and is coupled to a pertussis toxin-insensitive G(q) protein. The synthesis of cys-LTs from LTA(4) by endothelial cells is directly associated with the activation of the CysLT(2) receptor (EC(50) 0.64 μM) in a typical autocrine fashion.