Transcriptomic comparison of Drosophila snRNP biogenesis mutants reveals mutant-specific changes in pre-mRNA processing: implications for spinal muscular atrophy.
Survival motor neuron (SMN) functions in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) that catalyze pre-mRNA splicing. Here, we used disruptions in Smn and two additional snRNP biogenesis genes, Phax and Ars2, to classify RNA processing differences as snRNP-dependent or gene-specific in Drosophila Phax and Smn mutants exhibited comparable reductions in snRNAs, and comparison of their transcriptomes uncovered shared sets of RNA processing changes. In contrast, Ars2 mutants displayed only small decreases in snRNA levels, and RNA processing changes in these mutants were generally distinct from those identified in Phax and Smn animals. Instead, RNA processing changes in Ars2 mutants support the known interaction of Ars2 protein with the cap-binding complex, as splicing changes showed a clear bias toward the first intron. Bypassing disruptions in snRNP biogenesis, direct knockdown of spliceosomal proteins caused similar changes in the splicing of snRNP-dependent events. However, these snRNP-dependent events were largely unaltered in three Smn mutants expressing missense mutations that were originally identified in human spinal muscular atrophy (SMA) patients. Hence, findings here clarify the contributions of Phax, Smn, and Ars2 to snRNP biogenesis in Drosophila, and loss-of-function mutants for these proteins reveal differences that help disentangle cause and effect in SMA model flies.


Theoretical investigation of nonadiabatic and internal temperature effects on the collision-induced multifragmentation dynamics of Na5+ cluster ions.
In a continued effort to disentangle adiabatic, nonadiabatic, and internal temperature effects in the collision-induced multifragmentation of alkali-metal cluster ions at moderate energies, we report a theoretical study of this process for the Na5++He encounter in the 100 eV (center-of-mass) collision energy range. The investigation makes use of a diatomics-in-molecules based nonadiabatic molecular-dynamics (NAMD) method. All of the ten electronic 1A' molecular states of the cluster that can be formed by assembling ground-state monomers are considered explicitly. Cross sections for the corresponding 12 possible fragmentation channels are determined. As in the Na4++He case, we find that a few-channel characteristic of adiabatic fragmentation in the electronic ground state dominates. This owes primarily to the dominance of impulsive adiabatic mechanisms. Nonetheless, two significant nonadiabatic transitions take place: electronic excitation during the collision and electronic deexcitation in the postcollision stage. A large amount of the electronic excitation subsequently relaxes into the electronic ground state during the postcollision stage. This important intramolecular vibrational relaxation (IVR)-type mechanism enhances the population of channels characteristic of adiabatic fragmentation in the electronic ground state. The populations of the fragmentation channels are quite sensitive to the internal cluster temperature. This is discussed in terms of the conditions of occurrence of the fragmentation mechanisms and their competition. Comparisons with experimental results are presented and discussed.


The serum level of soluble CXCL16 is increased in preeclampsia and associated with hepatic/renal damage.
To compare the serum level of the chemokine, CXCL 16, in preeclamptic and healthy pregnant patients. This prospective case control study was conducted between January and December 2018 in a tertiary level hospital. The study group was formed of 70 pregnant women diagnosed with preeclampsia, and the control group was formed of 70 healthy pregnant women matched to the study group in respect of age, gestational week and body mass index (BMI). The study group was separated into two subgroups of mild preeclampsia (n = 35) and severe preeclampsia (n = 35). The groups were compared in terms of demographic and clinical parameters and the levels of serum CXCL 16. No statistically significant difference was determined between the study and control groups in respect of maternal age, gravida, parity, BMI, and gestational age at sampling. Neonatal birth weight was significantly lower in the study group than in the control group. Mean serum alanine aminotransferase (ALT), aspartate amino transferase (AST) and creatinine levels of the study group were significantly higher than those of the control group (p < .05 for all). There was a statistically significant difference between the study and control groups regarding the mean platelet count. Compared to the control group, the severe and mild preeclampsia groups had a significantly higher serum level of CXCL 16. The serum level of CXCL 16 was significantly higher in patients with severe preeclampsia than in patients with mild preeclampsia (2.94 ± 3.89 pg mL-1 vs. 1.08 ± 1.87 pg mL-1, p = .14). Correlation analysis revealed a significant positive correlation of serum CXCL 16 level with serum ALT level (r = 0.320, p ≤ .001) and serum AST level (r = 0.373, p ≤ .001) and serum creatinine level (r = 0.279, p = .01) in both groups. High values indicated presence of preeclampsia, with a diagnostic cut-off point of 0.225, sensitivity of 75.7% and specificity of 72.9% for CXCL 16 (area under curve: 0.820, p < .001 CI: 0.753-0.888). This is the first study in literature to show a significantly higher level of CXCL 16 in patients with severe preeclampsia compared to those with mild preeclampsia. The study can also be considered of value in respect of showing that CXCL 16 could play a role in the etiopathogenesis of preeclampsia and the emergence of renal-hepatic damage. Blocking the CXCL 16/CXCR six axis in preeclampsia treatment could lay the ground for the development of new drugs which could be used in the treatment of preeclampsia.


The use of two-dimensional nuclear-magnetic-resonance spectroscopy and two-dimensional difference spectra in the elucidation of the active center of Megasphaera elsdenii flavodoxin.
1H-1H 'through bond' correlated (COSY) and 1H-1H 'through space' (NOESY) two-dimensional NMR techniques were applied to study the structure of Megasphaera elsdenii flavodoxin in the oxidized and reduced state. It is shown that two-dimensional NOESY difference spectra between spectra of flavodoxin in the reduced and semiquinone state are sensitive to the active center of the fully reduced state. The sphere of the active center observed in the difference spectra can be varied easily by changing the relative amount of flavodoxin semiquinone in the second sample. The difference NOESY spectra simplified the analysis of the complex spectra. Resonances could be assigned to Ala-56, Tyr-89 and Trp-91, which are located in the direct vicinity of the protein-bound flavin. The relative positions and side-chain dihedral angles of these residues are compared for the two redox states. Ala-56 and Tyr-89 show identical relative positions and dihedral angles in the two redox states, although the rotational motion of Tyr-89 is enhanced in the oxidized state. In both redox states Trp-91 is immobilized and extremely close to the prosthetic group. However, a small displacement of Trp-91 towards the (N(5) atom of the flavin occurs upon reduction. The results obtained for Trp-91 are in excellent agreement with crystallographic results of the related flavodoxin from Clostridium MP. However, the latter studies showed a somewhat different position of the tyrosine residue compared with our results.


Current trends in laryngectomy rehabilitation: a survey of speech-language pathologists.
This study determined the perceptions of experienced speech-language pathologists regarding current practices in the speech rehabilitation of laryngectomy patients since the introduction of the tracheoesophageal puncture-voice prosthesis technique in 1980. The sample population consisted of 151 experienced speech-language pathologists, or 43% of those who were sent questionnaires. The speech-language pathologists ranked tracheoesophageal puncture-voice prosthesis as their most preferred speech rehabilitation method and the electrolarynx as their least preferred, even though the electrolarynx continues to be the most frequently used method. Variable use of the tracheoesophageal puncture procedure by otolaryngologists was reported, with only a small portion perceived as using it routinely. About 65% of the speech-language pathologists reported that more than half of the laryngectomy patients were being given choices among speech rehabilitation methods. Nearly 50% of the speech-language pathologists reported that fewer than six speech therapy sessions were necessary with tracheoesophageal puncture patients, whereas more than 20% reported the need for 10 sessions or more. Use of manual closure of the tracheostoma by tracheoesophageal puncture patients far outweighed their use of automatic speaking valves. Most speech-language pathologists reported that they were involved in teams with otolaryngologists to determine patient suitability for tracheoesophageal puncture and to troubleshoot problems. Eighteen different categories of medical and speech production problems were reported.


State-recycling and time-resolved imaging in topological photonic lattices.
Photonic lattices-arrays of optical waveguides-are powerful platforms for simulating a range of phenomena, including topological phases. While probing dynamics is possible in these systems, by reinterpreting the propagation direction as time, accessing long timescales constitutes a severe experimental challenge. Here, we overcome this limitation by placing the photonic lattice in a cavity, which allows the optical state to evolve through the lattice multiple times. The accompanying detection method, which exploits a multi-pixel single-photon detector array, offers quasi-real time-resolved measurements after each round trip. We apply the state-recycling scheme to intriguing photonic lattices emulating Dirac fermions and Floquet topological phases. We also realise a synthetic pulsed electric field, which can be used to drive transport within photonic lattices. This work opens an exciting route towards the detection of long timescale effects in engineered photonic lattices and the realisation of hybrid analogue-digital simulators.


N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo.
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a natural inhibitor of pluripotent hematopoietic stem cell proliferation, has been suggested as capable of promoting an angiogenic response. We studied whether Ac-SDKP stimulates endothelial cell proliferation, migration, and tube formation; enhances angiogenic response in the rat cornea after implantation of a tumor spheroid; and increases capillary density in rat hearts with myocardial infarction (MI). In vitro, an immortal BALB/c mouse aortic endothelial 22106 cell line was used to determine the effects of Ac-SDKP on endothelial cell proliferation and migration and tube formation. In vivo, a 9L-gliosarcoma cell spheroid (250-300 microm in diameter) was implanted in the rat cornea and vehicle or Ac-SDKP (800 microg.kg(-1).day(-1) ip) infused via osmotic minipump. Myocardial capillary density was studied in rats with MI given either vehicle or Ac-SDKP. We found that Ac-SDKP 1) stimulated endothelial cell proliferation and migration and tube formation in a dose-dependent manner, 2) enhanced corneal neovascularization, and 3) increased myocardial capillary density. Endothelial cell proliferation and angiogenesis stimulated by Ac-SDKP could be beneficial in cardiovascular diseases such as hypertension and MI. Furthermore, because Ac-SDKP is mainly cleaved by ACE, it may partially mediate the cardioprotective effect of ACE inhibitors.


Balancing the CAR T: perspectives on efficacy and safety of CAR T-cell therapy in hematologic malignancies.
Chimeric antigen receptor (CAR) T-cell therapy is an example of how immunotherapy is revolutionizing the treatment of hematologic malignancies with unprecedented response rates in patients with relapsed/refractory lymphoma, multiple myeloma, and acute lymphoblastic leukemia. The process for administering CAR T-cell therapy is complex, with multiple steps including CAR T-cell manufacturing, lymphodepleting chemotherapy, cellular therapy infusion, and management of short-term and long-term toxicities. While effective, broad use of CAR T-cell therapies is limited by potential for life-threatening toxicities, challenges related to manufacturing a patient-specific product, high costs and inadequate reimbursement, and incomplete or unsustained disease response. Pharmacists are intricately involved in the process of providing CAR T-cell therapy both at the organizational level of budgeting and coordinating therapy and in direct patient care roles providing counseling and support for adverse effect management. Research in CAR T-cell therapy is expected to improve tolerability and expand indications to more types of malignancies and earlier phases of disease. Managed care professionals should have an understanding of the clinical trial data and place in therapy in lymphoma, myeloma, and acute lymphoblastic leukemia as well as guideline recommendations for adverse effect management associated with CAR T-cell therapies.


Genetic algorithm optimized triply compensated pulses in NMR spectroscopy.
Sensitivity and resolution in NMR experiments are affected by magnetic field inhomogeneities (of both external and RF), errors in pulse calibration, and offset effects due to finite length of RF pulses. To remedy these problems, built-in compensation mechanisms for these experimental imperfections are often necessary. Here, we propose a new family of phase-modulated constant-amplitude broadband pulses with high compensation for RF inhomogeneity and heteronuclear coupling evolution. These pulses were optimized using a genetic algorithm (GA), which consists in a global optimization method inspired by Nature's evolutionary processes. The newly designed π and π/2 pulses belong to the 'type A' (or general rotors) symmetric composite pulses. These GA-optimized pulses are relatively short compared to other general rotors and can be used for excitation and inversion, as well as refocusing pulses in spin-echo experiments. The performance of the GA-optimized pulses was assessed in Magic Angle Spinning (MAS) solid-state NMR experiments using a crystalline U-(13)C, (15)N NAVL peptide as well as U-(13)C, (15)N microcrystalline ubiquitin. GA optimization of NMR pulse sequences opens a window for improving current experiments and designing new robust pulse sequences.


ASYMMETRIC LEAVES 2 and ASYMMETRIC LEAVES 2-LIKE are partially redundant genes and essential for fruit development in tomato.
Fruit size and shape are controlled by genes expressed during the early developmental stages of fruit. Although the function of ASYMMETRIC LEAVES 2 (AS2) in promoting leaf adaxial cell fates has been well characterized in Arabidopsis thaliana, the molecular mechanisms conferring freshy fruit development as a spatial-temporal expression gene in tomato pericarp remain unclear. In the present study, we verified the transcription of SlAS2 and SlAS2L, two homologs of AS2, in the pericarp during early fruit development. Disruption of SlAS2 or SlAS2L caused a significant decrease in pericarp thickness as a result of a reduction in the number of pericarp cell layers and cell area, leading to smaller tomato fruit size, which revealed their critical roles in tomato fruit development. In addition, leaves and stamens exhibited severe morphological defects in slas2 and slas2l single mutants, as well as in the double mutants. These results demonstrated the redundant and pleiotropic functions of SlAS2 and SlAS2L in tomato fruit development. Yeast two-hybrid and split-luciferase complementation assays showed that both SlAS2 and SlAS2L physically interact with SlAS1. Molecular analyses further indicated that SlAS2 and SlAS2L regulate various downstream genes in leaf and fruit development, and that some genes participating in the regulation of cell division and cell differentiation in the tomato pericarp are affected by these genes. Our findings demonstrate that SlAS2 and SlAS2L are vital transcription factors required for tomato fruit development.


Spike-independent release of ATP from Xenopus spinal neurons evoked by activation of glutamate receptors.
As the release of ATP from neurons has only been directly studied in a few cases, we have used patch sniffing to examine ATP release from Xenopus spinal neurons. ATP release was detected following intracellular current injection to evoke spikes. However, spiking was not essential as both glutamate and NMDA could evoke release of ATP in the presence of TTX. Neither acetylcholine nor high K(+) was effective at inducing ATP release in the presence of TTX. Although Cd(2+) blocked glutamate-evoked release of ATP suggesting a dependence on Ca(2+) entry, neither omega-conotoxin-GVIA nor nifedipine prevented ATP release. N-type and L-type channels are thus not essential for glutamate-evoked ATP release. That glutamate receptors can elicit release in the absence of spiking suggests a close physical relationship between these receptors, the Ca(2+) channels and release sites. As the dependence of ATP release on the influx of Ca(2+) through Ca(2+) channel subtypes differs from that of synaptic transmitter release, ATP may be released from sites that are distinct from those of the principal transmitter. In addition to its role as a fast transmitter, ATP may thus be released as a consequence of the activation of excitatory glutamatergic synapses and act to signal information about activity patterns in the nervous system.


The role of GABA in the regulation of GnRH neurons.
Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA) has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.


The role of different biomaterials on adhesion of nontransformed buccal epithelial cells.
The specific objective of this study was to investigate the effect of various biomedical polymers on the adhesion rate of buccal epithelial cells (BEC) as a model for biocompatibility. The BEC in this study were isolated, biotin labeled and seeded by following standard laboratory procedures. A total of 2.5 x 10(5) cells was plated in each microtiter-well pretreated with various concentrations of (0.01, 0.10 and 1% wt/vol) poly-L-valanine (P-Val), poly-L-alanine (P-Ala), poly-glycine (P-Gly), poly-L-tryptophan (P-Trp), poly-L-asparagine (P-Asn) and buffered control. At the end of 1, 4, and 24 hours the assay was developed by utilizing avidin-horseradish peroxidase and o-phenylenediamine dihydrochloride as substrate to measure biotin-labeled-BEC. Cell number was then determined using a standard curve prepared by using known BEC number vs. absorbance units. The data from this study suggest that: (I) the ease of adhesion of BEC was in the following order: P-Val > P-Gly = P-Trp = P-Ala > P-Asn > P-Asp = Control, (II) the rate of BEC spreading was strongly influenced by both incubation time and the polymer concentration, (III) the surface attachment of BEC to the polymer were demonstrated to vary depending on their chemical structure and level of microporosity. Thus, overall observation led us to conclude that the surface reactivity of polymer materials must always be taken into account in discussing their biocompatibility in vivo.


Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial.
to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus. this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05). participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling). the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.


Rare anaplastic sarcoma of the kidney: A case report.
Anaplastic sarcoma of the kidney (ASK) is a rare and newly recognized renal neoplasm. The tumor usually is extensive and cystic, characterized by pleomorphic spindle cells with marked atypia and associated with multinucleated cells. To date, only 27 cases have been reported in the literature. The authors present an additional case and summarize the relevant knowledge in the literature. A 27-year-old previously healthy woman presented with a palpable mass over the abdomen and right flank soreness for one year. After the computed tomography study, the patient underwent right radical nephrectomy obtaining a 1680-g tumor with a size of 18.4 cm × 14.5 cm × 11 cm. The tumor is chiefly composed of anaplastic spindle cells with marked nuclear atypia admixed with multinucleated cells. Immunohistochemical evaluation of tumor cells exhibited diffuse positivity for CD56, p53, and vimentin, and focally positive for desmin. The diagnosis of ASK was established. Unfortunately, a local tumor recurrence followed by a distant metastasis developed within months. The patient died 26 months after the initial surgery. Comparing to the previously 27 cases of ASK, the current case had a relatively worse prognosis, which might be potentially associated with older patient age, larger tumor size, and the lack of en-bloc resection of adjacent organs during the initial radical nephrectomy. This case points out the featured pathological findings for diagnosing ASK and suggests more aggressive management for patients with ASK.


Long-Term Outcomes and Growth Analysis of Costochondral Grafts for Hemifacial Microsomia: 24-Year Experience of a Single Surgeon.
Costochondral grafts (CCGs) can be used in mandibular reconstruction of Kaban-Pruzansky IIB/III hemifacial microsomia (HFM). Their growth is variable, occasionally necessitating secondary surgery. This study examined one surgeon's 24-year experience to better quantify long-term outcomes and surgical care required in CCG reconstruction of HFM mandibles. Serial three-dimensional computed tomography scans, from preoperative to most recent, were analyzed in patients with minimum four years of clinical follow-up following CCG reconstruction. Graft/ramus height, length, volume, bilateral mandibular body length, and chin deviation were measured. Changes in measurements were analyzed at preoperative, immediate postoperative, most recent imaging prior to secondary surgery, and most recent imaging overall. Growth rates per measure were calculated utilizing scans after CCG, but before secondary surgery. Thirteen patients were analyzed. Median clinical follow-up was 10.0 (5.1) years. One patient developed temporomandibular joint ankylosis secondary to stacked-graft malposition, which was repaired without further complications. CCG reconstruction led to immediate improvement in graft/ramus height (p=0.03), length (p=0.002), and volumetric symmetry (p=0.02). No difference was found between graft and native ramus height (p=0.4) and length measures (p=0.5), while graft volume and affected mandibular body grew significantly more slowly. By latest imaging, 63% of patients required secondary surgery, including distraction osteogenesis and/or orthognathic surgery due to differential graft/hemimandible growth behavior. By most recent clinical follow-up, this proportion increased to 93%. CCGs provide significant short-term mandibular and facial symmetry improvement in HFM IIB/III. Long-term analysis reveals frequent undergrowth requiring secondary intervention to promote and maintain symmetry.


Aggregation-induced emission of tetraphenylethene-hexaphenylbenzene adducts: effects of twisting amplitude and steric hindrance on light emission of nonplanar fluorogens.
A series of nonplanar tetraphenylethene (TPE)-hexaphenylbenzene (HPB) adducts was designed and synthesized by Diels-Alder reaction of the acetylene precursors and tetraphenylcyclopentadienone. All of the adducts showed aggregation-induced emission features. The twisting amplitude and steric hindrance of the TPE and HPB units were found to play a crucial role in their fluorescence behaviors in the aggregated state.


Model verification of thermal programmed desorption-mass spectrometry for estimation of release energy values for polycyclic aromatic hydrocarbons on mineral sorbents.
The physical availability of organic compounds in soil and sediment strongly influences their bioavailability and toxicity. Previous work has indicated that physical availability changes throughout the processes of aging and treatment and that it can be linked to the energy required to release the compound from its sorbent matrix, with a higher energy indicating a more tightly bound compound. This study focused on determining release energy values for various mineral geosorbents (glass beads, sand, and kaolin) contaminated with a 16 polycyclic aromatic hydrocarbon (PAH) mixture. The sorbents were analyzed using thermal program desorption/mass spectrometry (TPD/MS) and the release energy values were calculated from the resulting thermograms utilizing a nonlinear fit of the analytical solution to a simplified version of the Polanyi-Wigner equation. This solution method resulted in a series of combinations of values for the pre-exponential factor (v) and release energy (E) that produced desorption rate curves with similar errors when fit to actual data sets. These combinations can be viewed as an error surface, which clearly shows a valley of minimum error values spanning the range of both E and v. This indicates that this method may not provide a unique set of E- and v-values and suggests that the simplified version of the Polanyi-Wigner equation cannot be used to determine release energy based on TPD data alone.


Nanostructure of propylammonium nitrate in the presence of poly(ethylene oxide) and halide salts.
Nanoscale structure of protic ionic liquids is critical to their utility as molecular electrochemical solvents since it determines the capacity to dissolve salts and polymers such as poly(ethylene oxide) (PEO). Here we use quantum chemical molecular dynamics simulations to investigate the impact of dissolved halide anions on the nanostructure of an archetypal nanostructured protic ionic liquid, propylammonium nitrate (PAN), and how this impacts the solvation of a model PEO polymer. At the molecular level, PAN is nanostructured, consisting of charged/polar and uncharged/nonpolar domains. The charged domain consists of the cation/anion charge groups, and is formed by their electrostatic interaction. This domain solvophobically excludes the propyl chains on the cation, which form a distinct, self-assembled nonpolar domain within the liquid. Our simulations demonstrate that the addition of Cl- and Br- anions to PAN disrupts the structure within the PAN charged domain due to competition between nitrate and halide anions for the ammonium charge centre. This disruption increases with halide concentration (up to 10 mol. %). However, at these concentrations, halide addition has little effect on the structure of the PAN nonpolar domain. Addition of PEO to pure PAN also disrupts the structure within the charged domain of the liquid due to hydrogen bonding between the charge groups and the terminal PEO hydroxyl groups. There is little other association between the PEO structure and the surrounding ionic liquid solvent, with strong PEO self-interaction yielding a compact, coiled polymer morphology. Halide addition results in greater association between the ionic liquid charge centres and the ethylene oxide components of the PEO structure, resulting in reduced conformational flexibility, compared to that observed in pure PAN. Similarly, PEO self-interactions increase in the presence of Cl- and Br- anions, compared to PAN, indicating that the addition of halide salts to PAN decreases its utility as a molecular solvent for polymers such as PEO.


Mass Incarceration Through a Different Lens: Race, Subcontext, and Perceptions of Punitiveness of Correctional Alternatives When Compared to Prison.
In spite of documented harmful effects of mass incarceration, evidence to date suggests that Blacks perceive the experience of prison as less punitive than Whites. While these findings are well documented, little is known about the role of sociodemographic or contextual factors in shaping this pattern. Utilizing a quantitative intersectional framework, we analyze data from over 1000 Kentucky prison inmates who were within 12 months of their parole hearing or release date to examine the differential effects of various sociodemographic and contextual factors on perceptions of the punitiveness of regular probation, community service, and electronic monitoring (as opposed to prison) for Blacks and Whites. Findings confirm the presence of a racial gap in perceptions of the punitiveness of various alternatives to incarceration; however, results from models disaggregated by race highlight important differences in the effects of gender, parenting, and childhood locale on these perceptions. These findings demonstrate the role of various factors in shaping Blacks' and Whites' differential perceptions and reveal the contexts where these differences are most likely to be found.


Conservative treatment for leg oedema and the effect on nocturnal polyuria in patients with spinal cord injury.
To evaluate the possible influence of non-pharmacological interventions, such as compressive bandages and intermittent pneumatic compression (IPC), on leg oedema and nocturnal polyuria (NP), and the possible interrelation between both pathologies in patients with spinal cord injury (SCI), as patients with SCI often have leg oedema and during the night the oedema decreases as a result of natural drainage mechanisms that can cause NP. Patients with SCI who followed their first rehabilitation after their SCI with bilateral leg oedema and/or with as much or a larger urine volume at night as during the day. The patients were all wheelchair users and followed the rehabilitation programme daily for 3 weeks. In all, 24 patients, aged between 21 and 63 years, were selected for participation in the 3-week rehabilitation programme. During the first week, baseline data were collected. During the second week, IPC was executed from the moment the patient went to lie down. During the third week, the patients wore multilayer compressive bandages. Leg circumference was measured in the morning before sitting up and at the moment they went to lie down in bed. During each study week, a daily frequency-volume chart (24 h) was completed. The leg volume of both legs was significantly different between the morning and evening (right leg F = 103.90, P < 0.001; left leg F = 100.77, P < 0.001) and between the three treatments (right F = 9.70, P < 0.001; left F = 9.66, P < 0.001). There was a significant difference between the compressive bandages and the baseline period (right and left leg, both P < 0.001) and between the compressive bandages and IPC (right leg P = 0.009 and left leg P = 0.015). There was no significant difference between IPC and the baseline. When no treatment or IPC was used, urine production was significantly higher during the bed-rest period. The urine production was significantly lower comparing the use of compressive bandages to baseline and IPC, during bed rest (P = 0.009) and during sleep (P < 0.001). There was a significant decrease in absolute voided volume at night with the compressive bandages as treatment (P < 0.001). There was a significant positive association between the leg volume change during the day and the urine-production ratio, 100 mL increase in leg volume was associated with 8% increase in the log-transformed urine-production ratio. There are alternative treatment options for patients with SCI who have oedema or NP. Oedema formation and urine production appear to be related to each other. Therefore, the use of compressive bandages was shown to be a valuable treatment option to improve both leg oedema and NP.


An injectable PC10ARGD/Cu2+/DOX hydrogel for combined chemodynamic and chemotherapy of tumors.
Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility.


The relationship between childhood health anxiety, parent health anxiety, and associated constructs.
The purpose of the present investigation was to explore the relationship between self-reported childhood health anxiety and self-reported parent health anxiety and associated constructs. Participants were 77 children (8-15 years) and one parent or guardian of each child. Children completed a measure of health anxiety and parents completed measures of health anxiety, anxiety sensitivity, and depression. Results demonstrated a significant association between child health anxiety and all measures of self-reported parent measures, with the exception of the measure of anxiety sensitivity. No self-reported parent measures independently predicted child health anxiety. Future directions and implications are discussed.


Human pulmonary macrophages: the relationship of smoking to the presence of sea blue granules and surfactant turnover.
Human pulmonary macrophages from heavy smokers usually (17/21 cases) contain sea blue inclusion material in the cytoplasm. In non-smokers, sea blue material is rarely evident (1/21 cases). The sea blue material observed has the same properties as sea blue material identified in other conditions (viz, Sudan black and PAS positivity and autofluorescence). Evidence is presented which suggests that pulmonary macrophages from smokers contain extra surfactant and that it is this phospholipid complex that accounts for the sea blue reaction observed.


Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmission.
Butyrylcholinesterase (EC 22.214.171.124 BChE) is present in all human and mouse tissues, and is more abundant than acetylcholinesterase (EC 184.108.40.206 AChE) in all tissues except brain. People who have no BChE activity due to a genetic variation are healthy. This has led to the hypothesis that BChE has no physiological function. We tested this hypothesis by challenging BChE and AChE knockout mice, as well as wild-type mice, with the AChE specific inhibitors, (--)-huperzine A and donepezil, and with serine hydrolase inhibitors, echothiophate and chlorpyrifos oxon. (--)-Huperzine A and donepezil caused mortality and significant toxicity in the BChE-/- animals. The BChE heterozygote (BCHE+/-) mice with approximately one-half the BChE activity of the BChE wild type (BChE+/+) exhibited intermediate toxic symptoms, and survived a longer period. The BChE+/+ animals displayed comparatively minor toxic symptoms and recovered by 24h post-dosing. Plasma AChE activity was inhibited to the same extent in BChE-/-, +/-, and +/+ mice, whereas BChE activity was not inhibited. This indicated that the protective effect of BChE was not due to scavenging (--)-huperzine A. AChE-/- mice were unaffected by (--)-huperzine A and donepezil, demonstrating the specificity of these inhibitors for AChE. AChE-/- mice treated with chlorpyrifos oxon lost all BChE activity, had severe cholinergic symptoms and died of convulsions. This showed that BChE activity was essential for survival of AChE-/- mice. In conclusion, we propose that the protective effect of BChE is explained by hydrolysis of excess acetylcholine in physiologically relevant regions such as diaphragm, cardiac muscle, and brain. Thus, BChE has a function in neurotransmission. People with BChE deficiency are expected to be intolerant of standard doses of the anti-Alzheimer's drugs, (--)-huperzine A and donepezil.


Mutation Spectrum of Primary Lipid Storage Myopathies.
Lipid storage myopathies (LSM) constitute an important group of treatable myopathies. Genetic testing is essential for confirming the diagnosis and also helps in explaining phenotypic heterogeneity. The objective of this study was to describe the clinical features and genetic spectrum of LSM seen in a quaternary referral center in India. Eleven cases of suspected LSM underwent clinical, biochemical, histopathological and genetic evaluation. Tandem Mass Spectrometry and clinical exome sequencing with Sanger validation were performed. All patients had exertion induced myalgia and either progressive or episodic limb girdle muscle weakness (LGMW). The age of onset ranged 10 to 31 years (mean- 21 ± 6.7y), age at presentation- 14 to 49 years (mean- 26.5 ± 9.5y). Mutations identified: ETFDH = 5, CPT2 = 3, FLAD1 = 1, ACADVL = 1, FLAD1 = 1. Dropped head syndrome was seen in two patients with ETFDH mutations. Bulbar symptoms and Beevor's sign were noted in a patient with FLAD1 variant. Novel variants were identified in seven patients. This is the first report on the genetic spectrum of LSM from India. LSM should be considered in patients with exertion induced myalgias, LGMW, cranial nerve involvement or dropped head syndrome. Genetic testing is essential for identification of these treatable disorders.


How much stressful life events really matter? Conceptual and methodological difficulties in assessing the impact of self-reported events on adolescents' subjective stress.
Numerous studies have pointed to the strong impact of stressful life events on subjective stress and indirectly on the adolescents' mental health. However, the results of many such studies contain bias caused by the choice of measurement method or an incomplete theoretical framework. To estimate the extent of possible bias when using self-reports, we conducted research on a representative sample of 2201 Croatian adolescents aged 14-18 years. Using manipulation we examined the influence of measurement method and the number of constructs included in the model on the variance of subjective stress explained by stressful events. Structural equation modelling indicated that different measurement methods, occurrence-based and severity-based, provide a marked discrepancy in the impact size estimation. The occurrence-based method provided estimates of a much smaller proportion of the explained variance (6%-25%) compared to the severity-based approach, which estimated the explained variance in the range of 25%-55% depending on the model. The complexity of the tested models additionally contributed to the variation in the estimates. It is recommended that when using self-reports to measure stressful life events, occurrence-based and severity-based methods are used simultaneously and that impact estimates are expressed within intervals.


Naked reverse: unexpected plays for exceptional results.
Following the herd is easy when it comes to business ventures. But if you really want to start something new, you must first carefully think it through. Learn some ways to do that before you set out on a new path.


Cough and phlegm are important predictors of health status in smokers without COPD.
The health-related quality of life of smokers without COPD and that of ex-smokers has not been defined. If abnormal, the role of small airways disease and that of cough and phlegm have never been evaluated. Therefore, the aim of the study was to explore whether the differences in quality of life between smokers and ex-smokers could be explained by cough and phlegm, differences in pulmonary function tests, or exercise capacity. Observational, prospective. Pulmonary and Critical Care Division, COPD Center at St. Elizabeth's Medical Center. In 36 smokers, 21 ex-smokers (stopped smoking for > 20 years), 19 never-smokers with normal FVC and FEV(1) values, and 41 patients with COPD (FEV(1) 38 +/- 11% predicted [mean +/- SD]), the St. George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and a 6-min walk distance (6MWD) were performed. The total SGRQ scores were worse in current smokers (15 +/- 15) than in ex-smokers (6 +/- 4) or never-smokers (4 +/- 3) [p < 0.05]. As expected, the worst score was seen in COPD (50 +/- 15). After correcting for cough and phlegm, the difference in SGRQ scores between smokers and ex-smokers disappeared. In current and ex-smokers, the SGRQ score was associated with the exposure to pack-years smoking history (r = 0.45, p < 0.01, and r = 0.83, p < 0.0001, respectively) but independent of lung function or exercise parameters (6MWD). In smokers without COPD, the abnormal SGRQ score is due to the noxious effect of cigarette smoke, resulting in cough and phlegm, independent of its physiologic effects.


Could the Optiplex Borrelia assay replace the traditional, two-step method of diagnosing Lyme disease?
Serological assays for Lyme disease (LD) routinely performed in laboratories often give inconclusive results, thereby making correct diagnosis difficult and delaying treatment. The aim of the study was to assess the usefulness of a commercial Optiplex Borrelia (OB) assay in the serological diagnostics of LD. Based on the results obtained in a previous study on the seroreactivity of the sera of patients with LD to Borrelia spp. antigens using enzyme immunoassays (ELISA) and immunoblotting (IB), the same sera were re-analyzed using the OB assay. The assays carried out with the use of OB method showed a statistically significant lower number of positive/borderline results for the presence of IgM antibodies, compared to the ELISA assay. Moreover, statistically lower positive/borderline results were obtained for antibodies in the IgG class with use of the OB method, compared to the IB assay and a two-stage diagnostic protocol (ELISA with IB). The specificity analysis showed that in both the IB and OB assays, anti-OspC IgM and anti-p41 antibodies were detected. Additionally, high positive/borderline values were found in the OB assay for native antigens derived from B. afzelii lysate. The IB assay most frequently detected antibodies against OspC, p39 (BmpA) and VlsE proteins in the IgG class. There were fewer positives/borderlines for anti-p41-I B. afzelii antibodies in the OB assay and a higher number for antigens: VlsE-C6, p18 B. afzelii (DbpA), and p39 B. afzelii (BmpA). Answering the question whether the OB assay could replace the traditional, two-step method of LD diagnostics, it can be concluded that it could not. It can be used to diagnose LD only as a complementary assay and not as an optimal and dedicated method of Borrelia spp. infection detection.


The Effect of the Wooden Breast Fibrotic Myopathy in Broilers on Fibrillar Collagen Organization and Decorin-Collagen Binding.
The wooden breast myopathy is identified by the palpation of a rigid pectoralis major muscle and results in myofiber necrosis and fibrosis in fast-growing, meat-type broilers. The fibrosis in wooden breast-affected muscle is characterized by the replacement of myofibers with extracellular matrix proteins, especially fibril-forming collagens. Studies have shown differences in collagen organization in fast-growing broiler lines, with tightly packed and highly aligned collagen organizations having a higher phenotypic incidence of wooden breast. The objective of the current study was to analyze collagen fibril organization further in two fast-growing broiler lines (Lines A and B) with incidence of wooden breast compared with a slower growing broiler Line C with no phenotypically detectable wooden breast. The small leucine-rich proteoglycan decorin was also studied for its interaction with collagen by immunogold detection. Decorin binds to fibrillar collagens and organizes their alignment and crosslinking, both of which will affect collagen functional properties. Key findings from the study showed that collagen shifts to larger diameter collagen fibril bundles with the wooden breast myopathy. Specifically, broilers affected with wooden breast from Line A had a more dramatic shift toward larger collagen fibril bundles compared with those affected from Line B. Wooden breast-affected Line A had collagen fibril bundles up to 8.4 µm, whereas Line B maximum size was 5.1 µm. Although decorin-collagen binding was not different overall in the wooden breast myopathy or broiler line, for small-diameter collagen fibril bundles, wooden breast-affected Line A had more decorin-collagen binding than wooden breast-affected Line B. Taken together, these data provide further evidence that multiple fibrotic myopathies are likely in fast-growing meat-type broilers.


Delayed and advanced sleep phase symptoms.
Current criteria for circadian rhythm sleep disorders require a mismatch between the endogenous circadian sleep tendency and exogenous environmental requirements for sleep timing. To examine the prevalence of circadian rhythm sleep disorders by DSM-IV criteria, sleep complaints and objectively-measured sleep timing were sampled in a population aged 40-64 years. Randomly selected volunteers were interviewed concerning sleep complaints. Then, objective sleep timing was estimated from wrist activity recordings and environmental illumination data. In this age group, advance-related complaints (trouble staying awake until bedtime and troubled by waking up early in the morning) were found together in 7.4%. Less prevalent were delay-related complaints reported together in 3.1% (trouble falling asleep and trouble waking up in the morning). However, no significant correlations or clusters were found pairing these sleep complaints with recorded sleep timing. The distributions of objectively-recorded lights-out times and arising times were consistently later than the questionnaire-reported times. Thus, complaints suggesting circadian rhythm advance or delay mismatches were common, but evidently such complaints do not usually correspond with objective abnormalities of observed sleep timing.


On the continuity, change and clinical value of infant temperament in a prospective epidemiological study.
The temperament of 1855 children born in Helsinki during 1975-76 was recorded at the age of 6-8 months by parental questionnaires. In 1980-81 the continuity of temperamental dimensions was studied in a group of these children by using a temperament questionnaire for 3--7-year-old children. In addition, the clinical usefulness of infant temperament was assessed by analysing the infant temperamental dimensions used was almost negligible, because less than 10% of the total variance of each dimension could be explained by the corresponding dimensions at the infant age. The clinical usefulness of infant temperament questionnaires in prospective epidemiological studies was supported by the observation that children with later paediatric problems (behavioural problems, colic spasms, accidents) had had significantly different temperamental styles at the infant age from those without problems. The results support the importance of negative mood and high intensity of infant's behavioural style as risk factors for later paediatric problems.


Medical residents' mental distress in the COVID-19 pandemic: An urgent need for mental health care.
Medical residents' mental health is currently an issue of concern for medical educators worldwide. The COVID-19 pandemic has raised the greatest concerns given the psychological effects of this scenario on medical residents on the frontlines of the pandemic. To assess the psychological impact of the COVID-19 pandemic on physicians in residency training, the collective symptoms of burnout, depression and anxiety are used to identify the residents' beliefs and clinical practices related to COVID-19 patients and their behaviors concerning disease prevention. This observational study involved 3071 medical residents from all regions of Brazil. An online questionnaire assessed the presence of burnout using the Oldenburg Burnout Inventory, depressive symptoms using the Patient Health Questionaire-9, anxiety symptoms using the Generalized Anxiety Disorder-7, and COVID-19 Impact Questions to assess the residents' beliefs and clinical practices related to COVID-19 patients. Exploratory analyses, logistic regression and multinomial regression analysis were performed in this investigation. Moderate and severe depressive symptoms were the most common (67.7%) followed by anxiety symptoms (52.8%) and burnout (48.6%). The difference between residents with or without contact with COVID-19 patients was significant increased when analyzing different aspects of clinical practice, behavior, substance use and mental health. These results suggest an increase in depression and anxiety symptoms among medical residents dealing with COVID-19, upstaging previous concerns about medical residents' mental health. The prevalence of burnout is similar to that of a nonpandemic scenario. Considering the severity of the pandemic scenario and the overburden of healthcare services, medical residents' mental health deserves special care.


A national prevalence study on nosocomial infections 1988.
A National survey of N.I. in Thailand was done in April 1988. Twenty-three hospitals throughout the country were enrolled. Of the 6,805 patients studied, 52 per cent were males and 48 per cent were females. The prevalence rate of nosocomial infections was 11.7 per cent. The highest rate was found in the second biggest (regional) hospitals (18.8%). There were minor variations in the rates of infection in each age group. The infection rate was highest in intensive care units (35.1%) followed by orthopaedic (20.4%) and paediatric (15.7%) departments respectively. Urinary infections were the commonest (25.8%). Surgical wound infections ranked second (19.6%). Skin infections were as high as 11.8 per cent. P. aeruginosa were the commonest bacterial isolates (22%) followed by E. coli (18.1%) and Klebsiella species (14.0%). Antimicrobials were prescribed in 52 per cent of patients, and, in a large number, for prophylactic purposes. It is concluded that N.I. are the main health problems affecting more than 200,000 patients annually in Thailand. Urgent studies and interventions are clearly needed.


A new anatomic technique for type II SLAP lesions repair.
A new and more anatomical technique for SLAP II lesions repair is described. It consists in the reattachment of the medial aspect of the biceps anchor to the superior glenoid neck with a mattress stitch posterior and medial to the biceps anchor and a simple stitch placed anteriorly to the biceps. From 2011 to 2012, 14 patients matching the inclusion criteria were selected for the study. A visual analogic scale, ROWE, UCLA, ASES and Constant scores were used to make evaluation. The passive ROM before surgery, at final follow-up, and the resumption of sports activities were analysed. The Constant, ASES, UCLA and ROWE scores passed from 64.6 (SD 13.9), 76.9 (SD 22.4), 28.4 (SD 23.8) and 53.6 (SD 20.6) to, respectively, 92.6 (SD 11.8), 108.3 (SD 8.5), 33.6 (SD 2.7) and 96.5 (SD 7.2) at final follow-up. Of the four patients who had participated in agonistic overhead athletics preoperatively, all of them were able to return to their preinjury level. No complications were observed in the present study. In our technique, the anatomy is respected leaving the articular aspect of the superior labrum loose and reinforcing the medial side. The clinical relevance of this work is that probably this technique could improve clinical results, giving a better mobility of the shoulder and a return to the same preoperative level in overhead athletes.


Evaluating chemical extraction techniques for the determination of uranium oxidation state in reduced aquifer sediments.
Extraction techniques utilizing high pH and (bi)carbonate concentrations were evaluated for their efficacy in determining the oxidation state of uranium (U) in reduced sediments collected from Rifle, CO. Differences in dissolved concentrations between oxic and anoxic extractions have been proposed as a means to quantify the U(VI) and U(IV) content of sediments. An additional step was added to anoxic extractions using a strong anion exchange resin to separate dissolved U(IV) and U(VI). X-ray spectroscopy showed that U(IV) in the sediments was present as polymerized precipitates similar to uraninite and/or less ordered U(IV), referred to as non-uraninite U(IV) species associated with biomass (NUSAB). Extractions of sediment containing both uraninite and NUSAB displayed higher dissolved uranium concentrations under oxic than anoxic conditions while extractions of sediment dominated by NUSAB resulted in identical dissolved U concentrations. Dissolved U(IV) was rapidly oxidized under anoxic conditions in all experiments. Uraninite reacted minimally under anoxic conditions but thermodynamic calculations show that its propensity to oxidize is sensitive to solution chemistry and sediment mineralogy. A universal method for quantification of U(IV) and U(VI) in sediments has not yet been developed but the chemical extractions, when combined with solid-phase characterization, have a narrow range of applicability for sediments without U(VI).


Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling.
Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.


Congenital hereditary paresis of ramus marginalis nervus facialis in five generations.
We report a case of familial congenital paresis of ramus marginalis nervus facialis in 5 generations. The paresis varied in location, i.e., 2 right-sided and 3 left-sided, 1 side unknown. The primary patient, a 33-year-old female, presented with a complete right-sided congenital lower lip palsy. Electromyographic examination showed absent voluntary activity of the right depressor labii inferior muscle. There was no evidence of denervation of the paretic muscle. These findings may suggest either absence of the depressor labii inferior muscle or possibly absent voluntary activation due to a defect at brainstem level.


Assessment of provider-initiated HIV screening in Nigeria with sub-Saharan African comparison.
Despite Nigeria's high HIV prevalence, voluntary testing and counselling rates remain low. UNAIDS/WHO/CDC recommends provider-initiated testing and counselling (PITC) for HIV in settings with high HIV prevalence. We aimed to assess the acceptability and logistical feasibility of the PITC strategy among adolescents and adults in a secondary health care centre in Idekpa Benue state, Nigeria. All patients (aged ≥ 13 years) who visited the out-patient department and antenatal care unit of General Hospital Idekpa, Benue state, Nigeria were offered PITC for HIV. The intervention was implemented by trained health professionals for the period spanning (June to December 2010). Among the 212 patients who were offered PITC for HIV, 199 (94%) accepted HIV testing, 10 patients (4.7%) opted out and 3 patients (1.4%) were undecided. Of the 199 participants who were tested for HIV, 9% were HIV seropositive. The PITC strategy was highly acceptable and feasible, and increased the number of patients who tested for HIV by 5% compared to voluntary counselling and testing. Findings from this assessment were consistent with those from other sub-Saharan African countries (such as Uganda and South Africa). PITC for HIV was highly acceptable and logistically feasible, and resulted in an increased rate of HIV testing among patients. Public health initiatives (such as the PITC strategy) that facilitate early detection of HIV and referral for early treatment should be encouraged for broader HIV control and prevention in Nigerian communities.


Classification of clock reactions.
Autocatalytic systems are sometimes designated as clock reactions or reactions that exhibit clock behavior. To resolve the recent dispute over the term clock reaction, we describe a new approach to classify systems featuring clock behavior into three distinct groups: substrate-depletive clock reactions, autocatalysis-driven clock reactions, and systems that have pseudo clock behavior. Many of the well-known classical and recently discovered reactions can conveniently be put into these categories. We also provide a convincing argument for classifying some autocatalytic processes as clock reactions, but it does not necessarily mean that all autocatalytic processes should be classified as autocatalysis-driven clock reactions. This classification can be conveniently performed if the kinetic nature of the given system has been completely elucidated and understood.


The role of deleterious mutations in allopatric speciation.
Allopatric speciation is often assumed to occur as a consequence of adaptive divergence between two isolated populations. However, there are some scenarios in which reproductive isolation can be favored due to accumulated unconditionally deleterious mutations. If deleterious mutations have synergistic epistatic effects, it is shown here that the average fitness of recombinants between two parental lines with a given number of fixed mutations is lower than that of the parents in both the F1 and F2 generations. If individual mutations are only slightly deleterious, then they will tend to fixation at a high enough rate to cause lower hybrid fitness. If the fitness effects of mutation give rise to antagonistic epistasis, the hybrids tend to have a higher average fitness than the parental lines, suggesting a possible scenario for the origin of hybrid vigor. The other model of deleterious mutations investigated is the accumulation of knockout mutants in a duplicated gene family. While neutral in the parental lines, upon contact the F1 and later generations have a significant probability of carrying double knockouts. Under this scenario, selection may also favor reproductive isolation between the two lines. Even when the selection coefficients generated are too low to drive speciation, epistatic interactions between deleterious mutations offer a possible explanation for both outbreeding depression and hybrid vigor.


Are rural hospices at a financial disadvantage? Evidence from California.
Concerns have been voiced about financial pressures faced by rural hospices, because of possible implications for hospice access in rural areas. To assess whether financial performance differs between existing urban and rural hospices, we used the 2003 California Office of Statewide Health Planning and Development survey to compare revenues, costs, and profitability (with and without charitable donations). We adjusted for factors related to financial performance, including agency size, years in operation, profit status, whether hospices were freestanding or chain-, home-health-, or hospital-based, and the proportion of patients by insurance type and referral source, race/ethnicity, and diagnosis. One hundred forty-four (91%) hospices were urban, and 14 (9%) were rural. Mean values per patient for total revenue, total cost, and post-tax profit were $7203, $7440 and -$256, respectively, for urban hospices and $6726, $6274 and $452, respectively, for rural hospices. Compared with urban hospices, rural hospices were at least as profitable per patient-day (+$33, P=0.15). They were significantly more profitable (+$47, P=0.05) when charitable donations were excluded. In summary, we found that in California, rural hospices fared no worse financially than urban hospices. These counterintuitive findings underscore the need to examine urban-rural hospice financial differences using a national sample.


Distinct roles of VEGF-A and VEGF-C in tumour metastasis of gastric carcinoma.
The expression of VEGF-A and -C was investigated immunohistochemically in 51 specimens of gastric carcinoma. The expression intensity was evaluated by means of a semi-quantitative scoring system and a quantitative analysis. The results showed that VEGF-A and -C were located mainly in the cytoplasm of tumour cells: 68.6% (34/51) and 62.8% (32/51) positive for VEGF-A and VEGF-C. VEGF-C expression was more frequent in tumours of the deceased patients [88.2% (15/17)] compared to that in the survivors [47.0% (16/34)]. Quantitative VEGF-C levels in the deceased patients were 0.304+/-0.023, which was significantly elevated compared to that in the survivors (0.131+/-0.018) (p<0.01). The frequency of VEGF-C expression was higher in patients with lymph node metastases (80.0%, 28/35) compared to those with negative nodes (25%, 4/16). Accordingly, its levels were markedly elevated in the former (0.230+/-0.017) than in the latter (0.089+/-0.011) (p<0.01). Furthermore, tumour cell invasion into the enlarged lymphatic vessels was also associated with VEGF-C expression. Its expression levels were 0.271+/-0.028 in lymph vessel invasion and 0.153+/-0.021 in the absence of invasion (p<0.01). VEGF-A expression, although correlated with survival, distant metastasis, ascites formation, and blood vessel invasion, was not associate with lymph node metastasis, lymphatic vessel invasion. The expression levels of the two factors were inversely correlated with overall survival rates. It can be conclude that VEGF-C expression in tumour tissues is indicative of lymphatic metastasis, whereas VEGF-A expression is more likely to be associated with haematogenous metastasis. Both VEGF-A and -C could serve as a prognostic biomarker in patients with gastric carcinoma.


Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus.
We sought to determine whether intramuscular injection of a recombinant adeno-associated virus (rAAV) vector expressing human factor IX (hF.IX) could direct expression of therapeutic levels of the transgene in experimental animals. High titer (10(12)-10(13) vector genomes/ml) rAAV expressing hF.IX was prepared, purified, and injected into hindlimb muscles of C57BL/6 mice and Rag 1 mice. In the immunocompetent C57BL/6 mice, immunofluorescence staining of muscle harvested 3 months after injection demonstrated the presence of hF.IX protein, and PCR analysis of muscle DNA was positive for AAV DNA, but no hF.IX was detected in mouse plasma. Further studies showed that these mice had developed circulating antibodies to hF.IX. In follow-up experiments in Rag 1 mice, which carry a mutation in the recombinase activating gene-1 and thus lack functional B and T cells, similar results were seen on DNA analysis of muscle, but these mice also demonstrated therapeutic levels (200-350 ng/ml) of F. IX in the plasma. The time course of F.IX expression demonstrates that levels gradually increase over a period of several weeks before reaching a plateau that is stable 6 months after injection. In other experiments we demonstrate colocalization of hF.IX and collagen IV in intersitial spaces between muscle fibers. Collagen IV has recently been identified as a F.IX-binding protein; this finding explains the unusual pattern of immunofluorescent staining for F.IX shown in these experiments. Thus rAAV can be used to direct stable expression of therapeutic levels of F.IX after intramuscular injection and is a feasible strategy for treatment of patients with hemophilia B.


Traditional Chinese medicine: a promising candidate for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder, characterized clinically by insidious onset of memory and cognition impairment, emergence of psychiatric symptoms and behavioral disorder, and impairment of activities of daily living (ADL). Traditional Chinese medicine (TCM) is practiced in the Chinese health care system for more than 2,000 years. In recent years, scientists have isolated many novel compounds from herbs, some of which improve dementia with fewer side effects than conventional drugs and are regarded as potential anti-AD drugs. In this review, we summarize the latest research progress on TCM showing their possible role of treatment of AD and other demented diseases and possible pharmacological actions.


Defective glycoprotein C of the syncytial strain of herpes simplex virus type 1.
Glycoproteins of the herpes simplex virus type 1 (HSV-1) non-syncytial strain Kupka showed two times higher affinity for the Helix pomatia (HP) lectin than glycoproteins of the syncytial strain HSZP. As revealed by the results of immunoprecipitation test and by the comparison of the synthesis of virus glycoproteins, glycoprotein C (gC) was synthesized in sufficient amounts in the HSZP strain-infected cells. The difference in the binding to HP lectin was found to be caused by decreased affinity of gC of the strain HSZP for HP lectin. The decreased affinity for HP lectin was brought about by lower proportion of O-linked oligosaccharides in the gC molecule. The glycoproteins of either HSV-1 strain under study synthesized in BHK cells displayed higher affinity for HP lectin than those synthesized in VERO cells.


Rescue of primary incomplete microkeratome flap with secondary femtosecond laser flap in LASIK.
For laser-assisted in situ keratomileusis (LASIK) retreatments with a previous unsuccessful mechanical microkeratome-assisted surgery, some surgical protocols have been described as feasible, such as relifting of the flap or the creation of a new flap and even the change to a surface ablation procedure (photorefractive keratectomy (PRK)). This case shows the use of femtosecond technology for the creation of a secondary flap to perform LASIK in a cornea with a primary incomplete flap obtained with a mechanical microkeratome. As we were unable to characterize the interface of the first partial lamellar cut, a thick flap was planned and created using a femtosecond laser platform. As the primary cut was very thick in the nasal quadrant, a piece of loose corneal tissue appeared during flap lifting which was fitted in its position and not removed. Despite this condition and considering the regularity of the new femtosecond laser cut, the treatment was uneventful. This case report shows the relevance of a detailed corneal analysis with an advanced imaging technique before performing a secondary flap in a cornea with a primary incomplete flap. The femtosecond laser technology seems to be an excellent tool to manage such cases successfully.


[Variant Philadelphia chromosome identified by interphase fluorescence in situ hybridization (FISH) without evidence on G-banded karyotyping and metaphase FISH].
A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46,XY,t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[5]/46,XY[3]. Interphase FISH revealed nuc ish(ABL1,BCR) × 3(ABL1 con BCR × 2)[329/450]/(ABL1,BCR) × 4(ABL1 con BCR × 3)[5/450]/(AL1,BCR) × 3(ABL1 con BCR × 1)[44/450]. Metaphase FISH showed ish (9;22)(ABL1+,BCR1+;BCR+,ABL+)[22]/der(22)(BCR+,ABL1+)[3]. The other case was that of a 31-yr-old male patient diagnosed with CML in the blastic phase. G-banded karyotyping of all 20 metaphase cells showed 47,XYYc,dup(1)(q21q32),del(7)(p11.2),t(9;22)(q34;q11.2). Interphase FISH revealed nuc ish(ABL1,BCR) × 3(ABL1 con BCR × 2)[254/600]/(ABL1,BCR) × 3(ABL1 con BCR × 1)[191/600]. Metaphase FISH showed ish t(9;22)(ABL1+,BCR+;BCR+,ABL1+)[16]. These results suggest that typical t(9;22) and variant Ph may coexist in the same patient, and interphase FISH may facilitate the detection of the variant Ph that cannot be detected by G-banded karyotyping alone.


Combining Ruthenium(II) Complexes with Metal-Organic Frameworks to Realize Effective Two-Photon Absorption for Singlet Oxygen Generation.
Singlet oxygen ((1)O2), as a reactive oxygen species, has garnered serious attention in physical, chemical, and biological studies. In this paper, we designed and synthesized a new type of singlet-oxygen generation system by exchanging cationic ruthenium complexes (RCs) into anionic bio-MOF-1. The resulting bio-MOF-1&RCs can be used as effective photocatalysts for generation of singlet oxygen under both single-photon and two-photon excitation. Especially, the excellent two-photon absorption (TPA) behavior of bio-MOF-1&RCs aroused our interest greatly because their two-photon absorption band lies in the optical window of biological tissue. Here, we measured the ability of bio-MOF-1&RCs to generate (1)O2 by irradiation under both 490 and 800 nm wavelength light in DMF. 1,3-Diphenylisobenzofuran (DPBF) and 2',7'-dichlorofluorescein (DCFH) were used as typical (1)O2 traps to detect and evaluate the efficiency of generation of (1)O2 under single-photon and two-photon excitation, respectively. Results indicated that bio-MOF-1&[Ru(phen)3](2+) was able to effectively generate (1)O2 under both conditions. Our work creates a novel synergistic TPA system with the excellent photophysical properties of RCs and the unique microporous structure benefit of MOFs, which may open a new avenue for creation of a cancer treatment system with both photodynamic therapy and chemotherapy.


A High Sensitivity Impedimetric Biosensor Using the Tannin From Quercusmacrolepis as Biorecognition Element for Heavy Metals Detection.
A new poly(vinylchloride) (PVC) membrane electrode based on tannin from the bark of Quercusmacrolepis (acorn) as the ionophore was prepared and modified onto the surface of a gold electrode. The electrochemical impedance spectroscopy (EIS) technique was used to study the sensitivity of the electrode that was modified with a thin layer of polymeric biomembrane, in order to detect heavy metals ions in solution. The device shows a good sensitivity for Zn(2+), Ni(2+) ions and a little less for Cd(2+). The electrode indicates a good linear response for the three metals over a wide concentration range from 1.0×10(-9) to 1.0×10(-4) M, with a detection limit of 1.0×10(-9) M.


Pharmacophore based 3D-QSAR modeling, virtual screening and docking for identification of potential inhibitors of β-secretase.
The enzyme β-secretase-1 is responsible for the cleavage of the amyloid precursor protein, a vital step in the process of the formation of amyloid-β peptides which are known to lead to neurodegeneration causing Alzheimer's disease. Challenges associated with toxicity and blood brain permeation inability of potential inhibitors, continue to evade a successful therapy, thus demanding the search and development of highly active and effective inhibitors. Towards these efforts, we used a ligand based pharmacophore model generation from a dataset of known inhibitors whose activities against β-secretase hovered in the nano molar range. The identified 5 feature pharmacophore model, AHHPR, was validated via three dimensional quantitative structure activity relationship as indicated by r2, q2 and Pearson R values of 0.9013, 0.7726 and 0.9041 respectively. For a dataset of compounds with nano molar activity, the important pharmacophore features present in the current model appear to be similar with those observed in the models resulting from much wider activity range of inhibitors. Virtual screening of the ChemBridge CNS-Set™, a database having compounds with a better suitability for central nervous system based disorders followed by docking and analysis of the ligand protein interactions resulted in the identification of eight prospective compounds with considerable diversity. The current pharmacophore model can thus be useful for the identification, design and development of potent β-secretase inhibitors which by optimization can be potential therapeutics for Alzheimer's disease.


Awareness and use of over-the-counter pain medications: a survey of emergency department patients.
A survey study was done to determine basic knowledge about and use of over-the-counter (OTC) pain medications among patients seen in our emergency department (ED). The hypothesis was that knowledge about OTC pain medications would be correlated with demographic characteristics. The study was a prospective 21-question survey during randomized 4-hour shifts over a 6-week study period. Of the 213 subjects who participated, 143 (67%) reported having used some form of nonsteroidal anti-inflammatory drug (NSAID), and 127 (60%) had used acetaminophen products recently. Women were more aware of toxic interactions and gastrointestinal (GI) irritation related to these medications. Ibuprofen use correlated with age (younger individuals used more) and having no primary physician (those without a physician used less). Knowledge about GI effects correlated with age, sex, and education. Knowledge about renal and hepatic problems correlated with age and education. Many patients use OTC pain medications. Many are ill informed about their use and side effects. More education is needed.


Topical review: a comprehensive risk model for disordered eating in youth with type 1 diabetes.
Provide an updated literature review on prevalence, measurement, and correlates of disordered eating in youth with Type 1 diabetes (T1D), present a novel theoretical risk model (i.e., The Modified Dual Pathway Model) for disordered eating in youth with T1D incorporating psychosocial and physiological risk factors, and discuss clinical implications. Literature review of prevalence, correlates, risk factors, and outcomes of disordered eating behavior (DEB) in youth with T1D. Insulin treatment, subsequent weight gain, and disruptions to hunger and satiety regulation are hypothesized disease-related mechanisms through which the treatment of T1D may increase vulnerability to development of behavior characterized as DEB. The Modified Dual Pathway Model integrates these factors with a validated psychosocial risk (body dissatisfaction, depression, and abstinence violation) model for DEB in nondiabetic youth. The Modified Dual Pathway model of DEB in youth with T1D is a comprehensive representation of both psychosocial and T1D-related risk factors with the potential to inform future interventions for this population.


n-3 PUFA-enriched diet delays the occurrence of cancer cachexia in rat with peritoneal carcinosis.
The aim of this study was to evaluate the effects of a fish oil (FO) diet (rich in long chain, n-3, polyunsaturated fatty acid) on cancer cachexia symptoms in rats. To this end, peritoneal carcinosis (PC) was generated by an intraperitoneal injection of cancer cells in BDIX rats fed FO or standard (Std) diets. Food intake and body weight were recorded throughout the study until sacrifice. PC rats were sacrificed when food intake was significantly and severely reduced. Fat and skeletal muscles masses were weighed and serum inflammatory cytokines concentration measured at sacrifice. Occurrence of anorexia in PC rats was delayed in the FO diet group (median time was multiplied by 2.5) in comparison with Std diet. At the time of sacrifice, PC rats displayed a lower body weight gain as well as lower muscle and fat masses than pair-fed rats, suggesting the presence of a hypermetabolism state. Serum TNF-alpha was significantly increased in PC rats compared with controls rats. There was no effect of FO diet on tissue mass (skeletal muscle and fat) or on TNF-alpha concentration. In conclusion, FO diet delays the appearance of anorexia induced by PC in rats.


Community analysis of dental plaque and endotracheal tube biofilms from mechanically ventilated patients.
Mechanically ventilated patients are at risk for developing ventilator-associated pneumonia, and it has been reported that dental plaque provides a reservoir of respiratory pathogens that may aspirate to the lungs and endotracheal tube (ETT) biofilms. For the first time, metataxonomics was used to simultaneously characterize the microbiome of dental plaque, ETTs, and non-directed bronchial lavages (NBLs) in mechanically ventilated patients to determine similarities in respective microbial communities and therefore likely associations. Bacterial 16S rRNA gene sequences from 34 samples of dental plaque, NBLs, and ETTs from 12 adult mechanically ventilated patients were analyzed. No significant differences in the microbial communities of these samples were evident. Detected bacteria were primarily oral species (e.g., Fusobacterium nucleatum, Streptococcus salivarius, Prevotella melaninogenica) with respiratory pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcuspneumoniae, and Haemophilus influenzae) also in high abundance. The high similarity between the microbiomes of dental plaque, NBLs, and ETTs suggests that the oral cavity is indeed an important site involved in microbial aspiration to the lower airway and ETT. As such, maintenance of good oral hygiene is likely to be highly important in limiting aspiration of bacteria in this vulnerable patient group.


Angiotensinogen gene variation associated with variation in blood pressure in aboriginal Canadians.
We measured blood pressure and related clinical phenotypes in 497 adult native Canadians from an isolated community in Northern Ontario. We analyzed their DNA for genotypes of angiotensinogen. We found that the frequency of the T235 variant of the angiotensinogen gene was 0.89 in this sample. This variant was associated with a significantly increased systolic pressure but not diastolic pressure. We also found that sex and body mass were each highly significantly associated with variation in both systolic and diastolic pressures. We found a significant association between age and variation in systolic pressure but not diastolic pressure. We also found a highly significant association between plasma apolipoprotein B concentration and variation in diastolic pressure but not systolic pressure. The high frequency of the angiotensinogen T235 variant suggests that subjects in this young, essentially normotensive population might be predisposed to hypertension, which may become more apparent in the presence of secondary factors.


[Spontaneous abortion and genetic natural selection].
Author reviews the recent researches related to the genetic causes of spontaneous abortions as well as the results of the cytogenetic examinations of gametes, early embryos and clinical miscarriages. In the background of more than half of first trimester spontaneous pregnancy losses severe chromosomal aberration of the fetus can be found. About 60% of abnormal karyotypes is formed by autosomal trisomies, the rest is divided among polyploidies, X-monosomy and different structural anomalies. The incidence of fetal trisomies correlates with maternal age, besides balanced translocations of parents and delayed fertilisation can also play a role in the etiology of fetal chromosomal abnormalities. Regarding that most of these abnormalities accidentally develop because of meiotic or mitotic error there is no great risk of recurrence. Women who have had one spontaneous abortion will soon get pregnant again and give birth to a healthy child. The abortion of fetuses with abnormal karyotype is the appearance of natural genetic selection.


[Sonographic evaluation of periportal fibrosis in children living in a Schistosoma mansoni endemic region].
To assess with ultrasound periportal fibrosis due to chronic Schistosoma mansoni infection in children living in an endemic region. Materials and methods. A total of 441 children underwent two stool examinations and abdominal sonography. Liver echotexture was assessed by two observers and compared to pre-defined image patterns and a fibrosis score was assigned ranging from 0 to 8. Ultrasound features were correlated to age, sex, and parasitologic findings. Prevalence of Schistosoma mansoni infestation was 63%. Two cases of advanced fibrosis (E pattern or fibrosis score of 6) were observed. Fibrosis correlated with age. No correlation existed between fibrosis and intensity of egg-output. A correlation between the two examinors was noted in 84% of examinations with a kappa coefficient of 0.7. Although severe periportal fibrosis is a rare finding in this endemic region, follow-up sonography must be performed because it is the only non invasive and reliable tool for detection of periportal fibrosis.


On the drinking water situation on the Cape Verde Islands (Islands of Santiago).
On the Cape Verde Islands drinking water investigations were made. The drinking water was tested in chemical and bacteriological respects as well as on amoebas and rotaviruses. The isolated germs were investigated on their reaction against several antibiotics and chemotherapeutics by means of the agar diffusion test. The changing of drinking water quality from water supply places to households was investigated as well. The results make evident the urgency of extensive sanitations of water supply places on the Cape Verde Islands.


Adenovirus DNA polymerase is phosphorylated by a stably associated histone H1 kinase.
Adenovirus DNA polymerase (AdPol) exists as a complex with the preterminal protein (pTP) and is essential for both initiation and elongation stages of viral DNA replication. Recent evidence from our laboratory indicates that AdPol is a phosphoprotein and that the major in vivo phosphorylation site, serine 67, occurs within the consensus substrate recognition sequence for cdc2 kinases. In this study, we found that a protein kinase which also exhibits histone H1 phosphorylation activity is stably associated with AdPol. AdPol forms a multimeric complex with this histone H1 kinase and pTP in HeLa cells infected with adenovirus or coinfected with recombinant vaccinia viruses encoding AdPol and pTP. The associated protein kinase and the p34cdc2 kinase phosphorylate AdPol at the same sites which are utilized in vivo, suggesting that the p34cdc2 kinase or a related kinase may be involved in the in vivo phosphorylation of AdPol. Serine 67 is also one of the major in vitro phosphorylation sites, and the substitution of alanine for serine at this position abolishes DNA replication initiation activity of AdPol.


Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O-Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product.
We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL-1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL-1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic.


Adverse outcomes of measles infection during pregnancy and in the perinatal period.
Measles is a major public health concern. Recently, there has been an increase of measles infections worldwide due to low vaccination coverage in certain regions that allowed for the development of measles outbreak in susceptible populations. According to the World Health Organization (WHO), there have been significant measles outbreaks in all WHO regions, and below 10% of cases were reported [1]. It is difficult to measure the impact of measles virus infection on pregnancy outcome.


Real-world outcomes in patients with metastatic renal cell carcinoma according to risk factors: the STAR-TOR registry.
Aim: Examine outcomes in sunitinib-treated patients by International Metastatic RCC Database Consortium (IMDC) or Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors. Patients & methods: Patients enrolled in STAR-TOR registry (n = 327). End points included overall survival, progression-free survival and objective response rate. Results: Overall survival was similar for IMDC 0 versus 1 (p = 0.238) or 2 versus ≥3 (p = 0.156), but different for MSKCC (0 vs 1, p = 0.037; 2 vs ≥3, p = 0.001). Progression-free survival was similar for IMDC 2 versus 3 (p = 0.306), but different for MSKCC (p = 0.009). Objective response rate was different for IMDC 1 (41.9%) and 2 (29.5%) and similar for MSKCC 1 (34.4%) and 2 (31.0%). Conclusion: Outcome data varied according to IMDC or MSKCC. MSKCC model accurately stratify patients into risk groups. Clinical trial registration: NCT00700258 (ClinicalTrials.gov).


Treatment of depression in patients with opiate dependence.
Depression is common among opiate-dependent patients and has been associated with worse prognosis. This article reviews the literature on treatment of depressive disorders and symptoms among patients with opiate dependence. Depression bears a complex relationship to opiate dependence and may represent an independent disorder or may be engendered by psychosocial stress or toxic and withdrawal effects of drugs. Primary treatments for opiate dependence (e.g., methadone or buprenorphine maintenance or residential treatment) are associated with substantial improvements in depression. Studies of antidepressant medications have produced mixed results, some positive but more negative. It is not clear what accounts for these differences, and more research is needed to determine how to select opiate-dependent patients most likely to benefit from antidepressants. Fewer studies have examined psychosocial or behavioral interventions, but some of these also show promise. The data suggest a stepped model of care in which depression is evaluated and observed during the outset of treatment for opiate dependence and if it does not improve, specific psychosocial interventions or antidepressant medications tried. Research is needed on such integrated models of care and treatment algorithms to determine their efficacy and cost effectiveness.


Syntheses and reactivity of meso-unsubstituted azuliporphyrins derived from 6-tert-butyl- and 6-phenylazulene.
A series of six azuliporphyrins with substituents on the seven-membered ring were prepared by two different "3 + 1" routes from 6-tert-butyl- and 6-phenylazulene. The substituted azulenes can be converted into dialdehydes under Vilsmeier-Haack conditions, and these react with tripyrranes in the presence of TFA in CH2Cl2 to give azuliporphyrins in excellent yields. Alternatively, tripyrrane analogues can be prepared by reacting the substituted azulenes with an acetoxymethylpyrrole in the presence of acetic acid, and following a deprotection step, these condensed with a pyrrole dialdehyde to give the related azuliporphyrins in 45-51% yield. Five of the azuliporphyrins were sufficiently soluble in CDCl3 to afford high-quality proton and carbon-13 NMR data. The internal CH and NH resonances were observed near 3 ppm, although the precise values were dependent upon substituent effects. The presence of a tert-butyl group on the azulene moiety slightly enhanced the diatropicity of the macrocycle compared to the phenyl-substituted azuliporphyrins. Polar solvents also increased the downfield shifts to the external protons by stabilizing the dipolar resonance contributors that are responsible for the carbaporphyrinoid aromatic character. A tert-butyl-substituted azuliporphyrin also gave X-ray quality crystals, and this allowed the first structural analysis of a free base azuliporphyrin to be conducted. The macrocycle is near planar, and the azulene unit was only tilted out of the plane by 7.4 degrees. An analysis of the bond lengths suggests that a 17 atom delocalization pathway significantly contributes to the aromatic properties of this system. Protonation of azuliporphyrins affords dications with enhanced diamagnetic ring currents where the internal CH shifts to ca. -3 ppm. Again, the chemical shifts are influenced by the substituents and the presence of an electron-donating tert-butyl group on the azulene subunit increases the macrocyclic diatropicity. Two of the substituted azuliporphyrins were reacted with nickel(II) acetate or palladium(II) acetate in DMF to give the corresponding organometallic derivatives, and these stable complexes were isolated in excellent yields. Addition of pyrrolidine to NMR solutions of 23-substituted azuliporphyrins 19 demonstrated that nucleophilic addition products were present in equilibrium with the parent porphyrinoids, but these adducts are less favored than for azuliporphyrins lacking the 23-substituents. Although nucleophilic attack of a peroxide anion is believed to be the first step in the conversion of azuliporphyrins to benzocarbaporphyrins with t-BuOOH and KOH, the tert-butyl or phenyl substituents in azuliporphyrins 19a and 19b did not inhibit this chemistry. Two benzocarbaporphyrin products were isolated and characterized in each case, and mechanisms are proposed to explain the origins of these oxidative ring contraction products.


Palm oil diet may benefit mildly hypercholesterolaemic Chinese adults.
The effects on serum lipids and platelet function of diets prepared with palm oil (PA) and peanut oil (PE) were studied in two groups of mild hypercholesterolaemic volunteers (serum TC between 5.5 - 7.0 mmol/L, aged 32-68). There were 15 men and 11 women in PE group and 16 men and 9 women in PA group. Dietary fat provided about 30% of total calories, and the test oil accounted for 60-65% of total dietary fat. During the 3 weeks of pretest period, diets were prepared with peanut oil, the local habitual cooking oil for all subjects. During the next 6 weeks the subjects in PA group consumed a diet prepared with palm oil while subjects in PE group continued to consume a diet prepared with peanut oil. Compared to the entry-level values, the concentrations of serum TC (total cholesterol), LDL-C (low density lipoprotein cholesterol), TC/HDL-C (high density lipoprotein cholesterol) ratio and plasma TXB2/6-keto-PGF1a ratio were significantly decreased in PA group (-6.5%, -9.0%, -11.5%, and -22.4%) while not appreciably altered in PE group by the end of the test. No significant change was observed on the whole blood platelet aggregation in both groups. In connection with the results from our previous study in normocholesterolaemic Chinese volunteers, palm oil, used as cooking oil in Chinese diet, will not lead to any adverse effect on blood lipids and thus will not increase CVD risks.


The magnetism and spin-dependent electronic transport properties of boron nitride atomic chains.
Very recently, boron nitride atomic chains were successively prepared and observed in experiments [O. Cretu et al., ACS Nano 8, 11950 (2015)]. Herein, using a first-principles technique, we study the magnetism and spin-dependent electronic transport properties of three types of BN atomic chains whose magnetic moment is 1 μB for BnNn-1, 2 μB for BnNn, and 3 μB for BnNn+1 type atomic chains, respectively. The spin-dependent electronic transport results demonstrate that the short BnNn+1 chain presents an obvious spin-filtering effect with high spin polarization ratio (>90%) under low bias voltages. Yet, this spin-filtering effect does not occur for long BnNn+1 chains under high bias voltages and other types of BN atomic chains (BnNn-1 and BnNn). The proposed short BnNn+1 chain is predicted to be an effective low-bias spin filters. Moreover, the length-conductance relationships of these BN atomic chains were also studied.


Dietary Strategies and Novel Pharmaceutical Approaches Targeting Serum ApoA-I Metabolism: A Systematic Overview.
The incidence of CHD is still increasing, which underscores the need for new preventive and therapeutic approaches to decrease CHD risk. In this respect, increasing apoA-I concentrations may be a promising approach, especially through increasing apoA-I synthesis. This review first provides insight into current knowledge on apoA-I production, clearance, and degradation, followed by a systematic review of dietary and novel pharmacological approaches to target apoA-I metabolism. For this, a systematic search was performed to identify randomized controlled intervention studies that examined effects of whole foods and (non)nutrients on apoA-I metabolism. In addition, novel pharmacological approaches were searched for, which were specifically developed to target apoA-I metabolism. We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality. For the dietary components in particular, more knowledge about the underlying mechanisms is necessary, as increasing apoA-I per se does not necessarily translate into a reduced CHD risk.


Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera langsdorffi on acetic acid-induced colitis in rats.
Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.