Degradation and hemostatic properties of polyphosphate coacervates.
Sodium polyphosphate is a linear polymer formed from phosphate units linked together by sharing oxygen atoms. Addition of calcium to a solution of sodium polyphosphate results in phase separation and formation of a polyphosphate coacervate best described as a polymeric rich viscoelastic material. Polyphosphate coacervate is an interesting candidate as a biomaterial based on its ability to bind with different cations and to be loaded with drugs. Here, in vitro degradation and hemostatic properties of polyphosphate coacervates are comprehensively evaluated. We show that polyphosphate coacervates degrade and dissolve at a fast rate, losing half of their original mass in a week and transforming to mainly pyrophosphate after 4weeks. This burst dissolution phase happens earlier for the coacervate prepared from very short chain polyphosphate but overall using longer polyphosphate chains does not increase the coacervate longevity significantly. Substitution of Ca with Sr or Ba does not affect the hydrolysis of coacervates but slows down their dissolution into the media. In a whole blood clotting assay, coacervates profoundly decrease the clotting time especially when very long chain polyphosphates are used. While coacervate chain length and divalent cation type were found to significantly affect prothrombin time and thromboplastin time compared to the control, no discernible trends were observed. Platelets adhere in large numbers to coacervates, especially those containing long chain polyphosphate, but the cell morphology observed suggests that they might not to be fully activated. Overall, the long chain polyphosphate coacervate holds a great potential as a resorbable hemostatic agent. Divalent cation additions to a sodium polyphosphate solution result in polyphosphate coacervates, or highly viscous gel-like materials, having great potential in bio-applications such as drug delivery and hemostasis. As these coacervates degrade in aqueous environments, we undertook a comprehensive evaluation to better understand the impact of polyphosphate chain length and divalent cation substitution on this hydrolytic response in order to better predict degradation behavior in the body. Furthermore, there is great interest in the role of polyphosphates in hemostasis following recent publications showing that platelets secrete polyphosphates upon thrombin stimulation. In this paper, we evaluate the hemostatic potential of polyphosphate coacervates as bulk constructs, demonstrating that indeed these materials hold great potential as a degradable hemostatic agent.


New hole transporting materials based on hexaarylbenzene and aromatic amine moiety for organic light-emitting diodes.
Three different new hole transport compounds, namely DPAP-TB, 1-PNAP-TB and 2-PNAP-TB, were synthesized by Sonogashira coupling and Diels-Alder reaction. Synthesized materials exhibited high Tg in the range of 118 to 133 °C. These values are higher than that of NPB, which is commonly used as a hole transporting material. OLED devices were fabricated by the synthesized compounds using the solution process as a hole transporting layer. Device structure was ITO/PEDOT:PSS (40 nm)/synthesized compounds or NPB (20 nm)/Alq3 (70 nm)/LiF/Al. Luminance efficiencies and external quantum efficiencies of DPAP-TB, 1-PNAP-TB and 2-PNAP-TB devices were 3.98, 4.62, 4.22 cd/A, and 1.35, 1.56, 1.43% at 20 mA/cm2, respectively. In luminance efficiency and external quantum efficiency, 1-PNAP-TB especially had superior property to NPB.


Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells.
The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine to become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells.


Molecular identification of avian influenza virus subtypes H5N1 and H9N2 in birds from farms and live bird markets and in respiratory patients.
Avian influenza viruses (AIVs) have been endemic in Egypt since 2006, and the co-circulation of high-pathogenic avian influenza H5N1 and low-pathogenic avian influenza H9N2 subtypes in poultry has been reported; therefore, Egypt is considered a hotspot for the generation of new subtypes and genotypes. We aimed to characterize AIVs circulating on commercial farms and in live bird markets (LBMs) during the winters of 2015 and 2016 in the study area and to identify H5N1 and H9N2 viruses in respiratory patients. In total, 159 samples were collected from ducks, pigeons and quails on farms (n = 59) and in LBMs (n = 100) and screened by real-time RT-PCR for H5N1 and H9N2 subtypes. Clinical and postmortem examination was carried out on birds from the farms. Positive H5N1 samples were sequenced and analysed for mutations. Tracheal swabs were also collected from 89 respiratory patients admitted to respiratory hospitals in the same study area. Overall, H5N1 was identified in 13.6% of birds from farms, while it was detected in 17% of birds in LBMs. Subtype H9N2 was only identified from pigeons on farms (6.5%) and LBMs (11.4%). Sequencing of the haemagglutination gene (HA) in nine representative H5N1 isolates revealed a multi-basic amino acid motif at the cleavage site (321-PQGEKRRKKR/GLF-333), which is characteristic of highly pathogenic AIV, in five of our isolates, while the other four isolates showed an amino acid substitution (Q322K) at this cleavage site to make it (321-P K GEKRRKKR/GLF-333). All the isolates belonged to clade 18.104.22.168, and a comparison of HA sequences at the amino acid level showed 98.8-100% homology among the nine isolates, while they showed 94.1-96.1% identity with reference strains and the commonly used vaccine strain in Egypt. Out of 89 respiratory patients, 3.4% were positive for H5N1 and no patients were positive for H9N2. Our results indicated the circulation of the endemic H5N1 and H9N2 viruses among poultry in 2015 and 2016. Birds on farms and in LBMs are reservoirs playing a role in the dissemination of the virus and producing a public health risk. The application of proper hygienic measures in farms and LBMs to control the exposure of birds and humans to the source of infection along with continuous monitoring of the circulating viruses will provide information on understanding the evolution of the viruses for vaccine studies.


Automated portable array biosensor for multisample microcystin analysis in freshwater samples.
An automated array biosensor based on evanescent-wave excitation has been developed for the detection of microcystins (MCs) in freshwater samples. The sensing surface consisted of microcystin-leucine-arginine (MCLR) covalently immobilized onto a planar waveguide (microscope slide). The binding of anti-MCLR monoclonal antibodies, spiked in the sample, to the immobilized MCLR was competitively inhibited by MCLR in solution and the amount of antibody bound to the patterned antigens was revealed using Cy5-labeled rabbit anti-mouse IgG. Surface chemistry has been optimized to improve biosensor performance in terms of sensitivity, regeneration ability and to avoid non specific binding for further application to environmental monitoring. The optimized biosensor assay presents an IC(50) value of 0.34 ± 0.01 μg/L, a detection limit of 16 ± 3 ng/L and a dynamic range from 0.06 to 1.5 μg/L MCLR, improving the performance of previously reported devices. Cross-reactivity to other related MCs, such as microcystin-RR (MCRR, 90%), microcystin-RR desmethylated (dm-MCRR, 95%) and microcystin-YR (MCYR, 91%), was also evaluated. The automated microarray can assay up to six different samples in parallel, with a total analysis time of about 60 min. The sensing surface was regenerated with 50mM NaOH and each chip was reused for, at least, 15 assay-regeneration cycles without significant binding capacity loss. The immunosensor has been successfully applied to the direct analysis of MCs in surface water samples and the results were in close agreement with those provided by LC-MS/MS.


A prospective interventional study of effect of accelerated orthokeratology on the corneal curvature and refraction among young adults with myopia.
Orthokeratology with reverse geometry contact lens is a non-surgical alternative to conventional contact lenses for correction of myopia. However, the strength of evidence for its efficacy and safety is limited to retrospective studies and only a few prospective studies. This prospective study, the first on Indian subjects, evaluated the outcome of orthokeratology among young myopes. Fifty eyes of 25 young myopes (age 19-29 years) with myopia of -1 to 5.0 diopter underwent accelerated orthokeratology using the reverse geometry ortho K - LK lenses for correction of myopia. They were followed up prospectively with weekly vision, refraction, corneal topography, and pachymetry to assess the correction of myopia. The mean Log MAR vision corrected from 0.748 ± 0.225 at base line to 0.025 ± 0.0630 at 12 weeks with 86% achieving 6/6 unaided day time vision. This was associated with significant central corneal flattening and thinning. The lenses were well tolerated with no significant complications. Overnight accelerated orthokeratology effectively corrects moderate degree of myopia and provide excellent spectacle free day time vision without any significant adverse effects in the short term.


Imaging synapse formation during thymocyte selection: inability of CD3zeta to form a stable central accumulation during negative selection.
TCR signaling can result in cell fates ranging from activation to tolerance to apoptosis. Organization of molecules in an "immunological synapse" between mature T cells and APCs correlates with the strength of TCR signaling. To investigate synapse formation during thymic selection, we have established a reaggregate system in which molecular recruitment of GFP fusion proteins to thymocyte:stromal cell interfaces can be visualized in real time. We demonstrate that negative selection is associated with efficient conjugate formation and rapid recruitment of p56(lck) and CD3zeta to an immunological synapse. Interestingly, CD3zeta-GFP does not accumulate at the center of the synapse, as in mature T cells, but at the periphery across a wide range of ligand densities. This implicates differences in synapse geometry in initiation of alternate signals downstream of the TCR.


Last hope for the doomed? Thoughts on the importance of a parasexual cycle for the yeast Candida albicans.
The yeast Candida albicans, a commensal colonizer and occasional pathogen of humans, has a rudimentary mating ability. However, mating is a cumbersome process that has never been observed outside the laboratory, and the population structure of the species is predominantly clonal. Here we discuss recent findings that indicate that mating ability is under selection in C. albicans, i.e. that it is a biologically relevant process. C. albicans strains can only mate after they have sustained genetic damage. We propose that the rescue of such damaged strains by mating may be the primary reason why mating ability is under selection.


An anatomical demonstration of projections to the medullary dorsal horn (trigeminal nucleus caudalis) from rostral trigeminal nuclei and the contralateral caudal medulla.
This study demonstrates that the medullary dorsal horn (MDH), the most caudal subdivision of the spinal trigeminal nucleus, receives input from neurons located in the trigeminal main sensory nucleus, the more rostral subdivisions of the spinal trigeminal nucleus, and the contralateral MDH. Using the retrograde transport of horseradish peroxidase (HRP), we show here that the MDH receives ipsilateral projections from rostral trigeminal nuclei but not from adjacent areas of the retricular formation. The rostral pole of spinal trigeminal nucleus oralis (nucleus oralis, pars beta) contains the highest density of MDH projection neurons. In addition, the MDH on one side receives projections from contralateral MDH neurons located in layers I, III, IV, V, VII and VIII but not from neurons in layers II and VI. We conclude that: (1) specific subdivisions of rostral trigeminal nuclei send projections to the MDH that could modulate the activity of MDH neurons; (2) projections from trigeminal nuclei to layers V and VI of the MDH, but not from adjacent areas of the reticular formation, provide further evidence that these deeper layers are related functionally to the MDH and trigeminal sensory processes; and (3) several populations of MDH neurons send axons across the midline into the contralateral MDH and may mediate contralateral inhibitory effects.


Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae.
Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae (CMRNG strains) produce altered forms of penicillin-binding protein 2 (PBP2) that have decreased affinity for penicillin. A feature of PBP2 from all CMRNG strains is the presence of an additional residue (Asp-345A) that is absent from PBP2 of penicillin-sensitive strains. The role of the additional aspartic acid residue in the decreased affinity of PBP2 is unclear as PBP2 of all previously examined CMRNG strains possess several other amino acid sequence alterations, in addition to the insertion of Asp-345A, compared to PBP2 of penicillin-sensitive strains. Site-directed mutagenesis has been used to insert the Asp-345A codon into the penA gene from a penicillin-sensitive gonococcus. The resulting penA gene expressed an altered form of PBP2 that had a decreased affinity for benzylpenicillin and was able to transform a penicillin-sensitive strain of N. gonorrhoeae to an increased level of resistance to benzylpenicillin. Insertion of amino acids other than aspartic acid did not produce forms of PBP2 that provided increased resistance to penicillin. Removal of the Asp-345A codon from the penA gene of a CMRNG strain reduced its ability to transform a penicillin-sensitive strain to an increased level of penicillin resistance. The reduction in the affinity of PBP2 in CMRNG strains is therefore largely, although not exclusively, due to the insertion of Asp-345A. Clinical isolates that produce altered forms of PBP2 that differ from that of penicillin-sensitive strains only in the insertion of Asp-345A have been identified.


Evaluation of long-term antibody kinetics in healthcare workers vaccinated with inactivated COVID-19 Vero cell vaccine (CoronaVac), a propensity score-matched observational study.
This study aimed to evaluate the long-term antibody kinetics after vaccinating with an inactivated COVID-19 Vero cell vaccine (CoronaVac) in healthcare workers (HCWs) at a single center in Turkey. For this prospective observational study, Chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) were used for the determination of binding antibodies (bAb) and neutralizing antibodies (nAb), respectively. Antibody kinetics were compared for the potential influencing factors, and propensity score analysis was performed to match the subcohort for age. Early bAb and nAb response was achieved in all 343 participants. Titers of bAbs against SARS-CoV-2 on 42 days post-vaccination (dpv) were higher in HCWs who were aged <40 years and who had a history of COVID-19. SARS-CoV-2 bAb levels in HCWs on days 42 (n = 97), 90 (n = 97), and 180 (n = 97) were 175 IU/ml (3.9-250), 107 IU/ml (2.4-250), and 66.1 IU/ml (2.57-250), respectively (p<0.001). SARS-CoV-2 bAb (p<0.001) and nAb (p<0.001) titers decreased significantly over time. There was a high negative correlation between SARS-CoV-2 antibody titers and inverse optic density of nAb responses (Pearson correlation coefficient: -0.738, p<0.001). When the antibody responses were compared, it was seen that the vaccine immunogenicity was better in those who had prior COVID-19 history and were aged <40 years. In the course of time, it was determined that there was a significant decrease in bAb and nAb responses after the 90th day. These results may guide approval decisions for booster COVID-19 vaccines.


Lymphoreticular neoplasia in a dog resembling malignant histiocytosis (histiocytic medullary reticulosis) in man.
Malignant histiocytosis was diagnosed in a 4-year-old-dog. Major clinicopathologic findings included multiple cutaneous tumors, peripheral lymphadenopathy, hepatomegaly, lytic bone lesions, anemia, thrombocytopenia, and monoclonal IgA gammopathy. Pathologic findings included multi-systemic infiltration of erythrophagocytic malignant histiocytes. Chemotherapy was unsuccessful.


Fast and accurate online calibration of optical see-through head-mounted display for AR-based surgical navigation using Microsoft HoloLens.
The use of an optical see-through head-mounted display (OST-HMD) in augmented reality (AR) has significantly increased in recent years, but the alignment between the virtual scene and physical reality is still a challenge. A fast and accurate calibration method of OST-HMD is important for augmented reality in the medical field. We proposed a fast online calibration procedure for OST-HMD with the aid of an optical tracking system. Two 3D datasets are collected in this procedure: the virtual points rendered in front of the observer's eyes and the corresponding points in optical tracking space. The transformation between these two 3D coordinates is solved to build the connection between virtual and real space. An AR-based surgical navigation system is developed with the help of this procedure, which is used for experiment verification and clinical trial. Phantom experiment based on the 3D-printed skull is performed, and the average root-mean-square error of control points between rendered object and skull model is [Formula: see text] mm, and the time consumption of the calibration procedure can be less than 30 s. A clinical trial is also conducted to show the feasibility in real surgery theatre. The proposed calibration method does not rely on the camera of the OST-HMD and is very easy to operate. Phantom experiment and clinical case demonstrated the feasibility of our AR-based surgical navigation system and indicated it has the potential in clinical application.


Preparative electrophoresis: a general method for the purification of polyclonal antibodies.
Antibodies were purified from normal rabbit, sheep, goat, rat, human and bovine serum using preparative electrophoresis on a Gradiflow in a single-step process using an asymmetrical cartridge with three different pore size polyacrylamide membranes. Recoveries in each case were over 80% and were higher than those obtained using affinity chromatography on protein A, protein G or protein L. Degree of purity was at least comparable with these methods. These results suggest that preparative electrophoresis can be considered a general method for the purification of research quantities of antibodies from multiple serum sources and may be particularly useful where the reactivity with protein A, G or L is unknown.


The combined effect of folic acid and 365-405 nm light emitting diode for inactivation of foodborne pathogens and its bactericidal mechanisms.
The inactivation of Escherichia coli O157:H7 ATCC 35150 and methicillin-resistant S. aureus ATCC 33591 by a light emitting diode (LED) was investigated in the present study. Various wavelengths of LEDs (365, 385, and 405 nm) were used individually or combined with folic acid (LEDF), and inactivation curves were analyzed using the Weibull model to compare the bactericidal effects. Reduction levels of pathogens by combination treatment of LED and 100 μM folic acid were significantly higher than those by individual LED treatment for the wavelength used in this study. It was confirmed that the reactive oxygen species produced by folic acid degradation accelerated the bactericidal effect of LEDs. When applied in apple juice, the same trend was observed by 405 nm treatment, although the inactivation rates were higher than those of buffer due to the low pH of apple juice. Moreover, injured cells were not observed except 30 J/cm2 LED, LEDF and 36 J/cm2 LEDF treatments. Mode of inactivation by LEDF was suggested as DNA damage along with membrane damages. Moreover, it was validated that genes related to antimicrobial resistance would be mutated by LEDF treatment. Therefore, LEDF can be used effectively to control foodborne pathogens in apple juice.


Cloning of Monkeys by Somatic Cell Nuclear Transfer.
Somatic cell nuclear transfer (SCNT) is a promising method to establish genetically modified monkeys with identical genetic background as models in biomedical research. We have recently cloned monkeys by optimization of the SCNT protocols and inclusion of the epigenetic modulator. Here, we describe the protocol for generation of cloned monkeys by somatic cell nuclear transfer.


Activation of β1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.
Activation of β1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin.


Brown's syndrome.
Brown's syndrome is a well-recognized clinical disorder of ocular motility manifesting most notably a restriction of active and passive elevation in adduction. The original name, "superior oblique tendon sheath syndrome," is no longer appropriate, since it has been shown that the tissue surrounding the anterior superior oblique tendon is blameless as a restrictive force. "True" and "simulated" as descriptive modifiers should also be discarded, as they relate to the disproven sheath concept. Brown's syndrome occurs as a congenital or acquired, constant or intermittent condition; the common link is restriction of free movement through the trochlea pulley mechanism. The various etiologic theories are reviewed and the spectrum of medical and surgical treatments are described and evaluated. Evidence suggests that subtypes of Brown's syndrome lie on a single continuum and that spontaneous resolution occurs in each group, probably more often than previously recognized. A simplified classification scheme is encouraged and possible future directions in Brown's syndrome research are introduced.


An additional reference axis improves femoral rotation alignment in image-free computer navigation assisted total knee arthroplasty.
Few studies have demonstrated improvement in accuracy of rotational alignment using image-free navigation systems mainly due to the inconsistent registration of anatomical landmarks. We have used an image-free navigation for total knee arthroplasty, which adopts the average algorithm between two reference axes (transepicondylar axis and axis perpendicular to the Whiteside axis) for femoral component rotation control. We hypothesized that addition of another axis (condylar twisting axis measured on a preoperative radiograph) would improve the accuracy. One group using the average algorithm (double-axis group) was compared with the other group using another axis to confirm the accuracy of the average algorithm (triple-axis group). Femoral components were more accurately implanted for rotational alignment in the triple-axis group (ideal: triple-axis group 100%, double-axis group 82%, P<0.05).


Characterizing and Exploring the Formation Mechanism of Salt Deposition by Reusing Advanced-softened, Silica-rich, Oilfield-produced Water (ASOW) in Superheated Steam Pipeline.
To dispose of large volumes of oilfield-produced water, an environmentally friendly method that reuses advanced-softened, silica-rich, oilfield-produced water (ASOW) as feedwater was implemented via a 10-month pilot-scale test in oilfield. However, salt deposition detrimental to the efficiency and security of steam injection system was generated in superheated steam pipeline. To evaluate the method, the characteristics and formation mechanism of the deposition were explored. The silicon content and total hardness of the ASOW were 272.20 mg/L and 0.018 mg/L, respectively. Morphology and composition of the deposition were determined by scanning electron microscope-energy dispersive spectrometry (SEM-EDS), inductively coupled plasma-mass spectroscopy (ICP-MS), X-ray diffraction (XRD), laser Raman spectroscopy (LRS) and X-ray photoelectron spectroscopy (XPS). Na2Si2O5, Na2CO3 and trace silanes were identified in the deposition. In addition, the solubility of the deposition was about 99%, suggesting that it is very different from traditional scaling. The results of a simulation experiment and thermal analysis system (TGA and TG-FTIR) proved that Na2CO3 and Si(OH)4 (gas) are involved in the formation of Na2Si2O5, which is ascribed mainly to the temperature difference between the superheated steam and the pipe wall. These findings provide an important reference for improving the reuse of ASOW and reducing its deposition.


A monoclonal antibody which detects a 125 kd glycoprotein on embryonal carcinoma cells and is mitogenic for murine spleen cells.
The isolation and characterisation of a monoclonal antibody (2H9), selected for reactivity against murine teratocarcinoma stem cells, is described. This antibody recognizes one major glycoprotein on the surface of embryonal carcinoma (EC) cells but detects multiple glycoprotein species on various murine or human derived cell types. The binding of the antibody to cells is abolished by treatment with periodate or neuraminidase. These results suggest that 2H9 antibody detects a carbohydrate determinant; this is apparently distinct from other anti-EC reactive monoclonal antibodies and a variety of lectins. These antibodies are mitogenic for a population of lymphocytes in murine spleen. The antibodies recognize numerous cell surface glycoproteins on the surface of the spleen cells.


NMR spectroscopic study of a DNA duplex with mercury-mediated T-T base pairs.
Recently, we reported that T-T mismatches can specifically recognize Hg(II) (T-Hg(II)-T pair formation). In order to understand the properties of the T-Hg(II)-T pair, we recorded NMR spectra for a DNA duplex, d(CGCGTTGTCC).d(GGACTTCGCG), with two successive T-T mismatches (Hg (II)-binding sites). We assigned 1H resonances for mercury-free and di-mercurated duplexes, and performed titration experiments with Hg(II) by using 1D 1H NMR spectra. Because of the above mentioned assignments, we could confirm the existence of mono-mercurated species, because individual components gave independent NMR signals in the titration spectra.


Effects of cocaine on conflict behavior in the rat.
The present studies examined the effects of acute cocaine administration, chronic cocaine administration and cocaine withdrawal on behavior in the Conditioned Suppression of Drinking (CSD) conflict paradigm, an animal model for the study of anxiety. In daily 10-minute sessions, water deprived rats were trained to drink from a tube that was occasionally electrified (0.25 mA), electrification being signalled by a tone. Within 3-4 weeks, control (i.e., non-drug) CSD behavior stabilized (30-50 shocks and 10-12 ml/session) and drug studies were initiated. Acute administration of cocaine (30-min pretreatment) produced a selective pro-conflict effect only at a dose of 10 mg/kg cocaine, with lower doses (2.5, 5 mg/kg) exerting no effect on CSD behavior and a higher dose (20 mg/kg) depressing both punished and unpunished responding. In a second experiment, cocaine (10 mg/kg, IP, 2/day) or saline was administered to separate groups of subjects for 7 weeks. In this chronic treatment study, CSD testing was conducted 12 hours after each evening cocaine administration. Although it had no effect on CSD behavior during the first week of treatment, this chronic cocaine administration produced a significant and selective pro-conflict effect which was stable during the period from Weeks 2-7. In a final experiment, a high dose of cocaine (20 mg/kg, 3/day) or saline was given to separate groups of subjects for 2 weeks and the behavioral effects of these treatments and their subsequent termination were examined. In this study, CSD testing was conducted 8 hours after each evening cocaine treatment. During the first week of high dose cocaine treatment, a decrease in punished responding was observed; this parameter returned to baseline levels by Week 2. Discontinuation of this high dose chronic cocaine treatment resulted in a selective decrease in punished responding. This pro-conflict effect was greatest at 3 days, and lasted for 6 days after the last cocaine dose. These data are consistent with clinical findings demonstrating the anxiogenic effects of both acute and chronic cocaine treatment as well as cocaine withdrawal and suggest that conflict paradigms such as the CSD may be useful for the study of cocaine-induced anxiety states.


[Realization of an adaptive method of simulating the process of temperature change of a cadaver on a microcomputer].
Programme based on mathematical model of the process of dead body temperature changing was developed for estimation of postmortem interval. Automatic retrieval of problem solution was performed on programmable microcalculators of "Electronica MK-61" type using adaptive approach. Diagnostical accuracy in case of dead body being preserved in permanent cooling conditions is +/- 3%.


Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a biallelic mutation in the SMN1 gene, resulting in progressive muscle weakness and atrophy. Nusinersen is the first disease-modifying drug for all SMA types. We report on effectiveness and safety data from 120 adults and older children with SMA types 1c-3 treated with nusinersen. Patients were evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE; n = 73) or the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; n = 47). Additionally, the Revised Upper Limb Module (RULM) and 6-minute walk test (6MWT) were used in a subset of patients. Patients were followed for up to 30 months of nusinersen treatment (mean, SD; 23, 14 months). Subjective treatment outcomes were evaluated with the Patients Global Impression-Improvement (PGI-I) scale used in all patients or caregivers at each follow-up visit. An increase in the mean HFMSE score was noted at month 14 (T14) (3.9 points, p < 0.001) and month 30 (T30) (5.1 points, p < 0.001). The mean RULM score increased by 0.79 points at T14 (p = 0.001) and 1.96 points (p < 0.001) at month 30 (T30). The mean CHOP-INTEND increased by 3.6 points at T14 (p < 0.001) and 5.6 points at month 26 (p < 0.001). The mean 6MWT improved by 16.6 m at T14 and 27 m at T30 vs. baseline. A clinically meaningful improvement in HFMSE (≥ 3 points) was seen in 62% of patients at T14, and in 71% at T30; in CHOP INTEND (≥ 4 points), in 58% of patients at T14 and in 80% at T30; in RULM (≥ 2 points), in 26.6% of patients at T14 and in 43.5% at T30; and in 6MWT (≥ 30-meter increase), in 26% of patients at T14 and in 50% at T30. Improved PGI-I scores were reported for 75% of patients at T14 and 85% at T30; none of the patients reporting worsening at T30. Adverse events were mild and related to lumbar puncture. In our study, nusinersen led to continuous functional improvement over 30-month follow-up and was well tolerated by adults and older children with a wide spectrum of SMA severity.


The immunobiology of myeloid-derived suppressor cells in cancer.
The tumor microenvironment is a complex and heterogeneous milieu in which multiple interactions occur between tumor and host cells. Immunosuppressive cells which are present in this microenvironment, such as regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs), play an important role in tumor progression, via down-regulation of antitumor responses. MDSCs represent a heterogeneous group of cells originated from the myeloid lineage that are in the immature state. These cells markedly accumulate under pathologic conditions, such as cancer, infection, and inflammation, and use various mechanisms to inhibit both adaptive and innate immune responses. These immunosuppressive mechanisms include deprivation of T cells from essential amino acids, induction of oxidative stress, interference with viability and trafficking of T cells, induction of immunosuppressive cells, and finally polarizing immunity toward a tumor-promoting type 2 phenotype. In addition to suppression of antitumor immune responses, MDSCs can also enhance the tumor metastasis and angiogenesis. Previous studies have shown that increased frequency of MDSCs is related to the tumor progression. Moreover, various drugs that directly target these cells or reverse their suppressive activity can improve antitumor immune responses as well as increase the efficacy of immunotherapeutic intervention. In this review, we will first discuss on the immunobiology of MDSCs in an attempt to find the role of these cells in tumor progression and then discuss about therapeutic approaches to target these cells.


p62/SQSTM1 promotes mitophagy and activates the NRF2-mediated antioxidant and anti-inflammatory response restraining EBV-driven B lymphocyte proliferation.
Reactive oxygen species (ROS) and DNA repair, respectively, promote and limit oncogenic transformation of B cells driven by Epstein-Barr virus (EBV). We have previously shown that EBV infection reduced autophagy in primary B lymphocytes and enhanced ROS and interleukin 6 (IL-6) release, promoting B-cell proliferation and immortalization. In this study, we explored the role of p62/SQSTM1, accumulated as a consequence of autophagy reduction in EBV-infected B lymphocytes, and found that it exerted a growth-suppressive effect in these cells. At the molecular level, we found that p62 counteracted IL-6 production and ROS increase by interacting with NRF2 and promoting mitophagy. Moreover, p62/NRF2 axis sustained the expression level of H2AX and ataxia-telangiectasia mutated (ATM), whose activation has been shown to have growth-suppressive effects during the first steps of EBV infection, before latency is established. In conclusion, this study shows for the first time that the accumulation of p62 and the activation of p62/axis counteracted EBV-driven proliferation of primary B lymphocytes.


Citalopram-induced subacute cutaneous lupus erythematosus -- first case and review concerning photosensitivity in selective serotonin reuptake inhibitors.
This report describes a case of subacute cutaneous lupus erythematosus (SCLE) in a patient treated with citalopram and discusses evidence linking selective serotonin reuptake inhibitors (SSRIs) to the induction of photosensitivity. Case report and review of published literature. A 71-year-old woman with major depression developed 2 days after intake of 20 mg citalopram a strongly itching and largely dimensioned confluencing erythema with infiltrations and blisters all over the trunk with fever and malaise. Histological and laboratory investigations were consistent with the diagnosis of SCLE. After stopping citalopram intake, dermatologic symptoms significantly improved within 2 weeks. SSRIs have been associated with 14 cases of adverse cutaneous events as a result of SSRI-induced photosensitivity. No case of SSRI-induced SCLE has been described. In clinical practice, indication and dosage of citalopram and other SSRIs should be carefully monitored. In the case of a SSRI-induced photosensitivity, medication can be switched to an antidepressant from another class.


Urinary excretion of methylated purines in man and in the rat after the administration of theophylline.
Chromatographic characteristics of urinary metabolites of theophylline were studied by two-dimensional thin-layer chromatography, high-performance liquid chromatography and gas chromatography--mass spectrometry. Quantitative date for the urinary metabolites of theophylline in asthmatic children are given. It was shown that 1,3-dimethyluric acid is the predominant excretory product. In addition, smaller amounts of 1-methyluric acid, 3-methylxanthine and unchanged theophylline were found. Excretory patterns after theophylline ingestion before and during the administration of allopurinol in asthma patients and in rats suggest the existence of three metabolic pathways of theophylline. The administration of this drug to a patient with xanthine oxidase of theophylline. The administration of this drug to a patient with xanthine oxidase deficiency resulted in the excretion of 1-methyluric acid in addition to 1,3-dimethyluric acid, 3-methylxanthine, 1-methylxanthine and unchanged theophylline. It was concluded that in man the oxidation of theophylline is not catalysed by xanthine oxidase.


MammoSite accelerated partial breast irradiation: a single-institution outcomes analysis with 2 years of followup.
To provide longitudinal follow-up and assess the intermediate outcomes in breast cancer patients treated with the MammoSite radiation therapy system. Ninety-two patients with histologically proven stage 0-II breast cancer were treated with MammoSite accelerated partial breast irradiation after breast-conserving surgery. The catheter was placed at the time of surgery or postoperatively. Treatment prescription was 3.4Gy b.i.d. for a period of five days using high-dose-rate afterloading. Clinical and dosimetric parameters including dose to 90% of PTV, volume of PTV receiving 100% of dose, volume of PTV receiving 150% of dose, edited PTV, and dose homogeneity index were analyzed as variables correlating with late effects. All patients received the prescribed treatment. Seventy-seven percent of patients had intraoperative catheter placement, which was associated with a higher rate of persistent seroma (79%). The presence of seroma did not affect cosmesis. Ten patients developed telangiectasia at a median of 20.5 months. Skin dose and balloon-to-skin distance had a significant correlation with the development of telangiectasia that significantly affected cosmetic grading. The telangiectasia incidence for maximum skin dose of >100% and >125% of the prescription dose were 28% and 63%, compared with 0% (p=0.0001) and 4.2% (p=0.0001) for doses of < or =100% and < or =125%, respectively. Overall, most patients had excellent cosmetic results, and local control of disease was excellent. MammoSite radiation therapy system demonstrates excellent local control and cosmetic outcome with extended followup. The maximum skin dose should be kept below 100% to reduce late effects on skin and improve cosmetic outcome. The persistence of seroma is higher with intraoperative placement of the catheter, and therefore postoperative placement is preferred.


Intradialytic Protein Ingestion and Exercise do Not Compromise Uremic Toxin Removal Throughout Hemodialysis.
Dietary protein and physical activity interventions are increasingly implemented during hemodialysis to support muscle maintenance in patients with end-stage renal disease (ESRD). Although muscle maintenance is important, adequate removal of uremic toxins throughout hemodialysis is the primary concern for patients. It remains to be established whether intradialytic protein ingestion and/or exercise modulate uremic toxin removal during hemodialysis. We recruited 10 patients with ESRD (age: 65 ± 16 y, BMI: 24.2 ± 4.8 kg/m2) on chronic hemodialysis treatment to participate in this randomized cross-over trial. During hemodialysis, patients were assigned to ingest 40 g protein or a nonprotein placebo both at rest (protein [PRO] and placebo [PLA], respectively) and following 30 min of exercise (PRO + exercise [EX] and PLA + EX, respectively). Blood and spent dialysate samples were collected throughout hemodialysis to assess reduction ratios and removal of urea, creatinine, phosphate, cystatin C, and indoxyl sulfate. The reduction ratios of urea and indoxyl sulfate were higher during PLA (76 ± 6% and 46 ± 9%, respectively) and PLA + EX interventions (77 ± 5% and 45 ± 10%, respectively) when compared to PRO (72 ± 4% and 40 ± 8%, respectively) and PRO + EX interventions (73 ± 4% and 43 ± 7%, respectively; protein effect: P = .001 and P = .023, respectively; exercise effect: P = .25 and P = .52, respectively). Nonetheless, protein ingestion resulted in greater urea removal (P = .046) during hemodialysis. Reduction ratios and removal of creatinine, phosphate, and cystatin C during hemodialysis did not differ following intradialytic protein ingestion or exercise (protein effect: P > .05; exercise effect: P>.05). Urea, creatinine, and phosphate removal were greater throughout the period with intradialytic exercise during PLA + EX and PRO + EX interventions when compared to the same period during PLA and PRO interventions (exercise effect: P = .034, P = .039, and P = .022, respectively). The removal of uremic toxins is not compromised by protein feeding and/or exercise implementation during hemodialysis in patients with ESRD.


Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients.
A randomized phase II, open-label multicenter study evaluating oxaliplatin alone (OXA), infusional 5-fluorouracil alone (5-FU) and an oxaliplatin/infusional 5-FU combination (OXFU) in untreated, advanced pancreatic carcinoma (APC). Chemotherapy-naïve patients with advanced or metastatic, histologically/cytologically proven pancreatic carcinoma with measurable disease, received OXA [130 mg/m2, 2-h intravenous (i.v.) infusion] alone, OXA combined with 5-FU (1000 mg/m2/day, continuous i.v., days 1-4), or 5-FU alone, every 3 weeks. Sixty-three patients (42 males/21 females) were treated: 17 patients/52 cycles OXA, 31 patients/ 175 cycles OXFU, 15 patients/41 cycles 5-FU, with a median of three, six and two cycles/patient, respectively. Patient characteristics were similar in all arms. Median age was 57 years (range 21-75), and 83% of patients had PS 0-1. Most patients (62%) had moderate to well-differentiated tumors, 90% had metastatic disease, 81% with liver metastases. All responses (three partial responses; WHO) occurred in the OXFU arm (10% response rate). Five of 32 patients evaluable for clinical benefit were responders (OXA, 14%; OXFU, 21%). Median time to progression and overall survival were higher in the combination arm (4.2 and 9.0 months, respectively) than either single-agent arm (OXA, 2.0 and 3.4 months; 5-FU, 1.5 and 2.4 months, respectively). Moderate hematotoxicity without morbidity was seen in all arms. Two OXFU patients had grade 3 oxaliplatin neurosensory toxicity. With a 10% response rate, median overall survival of 9 months and an encouraging safety profile, the OXFU combination is effective, appears superior to infusional 5-FU and warrants further studies in APC patients.


[The effect of P6 acupressure for symptom control in pregnant women having hyperemesis gravidarum].
The purpose of this study was to determine the effects of Nei-Guan(P6) acupressure on nausea and vomiting in pregnant women having hyperemesis gravidarum. The research design was a randomized control-group pretest-posttest repeated measure design with counter balancing. For the experimental treatment, P6 acupressure was carried out for ten minutes. Data was collected from April 1, 2003 to April 30, 2004. The participants were 66 patients admitted with hyperemesis gravidarum. They were divided into three groups, a P6 acupressure group, placebo point group and a control group. Hyperemesis gravidarum patients who received P6 acupressure during admission experienced much less nausea and vomiting than the placebo acupressure and control group (F=8.259, p=.001). Nei-Guan(P6) acupressure is considered an effective intervention for reducing nausea and vomiting in pregnant women having hyperemesis gravidarum. Further more Nei-Guan(P6) acupressure maybe used as an independent nursing intervention method for pregnant women with severe nausea and vomiting.


Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children.
To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. The heterologous scheme was safe and immunogenic in children 3-18 y/o. https://rpcec.sld.cu/trials/RPCEC00000374.


Does lateral specialization apply to the frog's brain? An electron microscope observation.
The ultrastructure of polymorphic crystal-like inclusions occurring in the cytoplasm of neurons of only the medial portion of the left habenula has been studied in the adult frog Rana esculenta and in the tadpole with the use of three types of fixatives: osmium tetroxide, a mixture of aldehydes and potassium permanganate.


Sexual language usage in different interpersonal contexts: a comparison of gender and sexual orientation.
Previous investigators have demonstrated that gender differences exist in the use of sexual language in various interpersonal contexts. However, sexual orientation has not been addressed in any study regarding sexual language usage. This investigation examined the use of sexual language for female and male in different interpersonal contexts based upon sexual orientation. Respondents were 440 university students: 202 heterosexual female, 30 lesbian, 173 heterosexual male, and 35 gay male. Findings indicate that differences in sexual language usage in interpersonal contexts is significant for gender as well as for sexual orientation. Conjecture is made for the implications this may have on intimate relationships.


Ectomycorrhizal fungal community structure across a bog-forest ecotone in southeastern Alaska.
We examined the ectomycorrhizal (ECM) fungal community across a bog-forest ecotone in southeastern Alaska. The bog and edge were both characterized by poorly drained Histosols and a continuous layer of Sphagnum species, ericaceous shrubs, Carex species, and shore pine [Pinus contorta Dougl. ex Loud. var. contorta]. The forest had better-drained Inceptisols and Spodosols, a tree community comprised of western hemlock [Tsuga heterophylla (Raf.) Sarg.], yellow cedar (Thuja plicata Donn ex D. Don.), Sitka spruce [Picea sitchensis (Bong.) Carr.] and shore pine, and an understorey of ericaceous shrubs and herbs. ECM root tip density (tips cm(-3) soil) was significantly greater in the forest than the edge or bog and ECM colonization was significantly different in all three plant communities. The below ground ECM fungal taxa were analyzed using molecular techniques (PCR-RFLP and DNA sequencing). Three ECM fungal taxa, Suillus tomentosus (Kauffman) Singer, Cenococcum geophilum Fr.:Fr, and a Russula species, differed in relative frequency, yet were among the four most frequent in all three plant communities. Although differences in ECM fungal richness were observed across plant communities, unequal sampling of ECM roots due to root density and colonization differences confounded richness comparisons. Using resampling procedures for creating taxon-accumulation curves as a function of sampled ECM roots revealed similarities in cumulative ECM fungal taxa richness across the ecotone.


Effect of dextran-charcoal treatment on the dissociation kinetics of glucocorticoid-receptor complexes: possible involvement of lipid.
Dissociation kinetics were determined at 0 degrees C for molybdate-stabilized glucocorticoid-receptor complexes in rat thymus cytosol. Exposure of complexes to dextran-coated charcoal had no effect on their chromatographic properties or transformation status, but dissociation rates measured after charcoal treatment were significantly lower than those determined by displacement with excess competing steroid. The dissociation rate of the [2,4,6,7-3H]prednisolone-receptor complex was similarly modified by chromatography on Lipidex 1000, but not by chromatography on Sephadex G-25 or G-75. It is concluded that treatment of glucocorticoid-receptor complexes with dextran-charcoal or Lipidex 1000 brings about a change in dissociation rate as a consequence of the removal of a lipid component from the complex.


Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis.
An increased intraepithelial lymphocyte density in an architecturally normal proximal small intestinal mucosal biopsy is a common finding facing surgical pathologists dealing with gastrointestinal biopsy specimens. Approximately 1% to 2% of all proximal small intestinal biopsies will show this change. It is increasingly recognized by surgical pathologists that gluten-sensitive enteropathy is an important cause of this pattern; however, gluten-sensitive enteropathy accounts for the minority of all cases. A wide variety of immunologic stimuli can raise intraepithelial lymphocyte numbers. Among the other common associations are enteric infection, autoimmune disease, drugs, and gastric Helicobacter infection. To outline the causes of intraepithelial lymphocytosis, to highlight the importance and the difficulties faced in establishing gluten-sensitive enteropathy as the cause, and to aid the surgical pathologist in the routine sign out of these cases. A review of the literature detailing the causes or associations of proximal small intestinal intraepithelial lymphocytosis is presented. Increased lymphocyte numbers in the epithelium of architecturally preserved proximal small intestinal biopsies is a morphologic feature associated with a broad differential diagnosis.


Structural elucidation of 4'-epiadriamycin by nuclear magnetic resonance spectroscopy and comparison with adriamycin and daunomycin using quantum mechanical and restrained molecular dynamics approach.
The structural and electronic properties of 4'-epiadriamycin, adriamycin, and daunomycin have been studied using density functional theory (DFT) employing B3LYP exchange correlation. The chemical shifts of (1)H and (13)C resonances in nuclear magnetic resonance spectra have been calculated using Gauge-Invariant Atomic Orbital (GIAO) method as implemented in Gaussian 98 and compared with experimental spectra recorded at 500 MHz. (13)C resonances of drugs have been assigned for the first time. A restrained molecular dynamics approach was used to get the optimized solution structure of drugs using inter-proton distance constraints obtained from 2D NOESY spectra. The glycosidic angle C7-O7-C1'-C2' is found to show considerable flexibility by adopting 156 degrees -161 degrees (I), 142 degrees -143 degrees (II), and 38 degrees -78 degrees (III) conformations, of which the biological relevant structure appears to be the conformer II. The observed different conformations of the three drugs are correlated to the differential anticancer activity and the available biochemical evidence exhibited by these drugs.


Corneal graft rejection in African Americans at Howard University Hospital.
There is scarcity of data in the literature on cornel graft rejection rate in patients exclusively of African ancestry. The purpose of this study was to evaluate the rejection rate of corneal transplant surgery performed at Howard University Hospital on such patients over a 15 year period. A retrospective evaluation was performed of the cornea graft rejection and corneal graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal specialist at Howard University Hospital from January 1, 1990 to August 31, 2005. Of the 125 patients, 62 were eliminated from the study because of re-grafted eyes, non-African descent, primary graft failures, follow-up less than 1 month and lack of availability of charts. This study, therefore, studied and recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients. Episodes of graft rejection were documented in 23 eyes (36.5% of cases). Nine out of the 23 graft rejections manifested to secondary graft failure (39%). Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary graft failure over the past 15 years. The major diagnostic categories were bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch's dystrophy 4 (6.3%), other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy, and 8.7% and 22.2% for Fuch's dystrophy, respectively. Also, best visual acuity was looked at in patients with rejection episodes. None of the patients had a pre-op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and 20/150 was increased to 9 (39.1%). At 36% the prevalence of corneal graft rejection was one of the highest in the reported literature. But only 14% of those episodes resulted in graft failure which is one of the lowest in the published literature. This study demonstrates that patients of African ancestry may have a higher rejection rate which does not necessarily result in graft failure.


Neuropeptide Y (NPY) and peptide YY (PYY) inhibit prostaglandin E2-induced intestinal fluid and electrolyte secretion in the rat jejunum in vivo.
NPY, a recently discovered peptide consisting of 36 amino acids, is present in intrinsic intestinal nerves and in extrinsic noradrenergic nerves innervating intestinal blood vessels. We have investigated the influence of NPY and of the structurally related peptide YY (PYY) on the effect of PGE2-induced fluid and electrolyte secretion in the tied-off rat jejunum in vivo. Close intraarterial infusion of PGE2 (4.5-450 pmol X min-1) dose dependently reversed the net absorption of fluid, sodium and chloride into net secretion (P less than 0.01 for all three parameters). Additional i.a. infusion of NPY significantly inhibited the effect of PGE2 (45 pmol X min-1) on fluid transport at infusion rates of 0.4 and 4.0 pmol X min-1 (P less than 0.01). Infusion of 0.04 pmol X min-1 NPY was without effect. PGE2-induced sodium and chloride secretion were also significantly reduced by NPY at an infusion rate of 0.4 but not of 0.04 pmol X min-1. NPY alone was without any effect on fluid or electrolyte absorption in the controls. PYY, which is present in endocrine cells but not in nerves in the gut, was without effect at 0.4 pmol X min-1 and slightly but significantly reduced PGE2-induced fluid secretion at 4.0 pmol X min-1. It is concluded that NPY is a potent inhibitory factor in the neuronal control of intestinal fluid and electrolyte transport.


Utility of the Modified and High-Sensitivity Modified Glasgow Prognostic Scores for Hypopharyngeal Squamous Cell Carcinoma.
To determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC). Retrospective cohort study. Affiliated university hospital. We reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS). The 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05). Our study suggests that the HS-mGPS is useful as prognostic factor in HSCC.


Fabrication of eco-friendly nanofibrous membranes functionalized with carboxymethyl-β-cyclodextrin for efficient removal of methylene blue with good recyclability.
Considering the excellent thermo-mechanical properties, chemical stability and low cost of biodegradable aliphatic-aromatic copolyesters, they are an ideal matrix when functionalized for capturing pollutants in wastewater. In this work, biodegradable poly((butylene succinate-co-terephthalate)-co-serinol terephthalate) (PBSST) copolyesters with amino side group (-NH2) were first synthesized through copolymerization, followed by grafting carboxymethyl-β-cyclodextrin (CM-β-CD) into PBSST molecular chains via amidation reaction to prepare PBSST-g-β-CD. The corresponding nanofibrous membranes were then fabricated by electrospinning as adsorbents for efficiently removing cationic dye methyl blue (MB) from aqueous solutions. The adsorption performance of the nanofibrous membranes was fitted well with pseudo-second-order model and Langmuir isotherm model. The maximum adsorption capacity was 543.48 mg g-1 for MB along with a removal efficiency of 98% after five regeneration cycles, indicating the high adsorption capacity and good recyclability of nanofibrous membranes. The adsorbents possess features of high adsorption capacity, eco-friendliness and easy operation, and exhibit great potential for disposing of printing-dying wastewater.


Atrial fibrillation detected at screening is not a benign condition: outcomes in screen-detected versus clinically detected atrial fibrillation. Results from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study.
It is unknown whether screen-detected atrial fibrillation (AF) carries cardiovascular risks similar to clinically detected AF. We aimed to compare clinical outcomes between individuals with screen-detected and clinically detected incident AF. We studied 8265 participants (age 49 ± 13 years, 50% women) without prevalent AF from the community-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study. By design of the PREVEND study, 70% of participants had a urinary albumin concentration >10 mg/L. Participants underwent 12-lead ECG screening at baseline and every 3 years. AF was considered screen-detected when first diagnosed during a study visit and clinically detected when first diagnosed during a hospital visit. We analysed data from the baseline visit (1997-1998) up to the third follow-up visit (2008). We used Cox regression with screen-detected and clinically detected AF as time-varying covariates to study the association of screen-detected and clinically detected AF with all-cause mortality, incident heart failure (HF) and vascular events. During a follow-up of 9.8 ± 2.3 years, 265 participants (3.2%) developed incident AF, of whom 60 (23%) had screen-detected AF. The majority of baseline characteristics were comparable between individuals with screen-detected and clinically detected AF. Unadjusted, both screen-detected and clinically detected AF were strongly associated with mortality, incident HF, and vascular events. After multivariable adjustment, screen-detected and clinically detected AF remained significantly associated with mortality (HR 2.21 (95% CI 1.09 to 4.47) vs 2.95 (2.18 to 4.00), p for difference=0.447) and incident HF (4.90 (2.28 to 10.57) vs 3.98 (2.49 to 6.34), p for difference=0.635). After adjustment, screen-detected AF was not significantly associated with vascular events, whereas clinically detected AF was (1.12 (0.46 to 2.71) vs 1.92 (1.21 to 3.06), p for difference=0.283). Screen-detected incident AF was associated with an increased risk of adverse outcomes, especially all-cause mortality and incident HF. The risk of outcomes was not significantly different between screen-detected AF and clinically detected AF.


Biased cyclical electrical field-flow fractionation for separation of submicron particles.
The potential of biased cyclical electrical field-flow fractionation (BCyElFFF), which applies the positive cycle voltage longer than the negative cycle voltage, for characterization of submicron particles, was investigated. Parameters affecting separation and retention such as voltage, frequency, and duty cycle were examined. The results suggest that the separation mechanism in BCyElFFF in many cases is more related to the size of particles, as is the case with normal ElFFF, in the studied conditions, than the electrophoretic mobility, which is what the theory predicts for CyElFFF. However, better resolution was obtained when separating using BCyElFFF mode than when using normal CyElFFF. BCyElFFF was able to demonstrate simultaneous baseline separations of a mixture of 0.04-, 0.1-, and 0.2-μm particles and near separation of 0.5-μm particles. This study has shown the applicability of BCyElFFF for separation and characterization of submicron particles greater than 0.1-μm in size, which had not been demonstrated previously. The separation and retention results suggest that for particles of this size, retention is based more on particle size than on electrophoretic mobility, which is contrary to existing theory for CyElFFF.


MSW fly ash stabilized with coal ash for geotechnical application.
The solidification and stabilization of municipal solid waste (MSW) fly ash for the purpose of minimizing the geo-environmental impact caused by toxic heavy metals as well as ensuring engineering safety (strength and soaking durability) are experimentally evaluated. The mixtures of MSW fly ash stabilized with cement and fluidized bed combustion coal fly ash (FCA) were used for unconfined compressive strength tests, leachate tests, and soaking tests. The behavior of soluble salts contained in the MSW fly ash significantly affects strength development, soaking durability, and the hardening reaction of the stabilized MSW fly ash mixtures. The cement stabilization of the MSW fly ash does not have enough effect on strength development and soaking durability. The addition of cement only contributes to the containment of heavy metals due to the high level of alkalinity. When using FCA as a stabilizing agent for MSW fly ash, the mixture exhibits high strength and durability. However, the Cd leachate cannot be prevented in the early stages of curing. Using a combination of cement and FCA as a MSW fly ash stabilizer can attain high strength, high soaking durability, and the containment of heavy metals. The stabilized MSW fly ash with cement and FCA can be practically applied to embankments.


Challenges in delivering therapeutic peptides and proteins: A silk-based solution.
Peptide- and protein-based therapeutics have drawn significant attention over the past few decades for the treatment of infectious diseases, genetic disorders, oncology, and many other clinical needs. Yet, protecting peptide- and protein-based drugs from degradation and denaturation during processing, storage and delivery remain significant challenges. In this review, we introduce the properties of peptide- and protein-based drugs and the challenges associated with their stability and delivery. Then, we discuss delivery strategies using synthetic polymers and their advantages and limitations. This is followed by a focus on silk protein-based materials for peptide/protein drug processing, storage, and delivery, as a path to overcome stability and delivery challenges with current systems.


Adenylate kinase 2 is a biomarker related to the prognosis of glioma and the immune microenvironment.
Among the brain and the other central nervous system, gliomas are the most prevalent malignant primary tumors. Adenylate kinase 2 (AK2) is generally thought to be crucial for energy metabolism and signal transduction. Several disorders are correlated with its aberrant expression. However, it is unclear what functions AK2 might have in gliomas. We investigated the relationship between AK2 expression and clinicopathological features of glioma patients using information obtained from public databases and patient tissue microarrays. AK2 knockdown glioma cell lines were constructed to explore how AK2 affects glioma progress. The association between AK2 and the immune microenvironment in gliomas was evaluated by multiple methods. AK2 expression was higher in glioma samples than in normal brain tissues. Older patients and those with higher-grade, IDH-wildtype, 1p/19q codeletion-free, and MGMT-unmethylated tumors had higher levels of AK2 expression, linking to poor outcomes. Thus, gliomas with high AK2 expression have a worse prognosis. GO and KEGG analyses demonstrated that AK2 was relevant to cell division and DNA replication. Downregulation of AK2 suppresses cell proliferation, migration, and colony formation of glioma cell lines in vitro. AK2 expression was positively connected to the inhibitory immune checkpoints, also correlating with immune infiltration degree. In this study, AK2 may be a potential biological target for more precise molecular therapy of gliomas, since its high expression is associated with worse outcomes and a more malignant immune microenvironment.


The synthesis of cationic polyurethanes to study the effect of amines and structures on their DNA transfection potential.
Polyurethanes (PUs) are a class of biodegradable polymers that have been applied as tissue-engineering materials with minimum toxicity. In our study, a new series of cationic PUs containing tertiary amines in the backbone and primary, secondary and tertiary amines in the side chains (PU1, PU2 and PU3, respectively) was synthesized and used as nonviral vectors for gene delivery. In addition, we introduced glycidol into the structure of PU for greater solubility and biocompatibility and grafted various amines in the side chains (PUg1, PUg2, PUg3). The structural characteristics of PUs and the physicochemical properties of their formed complexes with DNA were determined and correlated with their transfection efficiency. The results reveal that PU1, PU3, PUg1 and PUg3 could bind with DNA and yielded positively charged complexes with a condensed size required for transfection. These PUs are considered to be noncytotoxic (hundred times less) compared to polyethylenimine (PEI) or poly(2-dimethylaminoethyl methacrylate), (PDMAEMA). The hydrolytical degradation studies indicate that PU-glycidyl systems (PUg1 and PUg3) can be degraded in 20 mM HEPES buffer at pH 7.4 in approximately 8 h but that PU1 and PU3 lasted much longer. PUg1 and PUg3 are the best amongst cationic PUs to transfect DNA into COS-7 cells with an efficacy comparable to the well-known gene carrier PDMAEMA. In addition, PUg1 and PUg3 possess greater biocompatibility and biodegradability. A new way to prepare cationic polymers without cytotoxicity but with highly transfecting activity could be very helpful to the in vivo gene transfection where large amounts of cationic polymers are required.


Pulmonary embolism bleeding score index (PEBSI): A new tool for the detection of patients with low risk for major bleeding on thrombolytic therapy.
Estimation of bleeding risk is an unmet need for individualized therapy in acute pulmonary embolism (PE) patients with increased mortality risk. We analyzed the association between various patients' characteristics and occurrence of major bleeding (MB) according to the modified International Society of Thrombosis and Hemostasis (ISTH) criteria ("overt" bleeding is the only modification from the original criteria) at 7 days from admission to the hospital and thrombolytic therapy with a tissue-plasminogen activator (tPA). Pulmonary embolism bleeding score index (PEBSI) was created using multivariate regression analyses, and finely, dichotomous index was used for the discrimination of patients with low risk for MB from those with high risk. During the 6-year period (2015-2021) 367 PE patients were treated with tPA and included in the Regional PE registry. Among them, 29 (7.9%) fulfilled the criteria for MB. Five factors were identified as significantly associated with MB and were used to build the PEBSI score: previous bleeding, recent surgery, diabetes, the use of drugs that could be associated with bleeding, and anemia. PEBSI score showed c-index for 7-day MB 0.794 (95CI% 0.698-0.889). Patients with PEBSI scores of 0 or 1 had a low risk for MB (2.8%) and those with scores>1 had a high risk for MB (18.6%) (p < 0.001). Internal validation of PEBSI score using a randomly, equally split method confirmed the discriminative value of the PEBSI score. Novel PEBSI score has significant power to discriminate patients with low risk for MB on thrombolytic therapy from those with high risk.


Physical activity, coronary artery calcium, and bone mineral density in elderly men and women: a preliminary investigation.
The aim of this study was to examine the relationship between cardiorespiratory fitness, coronary artery calcification (CAC), and bone mineral density (BMD) in older adults. Thirteen highly active, endurance-trained "master athletes" (7 male and 6 female) and 12 sedentary (6 male and 6 female) older adults (age 60-78 years) were recruited for this study. All subjects had CAC measured by electron beam computed tomography; BMD assessed by dual-energy X-ray absorptiometry; and plasma mineral regulatory proteins, including matrix Gla protein, fetuin-A, osteocalcin, osteopontin, and osteoprotegerin, measured by enzyme-linked immunosorbent assay. Furthermore, maximal oxygen consumption (VO2max) was measured in each subject to provide an objective measure of cardiorespiratory fitness. As expected, whole-body BMD was elevated in master athletes compared with sedentary adults (1.17 +/- 0.02 vs 1.09 +/- 0.02 g/cm2, P < .05). CAC score did not differ between activity groups, but was 8-fold lower in women compared with men (P < .05). The CAC score was not correlated with BMD, and there was no correlation between CAC and VO2max when both sexes were included in the analysis. When the sexes were analyzed separately, several relationships were evident in men only. There was a significant inverse correlation between VO2max and the number of calcified coronary artery lesions (r = -0.596, P < .05), and the correlation between VO2max and logCAC score approached significance (r = -.493, P = .08). Furthermore, fetuin-A, a systemic inhibitor of vascular calcification, was positively correlated with VO2max in men (r = 0.679, P < .05). These data provide preliminary evidence that chronic exercise may simultaneously inhibit CAC and increase BMD. The positive correlation between VO2max and plasma fetuin-A levels in men indicates a potential mechanism by which exercise may correlate negatively with CAC. Additional studies with larger sample sizes will be needed to determine if the protective effects of chronic exercise on CAC and BMD are sex specific or mediated through common mechanisms such as changes in circulating levels of mineral regulatory proteins.


De novo transcriptome assembly of two Vigna angularis varieties collected from Korea.
The adzuki bean (Vigna angularis), a member of the family Fabaceae, is widely grown in Asia, from East Asia to the Himalayas. The adzuki bean is known as an ingredient that adds sweetness to diverse desserts made in Eastern Asian countries. Libraries prepared from two V. angularis varieties referred to as Taejin Black and Taejin Red were paired-end sequenced using the Illumina HiSeq 2000 system. The raw data in this study can be available in NCBI SRA database with accession numbers of SRR3406660 and SRR3406553. After de novo transcriptome assembly using Trinity, we obtained 324,219 and 280,056 transcripts from Taejin Black and Taejin Red, respectively. We predicted a total of 238,321 proteins and 179,519 proteins for Taejin Black and Taejin Red, respectively, by the TransDecoder program. We carried out BLASTP on the predicted proteins against the Swiss-Prot protein sequence database to predict the putative functions of identified proteins. Taken together, we provide transcriptomes of two adzuki bean varieties by RNA-Seq, which might be usefully applied to generate molecular markers.


An aid to the selection of chemotherapy regimens for oral cavity carcinomas. Early results of a study of 5-year survival based on antioncogram selection of anti-cancer drugs.
The antioncogram is an aid to the selection of cytostatic drugs in the treatment of oral cavity carcinomas. In comparison with drug selection based on clinical experience, the antioncogram-oriented choice of the most promising drug in vitro results in improved survival rates.


[Maintenance of removable dentures. Nonexhaustive review of methods and current products].
The authors review various methods advocated to clean and disinfect removable prostheses. The effectiveness of most commercial preparations is quite relative, and some of them present definite risk for the appliance. Regular brushing of the prostheses remains absolutely necessary; it may be made easier but cannot be replaced.


Catalytic diversity of polyclonal RNA-hydrolyzing IgG antibodies from the sera of patients with systemic lupus erythematosus.
Various catalytic antibodies or abzymes have been detected in the sera of patients with several autoimmune pathologies, and recently we have shown that RNase activity is associated with IgGs and IgMs from the sera of patients with systemic lupus erythematosus (SLE) but not with those from the sera of normal humans. Here we present for the first time convincing evidence showing that highly purified SLE IgG, its F(ab) fragments and separated L-chains catalyze RNA hydrolysis. These IgGs hydrolyze RNA about one to three orders of magnitude faster than DNA. The enzymatic properties of the RNase activity of these polyclonal IgGs distinguish them from other known human RNases. Their specific activity in hydrolysis of ribooligoadenylates is 2-100-fold higher than that of RNase A and human serum RNases, and they are markedly more thermolabile. In addition, their specific activities with different oligonucleotide substrates, optimal pHs, apparent K(m) values for substrates, and substrate specificities varied very much for different patients. These findings show that a pool of polyclonal RNA-hydrolyzing IgG, which may be relatively small or extremely large, is generated by the immune system of SLE patients.


Masking Experiments in Humans and Birds Using Anthropogenic Noises.
This study investigated the masking of pure tones by anthropogenic noises in humans and birds. Bird experiments were conducted in the laboratory using operant conditioning and psychophysical procedures but with anthropogenic noises rather than white noise. Humans were tested using equivalent psychophysical procedures in the field with ambient background noise. Results show that for both humans and birds published critical ratios can be used to predict the masking thresholds for pure tones by these complex noises. Thus, the species' critical ratio can be used to estimate the effect of anthropogenic environmental noises on the perception of communication and other biologically relevant sounds.


Trans-sacral resection of a solitary fibrous tumor in the pelvis: report of a case.
Solitary fibrous tumors (SFTs) develop most commonly in the pleura, although they have occasionally been reported to arise in the pelvic cavity. We report a case of an SFT presenting as a painless nodule in the pelvis of a 56-year-old woman. Histologically, the tumor was composed of spindle-shaped cells arranged without pattern, with short and narrow fascicles and interspersed bundles of thick collagen, and numerous blood vessels with a focally hemangiopericytoma-like appearance. Immunohistochemically, the tumor cells strongly expressed vimentin, CD34, and bcl-2. The tumor was excised via a trans-sacral approach, without preoperative transcatheter embolization, and the patient remains well more than 2 years after her operation. To our knowledge, this is the first case of an SFT in the pelvis, which was excised completely via a trans-sacral approach.


A theoretical study on binding and stabilization of galactose and novel galactose analogues to the human α-galactosidase A variant causing Fabry disease.
α-galactosidase A (α-Gal A) catalyzes the hydrolysis of terminal α-galactosyl moieties from globotriaosylceramide, and mutations in this enzyme lead to the lipid metabolism disorder "Fabry disease". Mutation in α-Gal A possibly causes the protein misfolding, which reduces catalytic activity and stability of the enzyme. A recent study demonstrated that the binding of galactose on the α-Gal A catalytic site significantly increases its stability. Herein, the effect of mutation on secondary structure, structural energy, and galactose affinity of α-Gal A (wild type and A143T variant) was investigated using molecular dynamics simulations and free energy calculations based on MM/GBSA method. The results showed that A143T mutation caused the formation of unusual H-bonds that induced the change in secondary structure and binding affinities toward galactose. The amino acid residues involved in galactose binding were identified. The molecular binding mechanism obtained from this study could be helpful for optimizations and designs of new galactose analogs as pharmacological chaperones against Fabry disease.


The impact of the implementation of a mobile stroke unit on a stroke cohort.
Mobile stroke units (MSUs), specialized ambulances with a built-in computed tomography (CT) scanner and telemedicine connected stroke team, have been on the rise in recent years largely due to the 'time is brain' concept. We aim to report our initial experience since establishing our MSU, the first unit in the Tri-state area, and assess its impact on the stroke standards of care timeline. We conducted a retrospective analysis of a prospectively maintained database of all MSU dispatched cases from August 2019 to March 2020. Of 195 MSU responses, 101 were treated and transported by the MSU. The mean time (hr:mm) of dispatch to scene arrival was 0:07+0:03, scene arrival to CT start was 0:10+0:03, CT start to teleneuro start was 0:05+0:03, teleneuro start to scene departure was 0:06+0:05, scene departure to hospital arrival was 0:12+0:06, and hospital arrival to arterial puncture was 2:59+1:01. The mean time of dispatch to arterial puncture was 3:34+1:02. The mean teleneuro consult duration was 0:04+0:02. The mean time of last know well (LKW) to tPA administration was 1:28+0:48 with 4 (57.1 %) patients receiving tPA within 60 min of LKW and 5 (71.4 %) patients receiving tPA within 90 min. The mean time of dispatch to tPA was 0:37+0:09 and scene arrival to tPA administration was 0:28+0:07. MSUs may expedite each step along the stroke standards of care. In theory, this should drastically improve functional outcomes. However, the impact on functional outcomes or reductions in stroke-related morbidity is still unknown.


Association between tau H2 haplotype and age at onset in frontotemporal dementia.
The frontotemporal dementia (FTD) syndromes have been associated with the microtubule-associated tau protein since tau gene mutations have been demonstrated to be the cause of FTD and parkinsonism linked to chromosome 17. In cases of FTD without tau gene mutations, however, it is unclear whether genetic variability in the tau gene is associated with the development or modulation of FTD. To determine whether genetic variability in tau and apolipoprotein E (ApoE) modulates and contributes to the development of FTD. Design and Patients The distribution of tau gene haplotypes and the ApoE genotype were investigated in 86 patients with well-characterized FTD and 50 control subjects. No difference in the distribution of the tau H1 and H2 haplotypes between FTD cases and controls was observed, whereas the ApoE epsilon4 allele was more frequent in FTD cases. The presence of at least 1 tau H2 allele was found to be significantly associated with an earlier age of onset in patients with FTD. The association between the H2 allele and age at onset was not related to family history, clinical presentation, or ApoE genotype. These findings support a role of tau protein in modulating disease phenotype by influencing the age at onset in these FTD cases.


Clinical Challenges in Catecholaminergic Polymorphic Ventricular Tachycardia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disorder associated with exercise- and stress-induced sudden death in young individuals. Although important steps forward have been made in the comprehension and treatment of this disease, several aspects remain unclear. Firstly, from an epidemiological standpoint the actual prevalence of CPVT is still unknown and possibly underestimated. In addition, the diagnostic process remains very challenging and can be supported by genetic analysis in only about half of the cases. Finally, up to one third of CPVT patients continue to present complex arrhythmias despite beta blocker treatment; the role of newer therapeutic options, such as flecainide and left cardiac sympathetic denervation, needs to be further elucidated. All these points constitute challenges for the cardiologist in the management of CPVT patients and fuel research into new diagnostic, prognostic and therapeutic approaches.


Towards the differential diagnosis of prostate cancer by the pre-treatment of human urine using ionic liquids.
Prostate specific antigen (PSA) is the most widely used clinical biomarker for the diagnosis and monitoring of prostate cancer. Most available techniques for PSA quantification in human fluids require extensive sample processing and expensive immunoassays that are often unavailable in developing countries. The quantification of PSA in serum is the most common practice; however, PSA is also present in human urine, although less used in diagnosis. Herein we demonstrate the use of ionic-liquid-based aqueous biphasic systems (IL-based ABS) as effective pre-treatment strategies of human urine, allowing the PSA detection and quantification by more expedite equipment in a non-invasive matrix. If properly designed, IL-based ABS afford the simultaneous extraction and concentration of PSA (at least up to 250-fold) in the IL-rich phase. The best ABS not only allow to concentrate PSA but also other forms of PSA, which can be additionally quantified, paving the way to their use in differential prostate cancer diagnosis.


Development of a colorimetric aptasensor fabricated with a group-specific aptamer and AuNPs@Fe2+ nanozyme for simultaneous detection of multiple diarrheic shellfish poisons.
Okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2) are the main diarrheic shellfish poisons (DSPs). Detection methods to achieve simultaneous detection of the three toxins are urgently needed. In this paper, a terminal fixation design proposed in our previous study was further explored to engineer an aptamer with group-specific recognition ability from an original aptamer binding to one target. Both molecular docking assay and biolayer interferometry assay were applied to reveal the binding mechanisms between three DSPs and the engineered aptamer. Then, a label-free colorimetric aptasensor by fabricating the aptamer with AuNPs@Fe2+ nanozyme was constructed, which provided a wide linear detection range (0.4688-7.5 nM), a very low limit of detection (LOD, 86.28 pM), and good recoveries (96.02-104.9%) when analyzing DSPs in seawater and scallop samples, indicating the engineered aptamer and the developed aptasensor had great potential in recognizing and detecting multiple DSPs in real world.


Validation of a therapeutic scheme for the treatment of resistant hypertension.
We tested the hypothesis that a therapeutic strategy of substituting the diuretic (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if needed, the calcium channel blocker with the highest dose of the most commonly used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive patients not responding to spironolactone. The scheme was tested in a group of 76 patients who had true treatment resistant hypertension (24-hour mean blood pressure ≥130/80 mm Hg while receiving three or more drugs). An effective response to spironolactone was defined as 24-hour ambulatory systolic blood pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25-50 mg in 60 patients (78.9%). In patients with inadequate response to spironolactone (n = 16), we administered the triple combination plus the remaining therapy, a mean decrease of 29 mm Hg (95% CI 11-48; P = .004) for SBP and 12 mm Hg (95% CI: 4-20 mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the response was considered as insufficient. These data indicate the need for further testing this scheme that looks really promising to treat resistant hypertensive patients not responding to spironolactone.


Function and regulation of Alx4 in limb development: complex genetic interactions with Gli3 and Shh.
The role of the aristaless-related homeobox gene Alx4 in antero-posterior (AP-) patterning of the developing vertebrate limb has remained somewhat elusive. Polydactyly of Alx4 mutant mice is known to be accompanied by ectopic anterior expression of genes like Shh, Fgf4 and 5'Hoxd. We reported previously that polydactyly in Alx4 mutant mice requires SHH signaling, but we now show that in early Alx4-/- limb buds the anterior ectopic expression of Fgf4 and Hoxd13, and therefore disruption of AP-patterning, occurs independently of SHH signaling. To better understand how Alx4 functions in the pathways that regulate AP-patterning, we also studied genomic regulatory sequences that are capable of directing expression of a reporter gene in a pattern corresponding to endogenous Alx4 expression in anterior limb bud mesenchyme. We observed, as expected for authentic Alx4 expression, expansion of reporter construct expression in a Shh-/- background. Total lack of reporter expression in a Gli3-/- background confirms the existence of Gli3-dependent and -independent Alx4 expression in the limb bud. Apparently, these two modules of Alx4 expression are linked to dissimilar functions.


Dissociative experiences among Lebanese university students: Association with mental health issues, the economic crisis, the COVID-19 pandemic, and the Beirut port explosion.
Dissociative experiences are psychological manifestations characterized by a loss of connection and continuity between thoughts, emotions, environment, behavior, and identity. Lebanon has been facing indescribable events in the last few years, including the COVID-19 pandemic, the Beirut explosion, a crushing economic crisis with the highest inflation rate the country has known in over three decades. The aim of this study was to evaluate the correlation between dissociative experiences and post-traumatic stress symptoms from the economic crisis, the Beirut blast, the COVID-19 pandemic, and other mental health issues in a sample of Lebanese university students. This cross-sectional study enrolled 419 active university students (18-35 years) from all over Lebanon (May and August 2021). The respondents received the online soft copy of a survey by a snowball sampling technique through social media and messaging apps. The questionnaire included sociodemographic data, the Dissociative Experience Scale (DES-II), the PTSD Checklist Specific Version (PCL-S), the Financial Wellbeing Scale, the Beirut Distress Scale, the Lebanese Anxiety Scale, the Patient Health Questionnaire. The two-factor model of the DES fitted best according to CFI, RMSEA and χ2/df values, but modestly according to TLI. The two factors were absorption and amnesia/depersonalization. Higher stress (Beta = 0.95) and more PTSD from the Beirut blast (Beta = 0.29) and from the economic crisis (Beta = 0.23) were significantly associated with more absorption. A personal history of depression (Beta = 6.03), higher stress (Beta = 0.36) and more PTSD from the Beirut blast (Beta = 0.27) and from the COVID-19 pandemic (Beta = 0.16) were significantly associated with more amnesia/depersonalization. Significant rates of dissociative experiences and their sub-manifestations (amnesia/depersonalization and absorption) were found among Lebanese university students, with remarkable co-occurrence of a traumatic/stressful pattern, whether on an individual (history of PTSD) or a collective level (Post-traumatic manifestations from Beirut blast, COVID-19 pandemic and/or economic crisis), or whether correlated to an acute single event or to certain chronic stressors, or even to a personal history of depression. Such findings must raise the attention to serious mental and psychosocial alteration in the Lebanese national identity.


Reactivity to novelty during youth as a predictive factor of cognitive impairment in the elderly: a longitudinal study in rats.
A life-span study of certain behavioral traits was conducted in rats. Animals were repeatedly tested in a circular corridor for reactivity to novelty and in a recognition memory task for cognitive abilities. These measures revealed important inter-individual differences in young as well as in old subjects. Some of these differences appear with aging (memory deficits) and others disappear (high reactivity to novelty). Moreover, a relationship between high reactivity to novelty in youth and deficits in memory recognition in elderly was found. Rats that are high-responders to novelty had age-related memory impairments whereas the low-responder rats did not. While the biological mechanism linking these two behavioral traits remains to be demonstrated, this study shows that age-related impairments can be predicted by factors detectable early in life.


Fear of cancer recurrence: a significant concern among partners of prostate cancer survivors.
The aims of the study were to (1) describe the prevalence of fear of cancer recurrence (FCR) in partners of prostate cancer (PCa) survivors; (2) to compare the proportions of high FCR in partners with high FCR in PCa survivors; (3) to explore partners' demographic and survivors' clinical characteristics associated with high FCR in partners; and (4) to identify the relationship between high FCR and health-related quality of life (HRQoL) in partners. Questionnaires were sent to partners of disease-free PCa survivors. Outcomes included FCR severity (Cancer Worry Scale [CWS]) and HRQoL (RAND-36). The t and chi-square tests were used to compare partner FCR with survivor FCR. Regression analyses were performed to determine if demographic and clinical characteristics were significantly associated with partner FCR. The multivariate analysis of variance identified differences in HRQoL between partners with high and low FCR. Questionnaires were completed by 168 partners. Mean levels of FCR were comparable between partners and survivors (P = .144). Thirty-five percent of partners reported high FCR (CWS ≥ 14) compared to 38% of PCa survivors (CWS ≥ 13) (P = .542). Higher survivor FCR and younger partner age were significantly associated with higher partner FCR. Partners with high FCR scored significantly lower on social functioning, emotional role functioning, mental health, general health, and vitality than those with low FCR (all P < .05). Findings from this study illustrate that FCR is a significant concern for partners of PCa survivors. Clinicians should be aware of partner FCR when delivering care to men with PCa.


Online survey of consumer awareness and perceptions of a Massachusetts law for 12-month supply of contraception.
This study aimed to characterize awareness of a 2017 Massachusetts (MA) law that ensures access to a 12-month supply of short-acting contraceptive methods (e.g., pill, patch, and vaginal ring) among short-acting contraceptive users in MA and to identify perceived benefits and concerns of a 12-month supply. An online survey was administered to a Qualtrics panel of MA women who were using short-acting contraceptive methods and were insured by an eligible health plan. The survey's primary outcome was general awareness of the law; interest in, receipt of, and perceived benefits and risks of a 12-month supply were also elicited. Analysis included descriptive statistics and bivariate and multivariable analyses examining factors associated with awareness of the law. Among the 207 survey respondents, 76% were aware of the law, and 93% expressed interest in receiving a 12-month supply of a short-acting method; however, only 9% received it. Respondents identified as White (66%), privately insured (59%), and pill users (44%). Concerns about a 12-month supply included privacy, product expiration, and change in personal medical status. Perceived benefits included avoiding multiple trips to pharmacy and increased compliance. Multivariable analyses showed general awareness of the law was only associated with employer-based insurance, with those respondents having 75% lower odds of being aware of the law than respondents with Medicaid coverage. Although a high percentage of women surveyed were aware of the law and most were interested in receiving a 12-month supply of their short-acting method, the low percentage who have received a 12-month supply suggests barriers to policy uptake. This study describes perceptions of the 12-month supply provision of the contraception Act Advancing Contraceptive Coverage and Economic Security in our State law. Addressing consumer concerns may be important to improve the implementation and dissemination of this state policy change.