Biological therapy for ulcerative colitis: what is after anti-TNF.
Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD. Conventional therapy of UC quite commonly fails to avoid complications or colectomy and the therapeutic armamentarium remains still limited. New therapeutic options, such as, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucoapheresis, have been investigated recently. Biological therapy is focused on different targets involved in the inflammatory process. Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNF-α agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and more. We review the recent advances in biological therapy for UC treatment beyond the anti-TNFs.


Incidence of congenital CMV in children at a hearing rehabilitation center.
To evaluate the incidence of children with congenital CMV (cCMV) infection in a hearing rehabilitation center. This was a retrospective review of 309 children followed in a rehabilitation center for mild to total sensorineural hearing loss (SNHL). Seventy-five children had dried blood spots that we retrieved and retrospectively analyzed for the presence of CMV DNA by real time PCR. The children were born in Belgium after January 1996. The etiology of the SNHL was investigated for each child. The CMV DNA was detected in the dried blood spots for 8 of the 75 children tested (10.6%) by real time PCR. In three children, an alternative etiology of SNHL was suspected before the cCMV infection was diagnosed. The incidence of children infected with cCMV in a hearing rehabilitation center is high (10.6%). The detection of CMV DNA in dried blood spots is useful and improves the etiological diagnosis of SNHL.


[Periocular surgery and the impact of split-thickness skin grafts].
Oculoplastic surgery has to consider the specific characteristics of the periocular region and possible resulting functional consequences. Motility of eyelids, limited skin thickness with excellent wound healing conditions, lacrimal duct system and eyelid ligaments are important criteria for the individual choice of the surgical procedure. The use of split-thickness skin grafts represents an established method to repair periocular defects. Important medical conditions for split-thickness transplantation are colour of the skin, skin structure, photodamage of the skin, hair growth and other degenerative disorders. The recipient area should be treated as carefully as possible with diathermia until the bare area is completely dry. It is important that the size of the graft is slightly larger than the area to be covered because of postoperative shrinking. Small grafts tend to result in contraction which may lead to a defective position of the eyelids. For postoperative wound maintenance, gauze containing vaseline and wool wax can be used. This helps to keep the graft smooth and to prevent its detachment upon changes of dressing. Frequency and scope of complications are similar to flap surgery if adequate individual indications for split-thickness skin grafts are considered. Early onset complications are wound dehiscence, bleeding, formation of seroma, dislocation or loss of grafted skin. The postoperative maintenance of the donor site can be managed successfully with hydrocolloid dressing. Split-thickness skin grafts represent a good reconstruction technique if other tissue (full-thickness skin) from the periocular region is not available or whenever other surgical methods appear to be less promising or inapplicable. If available, ipsi- or contralateral full-thickness skin grafts are preferred because of the same skin type.


Androgen deficiency in women; role of accurate testosterone measurements.
Androgen deficiency in women has been recognized as a distinct clinical syndrome that affects thousands of women particularly women in the postmenopausal period of their life. This syndrome has been described by several names including female androgen deficiency syndrome as well as hypoactive, sexual desire disorder. A recent large survey concerning sexual problems in women also adds personal distress as a potential contributor to the low sexual desire found in some women with sexual dysfunction. Recognition of an androgen deficiency syndrome however, has been controversial and limited to a clinical diagnosis due to the lack of accurate and sensitive methods for measuring androgens in women. Up until now, available methods for measuring the sex steroids have been dependent on antibody based assays that employ a range of different detection systems including the use of isotopes such as tritium and I-125 or chemical signalling molecules that produce chemiluminescence. These assays have become increasingly more sensitive for the measurement of testosterone but are still incapable of providing the proper low-end sensitivity for analyzing testosterone in female blood specimens. Assays for testosterone performed either manually or with highly automated immunoassay instruments have been used to measure testosterone in women but with varying degrees of success. Existing immunoassay-based methods are quite adequate for measuring testosterone levels in males but lack sufficient sensitivity to accurately and reproducibly measure testosterone in females and pre-pubertal children. Recent advances with the use of ultrasensitive methods such as mass spectrometry coupled to either gas or liquid chromatography have improved the technology for measuring testosterone and other low concentration sex steroids like estradiol to the degree that mass spectrometry based methods are now capable of measuring the testosterone levels found in normal women and in women with extremely low levels of testosterone as observed in a true androgen deficiency disorder. This application of mass spectrometry for measuring testosterone should allow clinicians to better define female androgen deficiency and facilitate further investigation in the diagnosis and optimal management of androgen deficiency in women.


The Influence of Redox-Active Linkers on the Stability and Physical Properties of a Highly Electroactive Porphyrin Nanoprism.
Redox-active metal-organic nanocages are of interest for many applications, but the development of cages with extensive redox activity is often hindered by their limited stability and solubility across multiple charge states. This report reveals that these properties can be tuned for cages with redox-active walls by incorporating additional redox activity into the linkers. In particular, new +12 charged triangular nanoprisms 1a,b were formed from three electroactive tetrakis(3-pyridyl)porphyrin walls linked by six [(TMEDA)Pt]2+ (for 1a) or [(2,2'-bipy)Pt]2+ (for 1b) vertices, the latter of which are also electroactive. Thus, 1b exhibits extensive redox activity, consisting of two porphyrin-centered (x3) and two 2,2'-bipy-centered (x6) reductions that provide reversible access to +12, +9, +3, 0, and -6 charge states, whereas 1a undergoes only two, porphyrin-centered (x3) reversible reductions. Comparisons of 1a and 1b (and monomeric control compounds) by cyclic voltammetry and UV-vis-NIR spectroelectrochemistry show that the redox-activity of the linkers in 1b lowers the second reduction potential of the porphyrins by 100 mV and improves the stability and solubility of this structure under highly reducing conditions (e.g., -2.25 V vs Fc+/0 in MeCN). These findings reveal new principles for controlling the properties of highly electroactive molecular nanostructures. Anion exchange rates (≫103 s-1) were also probed, showing that the narrow apertures (≤3 Å van der Waals width) of 1a,b do not impede the loss/gain of PF6- anions during redox processes.


[Dynamics of change of ureaplasma laboratory strain titers and quantity of their DNA in transport medium at varying temperature].
Study of preservation dynamics of ureaplasma laboratory strain live cultures and their DNA in transport medium at varying temperature. The study was carried out in laboratory strains Ureaplasma urealyticum serotype 8 and Ureaplasma parvum serotype 1. The quantity of live ureaplasmas was determined by method of tenfold dilutions in liquid medium. The growth of ureaplasmas was registered by changes in the color of the cultivation medium due to its alkalization by metabolism products and expressed in CCU/ml. DNA quantity in samples was determined by real time PCR performed by using Florocenosis-micoplasmas-FL test system produced by ILS. Live ureaplasmas wer shown to be preserved in transport medium at 4 degrees C for 12 - 29 days, at 18 - 22 degrees C--for 9 - 20 days and at 37 degrees C--for only 2 days. In samples incubated at 37 degrees C the quantity of live ureaplasmas increased and then sharply decreased to 0, at lower temperature titers of the cells decreased smoothly. The quantity of ureaplasma DNA in the process of their incubation did not change significantly. Fundamental differences in the duration of survival of U. urealyticum strain and U. parvum strain in transport medium at varying temperature were not detected. Based on the studies performed a practical conclusion can be drawn that in cases of emergency when clinical material transportation is necessary its storage in transport medium for several days is acceptable.


[Adaptation of a Bacillus subtilis strain, containing a recombinant plasmid with a human interferon-alpha2 gene, to various environmental conditions].
Adaptation of the Bacillus subtilis strain 2335/105 (Km Inf+) containing a recombinant plasmid encoding the extracellular human interferon alpha 2 was studied under various conditions. Stability of the plasmid in the population of B. subtilis 2335/105 was estimated under nonselective conditions. The plasmid-free cells and cells with a low number of plasmid copies were found to accumulate progressively, constituting 80% of the population after 10 culture passages, indicating the poor competitiveness of cells carrying a high number of plasmid copies. The behavior of vegetative cells of the recombinant strain introduced into aquatic microcosms differing in trophic chain length was studied. Within the first 10 days, the lysis of vegetative cells of B. subtilis 2335/105 occurred; the number of viable spores was very low but remained constant for half a year.


False recognition of unfamiliar faces following right hemisphere damage: neuropsychological and anatomical observations.
False recognition of unfamiliar faces was investigated in patients with focal right hemisphere damage (RHD) in order to define the neuropsychological and anatomical correlates of the recognition impairment and examine its relationship to prosopagnosia. Findings are discussed within the framework of the Bruce and Young (1986) model of face processing. Although false recognition and prosopagnosia were both present in some RHD patients, the two types of face recognition impairments were dissociable in others. Processing deficits in subjects with both false recognition and prosopagnosia were associated with posterior right hemisphere lesion sites and included severe face perception impairment and partial damage to face recognition units (FRUs). Prosopagnosia without false recognition was seen following near complete destruction of FRUs, but this type of dissociation could also occur when FRUs become disconnected. The opposite dissociation, false recognition without prosopagnosia, was observed following right prefrontal damage. We propose that false recognition in frontal patients results from the breakdown of strategic decision making and monitoring functions critical for determining whether a face is indeed that of a familiar person or whether there is merely a resemblance to a known individual. False recognition following prefrontal damage may also be related to confabulation, in which case familiarity or even specific identity are erroneously attributed to facial stimuli without the activation of an underlying memory representation.


The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design.
The task of epitope discovery and vaccine design is increasingly reliant on bioinformatics analytic tools and access to depositories of curated data relevant to immune reactions and specific pathogens. The Immune Epitope Database and Analysis Resource (IEDB) was indeed created to assist biomedical researchers in the development of new vaccines, diagnostics, and therapeutics. The Analysis Resource is freely available to all researchers and provides access to a variety of epitope analysis and prediction tools. The tools include validated and benchmarked methods to predict MHC class I and class II binding. The predictions from these tools can be combined with tools predicting antigen processing, TCR recognition, and B cell epitope prediction. In addition, the resource contains a variety of secondary analysis tools that allow the researcher to calculate epitope conservation, population coverage, and other relevant analytic variables. The researcher involved in vaccine design and epitope discovery will also be interested in accessing experimental published data, relevant to the specific indication of interest. The database component of the IEDB contains a vast amount of experimentally derived epitope data that can be queried through a flexible user interface. The IEDB is linked to other pathogen-specific and immunological database resources.


Facilitation of neuronal responses by intrinsic default mode network activity.
Default mode network (DMN) shows intrinsic, high-level activity at rest. We tested a hypothesis proposed for its role in sensory information processing: Intrinsic DMN activity facilitates neural responses to sensory input. A neural network model, consisting of a sensory network (Nsen) and a DMN, was simulated. The Nsen contained cell assemblies. Each cell assembly comprised principal cells, GABAergic interneurons (Ia, Ib), and glial cells. We let the Nsen carry out a perceptual task: detection of sensory stimuli. During DMN activation, glial cells were hyperpolarized by Ia-to-glia circuitry, by which glial membrane transporters imported GABA molecules from the extracellular space and decreased ambient GABA concentration. Acting on extrasynaptic GABA receptors, the decrease in ambient GABA concentration reduced inhibitory current in a tonic manner. This depolarized principal cells below their firing threshold during the ongoing spontaneous time period and accelerated their reaction speed to a sensory stimulus. During the stimulus presentation period, the Nsen inhibited the DMN and caused DMN deactivation. The DMN deactivation made Nsen Ia cells cease firing, thereby stopping the glial membrane hyperpolarization, quitting the GABA import, returning to the basal ambient GABA level, and thus enhancing global inhibition. Notably, the stimulus-relevant P cell firing could be maintained when GABAergic gliotransmission via Ia-glia signaling worked, decreasing ambient GABA concentration around the stimulus-relevant P cells. This enabled the Nsen to reliably detect the stimulus. We suggest that intrinsic default model network activity may accelerate the reaction speed of the sensory network by modulating its ongoing-spontaneous activity in a subthreshold manner. Ambient GABA contributes to achieve an optimal ongoing spontaneous subthreshold neuronal state, in which GABAergic gliotransmission triggered by the intrinsic default model network activity may play an important role.


Effects of arm frequency during synchronous and asynchronous wheelchair propulsion on efficiency.
To further understand the possible underlying mechanisms of the low efficiencies in hand rim wheelchair propulsion, this study examined efficiency indices at different arm frequencies during two propulsion modes (synchronous and asynchronous). Fourteen male able-bodied participants performed VO2PEAK tests for both propulsion modes. Subsequently two sub-maximal exercise tests examining synchronous and asynchronous propulsion were completed at an individualised velocity (60% of VO2PEAK). The freely chosen arm frequency (FCF), followed by four counter-balanced trials at 60, 80, 120, and 140% of FCF were performed. Gross, net, and work efficiency were determined. Gross efficiency was significantly lower (p<0.05) at arm frequencies >100%, and participants were more efficient between 60 to 100% FCF. These arm frequencies corresponded to 76+/-22 to 126+/-36 and 70+/-18 to 116+/-30 pushes x min(-1) (synchronous and asynchronous respectively). Trends in VO2, gross and work efficiency suggest that 80% of FCF produced the best economy and efficiency during both propulsion modes (non-significant). Gross and work efficiency at 80% FCF were 6.8+/-0.7% and 13.0+/-4.6% for synchronous and 7.0+/-0.8% and 11.5+/-1.6% for asynchronous respectively. The results suggest that during both modes of propulsion the FCF is not necessarily the most efficient.


[CAR-T therapy for multiple myeloma].
Immune cell therapies targeting B-cell maturation antigen (BCMA) have been developed for relapsed and refractory multiple myeloma (RR-MM). Chimeric antigen receptor (CAR)-T cell therapies appear promising for RR-MM, and two BCMA-targeting CAR-T cell products, idecabtagene vicleucel and ciltacabtagene autoleucel, have achieved the highest response rates in heavily treated patients to date. These CAR-T products have been approved for RR-MM previously treated with 3 agents (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies) in Japan. Despite the promising efficacy of CAR-T therapy, several issues remain to be resolved to establish its best use in routine clinical practice. In addition, most patients who receive CAR-T cell therapy eventually relapse after a long or short remission, and a better understanding of mechanisms of resistance and relapse following CAR T-cell therapy for MM will be necessary to overcome resistance to CAR-T therapy. In the near future, early initiation of CAR-T therapy for RR and development of next-generation CAR-T cell products should further improve prognosis in patients with MM.


Neutral hydrogen survey of andromeda galaxy.
A neutral hydrogen survey of the Andromeda galaxy (M31) has been conducted with the 260-foot (80m) Ohio State University radio telescope. The neutral hydrogen is concentrated in the spiral arm regions, with but relatively small amounts near the center of the galaxy. Similar deficiencies have been found near the center of M33 and our galaxy, suggesting similar evolutionary processes in the three galaxies.


Discovery of New Broad-Spectrum Anti-Infectives for Eukaryotic Pathogens Using Bioorganometallic Chemistry.
Drug resistance observed with many anti-infectives clearly highlights the need for new broad-spectrum agents to treat especially neglected tropical diseases (NTDs) caused by eukaryotic parasitic pathogens, including fungal infections. Herein, we show that the simple modification of one of the most well-known antifungal drugs, fluconazole, with organometallic moieties not only improves the activity of the parent drug but also broadens the scope of application of the new derivatives. These compounds were highly effective in vivo against pathogenic fungal infections and potent against parasitic worms such as Brugia, which causes lymphatic filariasis and Trichuris, one of the soil-transmitted helminths that infects millions of people globally. Notably, the identified molecular targets indicate a mechanism of action that differs greatly from that of the parental antifungal drug, including targets involved in biosynthetic pathways that are absent in humans, offering great potential to expand our armamentarium against drug-resistant fungal infections and neglected tropical diseases (NTDs) targeted for elimination by 2030.


Cloning and characterization of two human polyspecific organic cation transporters.
Previously we cloned a polyspecific transporter from rat (rOCT1) that is expressed in renal proximal tubules and hepatocytes and mediates electrogenic uptake of organic cations with different molecular structures. Recently a homologous transporter from rat kidney (rOCT2) was cloned but not characterized in detail. We report cloning and characterization of two homologous transporters from man (hOCT1 and hOCT2) displaying approximately 80% amino acid identity to rOCT1 and rOCT2, respectively. Northern blots showed that hOCT1 is mainly transcribed in liver, while hOCT2 is found in kidney. Using in situ hybridization and immunohistochemistry, expression of hOCT2 was mainly detected in the distal tubule where the transporter is localized at the luminal membrane. After expression in Xenopus laevis oocytes, hOCT1 and hOCT2 mediate tracer influx of N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), and 1-methyl-4-phenylpyridinium (MPP). For cation transport by hOCT2 apparent K(m) and K(i) values were determined in tracer flux measurements. In addition, electrical measurements were performed with voltage-clamped oocytes. Similar to rOCT1, cation transport by hOCT2 was pH independent, electrogenic, and polyspecific; however, the cation specificity was different. In voltage-clamped hOCT2-expressing oocytes, inward currents were induced by superfusion with MPP, TEA, choline, quinine, d-tubocurarine, pancuronium, and cyanine863. Cation transport in distal tubules is indicated for the first time. Here hOCT2 mediates the first step in cation reabsorption. hOCT1 may participate in hepatic excretion of organic cations.


Validation of tetrapolar bioelectrical impedance method to assess human body composition.
This study was conducted to validate the relationship between bioelectrical conductance (ht2/R) and densitometrically determined fat-free mass, and to compare the prediction errors of body fatness derived from the tetrapolar impedance method and skinfold thicknesses, relative to hydrodensitometry. One-hundred and fourteen male and female subjects, aged 18-50 yr, with a wide range of fat-free mass (34-96 kg) and percent body fat (4-41%), participated. For males, densitometrically determined fat-free mass was correlated highly (r = 0.979), with fat-free mass predicted from tetrapolar conductance measures using an equation developed for males in a previous study. For females, the correlation between measured fat-free mass and values predicted from the combined (previous and present male data) equation for men also was strong (r = 0.954). The regression coefficients in the male and female regression equations were not significantly different. Relative to hydrodensitometry, the impedance method had a lower predictive error or standard error of the estimates of estimating body fatness than did a standard anthropometric technique (2.7 vs. 3.9%). Therefore this study establishes the validity and reliability of the tetrapolar impedance method for use in assessment of body composition in healthy humans.


Doxorubicin dose for congestive heart failure modeling and the use of general ultrasound equipment for evaluation in rats. Longitudinal in vivo study.
For the evaluation of the congestive heart failure (CHF) in rat models, the use of special equipment for echocardiography for dynamic evaluation is suggested. The optimal doxorubicin dose for CHF induction has still not been established. The aims of our study was to find a reliable doxorubicin CHF rat model using a general ultrasound (US) equipment for in vivo ultrasound examination of the systemic circulation, to establish the optimal doxorubicin dose, and to assess the feasibility of US guided administration of the drug. Sixty Wistar rats, weighing 180-200 g were assigned to 3 groups (n=20 in each): group A - 4 time intraperitoneal doxorubicin "Sigma"administration, cumulative dose 2.49 mg/animal or 12.45 mg/kg; group B and 5 time doxorubicin administration, cumulative dose 3.03 mg/animal or 15.15 mg/kg; and group C- controls (injected same volume of saline). Dynamic US using linear 12 MHz transducer was used to establish the CHF modifications. Two rats with CHF were injected under US guidance in the pleural cavity with 0.06 ml cardiotropic drug levosimendan and two rats in the pericardial cavity. We established the optimal cumulative doxorubicin dose for CHF induction at 12.45 mg/kg. At a higher dose, more than 40% of animals died. A lower dose did not induce significant clinical and US CHF criteria. Congestion (followed by weight gain) led to lower animal mortality. Preliminary results indicate a similar positive cardioprotective effect of drug injection into pericardial and pleural cavities under US guidance, demonstrating that this technique is useful for drug administration. US is an effective modality for in vivo monitoring of the rat organs for the study of cardiovascular function or for drug administration under US guidance. Suggested model (optimal dose of doxorubicin for simulation of CHF of 2.5 mg/animal, a cumulative dose of 12.45 mg/kg in 4 injections every 3 days) can be used for research purposes.


Risk Factors for Development of Keratoconus: A Matched Pair Case-Control Study.
Keratoconus, a progressive ectatic corneal disorder, is believed to be multifactorial in etiology with interaction between genetic and environmental factors. To date, risk factors for the development of the disease are extensively debated and need to be identified since they play a critical role in disease prevention and management. This study aimed to analyze associations between several hereditary and environmental predictors and the development of keratoconus. This was a retrospective matched pair case-control study. The study was conducted in Ibn-Alhaitham eye teaching hospital between March 2016 and April 2017. Patients with keratoconus (cases) and their age- and gender-matched controls were asked about childhood and early teenage eye rubbing, ocular trauma, obesity, contact lens wear, smoking and sunlight exposure, family history of keratoconus, parental consanguinity and information related to socio-economic status. Univariable and multivariable conditional logistic regression analyses were used to test the significance of associations. A total of 166 individuals (83 cases and 83 controls; 60.2% female) were included. On univariable analysis, eye rubbing, family history of keratoconus and parental consanguinity were significant risk factors for keratoconus, whereas all other factors were non-significant. On multivariable analysis, eye rubbing (odds ratio: 4.93; P < 0.01), family history of keratoconus (odds ratio: 25.52; P < 0.01) and parental consanguinity (odds ratio: 2.89; P = 0.02), again, emerged as significant risk factors for disease development. Family history of keratoconus, eye rubbing, and parental consanguinity were significant risk factors for keratoconus development. These results support the evidence for multifactorial etiology, the most important factor being hereditary predisposition.


Formulation and characterization of radio-opaque conjugated in situ gelling materials.
X-ray visibility is an integral design component of in situ gelling embolization systems for neurovascular treatment. The goals of this project included the synthesis and characterization of a unique intrinsically radio-opaque in situ gelling material for neurovascular embolization. The gels formed using Michael-Type Addition between pentaerythritol tetrakis 3-mercaptopropionate (QT) thiols and poly(propylene glycol) diacrylate (PPODA) with the addition of the new material Iodobenzoyl poly(ethylene glycol) acrylate (IPEGA), a radio-opaque agent, synthesized successfully as confirmed with (1)H NMR. The PPODA and IPEGA were mixed using a syringe coupler with QT and buffer at pH 11 for 90 seconds. Gel mixes were weighed to provide equal molar thiols and acrylate groups, changing the present acrylate-bearing compounds wt % ratios from 100 PPODA: 0 IPEGA, 90:10, 80:20, 70:30, 60:40, 50:50, and 0:100. Formulations with 10% and above of IPEGA were X-ray visible. Rheology showed that increasing the amount of IPEGA decreased the storage. Kinetic FT-IR studies indicate that the amphiphilic nature of the PEG backbone increased the reaction rate of the phase segregated reactants. Second order reaction constant modeling showed a change in initial reaction rate from 0.0029 to 0.0187 (M sec)(-1) from the 10% to 50% IPEGA formulations respectively.


The Interrelationship between Abscisic Acid and Reactive Oxygen Species Plays a Key Role in Barley Seed Dormancy and Germination.
Seed dormancy is one of the adaptive responses in the plant life cycle and an important agronomic trait. Reactive oxygen species (ROS) release seed dormancy and promote seed germination in several cereal crops; however, the key regulatory mechanism of ROS-mediated seed dormancy and germination remains controversial. Here, we focused on the relationship between hydrogen peroxide (a ROS) and abscisic acid (ABA) in dormant and non-dormant barley seeds. The hydrogen peroxide (H2O2) level produced in barley seed embryos after imbibition was higher in non-dormant seeds than in dormant seeds. H2O2 regulated the ABA content in the embryos through ABA-8'-hydroxylase, an ABA catabolic enzyme. Moreover, compared with non-dormant seeds, in dormant seeds the activity of NADPH oxidase, which produces ROS, was lower, whereas the activity of catalase, which is a H2O2 scavenging enzyme, was higher, as was the expression of HvCAT2. Furthermore, precocious germination of isolated immature embryos was suppressed by the transient introduction of HvCAT2 driven by the maize (Zea mays) ubiquitin promoter. HvCAT2 expression was regulated through an ABA-responsive transcription factor (HvABI5) induced by ABA. These results suggest that the changing of balance between ABA and ROS is active in barley seed embryos after imbibition and regulates barley seed dormancy and germination.


The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions.
There is evidence for the benefits of exercise training in persons with multiple sclerosis (MS). However, these benefits have primarily been established in individuals with mild-to-moderate disability (i.e., Expanded Disability Status Scale [EDSS] scores 1.0-5.5), rather than among those with significant mobility impairment. Further, the approaches to exercise training that have been effective in persons with mild-to-moderate MS disability may not be physically accessible for individuals with mobility limitations. Therefore, there is a demand for an evidence-base on the benefits of physically accessible exercise training approaches for managing disability in people with MS with mobility impairment. To conduct a systematic review of the current literature pertaining to exercise training in individuals with multiple sclerosis (MS) with severe mobility disability. Four electronic databases (PubMed, EMBASE, OvidMEDLINE, and PsychINFO) were searched for relevant articles published up until October 2016. The review focused on English-language studies that examined the effect of exercise training in people with MS with severe mobility disability, characterized as the need for assistance in ambulation or EDSS score ≥ 6.0. The inclusion criteria involved full-text articles that: (i) included participants with a diagnosis of MS; (ii) included primarily participants with a reported EDSS score ≥ 6.0 and/or definitively described disability consistent with this level of neurological impairment; and (iii) implemented a prospective, structured exercise intervention. Data were analyzed using a descriptive approach and summarized by exercise training modality (conventional or adapted exercise training), and by outcome (disability, physical fitness, physical function, and symptoms and participation). Initially, 1164 articles were identified and after removal of duplicates, 530 articles remained. In total, 512 articles did not meet the inclusion criteria. 19 articles were included in the final review. Five studies examined conventional exercise training (aerobic and resistance training), and thirteen studies examined adapted exercise modalities including body-weight support treadmill training (BWSTT), total-body recumbent stepper training (TBRST), and electrical stimulation cycling (ESAC). Outcomes related to mobility, fatigue, and quality of life (QOL) were most frequently reported. Two of five studies examining conventional resistance exercise training reported significant improvements in physical fitness, physical function, and/or symptomatic and participatory outcomes. Nine of 13 studies examining adapted exercise training reported significant improvements in disability, physical fitness, physical function, and/or symptomatic and participatory outcomes. There is limited, but promising evidence for the benefits of exercise training in persons with MS with severe mobility disability. Considering the lack of effective therapeutic strategies for managing long-term disability accumulation, exercise training could be considered as an alternative approach. Further research is necessary to optimize the prescription and efficacy of exercise training for adults with MS with severe mobility disability.


Effect of artificial endolymph injection into the cochlear duct on perilymph potassium.
To investigate the relationship between endolymphatic hydrops and perilymphatic potassium. 20 pigmented guinea pigs were used: 10 for scala vestibuli study and 10 for scala tympani study. Acute endolymphatic hydrops was produced by microinjection of an artificial endolymph into the scala media. Injections were performed in the second turn at rates up to 500 nl/min for a period of 10 min. The injection volume was up to 5 microl. Endocochlear potential (EP) was monitored during injections. Simultaneous with the injections, the potassium concentrations in scala vestibuli (K(SV)) or tympani (K(ST)) perilymph were measured with ion-sensitive double-barreled microelectrodes sealed into in the scalae in the 3rd turn with cyanoacrylate glue. For endolymphatic injections of <or=3 microl, perilymphatic K(SV) and K(ST) changes were generally small. With larger volume injections, substantial increases in both K(ST) and K(SV) were observed, with larger increases observed in K(SV) compared to K(ST). An increase of perilymph potassium ion concentration is associated with endolymphatic hydrops and the perilymphatic increase could contribute to the inner ear dysfunction of patients with Ménière's disease. Although mild hydrops may not cause perilymphatic changes, extended hydrops may increase perilymphatic K which could contribute to vertigo and/or hearing loss during the attack.


Effects of 1,25(OH)2 D3 and 25(OH)D3 on C2C12 Myoblast Proliferation, Differentiation, and Myotube Hypertrophy.
An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2 D by 1α-hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2 D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . We show that myoblasts not only responded to 1,25(OH)2 D3 , but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2 D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2 D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α-hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2 D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2 D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2 D3 . J. Cell. Physiol. 231: 2517-2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.


Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.
Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P < 0.0001). During progressive graded ischemia, the development of IC (percentage of total hearts) was similar in both EXAC and EX hearts; the only significant difference was confined to the 1- vs. 2-mo groups. The onset of IC was delayed in the EXAC hearts and, on reperfusion, recovery, particularly of DP, was significantly improved in the latter. After TI, EXAC hearts retained 30% of the ATP pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.


[Immune hemolytic diseases caused by irregular antibodies and its research advance in clinic].
The irregular antibodies are other than antibodies from ABO blood group system because of pregnancies and blood transfusions, clinical autoimmune, drug-induced etc. The irregular IgG and/or IgM antibodies emerge and lead to the difficult identification of clinical blood type, difficult matching of blood, hemolytic disease of newborn, hemolytic transfusion reaction, and so on. It is very necessary to screen and identify the irregular antibodies before blood transfusion or antepartum. For some difficult identifying samples, some detections on serological level should be done firstly, combining with flow cytometry analysis, the difficult-matching patients' genotypes and fetal genotypes were detected by molecular biology techniques such as PCR and PCR-SSP in order to further predict fetal hemolytic disease of newborn and to provide the right blood to difficult-matching patients, and free fetal DNA extracted from maternal plasma. So that some measures must early be taken for clinical prevention and treatment to reduce immune hemolytic reactions. In this paper, the emergence of irregular antibodies, species, laboratory testing, pathogenesis, clinical symptoms and the current research are reviewed.


Rewiring of posttranscriptional RNA regulons: Puf4p in fungi as an example.
It has been increasingly clear that changes in gene regulation play important roles in physiological and phenotypic evolution. Rewiring gene-regulatory networks, i.e., alteration of the gene-regulation system for different biological functions, has been demonstrated in various species. Posttranscriptional regulons have prominent roles in coordinating gene expression in a variety of eukaryotes. In this study, using Puf4p in fungi as an example, we demonstrate that posttranscriptional regulatory networks can also be rewired during evolution. Although Puf4p is highly conserved in fungi, targets of the posttranscriptional regulon are functionally diverse among known fungal species. In the Saccharomycotina subdivision, target genes of Puf4p mostly conduct function in the nucleolus; however, in the Pezizomycotina subdivision, they are enriched in the mitochondria. Furthermore, we demonstrate different regulation efficiencies of mitochondrial function by PUF proteins in different fungal clades. Our results indicate that rewiring of posttranscription regulatory networks may be an important way of generating genetic novelties in gene regulation during evolution.


Restoring the intrinsic optical properties of CVD-grown MoS2 monolayers and their heterostructures.
This study investigated the intrinsic optical properties of MoS2 monolayers and MoS2/WS2 van der Waals (vdW) heterostructures, grown using chemical vapor deposition. To understand the effect of the growth substrate, samples grown on a SiO2/Si surface were transferred and suspended onto a porous substrate. This transfer resulted in a blue shift of the excitonic photoluminescence (PL) peak generated by MoS2 monolayers, together with an intensity increase. The blue shift and the intensity increase are attributed to the release of lattice strain and the elimination of substrate-induced non-radiative relaxation, respectively. This suspension technique also allowed the observation of PL resulting from interlayer excitons in the MoS2/WS2 vdW heterostructures. These results indicate that the suppression of lattice strain and non-radiative relaxation is essential for the formation of interlayer excitons, which in turn is crucial for understanding the intrinsic physical properties of vdW heterostructures.


Patient Activation: A Key Component of Successful Advance Care Planning.
Background: Patient activation-or knowledge, confidence, and skill managing overall health-is associated with improved health behaviors such as exercise; it is unknown whether it is associated with advance care planning (ACP). Objective: To determine whether patient activation is associated with ACP. Design: This is a cross-sectional study. Setting/Subjects: A total of 414 veterans (≥60 years) with serious and chronic illness enrolled in an ACP trial. Measures: Patient characteristics and self-report surveys included the validated 13-item patient activation measure (PAM, five-point Likert) (e.g., "Taking an active role in your own healthcare is the most important factor…") categorized into four levels (e.g., Level 1: "disengaged and overwhelmed" to Level 4: "maintaining behaviors"). ACP was measured with the ACP Engagement Survey including 57-item process scores (i.e., knowledge, contemplation, self-efficacy, readiness, 5-point Likert scale) and 25-item action scores (i.e., surrogate designation, yes/no items). Associations were determined with linear regression. Results: Participants were 71.1 ± 7.8 years of age, 43% were non-white, 9% were women, and 20% had limited health literacy. Higher PAM levels were associated with higher finances, having adult children, lower comorbidity, and more social support (p < 0.05). After adjusting for these characteristics, higher PAM (Level 4 vs. Level 1) was associated with higher ACP engagement (ACP process scores, 2.8 ± 0.7 vs. 3.8 ± 0.7 and action scores 9.7 ± 4.4 vs. 15.1 ± 6.0, p < 0.001). Conclusions: Higher patient activation to manage one's overall healthcare is associated with higher engagement in ACP. Interventions designed to foster general patient activation and self-efficacy to engage in health behaviors and disease management may also improve engagement in the ACP process.


A customizable, low-power, wireless, embedded sensing platform for resistive nanoscale sensors.
Customizable, portable, battery-operated, wireless platforms for interfacing high-sensitivity nanoscale sensors are a means to improve spatiotemporal measurement coverage of physical parameters. Such a platform can enable the expansion of IoT for environmental and lifestyle applications. Here we report a platform capable of acquiring currents ranging from 1.5 nA to 7.2 µA full-scale with 20-bit resolution and variable sampling rates of up to 3.125 kSPS. In addition, it features a bipolar voltage programmable in the range of -10 V to +5 V with a 3.65 mV resolution. A Finite State Machine steers the system by executing a set of embedded functions. The FSM allows for dynamic, customized adjustments of the nanosensor bias, including elevated bias schemes for self-heating, measurement range, bandwidth, sampling rate, and measurement time intervals. Furthermore, it enables data logging on external memory (SD card) and data transmission over a Bluetooth low energy connection. The average power consumption of the platform is 64.5 mW for a measurement protocol of three samples per second, including a BLE advertisement of a 0 dBm transmission power. A state-of-the-art (SoA) application of the platform performance using a CNT nanosensor, exposed to NO2 gas concentrations from 200 ppb down to 1 ppb, has been demonstrated. Although sensor signals are measured for NO2 concentrations of 1 ppb, the 3σ limit of detection (LOD) of 23 ppb is determined (1σ: 7 ppb) in slope detection mode, including the sensor signal variations in repeated measurements. The platform's wide current range and high versatility make it suitable for signal acquisition from resistive nanosensors such as silicon nanowires, carbon nanotubes, graphene, and other 2D materials. Along with its overall low power consumption, the proposed platform is highly suitable for various sensing applications within the context of IoT.


Light-stimulated bacterial production and amino acid assimilation by cyanobacteria and other microbes in the North Atlantic ocean.
We examined the contribution of photoheterotrophic microbes--those capable of light-mediated assimilation of organic compounds--to bacterial production and amino acid assimilation along a transect from Florida to Iceland from 28 May to 9 July 2005. Bacterial production (leucine incorporation at a 20 nM final concentration) was on average 30% higher in light than in dark-incubated samples, but the effect varied greatly (3% to 60%). To further characterize this light effect, we examined the abundance of potential photoheterotrophs and measured their contribution to bacterial production and amino acid assimilation (0.5 nM addition) using flow cytometry. Prochlorococcus and Synechococcus were abundant in surface waters where light-dependent leucine incorporation was observed, whereas aerobic anoxygenic phototrophic bacteria were abundant but did not correlate with the light effect. The per-cell assimilation rates of Prochlorococcus and Synechococcus were comparable to or higher than those of other prokaryotes, especially in the light. Picoeukaryotes also took up leucine (20 nM) and other amino acids (0.5 nM), but rates normalized to biovolume were much lower than those of prokaryotes. Prochlorococcus was responsible for 80% of light-stimulated bacterial production and amino acid assimilation in surface waters south of the Azores, while Synechococcus accounted for on average 12% of total assimilation. However, nearly 40% of the light-stimulated leucine assimilation was not accounted for by these groups, suggesting that assimilation by other microbes is also affected by light. Our results clarify the contribution of cyanobacteria to photoheterotrophy and highlight the potential role of other photoheterotrophs in biomass production and dissolved-organic-matter assimilation.


In vivo analysis of the 3' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: persistent infection in a transfected tamarin.
GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV.


Sitting and looking: a comparison of stability and visual exploration in infants with typical development and infants with motor delay.
This longitudinal study focused on the interaction of developing sitting postural control with look time, which served as a measure for cognitive processing. Twenty-eight typically developing infants and 16 infants with motor delays were evaluated using center-of-pressure measures to assess stability of sitting postural control and videography to assess look time at objects, at three progressive stages of sitting development. Results indicated that look time decreased significantly (p < .001) in conjunction with a significant increase in postural stability (p < .001) in both groups as sitting progressed to independence. Infants with motor delays showed significantly longer looks when compared to typical infants (p = .02) at the middle stage of sitting. We conclude that developmental changes in look time are related to changes in sitting postural control, and infants with motor delay may have greater difficulty looking during emerging postural control skills in sitting. Early interventionists may use look time as an indicator of sitting effort and cognitive processing during assessment and program planning.


Schistosomiasis: Still a Cause of Significant Morbidity and Mortality.
Tropical diseases remain severe threats to global health with acute or chronic debility. Public health issues are regularly monitored and reported by the WHO. Conditions with high prevalence and virulence such as Schistosomiasis or Malaria still need active treatment. Advances over the decades in the treatment and management of Schistosomiasis have reduced morbidity and mortality in patients. However, poverty, adverse environments, lack of education and awareness, with parasites and vectors that can thrive if uncontrolled, remain issues for the successful global eradication of Schistosomiasis. From the disease's discovery in 1850, the author relates historical details to its current status. Several countries previously affected, including Japan and Tunisia, have eliminated the disease while others seek the same goal. Africa remains the most severely affected continent with vulnerable women and children, although the infection persists in South America and the Far East of Asia as well. Realistic improvements for continuing health conditions are vogue and emphasized for those at risk or afflicted by the infection, illustrating success models of concerted efforts of extirpation. Constant proximity to infected water, with a parasite host, are hurdles in reducing exposure. Effective medication for acute treatment is available, and prophylaxis by vaccination is promising. Where endemic Schistosomiasis is prevalent, significant morbidity and mortality have far-reaching complications in multiple human organ systems, including irreversible pulmonary hypertension, renal, genitourinary, central nervous system conditions, and neoplasia. Two hundred and thirty million people are estimated to have contracted Schistosomiasis globally, with up to 700 million still at risk of infection, and 200,000 deaths occur annually. The disease may be more prevalent than thought after newer tests have shown increased sensitivity to pathological antigens. The author discusses infectivity risks, investigations, prognosis, treatment, and management, as well as morbidity and mortality.


The Effectiveness of the Personality Assessment Inventory With Feigned PTSD: An Initial Investigation of Resnick's Model of Malingering.
Malingered posttraumatic stress disorder (PTSD) poses a formidable clinical challenge because of the apparent ease in feigning PTSD. As an additional confound, some patients with genuine PTSD produce elevated profiles on feigning indicators that are difficult to distinguish from feigned PTSD. The current study utilized 109 inpatients from a trauma unit to examine whether the Personality Assessment Inventory and the Detailed Assessment of Posttraumatic Stress can effectively differentiate between genuine and feigned PTSD. As a primary focus, Resnick's model of malingered PTSD was evaluated with its three subtypes: pure malingering, partial malingering, and false imputation. They were tested on their ability to (a) effectively simulate PTSD and (b) avoid being classified as feigning. The partial malingering group proved to be the best feigning group in achieving these two goals. Overall, the Personality Assessment Inventory Malingering Index and Negative Distortion Scale were the most effective at identifying feigning.


Measurement of tumor cell cohesion and suppression of invasion by E- or P-cadherin.
Invasiveness of carcinomas was connected early to decreased cohesiveness and has more recently been associated with loss or decreased activity of E-cadherin. In the first thermodynamic measurements of cohesive intensities among malignant cells, we here find the cohesive intensities of Lewis lung carcinoma cells to fall within the range measured previously for cells from a series of noninvasive embryonic tissues. Thus, too-low cohesiveness is itself an insufficient explanation for invasiveness. Nevertheless, transfection-mediated cadherin expression sufficient to increase cohesiveness by as little as 26% suffices to greatly reduce invasion of aggregates of Lewis lung carcinoma cells into Matrigel. This property is not restricted to E-cadherin but is shared by P-cadherin. The same cadherin-transfected cells do not display this invasion suppression when plated sparsely, indicating that invasion-suppression activity of cadherins requires cell-cell contact. These facts are consistent with the invasion-suppression activity of cadherins resulting either from the physical restraint of increased cohesion per se or from another cadherin activity mediated through cell-cell contact.


A pilot study on prostate cancer risk and pro-inflammatory genotypes: pathophysiology and therapeutic implications.
Host genetic factors are crucial risk determinants for many human cancers. In this framework, an interesting model is represented by prostate cancer (PC), which is featured by a complex pathophysiology with a strong genetic component. Multiple genes seem to influence PC risk and several single nucleotide polymorphisms (SNPs) of candidate genes modifying PC susceptibility have been identified. It is noteworthy the potential association of common SNPs in pro-inflammatory genes with PC risk, since chronic inflammation is assumed to play a key role in prostate carcinogenesis. With the aim to identify candidate genes as an experimental basis to develop new strategies for both prevention and treatment of PC, we have investigated the potential role of common SNPs of a gene cluster (TLR4, TLR2, PTGS2 and 5-Lo), involved in innate and inflammatory response, in PC cases, age-matched controls and centenarians from Sicily. Six SNPs were genotyped and their association with PC risk determined. Statistical analysis evidenced a significant association of some pro-inflammatory gene SNPs with an increased risk of PC. Furthermore, significant differences were observed comparing the three groups in the combined presence of a "high responder" pro-inflammatory profile. Overall, the present results suggest the likely association of these SNPs and PC risk, clearly motivating the need of larger studies to confirm the role of these genes in PC development and/or progression.


Acute affective responses to prescribed and self-selected exercise intensities in young adolescent boys and girls.
This study examined the patterning of acute affective responses to prescribed and self-selected exercise intensities in a young adolescent population. Twenty-two young adolescents (13.3 +/- .33 years) completed a maximal exercise test to identify ventilatory threshold (VT). Participants then completed two prescribed intensities (one set above and one below the VT) and a self-selected intensity. Pre-, during, and postexercise affective valence was measured. Results revealed that during exercise, affective valence assessed by the Feeling Scale (FS) remained positive in the self-selected and low-intensity conditions but declined in the high-intensity condition. Postexercise FS responses rebounded to preexercise levels, eradicating divergent trends that occurred during exercise.


Reversing Ferroptosis Resistance in Breast Cancer via Tailored Lipid and Iron Presentation.
Ferroptotic cancer therapy is promising in many scenarios where traditional cancer therapies show a poor response. However, certain types of cancers lack the long-chain acyl-CoA synthetase 4 (ACSL4), a key modulator of ferroptosis, resulting in therapy resistance and tumor relapse. Because ACSL4 is in charge of the synthesis of ferroptotic lipids (e.g., arachidonoylphosphatidylethanolamine/PE-AA), we postulated that direct delivery of PE-AA may reverse ferroptosis resistance induced by ACSL4 deficiency. To further increase the ferroptosis sensitivity, we employed the ferrocene-bearing polymer micelles to co-load PE-AA with an FDA-approved redox modulator, auranofin (Aur), targeting the thioredoxin reductase. The presence of ferrocene enabled triggered cargo release and iron production, which can sensitize ferroptosis by boosting autoxidation-mediated PE-AA peroxidation. The micellar system could impair redox homeostasis and induce lipid peroxidation in ACSL4-deficient MCF-7 cells. Moreover, the tailored micelles potently induced ferroptosis in MCF-7 tumors in vivo, suppressed tumor growth, and increased the mice's survival rate. The current work provides a facile means for reversing the ferroptosis resistance in ACSL4-deficient tumors.


3-Fluoro-4-hexylthiophene as a building block for tuning the electronic properties of conjugated polythiophenes.
3-Fluoro-4-hexylthiophene has been prepared by a synthetic route involving perbromination of 3-hexylthiophene followed by protection of the 2- and 5-positions of thiophene by trimethylsilyl groups and bromine/fluorine exchange. As expected, 3-hexyl-4-fluorothiophene oxidizes at a higher potential than 3-hexylthiophene; however, all attempts to electropolymerize this new thiophenic monomer have remained unsuccessful. Three terthienyls containing 3-hexylthiophene, 3-fluoro-4-hexylthiophene, and 3-bromo-4-hexylthiophene as the median group have been synthesized and used as substrates for electropolymerization. The electronic properties of the starting terthienyls and the resulting polymers have been analyzed by cyclic voltammetry and UV-vis spectroscopy, and the effects of substitution of the median thiophene ring are discussed.


Text Messaging and Home Blood Pressure Monitoring for Patients with Uncontrolled Hypertension: Proposal for a Feasibility Pilot Randomized Controlled Trial.
A decrease in blood pressure, even modestly (ie, 2 mmHg), lowers cardiovascular morbidity and mortality. Low patient adherence to antihypertensive medication is the most significant modifiable patient-related barrier to achieving controlled blood pressure. Preliminary studies have shown that SMS text messaging and home blood pressure monitoring (HBPM) can be effective in promoting medication adherence and blood pressure control. The best strategy to engage with older patients of low socioeconomic status who are low adopters of technology and disproportionally affected by uncontrolled hypertension is still unknown. The objective of this study is to improve blood pressure control in the older, low socioeconomic status population. The study will test two aims: First, we aim to evaluate the feasibility of conducting a randomized controlled trial by using an SMS-based approach among nonadherent, older patients of low socioeconomic status who have uncontrolled hypertension. Feasibility will be assessed in terms of recruitment rates per month (primary outcome); patient acceptability will be evaluated by monitoring retention rates and SMS response rates and using the validated Systems Usability Scale (secondary outcomes). Second, we aim to estimate the effects of the SMS approach on lowering blood pressure and adherence to antihypertensive medications. We will recruit 24 patients of low socioeconomic status with uncontrolled hypertension (systolic BP>140 mmHg or diastolic BP>90 mmHg) showing low medication adherence and taking at least two antihypertensives, who have presented to two outpatient clinics of Wake Forest Baptist Health (Winston Salem, North Carolina, USA). Participants will be randomly assigned to either SMS and HBPM (n=12) or usual care and HBPM (n=12) intervention. Clinicians adjusting the patients' medications will be blinded to the study assignment. Text messages will be sent from a secure platform to assess medication adherence and HBPM on a weekly basis. The content and delivery frequency of the proposed SMS intervention are based on input from three focus groups conducted in Spring 2019. Participants in both study arms will receive education on HBPM and using an HBPM device. We hypothesize that we will successfully recruit 24 participants and the intervention will be acceptable to the participants. It will also improve medication adherence (assessed by question Medication Adherence Questionnaire scores) and blood pressure control. Our study was funded in July 2020. As of May 2021, we have enrolled 6 participants. Our findings will help design a larger efficacy trial to advance the field of eHealth delivery systems particularly for older adults of low socioeconomic status. This study addresses a highly significant topic and targets a population of high morbidity and mortality that has been traditionally underrepresented in clinical trials. ClinicalTrials.gov NCT03596242; https://clinicaltrials.gov/ct2/show/NCT03596242. PRR1-10.2196/18984.


Conflict and societal change in late prehistoric eastern North America.
As recently as the 1980s, archeologists focusing on prehistoric eastern North America paid little attention to intergroup conflict. Today the situation is quite different, as indicated by this Special Issue. Archeologists now face three principal challenges: to document the temporal and spatial distribution of evidence of conflict; to identify the cultural and environmental conditions associated with variation in the nature and frequency of warfare over long periods of time and large geographical areas; and to determine the extent to which intergroup tensions contributed to or resulted from changes in sociopolitical complexity, economic systems, and population size and distribution. We present data from habitation and mortuary sites in the Eastern Woodlands, notably the midcontinent, that touch on all three issues. Palisaded sites and victims of attacks indicate the intensity of conflicts varied over time and space. Centuries-long intervals of either high or low intergroup tensions can be attributed to an intensification or relaxation of pressure on resources that arose in several ways, such as changes in local population density; technological innovations, including subsistence practices; and the natural environment.


Assessment of central venous physiology of Fontan circulation using peripheral venous pressure.
Elevated central venous pressure is a major cause of morbidity and mortality after the Fontan operation. The difference between mean circulatory filling pressure and central venous pressure, a driving force of venous return, is important in determining dynamic changes in central venous pressure in response to changes in ventricular properties or loading conditions. Thus, noninvasive central venous pressure and mean circulatory filling pressure estimation may contribute to optimal management in patients undergoing the Fontan operation. We tested the hypothesis that central venous pressure and mean circulatory filling pressure in those undergoing the Fontan operation can be simply estimated using peripheral venous pressure and arm equilibrium pressure, respectively. This study included 30 patients after the Fontan operation who underwent cardiac catheterization (median 8.6, 3.4-42 years). Peripheral venous pressure was measured at the peripheral vein in the upper extremities. Mean circulatory filling pressure was calculated by the changes of arterial pressure and central venous pressure during the Valsalva maneuver. Arm equilibrium pressure was measured as equilibrated venous pressure by rapidly inflating a blood pressure cuff to 200 mm Hg. Central venous pressure and peripheral venous pressure were highly correlated (central venous pressure = 1.6 + 0.68 × peripheral venous pressure, R = 0.86, P < .0001). Stepwise multivariable regression analysis showed that only peripheral venous pressure was a significant determinant of central venous pressure. Central venous pressure was accurately estimated using regression after volume loading by contrast injection (R = 0.82, P < .0001). In addition, arm equilibrium pressure measurements were highly reproducible and robustly reflected invasively measured mean circulatory filling pressure (mean circulatory filling pressure = 9.1 + 0.63 × arm equilibrium pressure, R = 0.88, P < .0001). Central venous pressure and mean circulatory filling pressure can be noninvasively estimated by peripheral venous pressure and arm equilibrium pressure, respectively. This should help clarify unidentified Fontan pathophysiology and the mechanisms of Fontan failure progression, thereby helping construct effective tailor-made approaches to prevent Fontan failure.


Palladium complexes of N-heterocyclic carbenes displaying an unsymmetrical N-alkylfluorenyl/N'-aryl substitution pattern and their behaviour in Suzuki-Miyaura cross coupling.
A series of new Pd-PEPPSI complexes containing imidazolylidene ligands with a mixed 9-alkyl-9-fluorenyl/aryl N,N'-substitution pattern have been synthesised. Single crystal X-ray diffraction studies were carried out for four complexes, which revealed that the N-heterocyclic carbene ligands display a semi-open, unsymmetrical space occupancy about the metal. Despite their particular unsymmetrical shape, the new complexes were found to perform as well in Suzuki-Miyaura cross coupling (dioxane, 80 °C) as previously reported, highly active analogues bearing two sterically protecting 9-alkylfluorenyl substituents. They were further found to be considerably more active than the standard Pd-PEPPSI complexes [PdCl2IMes(pyridine)] and [PdCl2IPr(pyridine)]. Surprisingly, unlike the latter, the unsymmetrical complexes of this study were practically inactive in isopropanol at 80 °C. Under these conditions the complexes appear to decompose with formation of non-stabilised nanoparticles.


Modulation of senoinflammation by calorie restriction based on biochemical and Omics big data analysis.
Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs. We have previously proposed a novel concept of senescent (seno)-inflammation and provided its frameworks. This review summarizes senoinflammation concept and additionally elaborates modulation of senoinflammation by calorie restriction (CR). Based on aging and CR studies and systems-biological analysis of Omics big data, we observed that senescence associated secretory phenotype (SASP) primarily composed of cytokines and chemokines was notably upregulated during aging whereas CR suppressed them. This result further strengthens the novel concept of senoinflammation in aging process. Collectively, such evidence of senoinflammation and modulatory role of CR provide insights into aging mechanism and potential interventions, thereby promoting healthy longevity. [BMB Reports 2019; 52(1): 56-63].


Approaches to the measurement of the in vivo response to factor VIII concentrate infusion.
The in vivo response to the infusion of 12 lots of Factor VIII Concentrate was determined in a five Centre collaborative study. The principal aim of the study was to compare the responses obtained, after infusion into a single haemophiliac, of several lots of Factor VIII Concentrate made by a newly licensed process with those obtained after the infusion of several lots of Factor VIII Concentrate made by a previous process. Factor VIII Concentrates made by two other manufacturers were also evaluated. There was considerable inter-laboratory variation in the results obtained for the Factor VIII:C content of both the Factor VIII Concentrates and the ex vivo plasma samples. However, on pooling the data, the mean in vivo recovery was not statistically different from the expected response based on the potency assigned by the manufacturers. These data indicate that the results from a single laboratory may not be reliable in ascertaining either the in vitro or the in vivo potency of a particular lot of Factor VIII Concentrate and suggest that in the absence of a Factor VIII inhibitor, the in vitro and in vivo potency of a particular lot of Factor VIII Concentrate should be ascertained by several laboratories and the results pooled. Such pooled information then can be used to predict reliably the in vivo recovery of factor VIII: C activity without resorting to a formal in vivo response study.


Amygdala and hippocampal volumes in relatives of patients with bipolar disorder: a high-risk study.
Bipolar disorders (BD) have a strong genetic underpinning, yet no biological vulnerability markers for BD have yet been identified. To test whether amygdala or hippocampal volumes represent an endophenotype for BD, we measured mesiotemporal volumes in young affected and unaffected relatives of patients with BD (high-risk design). High-risk participants (aged 15 to 30 years) were recruited from families multiply affected with BD. They included 20 affected and 26 unaffected offspring of parents with primary mood disorders, matched by age and sex with 31 control subjects without a personal or family history of psychiatric disorders. Amygdala and hippocampal volumes were measured on 1.5 Tesla 3-dimensional anatomical magnetic resonance images using standard methods. We found comparable amygdala and hippocampal volumes among unaffected relatives, affected high-risk patients, and control subjects. The exclusion of 6 medicated patients did not change the results. There were no differences between participants with family history of BD I, compared with participants with family history of BD II, or between subjects with family history of BD with psychotic symptoms, compared with subjects with family history of BD without psychotic symptoms. Hippocampal and amygdala volume abnormalities were absent in unaffected and affected relatives of patients with BD and thus did not meet criteria for endophenotype.


Correlates of HIV-status awareness among adults in Nairobi slum areas.
The prevalence of HIV in the adult population in slum areas in Nairobi, Kenya, is higher than for residents in the city as a whole. This disparity suggests that the characteristics of slum areas may adversely influence the HIV-prevention strategies directed at reducing the national prevalence of HIV. The objective of the study was to identify some of the sociodemographic and behavioural correlates of HIV-status awareness among the adult population of two slums in Nairobi. In a household-based survey conducted by the African Population and Health Research Center (APHRC), 4 767 men and women aged between 15 and 54 years were randomly sampled from two slums (Korogocho and Viwandani) in Nairobi and data were collected on the social and health context of HIV and AIDS in these settlements. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with HIV-status awareness. The proportion of respondents that had ever been tested and knew their HIV status was 53%, with the women having greater awareness of their HIV status (62%) than the men (38%). Awareness of HIV status was significantly associated with age, sex, level of education, marital status and slum of residence. The lower level of HIV-status awareness among the men compared with the women in the slums suggests a poor uptake of HIV-testing services by males. Innovative strategies are needed to ensure greater access and uptake of HIV-testing services by the younger and less-educated residents of these slums if the barriers to HIV-status awareness are to be overcome.


Inhibition of nucleic acid and protein synthesis mouse spleen cells in vitro by azathioprine.
The effect of azathioprine on macromolecular biosynthesis was studied in mouse spleen cells cultured in vitro. The rate of incorporation of (3)H-thymidine, (3)H-uridine, and (14)C-leucine into acid-insoluble material was used to measure deoxyribonucleic acid, ribonucleic acid, and protein synthesis. Results indicate that azathioprine inhibited nucleic acid and protein synthesis at levels which did not decrease cell viability.


A community-engaged cardiovascular health disparities research training curriculum: implementation and preliminary outcomes.
To overcome cardiovascular disease (CVD) disparities impacting high-risk populations, it is critical to train researchers and leaders in conducting community-engaged CVD disparities research. The authors summarize the key elements, implementation, and preliminary outcomes of the CVD Disparities Fellowship and Summer Internship Programs at the Johns Hopkins University Schools of Medicine, Nursing, and Bloomberg School of Public Health. In 2010, program faculty and coordinators established a transdisciplinary CVD disparities training and career development fellowship program for scientific investigators who desire to conduct community-engaged clinical and translational disparities research. The program was developed to enhance mentorship support and research training for faculty, postdoctoral fellows, and predoctoral students interested in conducting CVD disparities research. A CVD Disparities Summer Internship Program for undergraduate and preprofessional students was also created to provide a broad experience in public health and health disparities in Baltimore, Maryland, with a focus on CVD. Since 2010, 39 predoctoral, postdoctoral, and faculty fellows have completed the program. Participating fellows have published disparities-related research and given presentations both nationally and internationally. Five research grant awards have been received by faculty fellows. Eight undergraduates, one postbaccalaureate, and two medical professional students representing seven universities have participated in the summer undergraduate internship. Over half of the undergraduate students are applying to or have been accepted into medical or graduate school. The tailored CVD health disparities training curriculum has been successful at equipping varying levels of trainees (from undergraduate students to faculty) with clinical research and public health expertise to conducting community-engaged CVD disparities research.


Quantitative energy dispersive X-ray microanalysis of electron beam-sensitive alloyed nanoparticles.
An energy dispersive X-ray spectrometry (EDXS) method is developed to evaluate the composition of alloyed nanoparticles (NPs) where one of the alloying elements is removed under the electron beam during microanalysis with a transmission electron microscope (TEM). The method is demonstrated for alloyed Au-Ag NPs of a diameter ranging from 6 to 20 nm produced by laser evaporation of a water-suspended Ag-Au powder mixture of varying composition. Series of EDXS spectra are recorded for 30 NPs from samples with five different Ag:Au ratios revealing Ag depletion from NPs during electron irradiation. By studying the evolution of NPs composition as a function of dose, the initial Ag content for each NP is extrapolated. The rate of Ag depletion is discussed in terms of sputtering and knock-on damage. On average, approximately one Ag atom is lost from the NP for each Ag L X-ray detected. To assess the limitations of microanalysis in these sensitive nanoscale structures, the concept of detectability limit is adapted to our method. This benchmark is then evaluated for Ag in Au-Ag NPs of various sizes and acquisition times. This study should be regarded as a guide for the design of analytical TEM measurements of beam-sensitive NPs.


Different differences: the use of 'genetic ancestry' versus race in biomedical human genetic research.
This article presents findings from our ethnographic research on biomedical scientists' studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetic analysis. Their method allows them to operationalize their concept of 'genetic ancestry' without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software's algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease.We introduce the concept of'genome geography' to analyze how some researchers studying human genetic variation'locate' stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Nevertheless, we also highlight the slipperiness of genome geography and the tenacity of race and race concepts.


Exocrine pancreas in type 1 and type 2 diabetes: different patterns of fibrosis, metaplasia, angiopathy, and adiposity.
The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed systematic analysis of wellpreserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20), type 2 diabetes (T2D, n = 25), and donors with no diabetes (ND, n = 74). Among ND donors, we found that acinar-to-ductal metaplasia (ADM), angiopathy, and pancreatic adiposity increased with age, while ADM and adiposity also increased with BMI. Compared to age- and sex-matched ND organs, T1D pancreata had greater acinar atrophy and angiopathy with fewer intralobular adipocytes. T2D pancreata had greater ADM, angiopathy, and total T lymphocytes, but no difference in adipocyte number, compared to ND organs. While total pancreatic fibrosis was increased in both T1D and T2D, the pattern was different with T1D pancreata having greater periductal and perivascular fibrosis, whereas T2D pancreata had greater lobular and parenchymal fibrosis. Thus, the exocrine pancreas undergoes distinct changes as individuals age or develop T1D or T2D.


Primary retroperitoneal transitional cell carcinoma presenting as a dumb-bell tumour.
We report a retroperitoneal transitional cell carcinoma arising from the primitive urogenital remnants of a 56-year-old married Indian woman. She presented with a huge cystic mass in the hypogastrium and right iliac fossa, which extended into the right thigh as a massive dumb-bell tumour. On exploration, it was found not to be arising from any known retroperitoneal structure. The mass was excised, and the histopathology confirmed transitional cell carcinoma with positive margins. Though she received postoperative chemotherapy with cyclophosphamide, adriamycin and cisplatin, she developed extensive local recurrence and hepatic secondaries, and succumbed to the disease after ten months of follow-up. We highlight the rarity of the disease, its atypical presentation as a cystic dumb-bell lump, its diagnostic challenges and aggressive behaviour, and review the literature on primary retroperitoneal transitional cell carcinomas.


[Lingual actinomycosis: diagnostic problems. Review of the literature].
Actinomycosis of the cervicofacial area is a rare infection with a difficult clinical diagnosis. We report a case of lingual actinomycosis which was diagnosed after a long remission with empirical antibiotic treatment, two years after onset. The clinical characteristics, differential diagnosis, and therapeutic options in this unusual infection are discussed.


Positive emotion enhances association-memory.
The influence of emotion on association-memory is often attributed to arousal, but negative stimuli are typically used to test for these effects. While prior studies of negative emotion on association-memory have found impairments, theories suggest that positive emotion may have a distinct effect on memory, and may lead to enhanced association-memory. Here we tested participants' memory for pairs of positive and neutral words using cued recall, supplemented with a mathematical modeling approach designed to disentangle item- versus association-memory effects that may otherwise confound cued-recall performance. In our main experiment, as well as in additional supplemental experiments, we consistently found enhanced association-memory due to positive emotion. Interestingly, we observed enhanced association-memory in pairs composed of two positive words, but not in pairings of one positive and one neutral word, indicating that this enhancement may only when a sufficient amount of positive emotion is present. These results provide further evidence that positive information is processed differently than negative and that, when examining association formation, valence as well as arousal must be considered. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Acromial stress fracture following reverse total shoulder arthroplasty: incidence and predictors.
Increased use of reverse total shoulder arthroplasty (RTSA) has led to an understanding of unique complications such as acromial stress fractures (ASFs). The factors associated with ASFs are not fully known. This study investigates the incidence and predictors of ASFs following RTSA. All RTSAs performed at a single tertiary referral hospital were retrospectively reviewed. ASF findings were classified as a definitive acromial or scapular spine stress fracture based on radiographic findings or stress reaction based on clinical findings (pain and tenderness at the acromion or acromial spine) without radiographic changes. Preoperative and postoperative radiographs were reviewed for radiographic predictors of postoperative acromial stress pathology. Clinical factors and implant characteristics were also investigated. Between September 2010 and January 2017, a total of 1170 RTSAs were performed, with 958 cases (81.9%) having at least 3 months' clinical follow-up (mean, 407 days; range, 90-1698 days). There were 40 ASFs (4.2%) and 61 acromial stress reactions (6.4%). For fractures and reactions, symptom onset averaged 8.8 and 7.3 months (P = .37), respectively, with durations of 4.5 and 2.9 months (P = .02), respectively, following RTSA. Independent predictors of acromial stress pathology were female sex, decreased change in deltoid length, and increased preoperative glenohumeral center-of-rotation medialization. Acromion-related symptoms are common following RTSA. Female patients with increased preoperative center-of-rotation medialization had an increased incidence of ASFs. Although this study establishes which patients are at risk of ASFs, methods for prevention of ASFs in these patients remain unclear.


Acetylcholine receptors in the human retina.
Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3H-propylbenzilylcholine mustard (3H-PrBCM) to label muscarinic receptors. 3H- or 125I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. The work reported here is consistent with earlier data on cholinergic neurons in the retina of other mammalian species, as well as with previous work on the psychophysical effects of cholinergic agonists on human vision. This study provides evidence for cholinergic neurotransmission in the human retina.


Temporary abdominal closure.
The increasing recognition of abdominal compartment syndrome's adverse effect on patient outcome has been coupled with our expanding knowledge of techniques of temporary abdominal closure. Temporary abdominal closure can be used prophylactically to prevent abdominal compartment syndrome developing and more commonly in the treatment of patients with progressing or advanced abdominal compartment syndrome. The preferred technique involves a negative suction dressing protecting the fascial and skin edges, collecting intraperitoneal fluid and reducing contamination. Attempts of early closure will facilitate recovery.


Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke.
Several lines of evidence indicate that the extent of ischemic injury is not defined immediately after arterial occlusion, but that infarction expands over time. Episodes of spreading depression have been linked to this secondary increase in infarct volume. Tissue bordering the infarction fails to repolarize following spreading depression and is incorporated into the lesion. The result is that ischemic infarctions expand stepwise after each episode of spreading depression. Another line of evidence has demonstrated that gap junction blockers effectively inhibit spreading depression. These observations suggest that traffic of potentially harmful cytosolic messengers between ischemic cells and surrounding nonischemic cells might cause amplification of injury in focal stroke. It is therefore conceivable that minimizing gap junction permeability might reduce final infarct volume. To test this hypothesis, the authors pretreated rats with the gap junction blocker, octanol, before occluding the middle cerebral artery and compared the sizes of the ischemic lesions to those in rats that received the vehicle, dimethyl sulfoxide, prior to arterial occlusion. Histopathological analysis was performed 24 hours later. The 12 octanol-treated animals showed a significantly decreased mean infarction volume (80 +/- 16 mm3) compared with the nine control rats (148 +/- 9 mm3). In a separate set of experiments, the frequency of experimentally induced waves of spreading depression was evaluated after octanol treatment. Octanol pretreatment resulted in complete inhibition in two of nine animals, transient inhibition in five, and no inhibition in two. The results indicate that gap junction inhibitors, when not limited by toxicity, have significant therapeutic potential in the treatment of acute stroke.


Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells.
The Gram-negative bacterium Helicobacter pylori is the most common bacterial pathogen in humans, infecting 24-79% of the population at any time. Standard eradication protocols involve multi-target therapy including combinations of antibiotics, which has promoted the emergence of resistant strains. To address this challenge, we prepared antibiotic-free colloidal nanoparticles designed to interfere with the adhesion mechanisms of H. pylori and thus prevent both the onset and recurrence of infection. Our colloidal particles comprised a nanocapsule (NC) formulation based on an oil-core nanoemulsion co-stabilized with lysozyme and lecithin, coated with negatively charged low-molecular-weight (DexS40-NC) or high-molecular-weight (DexS500-NC) dextran sulfate, or positively charged chitosan (CSHMC+30-NC). The oil core of all NC formulations was also loaded with curcumin, a model lipophilic phytochemical substance with well-documented anti-inflammatory and anti-tumor activities. Our proof-of-principle experiments showed that the DexS40-NC formulation inhibited the adhesion of H. pylori to AGS stomach cells in a dose-dependent manner. DexS40-NC achieved more potent inhibition than DexS500-NC or uncoated control nanoemulsions, whereas the effect of CSHMC+30-NC was not clear-cut given the ability of this formulation to aggregate bacteria. DexS40-NC, unlike DexS500-NC, showed no cytotoxic effects against AGS, Caco-2, or MDCK cell lines. DexS40-NC is, therefore, a promising candidate for further development as an alternative or complementary therapy against H. pylori infections.


COVID-19 Vaccination Personas in Yemen: Insights from Three Rounds of a Cross-Sectional Survey.
We used three rounds of a repeated cross-sectional survey on COVID-19 vaccination conducted throughout the entire territory of Yemen to: (i) describe the demographic and socio-economic characteristics associated with willingness to be vaccinated; (ii) analyse the link between beliefs associated with COVID-19 vaccines and willingness to be vaccinated; and (iii) analyse the potential platforms that could be used to target vaccine hesitancy and improve vaccine coverage in Yemen. Over two-thirds of respondents were either unwilling or unsure about vaccination across the three rounds. We found that gender, age, and educational attainment were significant correlates of vaccination status. Respondents with better knowledge about the virus and with greater confidence in the capacity of the authorities (and their own) to deal with the virus were more likely to be willing to be vaccinated. Consistent with the health belief model, practising one (or more) COVID-19 preventative measures was associated with a higher willingness to get a COVID-19 vaccination. Respondents with more positive views towards COVID-19 vaccines were also more likely to be willing to be vaccinated. By contrast, respondents who believed that vaccines are associated with significant side effects were more likely to refuse vaccination. Finally, those who relied on community leaders/healthcare workers as a trusted channel for obtaining COVID-19-related information were more likely to be willing to be vaccinated. Strengthening the information about the COVID-19 vaccination (safety, effectiveness, side effects) and communicating it through community leaders/healthcare workers could help increase the COVID-19 vaccine coverage in Yemen.


Recent Developments in Carbon-Based Nanocomposites for Fuel Cell Applications: A Review.
Carbon-based nanocomposites have developed as the most promising and emerging materials in nanoscience and technology during the last several years. They are microscopic materials that range in size from 1 to 100 nanometers. They may be distinguished from bulk materials by their size, shape, increased surface-to-volume ratio, and unique physical and chemical characteristics. Carbon nanocomposite matrixes are often created by combining more than two distinct solid phase types. The nanocomposites that were constructed exhibit unique properties, such as significantly enhanced toughness, mechanical strength, and thermal/electrochemical conductivity. As a result of these advantages, nanocomposites have been used in a variety of applications, including catalysts, electrochemical sensors, biosensors, and energy storage devices, among others. This study focuses on the usage of several forms of carbon nanomaterials, such as carbon aerogels, carbon nanofibers, graphene, carbon nanotubes, and fullerenes, in the development of hydrogen fuel cells. These fuel cells have been successfully employed in numerous commercial sectors in recent years, notably in the car industry, due to their cost-effectiveness, eco-friendliness, and long-cyclic durability. Further; we discuss the principles, reaction mechanisms, and cyclic stability of the fuel cells and also new strategies and future challenges related to the development of viable fuel cells.


Nebrodeolysin, a novel hemolytic protein from mushroom Pleurotus nebrodensis with apoptosis-inducing and anti-HIV-1 effects.
A novel hemolysin was isolated from the edible mushroom Pleurotus nebrodensis by ion exchange and gel filtration chromatography on DEAE-Sepharose and Sephacryl S-100. The hemolysin from Pleurotus nebrodensis hemolysin (nebrodeolysin) is a monomeric protein with a molecular weight of approximately 27 kDa as determined by gel filtration and SDS-PAGE. Nebrodeolysin exhibited remarkable hemolytic activity towards rabbit erythrocytes and caused efflux of potassium ions from erythrocytes. Subsequently, this hemolysin showed strong cytotoxicity against Lu-04, Bre-04, HepG2, L929, and HeLa cells. It was also found that this hemolysin induced apoptosis in L929 and HeLa cells as evidenced by microscopic observations and DNA ladder, respectively. Moreover, this hemolysin was shown to possess anti-HIV-1 activity in CEM cell culture.


Variation in marital quality in a national sample of divorced women.
Previous work has compared marital quality between stably married and divorced individuals. Less work has examined the possibility of variation among divorcés in trajectories of marital quality as divorce approaches. This study addressed that hole by first examining whether distinct trajectories of marital quality can be discerned among women whose marriages ended in divorce and, second, the profile of women who experienced each trajectory. Latent class growth analyses with longitudinal data from a nationally representative sample were used to "look backward" from the time of divorce. Although demographic and socioeconomic variables from this national sample did not predict the trajectories well, nearly 66% of divorced women reported relatively high levels of both happiness and communication and either low or moderate levels of conflict. Future research including personality or interactional patterns may lead to theoretical insights about patterns of marital quality in the years leading to divorce.