Frequency of familial pituitary adenoma syndromes among patients with functioning pituitary adenomas in a reference outpatient clinic.
Pituitary adenomas (PA) occur mainly as sporadic disease, but familial syndromes are found in approximately 5% of cases. Identification of these syndromes is important in order to diagnose individuals at risk at an earlier stage. To evaluate the frequency of familial PA in a reference outpatient clinic devoted to PA treatment and to identify family members suspected to have pituitary disease. Patients with PA were interviewed with respect to the presence of family members with diagnosis of PA or with signs or symptoms suggestive of them. The family members who had a clinical picture suggestive of pituitary disease were further evaluated in an attempt to identify new PA cases. In families with familial disease, the AIP gene was sequenced. 262 patients were evaluated and familial syndrome was found in 13 (5%). Ten (3.8%) patients had familial isolated PA (FIPA) and three (1.2%) had multiple endocrine neoplasia type 1. After evaluation of family members' symptomatology, 110 were considered suspected of having pituitary disease, but only 24 participated in the study. Of these 24, 1 was diagnosed with a corticotropinoma. AIP mutations were found in 20% of FIPA families. We found a frequency of familial PA similar to that previously described, as well as a similar frequency of AIP mutations among FIPA families. An active search of the affected family members was able to identify one case of Cushing´s disease. Patients should be aware of pituitary disease's clinical picture to identify possibly affected family members.


Was Kaposi's sarcoma-associated herpesvirus introduced into China via the ancient Silk Road? An evolutionary perspective.
Kaposi's sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A and 82 subtype C, with C2 (n = 56) being the predominant subtype. The times to the most recent common ancestors (tMRCAs) of KSHV were 29,872 years (95% highest probability density [HPD], 26,851-32,760 years) for all analysed sequences and 2037 years (95% HPD, 1843-2229 years) for Xinjiang sequences in particular. The tMRCA of Xinjiang KSHV was exactly matched with the time period of the ancient Silk Road approximately two thousand years ago. This route began in Chang'an, the capital of the Han dynasty of China, and crossed Central Asia, ending in the Roman Empire. The evolution rate of KSHV was slow, with 3.44 × 10-6 substitutions per site per year (95% HPD, 2.26 × 10-6 to 4.71 × 10-6), although 11 codons were discovered to be under positive selection pressure. The geographic distances from Italy to Iran and Xinjiang are more than 4000 and 7000 kilometres, respectively, but no explicit relationship between genetic distance and geographic distance was detected.


Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohn's disease.
The pH and transit times of the gut are important for the delivery of active drug from several tablets used in the treatment of Crohn's disease (CD). Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH and transit time. The effect of ileocecal resection on these variables has not previously been studied. Intraluminal pH and transit time were measured in nine ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive radiocapsules. Small intestinal transit time (SITT) was significantly shorter in ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small intestine were identical in patients and controls, whereas cecal pH was 0.9 pH units higher in resected CD patients. The time spent with pH higher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There was no correlation between the SITT and the length of resected ileum or between the SITT and the time elapsed since the resection. We conclude that ileocecal resection decreases the SITT and the time with pH higher than 5.5-7.0. The study indicates that this reduction of the SITT is mainly due to the resection of the ileocecal valve and is, to a certain extent, independent of the length of resected ileum. An ileocecal resection might therefore affect the delivery of active drug from tablets with pH-dependent delivery.


Atorvastatin prolongs the lifespan of radiation‑induced reactive oxygen species in PC-3 prostate cancer cells to enhance the cell killing effect.
Studies have reported that atorvastatin (ATO) may increase the radiosensitivity of malignant cells. However, the influence of ATO on reactive oxygen species (ROS) levels before and after irradiation has not been fully illustrated. In the present study, radiosensitivity was evaluated by a clonogenic assay and a cell survival curve and cell apoptosis was measured by flow cytometry. ROS were detected by a laser scanning confocal microscope and flow cytometry with a DCFH-DA probe. NADPH oxidases (NOXs) and superoxide dismutase (SOD) proteins were detected by immunoblotting, and total SOD activity was measured using an SOD kit. We also conducted transient transfection of NOX2 and NOX4 genes to increase intracellular ROS generation and applied SOD mimetic tempol to enhance ROS elimination ability. Our results demonstrated that, with ATO-alone treatment, the survival fractions of irradiated PC-3 cells were significantly decreased. Meanwhile, the apoptosis rate of the irradiated cells increased significantly (P<0.05). The ROS levels of the study group decreased obviously before irradiation (P<0.01), however, the radiation-induced ROS of the study group was at a high level even when irradiation had been terminated for 2 h (P<0.01). Moreover, NOX2 and NOX4 levels and total SOD activity decreased (P<0.01), while the levels of SOD1 were stably maintained (P>0.05). On the other hand, the decreased survival fractions and high radiation-induced ROS levels were abrogated by increasing the level of NOXs by gene transfection or by enhancing the ability of SOD utilizing the addition of tempol. In conclusion, ATO enhanced the cell killing effect of irradiation by reducing endogenous ROS levels and prolonging the lifespan of radiation‑induced ROS via a decrease in the level of NOXs and SOD activity.


7-Pyridylindoles: synthesis, structure, and properties.
A series of three isomeric 7-pyridylindoles (7-PIs) are prepared where the pyridine attachment is through C2, C3, or C4. These systems are prepared by a combination of the Bartoli reaction and the Stille coupling with an appropriate pyridyl stannane. By treatment with CH(3)I, the 7-PIs can be converted to their pyridinium salts. Deprotonation at the NH of these salts leads to a zwitterion which, in the 4-pyridyl system, also exists as a neutral isomer. The photophysical and NMR properties of these systems are discussed. All three pyridylindoles are analyzed by X-ray crystallography and shown to exist in different states of aggregation dictated by the formation of intra- and intermolecular H-bonds.


Cortical and spinal excitability changes after robotic gait training in healthy participants.
Recent studies have proposed a role for robotic gait training in participants with acquired brain injury, but the effects on the excitability of cortical and spinal neurons even in healthy participants are uncertain. To investigate changes in corticospinal excitability in healthy participants after active and passive robotic gait training in a driven gait orthosis (DGO), the Lokomat. Thirteen healthy participants took part in 2 experiments. Each participant performed 20 minutes of active and passive gait training in a DGO. Motor evoked potentials (MEP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), F-wave frequency, and Mmax were measured in the right tibialis anterior muscle before and after training. Active training led to a decline in MEP amplitude and F-wave frequency. The MEP decline was associated with subjective muscle fatigue. Passive training induced a decrease in SICI lasting for 20 minutes after training. The decline in MEP after active training is most likely because of central fatigue, whereas the decreased F-wave frequency might represent short-term plastic changes in the spinal cord. The decrease in SICI after passive training probably reflects a decrease in intracortical GABA activity, which could benefit the acquisition of new motor skills.


Cell interactions in the control of size in Drosophila wings.
The vein locus (vn) includes lethal alleles (designated also defective dorsal discs) that prevent growth of dorsal discs and in viable genetic combinations reduce the number of cells of the adult wing. Those effects are prominent in genetic mosaics. Cell proliferation is reduced in all regions of the wing blade in a local autonomous way. These effects are more extreme when mutant clones occupy full intervein regions bordering veins. Clones have, in addition, nonautonomous effects (accommodation) in the proliferation of wild-type cells of the same wing. These effects are more extreme in double mutant vn (ddd) and ve (rhomboid) allelic combinations. Developmental analysis shows that cell proliferation stops earlier in larval development the stronger the vn allele considered. A model is discussed of how cell proliferation is controlled by cellular interactions.


Insulinoma diagnosed as drug-refractory epilepsy in an adolescent boy: a case report.
Solitary insulinoma is a rare pancreatic tumor in all age groups with an estimated incidence of 1 in 250 000 persons a year. It is even rarely in childhood and mostly shows benign behavior. Cases with uncertain or malignant biology are extremely rare with less than 30 cases described in the literature. Here we report a case of pediatric insulinoma, the first in our department files in the past 20 years, with rapid clinical course following a clinical misdiagnosis as juvenile myoclonic epilepsy, which was complicated with low glucose level (20 mg/dL) and neuroglycopenia. Our case underlines some unusual features of a pediatric insulinomas presented without past medical and family history, after surgery complicated with mental retardation and recurrent epileptiform episodes. Despite the small tumor size, low Ki67 index/mitotic rate and benign immunophenotype marked by positivity for pro-insulin but negativity for β-HCG, the diagnosis was concluded as insulinoma of uncertain biological behavior due to vascular tumor invasion in agreement with the 2003 WHO Classification for Pancreatic Endocrine Neoplasms. Besides these features, perineural invasion can differentiate insulinomas of uncertain outcome from benign insulin producing tumors. Pediatric insulinomas may present misleading symptoms of epilepsy in neglected cases coming from poor socioeconomic background. Chronic insufficient blood glucose level might contribute to mental retardation and epilepsiform myoconvulsions to be prevented. Differentiation between insulinoma with benign and uncertain behavior is difficult where histological pattern and tumor immunophenotype are less important than the critical morphological parameters. Life long follow-up including regular control of blood glucose and abdominal status of patients are essential for proper assessment of clinical outcome of pediatric insulinoma.


Elizabethkingia miricola: A rare non-fermenter causing urinary tract infection.
Elizabethkingia miricola (E. miricola) is a gram-negative non-fermentative bacterium which is rarely encountered. It is usually misidentified or considered as a contaminant in routine microbiology laboratories due to the limitations in conventional biochemical techniques. However, with the advent of the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), the identification of non-fermenters has become easy and this has led to enhanced understanding of the clinical significance of these uncommonly isolated microorganisms. The genus Elizabethkingia has only two species E. meningoseptica and E. miricola. Both of these organisms are known to be multi-drug resistant and therefore, their accurate identification and antimicrobial susceptibility testing are necessary prior to the initiation of appropriate therapy. In the world literature till date, only 3 cases of sepsis caused by E. miricola have been reported. We present the first case of E. miricola association with urinary tract infection.


Studies on the effects of primary therapy for DIC following circulatory arrest.
Comparative studies in early treatment for DIC caused by circulatory arrest were carried out on three groups of dogs during 300 min from the recovery of circulatory arrest: a heparin group, a FOY (gabexate mesilate) group, and a FUT-175 (nafamostat mesilate) group. The parameters employed were platelet count, prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen, antithrombin-III (AT-III), and fibrin or fibrinogen degradation products (FDP). In the heparin group, there was less of a drop in the platelet count and the level of AT-III than in the control group, but the FDP levels were the same as in the control group. The PT and APTT remained within normal limits in the FOY group and no decrease was observed in either platelet count or AT-III levels. In addition, FDP levels were kept within normal limits. In the FUT-175 group, prolongation of APTT, no decline in the platelet count and AT-III levels, and normal levels of FDP were observed. The results of these experiments indicate the importance of early treatment for DIC. Judging from the parameters, better results were obtained in the FOY and FUT-175 group than in the heparin group.


Missing data: An update on the state of the art.
The year 2022 is the 20th anniversary of Joseph Schafer and John Graham's paper titled "Missing data: Our view of the state of the art," currently the most highly cited paper in the history of Psychological Methods. Much has changed since 2002, as missing data methodologies have continually evolved and improved; the range of applications that are possible with modern missing data techniques has increased dramatically, and software options are light years ahead of where they were. This article provides an update on the state of the art that catalogs important innovations from the past two decades of missing data research. The paper addresses topics described in the original paper, including developments related to missing data theory, full information maximum likelihood, Bayesian estimation, multiple imputation, and models for missing not at random processes. The paper also describes newer factored regression specifications and missing data handling for multilevel models, both of which have been a focus of recent research. The paper concludes with a summary of the current software landscape and a discussion of several practical issues. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Structure-activity relationships of 8-cycloalkyl-1,3-dipropylxanthines as antagonists of adenosine receptors.
8-Substituted xanthines currently represent the most potent class of adenosine-receptor antagonists. A series of 8-substituted 1,3-dipropylxanthines was prepared and their potency as antagonists of A1 and A2 adenosine receptors of human platelets and rat adipocytes, respectively, were determined. No agents studied were as potent as 8-cyclopentyl-1,3-dipropylxanthine as antagonists of the A1 adenosine receptor, but 8-(2-methylcyclopropyl)-1,3-dipropylxanthine was at least 1000-fold more potent as an antagonist of A1 than of A2 adenosine receptors. While most substitutions on the 8-cycloalkyl moiety caused decreased potency to inhibit both A1 and A2 adenosine receptors, 8-[trans-4-(acetamidomethyl)cyclohexyl]-1,3-dipropylxanthine was nearly equipotent as an antagonist of the two receptors and appeared to be the most potent antagonist of A2 adenosine receptors reported to date.


Ten-year experience using antegrade enemas in children.
To describe a single-center, 10-year experience with the use of antegrade enemas. Retrospective analysis of 99 patients treated with antegrade enemas at Nationwide Children's Hospital. Study subjects (median age 8 years) were followed for a mean time of 46 months (range 2-125 months) after cecostomy placement. Seventy-one patients had the cecostomy placed percutaneously and 28 by surgery. Thirty-five patients had functional constipation and 64 patients an organic disease (spinal abnormalities, cerebral palsy, imperforate anus, Hirschsprung's disease). While using antegrade enemas, 71% became symptom-free, in 20 subjects symptoms improved, in 2 subjects symptoms did not change, and in 7 subjects symptoms worsened. Poor outcome was associated with surgical placement of the cecostomy (P < .001), younger age (P = .02), shorter duration of symptoms (P = .01), history of Hirschsprung's disease (P = .05), cerebral palsy (P = .03), previous abdominal surgery (P = .001), and abnormal colonic manometry (P = .004). In 88%, successful irrigation solution included use of a stimulant laxative, and subjects who used a stimulant did significantly better (P < .001) than subjects who started without a stimulant. In 13 patients, the cecostomy was removed 49.7 months after placement without recurrence of symptoms. Major complications occurred in 12 patients and minor complications in 47. Antegrade enemas represent a successful and relatively safe therapeutic option in children with severe defecatory disorders. Prognostic factors are identified.


Theoretical insights into the catalytic mechanism of propylene hydroformylation over Co-N-C materials.
M-N-C was recently reported to be a high activity catalyst for hydroformylation compared with a metal nanocluster. However, the nature of M-N-C sites and the dominant path of propylene hydroformylation on M-N-C sites with different structures are poorly understood. In this work, five different Co-N-C models (Co-N3-C, Co-N4-C, 0N-bridged Co2-N6-C, 1N-bridged Co2-N7-C and 2N-bridged Co2-N6-C) were constructed to simulate the Co active sites with different coordination that may exist on the surface of MOF-derived Co-based carbon materials. DFT combined with kinetic Monte Carlo (kMC) methods were used to study the catalytic performance for hydroformylation of different Co-N-C models. The results of the DFT calculations show that the coordination number and mode of N atoms could regulate the electronic density of the Co sites. The electronic density of the Co sites further affects the catalytic activity. The higher the electronic density is, the lower the energy barrier for partial hydrogenation of propylene and CO insertion reactions. Besides, the catalytic activity is also affected by the strong interaction in closer neighboring Co atoms in some Co2-Nx-C models. The strong interaction affects the adsorption state and energy of species, which also reduces the overall reaction energy barrier. The kMC simulation results further showed that the dominant path of propylene hydroformylation was the n-butylaldehyde path for the 0N-bridged model, and the isobutylaldehyde path for Co-N3-C and 2N-bridged models.


Activation of phospholipase C-epsilon by heterotrimeric G protein betagamma-subunits.
PLC-epsilon was identified recently as a phosphoinositide-hydrolyzing phospholipase C (PLC) containing catalytic domains (X, Y, and C2) common to all PLC isozymes as well as unique CDC25- and Ras-associating domains. Novel regulation of this PLC isozyme by the Ras oncoprotein and alpha-subunits (Galpha(12)) of heterotrimeric G proteins was illustrated. Sequence analyses of PLC-epsilon revealed previously unrecognized PH and EF-hand domains in the amino terminus. The known interaction of Gbetagamma subunits with the PH domains of other proteins led us to examine the capacity of Gbetagamma to activate PLC-epsilon. Co-expression of Gbeta(1)gamma(2) with PLC-epsilon in COS-7 cells resulted in marked stimulation of phospholipase C activity. Gbeta(2) and Gbeta(4) in combination with Ggamma(1), Ggamma(2), Ggamma(3), or Ggamma(13) also activated PLC-epsilon to levels similar to those observed with Gbeta(1)-containing dimers of these Ggamma-subunits. Gbeta(3) in combination with the same Ggamma-subunits was less active, and Gbeta(5)-containing dimers were essentially inactive. Gbetagamma-promoted activation of PLC-epsilon was blocked by cotransfection with either of two Gbetagamma-interacting proteins, Galpha(i1) or the carboxyl terminus of G protein receptor kinase 2. Pharmacological inhibition of PI3-kinase-gamma had no effect on Gbeta(1)gamma(2)-promoted activation of PLC-epsilon. Similarly, activation of Ras in the action of Gbetagamma is unlikely, because a mutation in the second RA domain of PLC-epsilon that blocks Ras activation of PLC failed to alter the stimulatory activity of Gbeta(1)gamma(2). Taken together, these results reveal the presence of additional functional domains in PLC-epsilon and add a new level of complexity in the regulation of this novel enzyme by heterotrimeric G proteins.


Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: what studies are still needed?
The use of antibiotics in acute exacerbations of chronic bronchitis (AECBs) remains the subject of controversy despite considerable medical and socioeconomic implications. First, the contribution of bacterial infection to AECBs is difficult to assess in patients with chronic obstructive pulmonary disease (COPD) who are chronically colonized with respiratory pathogens. In addition, several studies suggest a major role of viral infections in AECBs. Secondly, it is unlikely that all COPD patients will benefit from antibiotics during AECBs. In particular, the benefit in mild COPD remains uncertain. Unfortunately, the number of studies complying with evidence-based medicine requirements is too small for definite recommendations in AECBs to be drawn up. Considering the impact of acute exacerbations of chronic bronchitis on chronic obstructive pulmonary disease patients, as well as the community, and the impact of antibiotic therapy on the development of bacterial resistance, there is an urgent need for the design of appropriate multicentric studies to define the usefulness of this type of treatment in acute exacerbations of chronic bronchitis.


Mesenchymal stem/stromal cells (MSC) transfected with stromal derived factor 1 (SDF-1) for therapeutic neovascularization: enhancement of cell recruitment and entrapment.
Recruited bone marrow-derived circulating cells (RBCCs) play a key role in therapeutic neovascularization. Several important steps take place during this process, which include mobilization, migration, recruitment, adhesion and invasion, entrapment, differentiation, as well as paracrine functions. Recent study indicated that recruitment and entrapment of RBCCs are vital steps in vascular endothelial growth factor (VEGF)-induced angiogenesis. This entrapment is modulated by another important chemokine: stromal derived factor 1 (SDF-1). We reason that the enhancement of entrapment might be a novel target for therapeutic neovascularization. Therefore we hypothesize that mesenchymal stem/stromal cells that secrete VEGF in situ could be transfected with SDF-1 (MSC(SDF-1)). Their combination could augment mobilization, recruitment, survival, and above all the entrapment of RBCCs, all of which might greatly augment the angiogenesis pathway. For these reasons, we further hypothesize that MSC(SDF-1) might become a next generation cell/chemokine therapy for therapeutic neovascularization.


Voluntary exercise increases oligodendrogenesis in spinal cord.
Exercise has been shown to increase hippocampal neurogenesis, but the effects of exercise on oligodendrocyte generation have not yet been reported. In this study, we evaluated the hypothesis that voluntary exercise may affect neurogenesis, and more in particular, oligodendrogenesis in the thoracic segment of the intact spinal cord of adult nestin-GFP transgenic mice. Voluntary exercise for 7 and 14 days increased nestin-GFP expression around the ependymal area. In addition, voluntary exercise for 7 days significantly increased nestin-GFP expression in both the white and gray matter of the thoracic segment of the intact spinal cord, whereas, 14-day exercise decreased nestin-GFP expression. Markers for immature oligodendrocytes (transferrin and CNPase) were significantly increased after 7 days of voluntary exercise. These results suggest that voluntary exercise positively influences oligodendrogenesis in the intact spinal cord, emphasizing the beneficial effects of voluntary exercise as a possible co-treatment for spinal cord injury.


Kepone distribution in the water column of the James River estuary--1976-78.
Concentration of Kepone residues in water collected from the James River estuary in 1976-78 ranged from 0 to 1.20 ppb. The majority of water samples collected showed no detectable residues. Kepone concentrations at the surface and bottom of the water column were similar. Water column residues varied according to seasonal and spatial differences. Levels peaked during the summer months and averaged higher in the middle reach of the estuary. Residues in the water were 1-5 orders of magnitude lower than reported residues in James River bed sediments. There was a significant correlation between water column and underlying bed sediment residues.


Identifying Desistance Pathways in a Higher Education Program for Formerly Incarcerated Individuals.
The link between education and crime is a topic that requires special attention with respect to the converging influence of individual, social, and environmental factors. This article will investigate the educational pathways followed by students in a higher education program for formerly incarcerated individuals at a large state university in the northeastern United States. Specifically, it will explore the extent to which their postincarceration educational experiences served as a "hook for change" and also related impediments tied to street influences, financial constraints, stigma, academic and social development. Data were collected from a sample of 34 current and former students in the program, each of whom participated in a face-to-face interview. The higher education program played a key role in propelling the desistance process for research participants. This article will discuss how personal agency can be sustained through participation in higher education post release and the implications for future research on crime avoidance.


Recoil effects in valence band photoemission of organic solids.
Recoil effects in valence band X-ray photoelectron spectroscopy (XPS) are studied for both abb-trifluorostyrene and styrene molecular crystal systems. The gradual changes of XPS spectra excited by several photon energies are theoretically investigated within the tight-binding approximation and harmonic approximation of lattice vibrations and have been explained in terms of not only atomic mass but also atomic orbital (AO) population. The recoil effect of valence band photoemission strongly depends on the population and partial photoionization cross section (PICS) of AOs as well as the masses of composite atoms. In abb-trifluorostyrene F 2p dominant bands show the recoil shift close to free F atom recoil shift, and C 2s dominant bands show that to free C atom recoil shift, whereas the mixed bands of C and F give rise to the peak asymmetries due to their different recoil shifts. For these systems, hydrogen contribution is negligibly small which is in contrast to our previous results for the crystals composed of small organic molecules. We also discuss some potential uses of the recoil shifts for these systems.


Recent Advances on Cytotoxic Sesquiterpene Lactones.
Sesquiterpene lactones are naturally occurring compounds that have attracted considerable attention because to their vast array of biological activities. These plant-derived compounds contain the α-methylene-γ- butyrolactone functional group, which is the structural requirement for their pharmacological activities. Many of them exhibit cancer cell cytotoxicity and are promising anticancer agents through multiple mechanisms of action. Sesquiterpene lactones are alkylating agents that form covalent adducts in vivo and inhibit enzymes and key proteins. They are also potent apoptotic inducers in several cancer cells. This kind of cell death is recognized as a property that is useful for identifying anticancer drugs. This review focuses on the advances on cytotoxic sesquiterpene lactones and specifically the signal transduction pathways of cell death triggered in cancer cells.


Age-Related Changes of the Zygomatic Ligament: An Experimental Animal Study.
Facial aging is a multifactorial process involving the skin, fat, muscles, bones, and ligaments. The role of facial ligaments in the facial aging process remains elusive. The aim of this study was to identify whether age-related changes in facial ligaments exist and how to best quantify such changes when investigating the zygomatic ligament in the rat. A total of 30 male Sprague-Dawley rats (10 young, 10 middle-aged, 10 mature) were investigated to visualize the zygomatic ligament. Samples of the ligaments spanning the zygomatic arch and the skin were taken and histologically examined with hematoxylin-eosin, Masson, Verhoeff's elastic, and picrosirius red staining. Quantification of the Type I/III collagen ratio and collagen content was performed by color deconvolution and electron microscopic imaging. With increasing age, collagen fibers inside of the examined ligaments appeared thicker and more closely arranged. The Type I/III collagen ratio was measured to be 1.74 in young animals, 3.93 in middle-aged animals, and 5.58 in mature animals. The ultra-microstructure of the ligament was less coordinated in direction and orientation in young and middle-aged animals than in mature animals, in which collagen fibers were bundled together in a strong and oriented mesh. Ligaments appeared thinner, transparent, more elastic, and less robust in young animals, whereas ligaments in mature animals appeared thicker, more fascia-like, less elastic, and more robust. An increase in the Type I/III collagen ratio, indicating greater stiffness and reduced elasticity, was observed with higher age of the investigated animals. These findings indicate that ligaments might increase in stiffness and rigidity with age.


Effects of Virtual Reality training on medical students' learning motivation and competency.
To determine the need of contemporary immersive approaches (Virtual Reality) in teaching and training at medical sector. The main objective of this study was to explore the effects of text, video and immersive technologies learning methodologies for participants' learning in public and private medical colleges and universities of Pakistan. In this quantitative research 87 medical students of 4th year from three public and five private medical colleges and universities participated. A laparoscopy operation was selected in consultation with senior medical consultants for this experiment. The experimental material was arranged in virtual reality, video and text based learning. At completion of each of which, participants completed a questionnaire about learning motivation and learning competency through the different mediums. Statistical t-test was selected for the analysis of this study. By comparing the mean values of virtual reality, video, and text based learning methodologies in medical academics; result of virtual reality is at top of others. All performed model are statistically significant (P=0.000) and results can be applied at all population. Through this research, we contribute to medical students learning methodologies. In medical studies, both theoretical and practical expertise has a vital role, while repetition of hands-on practice can improve young doctors' professional competency. Virtual reality was found best for medical students in both learning motivation and learning competency. Medical students and educationist may select virtual reality as new learning methodology for curriculum learning.


[Evidence based treatment of dyslipidemia associated with diabetes mellitus].
Diabetic patients are more prone to develop atherosclerosis. Coronary heart disease (CHD), cerebrovascular disease(CVD), and peripheral arterial disease(PAD) are three main life-threatening macrovascular complications in diabetes. Previous studies indicate that glycemic control is important. They also indicate that glycemic control does not sufficiently prevent the development of atherosclerotic diseases in diabetic patients. It is now clear that treatment of dyslipidemia and hypertension are as important as good glycemic control. Diabetic patients tend to develop dyslipidemia and hypertension, as both derives from insulin resistance. Many randomized control studies have proved that lowering of LDL-cholesterol is beneficial for preventing the development of CHD or CVD. Sub-analyses of RCT of statins suggest that lipid lowering therapy helps prevent the development of these macrovascular complications.


OnabotulinumtoxinA (Botox) nerve blocks provide durable pain relief for men with chronic scrotal pain: a pilot open-label trial.
Chronic scrotal pain (CSP) is a common, often debilitating, condition affecting approximately 4.75% of men. While nerve blocks using local anesthetics usually provide temporary pain relief, there are no publications on the use of longer acting nerve blocks to provide more durable pain relief for men with CSP. The aim of this study was to determine if onabotulinumtoxinA (Botox) cord blocks provide durable pain relief for men with CSP. In this pilot open-label study, men with CSP who had failed medical management but experienced temporary pain relief from a standard cord block underwent a cord block with 100U Botox. The outcomes measured were changes 1, 3, and 6 months post-Botox injection in (i) a 10-point visual analog scale (VAS) pain score; (ii) scrotal tenderness on a three-point scale as rated by physical examination; and (iii) the Chronic Epididymitis Symptom Index (CESI) to measure the severity and impact of scrotal pain on men. Paired t-tests were used to compare groups. Eighteen patients with CSP seen between April and September 2013 had Botox injected as a cord block. At the 1-month follow-up, pain reduction was reported by 72% of patients (mean VAS score: 7.36 vs. 5.61, P < 0.003), while by physical examination 44 and 34% of the men had either complete or partial resolution of scrotal tenderness. In addition, there was also a significant reduction in CESI scores (22.19 vs. 19.25, P < 0.04). At 3 months, 56% had both sustained pain reduction and reduced tenderness based on the VAS score (mean: 7.36 vs. 6.02, P < 0.05) and physical exam. The CESI score continued to be significantly lower. Unfortunately, by 6 months, most men had a return to their baseline levels of pain and tenderness. Our pilot study found that Botox cord blocks provide pain reduction for 3 months or more for most men with CSP.


Lifestyle, stress, and genes in peptic ulcer disease: a nationwide twin cohort study.
The familial accumulation of peptic ulcer disease observed in several studies may be attributable to genetic effects, aggregation of environmental exposure (shared environment), or both. The intrafamilial spread of Helicobacter pylori infection has raised the question whether shared environment could explain the familial aggregation of peptic ulcer disease rather than genetic similarity of family members. To examine the contribution of genetic and environmental factors to the pathogenesis of peptic ulcer disease in a nationwide population-based cohort of adult twins. The Finnish Twin Cohort consists of all same-sexed twin pairs born before 1958 with both twins alive in 1975. The total number of twin pairs is 13888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ) twins. Questionnaire surveys of twins were carried out in 1975, 1981, and 1990, including medical and psychosocial questions. One question asked whether a physician had ever made a diagnosis of gastric or duodenal ulcer. In addition, hospital discharge data from 1972 to 1991 were linked with the twin cohort to obtain those twin individuals who had been treated for gastric or duodenal ulcer. The prevalence of and concordance for peptic ulcer disease were examined in MZ and DZ twins. Model-fitting analysis was used to specify the relative roles of genetic and environmental factors. The contribution of lifestyle factors and stress was examined prospectively in an incidence study and by comparison of discordant pairs. The prevalence of peptic ulcer disease was 6.2% in men and 2.8% in women in 1975. There were 63 MZ and 86 DZ pairs concordant for peptic ulcer disease. Concordance for disease was significantly higher in MZ than in DZ twin pairs; the probandwise concordance rate was 23.6% (95% confidence interval [CI], 20.9%-26.3%) in MZ twins and 14.8% (95% CI, 13.3%-16.3%) in DZ twins. In the model-fitting analysis, a model with both additive genetic and unshared environmental effects had the best goodness-of-fit. Thirty-nine percent (95% CI, 32%-47%) of the liability to peptic ulcer disease was explained by genetic factors and 61% (95% CI, 53%-68%) by individual environmental factors. In the incidence study (logistic regression analysis of the entire cohort initially free of peptic ulcer disease, with subjects diagnosed as having peptic ulcer after 1975 as cases), current smoking (relative risk, 2.2; 95% CI, 1.5-3.2) and high stress levels (relative risk, 3.2; 95% CI, 1.4-7.6) in men and regular use of analgesics (relative risk, 3.3; 95% CI, 1.3-8.1) in women predicted peptic ulcer disease during the follow-up from 1976 to 1991. In the analysis of discordant pairs, smoking in men and regular use of analgesics in both sexes were predictors of peptic ulcer disease. The questionnaire and hospital usage data on peptic ulcer disease in the population-based twin cohort suggest that the familial aggregation of the disease is modest, and attributable almost solely to genetic factors. Environmental effects not shared by family members were significant predictors of disease, and they were attributable to smoking and stress in men and the use of analgesics in women. The minor effects of shared environment to disease liability do not support the concept that the clustering of risk factors, such as H pylori infection, would explain the familial accumulation of peptic ulcer disease.


[Red-cell sodium-lithium countertransport in patients with IgA nephrology and renal hypertension].
To find changes in activity of red-cell sodium-lithium counter transport (RBC Na+/Li+CT) in IgA nephropathology (IgAN) and renal hypertension (RHT), we measured the activity of RBC Na+/Li+CT in 21 patients with IgAN and 13 patients with RHT and compared it with that in 23 normal persons and 17 essential hypertension (EHT) patients by improved Canessa's method. RBC Na+/Li+CT activity in the EHT patients and EHT patients with positive family history was significantly higher than that in normal group. The activity of TBC Na+/Li+CT in the hyperlipidemic RHT patients was increased as compared with the normal group. The activity of RBC Na+/Li+CT in IgAN patients with hyperlipidemia and hyperlipidemic hypertensive IgAN patients was significantly higher than that in normal group. There was positive correlation between the activity of RBC Na+/Li+CT and serum cholesterol level in 34 patients with renal disease. The results indicate that enhanced activity of Na+/Li+ CT is a genetic marker for EHT patients, and hyperlipidemia is probably related to the enhanced activity of RBC Na+/Li+CT in parts of RHT patients and IgAN patients.


The effect of nonpharmacologic therapy on global cognitive functions in patients with Alzheimer's disease: an updated meta-analysis of randomized controlled trials.
Background: The effectiveness of non-pharmacologic therapy (NPT) in treating the global cognition dysfunction associated with Alzheimer's disease (AD) has not been clearly demonstrated. Therefore, we performed a meta-analysis to address this issue.Methods: The Cochrane Central Register of Controlled Trials, PUBMED, EMBASE and other databases were searched, and outcomes measured by the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) were analysed.Results: Seven types of NPT were included, 25 randomized controlled trials (RCTs) were selected and 3238 participants were included in the meta-analysis. There were significant differences between the NPT and control groups in the MMSE and ADAS-cog scores.Conclusions: Although more extensive trials need to be performed, NPT has been observed to be beneficial in AD patients.


Reduced Need for Rescue Antiemetics and Improved Capacity to Eat in Patients Receiving Acupuncture Compared to Patients Receiving Sham Acupuncture or Standard Care during Radiotherapy.
Objective. To evaluate if consumption of emesis-related care and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Methods. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (median 12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only and delivered these data once. Results. More patients in the verum (n = 73 of 89 patients still undergoing radiotherapy; 82%, Relative Risk (RR) 1.23, 95% Confidence Interval (CI) 1.01-1.50) and the sham acupuncture group (n = 79 of 95; 83%, RR 1.24, CI 1.03-1.52) did not need any antiemetic medications, as compared to the standard care group (n = 42 out of 63; 67%) after receiving 27 Gray dose of radiotherapy. More patients in the verum (n = 50 of 89; 56%, RR 1.78, CI 1.31-2.42) and the sham acupuncture group (n = 58 of 94 answering patients; 62%, RR 1.83, CI 1.20-2.80) were capable of eating as usual, compared to the standard care group (n = 20 of 63; 39%). Conclusion. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture.


Sulfhydryl-modifying reagents reversibly inhibit binding of glucocorticoid-receptor complexes to DNA-cellulose.
Glucocorticoid -receptor complexes from intact rat thymus cells incubated with [3H]dexamethasone at 0 degree C are in the nonactivated form and do not bind to DNA-cellulose. Upon being warmed, they are transformed to activated complexes that bind to DNA-cellulose at 0 degree C. We have found that treatment of dexamethasone-receptor complexes with the sulfhydryl-modifying reagents methyl methanethiosulfonate ( MMTS ) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), either before or after the warming, inhibits subsequent binding to DNA-cellulose. The effects of these reagents can be reversed at 0 degree C by dithioerythritol and other sulfhydryl-containing compounds. These results provide the first clear evidence that sulfhydryl-modifying reagents inhibit the binding of activated dexamethasone-receptor complexes to DNA-cellulose and suggest that sulfhydryl groups may be located in or near the DNA binding domain of the rat thymus glucocorticoid-receptor complex. Furthermore, addition of dithioerythritol at 0 degree C to nonactivated receptor complexes that have been treated with MMTS or DTNB produces a substantial increase in the capacity of these complexes to bind to DNA-cellulose, raising the possibility that sulfhydryl groups may be associated with a region on the receptor that plays a critical role in the activation process.


Gordon Memorial Lecture. A holistic view of poultry science from a reductionist perspective.
1. The success of the poultry industry has been dependent upon development of a precise understanding of poultry biology. 2. The advent of tools and probes that reveal the molecular and cellular organisation of complex physiological systems should be embraced by the poultry industry to gain insights into recurring problems such as egg shell quality and ascites. 3. The ability to modify the genome of chickens provides an opportunity to breed chickens with unprecedented precision. 4. The judicious use of time and resources will require a working knowledge of molecular and cellular biology and the poultry industry. There is an urgent need for educational facilities that provide both perspectives.


Wedge resection versus segmentectomy in patients with stage I non-small-cell lung cancer unfit for lobectomy.
The present study aimed to compare the outcomes of wedge resection and segmentectomy in patients with clinical stage I non-small-cell lung cancer (NSCLC) who were unfit for lobectomy. Between April 2007 and December 2015, 99 patients with stage I NSCLC who were considered unfit for lobectomy and had undergone sublobar resection were identified. Propensity scores were estimated for multivariable analyses, and surgical outcomes were compared between patients who underwent wedge resection and those who underwent segmentectomy. Sixty patients underwent wedge resection and 39 underwent segmentectomy. Severe postoperative complications (>Grade IIIa) were more frequent in segmentectomy (15.4%) than in wedge resection (3.3%, P = 0.054). Propensity score-adjusted multivariable analysis revealed that operative procedure was an independent predictive factor for severe postoperative complication (segmentectomy, odds ratio = 8.18; P = 0.021). Overall survival (OS) and recurrence-free survival (RFS) were not significantly different between wedge resection (5-year OS, 61.3%, 5-year RFS, 49.4%) and segmentectomy (5-year OS, 68.2%, 5-year RFS, 56.8 %, P = 0.95, P = 0.93, respectively). Propensity score-adjusted multivariable Cox analysis revealed that operative procedure was not an independent factor for OS (segmentectomy, hazard ratio = 1.21, P = 0.62) or RFS (segmentectomy, hazard ratio = 1.07, P = 0.84). Segmentectomy was more toxic but failed to show the superiority of survival compared with wedge resection. Wedge resection may be the optimal procedure for patients with clinical stage I NSCLC who are considered to be unfit for lobectomy.


Self-Healing pH- and Enzyme Stimuli-Responsive Hydrogels for Targeted Delivery of Gemcitabine To Treat Pancreatic Cancer.
A novel, multifunctional hydrogel that exhibits a unique set of properties for the effective treatment of pancreatic cancer (PC) is presented. The material is composed of a pentablock terpolypeptide of the type PLys- b-(PHIS- co-PBLG)-PLys- b-(PHIS- co-PBLG)- b-PLys, which is a noncytotoxic polypeptide. It can be implanted via the least invasive route and selectively delivers gemcitabine to efficiently treat PC. Simply mixing the novel terpolypeptide with an aqueous solution of gemcitabine within a syringe results in the facile formation of a hydrogel that has the ability to become liquid under the shear rate of the plunger. Upon injection in the vicinity of cancer tissue, it immediately reforms into a hydrogel due to the unique combination of its macromolecular architecture and secondary structure. Because of its pH responsiveness, the hydrogel only melts close to PC; thus, the drug can be delivered directionally toward the cancerous rather than healthy tissues in a targeted, controlled, and sustained manner. The efficacy of the hydrogel was tested in vivo on human to mouse xenografts using the drug gemcitabine. It was found that the efficacy of the hydrogel loaded with only 40% of the drug delivered in one dose was equal to or slightly better than the peritumoral injection of 100% of the free drug delivered in two doses, the typical chemotherapy used in clinics so far. This result suggests that the hydrogel can direct the delivery of the encapsulated drug effectively in the tumor tissue. Enzymes lead to its biodegradation, avoiding removal by resection of the polypeptidic carrier after cargo delivery. The unique properties of the hydrogel formed can be predetermined through its molecular characteristics, rendering it a promising modular material for many biological applications.


Covalent and non-covalent strategies for the immobilization of Tobacco Etch Virus protease (TEVp) on superparamagnetic nanoparticles.
Proteases with highly specific activities have numerous applications, including the cleavage of affinity tags (Flag; HA; His6X) and solubility promoting partners (GST; MBP) within the context of protein isolation and purification schemes. However, commercially sourced proteases such as Tobacco Etch Virus protease (TEVp) and Human Rhinovirus (HRV) 3C protease are typically applied as single use aliquots, which limits their cost-effectiveness. In addition, the presence of residual proteases in downstream applications can complicate analysis of the protein of interest. Thus, the creation of immobilized, reusable site-specific proteases would be of significant value to the life science community. In this work, we explore two strategies for the immobilization of TEV protease onto superparamagnetic iron oxide nanoparticles (SPIONs). In one strategy, a MBP-TEVp-Streptavidin fusion protein is immobilized on biotin-functionalized SPIONs. In a second strategy, TEV protease is covalently coupled onto SPIONs directly, via amine-mediated attachment, and indirectly, via HALO-tag mediated attachment. We demonstrate activity of our immobilized proteases in the presence of a MBP-GFP fusion protein containing the TEV protease target sequence (ENLYFQ|S). We then analyze time-dependent activity, longevity, and reuse of these immobilized protein preparations, comparing each approach. The protease immobilization strategies described in this work may be useful tools for simplifying challenging protein purification protocols, in addition to providing general methods for enzyme immobilization on SPIONs.


Segmental Erythema Multiforme: An Unusual Drug Reaction to Anastrozole.
Erythema multiforme (EM) is an immune-mediated, mucocutaneous hypersensitivity syndrome that can occur as a result of various medications, including a wide range of antineoplastic and hormonal drugs. Anastrozole, a nonselective aromatase inhibitor used in breast cancer management has been associated with different cutaneous side effects, of which EM is rarely seen and usually in a minor or major form with typical target lesions. This is a short report of a patient who developed a rare cutaneous side effect after the use of aromatase inhibitor anastrozole - segmental erythema multiforme in cancer-affected area. Cutaneous adverse effects limited to cancer-affected breast are extremely rare but should be considered in everyday dermatological practice. We find this case instructive not only because of the rarity of the segmental EM, but also because, contrary to classical teaching, drug eruption due to anastrozole occurred months, not days after the initiation of therapy.


Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence.
1. Studies on canine lower oesophageal sphincter (LOS) evaluated the existence and function of a myogenic, nitric oxide synthase (NOS) by use of immunocytochemistry for NOS isozymes, NADPH-d histochemistry, [3H]-L-arginine to [3H]-L-citrulline transformation. In addition, functional studies in the muscle bath were performed. 2. Smooth muscle bundles or freshly isolated smooth muscle cells of LOS were NADPH-d reactive but did not recognize some antibodies against neural, endothelial or inducible NOS. NADPH-d reactivity and immunoreactivity to a neural NOS antibody were colocalized in LOS enteric nerves. Muscle plasma membrane-enriched fractions from fresh and cultured LOS cells converted [3H]-L-arginine to [3H]-L-citrulline; activity was mostly Ca2+/calmodulin-dependent. 3. N-Nitro-L-arginine (L-NOARG) persistently increased tone (blocked by L-arginine) in muscle strips despite blockade of nerve function. Nifedipine prevented or abolished L-NOARG-induced, but not carbachol-induced, contraction showing that tone increase by L-NOARG required functional L-Ca channels. 4. Membrane-bound, myogenic NOS in canine LOS may release NO continuously when Ca2+ entry through L-Ca channels occurs under physiological conditions and thereby modulate tone in LOS.


Addressing Polarization Phenomena in Molecular Machines Containing Transition Metal Ions with an Additive Force Field.
Modeling transition metals in supramolecular assemblies, in general, is extremely challenging due to polarization and charge transfer. In this work, we demonstrate that the inherent shortcomings of additive force fields in modeling Cu+-ether-O and Cu+-olefin-C interactions are rooted in the Lorentz-Berthelot rules. A general method for investigating transition-metal-containing molecular assays using classical force fields is, therefore, proposed. In this strategy, QM/MM calculations have been performed to determine the potential of mean force (PMF) describing the interaction of a cation and a specific functional group. van der Waals parameters for the corresponding pairs of particles have then been optimized using the NBFIX feature of the CHARMM force field to fit the QM/MM PMF. This method has been applied to decipher the mechanism underlying the "dialing" of a molecular machine controlled by Li+ and Cu+ cations, indicating that the process is controlled by the competition between cation-ether-O and cation-olefin-C interactions.


[Mortality of patients with myocardial infarction at a young age].
Among patients with myocardial infarction, patients up to 40 years of age accounted for 5.1% (5.4% men and 4.1% women). Early mortality due to myocardial infarction was in the all material 42.6% and depended mainly on deaths of men in the prehospitalization period. Prehospitalization mortality varied between men and women. It was 45.3% for men and 11.2% for women. Hospital mortality was low, accounting for 7.8% of the treated subjects.


Capacitive behavior of carbon nanotube thin film induced by deformed ZnO microspheres.
Multiwalled carbon nanotubes (CNTs) are uniformly distributed with piezoelectric microspheres. This leads to a large strain gradient due to an induced capacitive response, providing a 250% enhancement in electromechanical response compared with pristine CNTs. The fabricated large-area flexible thin film exhibits excellent pressure sensitivity, which can even detect an arterial pulse with a much faster response time (∼79 ms) in a bendable configuration. In addition, the film shows a rapid relaxation time (∼0.4 s), high stability and excellent durability with a rapid loading-unloading cycle. The dominant contribution of piezoelectric microspheres in a CNT matrix as opposed to nanoparticles showed a much higher sensitivity due to the large change in capacitance. Therefore, hybrid microstructures have various potential applications in wearable smart electronics, including detection of human motion and wrist pulses.


[Multiple maxillofacial brown tumors as primary hyperparathyroidism manifestation].
In order to analyze the differential diagnosis of giant-cell lesion in facial bones, we present a case of a patient without a previously diagnosed primary hyperparathyroidism that displayed multiple maxillofacial brown tumors as the initial clinical manifestation of the disease. A 70 year-old female with amandible tumor and one year of disease progression. Tumor biopsy confirmed the presence of a giant-cell lesion. Radiologically, we confirmed the presence of another two lytic lesions in the maxillofacial region. During biochemical evaluation prior to surgery, the possibility of hyperparathyroidism was considered. Using computed tomography, we noted a parathyroid tumor in an atypical location. Surgical resection confirmed the presence of an adenoma. Postoperatively, the patient developed symptomatic hypocalcemia and was managed with calcium supplementation in addition to calcitriol. At 4 months after surgery mandibular swelling had regressed partially and serum calcium levels returned to normal levels. The detection of giant-cell bone lesions in the maxillofacial region is a strategic diagnostic finding as several entities, among these brown tumor hyperparathyroidism can display similar histologic imaging findings. Only systematic clinical, radiologic, and biochemical evaluation can allow for a definitive diagnosis. The presence of multiple simultaneous maxillofacial brown tumors in primary hyperparathyroidism is an infrequent ocurrence, and only on rare occasions can this be the first sign of the disease.


To rewire or not to rewire: To what extent rewiring to surviving partners can avoid extinction?
Research Highlight: Leimberger, K.G., Hadley, A.S., & Betts, M.G. (2023). Plant-hummingbird pollination networks exhibit minimal rewiring after experimental removal of a locally abundant plant species. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.13935. In this paper, Leimberger, Hadley and Betts (2023) explore the effects of removing a locally abundant plant species on plant-hummingbird pollination networks. They experimentally prevented access of hummingbirds to flowers of Heliconia tortuosa and assessed subsequent changes in the interactions between plants and hummingbirds. Their main hypothesis postulated that the loss of a highly connected species would lead to interaction rewiring and niche expansions by hummingbirds, decreasing individual, species and network specialization. However, they found that the overall structure of the plant-hummingbird networks remains mostly unaltered, with limited rewiring and minimal changes in specialization. The main contributions of this study can be summarized as (i) it adds to a limited number of manipulative studies on the capacity of species to rewire their interactions following the loss of partners, and importantly, it is the first study from the tropics and with vertebrate pollinators, for which experimental studies at appropriate scales is intrinsically more challenging; and (ii) innovates by evaluating change in specialization for the individual level, carried out through pollen sampling on the body of hummingbirds. The limited change in species interactions highlights that network stability through interaction rewiring may have been overestimated in previous studies, calling for further manipulative studies in the field. At the same time, it also indicated that even the loss of a highly abundant plant species has an overall small effect on network structure. Thus, this study contributes timely findings regarding the capacity of ecological communities to respond to species extinctions.


[Public Mental Health as One of the Key Factors in Dealing with COVID-19].
The aim of the article is to point out the important role of prevention and reduction of mental stress in the general population and in sensitive groups in the context of the coronavirus disease 2019 (COVID-19) pandemic. This article includes the analysis and evaluation of studies and recommendations from organizations such as the World Health Organization (WHO) that have examined the psychological consequences of epidemics/pandemics on people and their impact on the further course. Fear-related behaviors can adversely affect the course of epidemics. Past outbreaks of infectious diseases (Ebola and Zika virus) have shown that maladaptive behavior, related to increased psychological stress and anxiety, can interfere with the implementation of treatment strategies and actions and can contribute to a further spread. Hereby, strategies for dealing with infectious diseases, that include the suppression of fear, can trigger a vicious circle in which fear and suppression mutually reinforce each other. The COVID-19 pandemic poses an immense challenge to governments, health systems and people, with an uncertain outcome, which is associated with a significant burden of mental health in the population. In line with WHO recommendations, national guidelines and preventive measures should include the psychological consequences, the acceptance and normalization of fears and the promotion of resilience in the population in dealing with COVID-19 in order to counteract a further spread.


Acute admissions with atrial fibrillation in a British multiracial hospital population.
To assess the clinical characteristics and management of patients with atrial fibrillation (AF), we performed a prospective survey of all acute medical admissions over six months to our hospital. Of 7,451 such admissions, 245 had AF (110 male, 135 female; mean age 74.4 years). Of these, 213 were Caucasian, 10 black/Afro-Caribbean and 22 Asian. Complete data were available for 185 patients. Of these, 82 had newly diagnosed AF, 83 had previous chronic AF and 20 had paroxysmal AF. The main presenting features was dyspnoea, stroke and syncope. A history of ischaemic heart disease was present in 64, heart failure in 46, hypertension in 51 and rheumatic heart disease in 13, while 31 had a previous stroke. Chest X-ray showed cardiomegaly and pulmonary oedema in 121 patients, but was normal in 28. Echocardiography showed poor cardiac function in eight patients and enlarged left atria in five. Only 28% of those with previously diagnosed AF were on anticoagulation. Of the newly diagnosed patients, only 18% were started on anticoagulants. Cardioversion was attempted or planned in only 6%. The primary diagnosis on discharge was heart failure in 45, stroke in 24 and myocardial infarction in 12. AF remains a common arrhythmia among acute medical admissions and is commonly associated with heart failure and a high mortality. There is still a reluctance to start anticoagulant therapy or to perform cardioversion in such patients.


Diazepam and propranolol in panic disorder and agoraphobia.
The response to diazepam and propranolol hydrochloride was compared in 21 patients who (with one exception) met DSM-III criteria for panic disorder and agoraphobia. Each drug was administered for two weeks in double-blind fashion according to a crossover design. The response to diazepam was significantly superior on all measures. By observer rating, 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol. Panic attacks and phobic symptoms responded to diazepam, but not to propranolol. The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders.


Natural Appetite Control: Consumer Perception of Food-Based Appetite Regulating Aromas.
According to the WHO, the number of overweight people (BMI ≥ 25) and obese people (BMI ≥ 30) is constantly growing. On the other hand, the number of elderly people (≥60 years old) in 2020 reached 1.4 billion worldwide. Both mentioned groups demonstrate their individual and characteristic appetite disorders. In light of the side effects of appetite stimulating drugs, which interfere with diabetics, hypertension and thrombosis medicines or diet supplements with doubtful effectiveness in reducing appetite, new and natural alternatives are highly demanded. Therefore, the present study focusses on the search for natural food aromas, which may have potential for appetite regulation. A survey was carried out among consumers with excess body weight (BMI ≥ 25) and the elderly (≥60 years old). Food products and meals pointed out by the survey participants were subjected to volatile analysis by HS-SPME Arrow followed by GC-MS. As a result, a group of volatiles and their odor characteristic were determined for appetite stimulation or reduction, which may suggest that the actual composition of food aroma is more significant than the character of the aroma. Those results may be a basis for designing appetite regulating agents, in which the mechanism of action will be based only on olfaction activity.


Postictal but not interictal hemispatial neglect in patients with seizures of lateralized onset.
Unilateral spatial neglect, defined as a failure to report, respond, or orient to stimuli that are presented contralaterally, has been widely documented after brain damage to right, and to a lesser degree, left frontotemporoparietal networks. Group studies involving patients with seizures with a lateralized focus have demonstrated transient dysfunctions in memory and language; however, so far, only two case reports have described transient neglect after an epileptic seizure. To assess the existence and consistency of this phenomenon, we evaluated 33 epilepsy patients on a line-bisection task in interictal and postictal states as compared with an age- and sex-matched control group. Spatial neglect, as determined by this test, was found in the postictal but not interictal examination in patients with right parietal epileptic foci and was maximal for the left-positioned lines, whereas no neglect was found in other groups. Our findings indicate that patients with right parietal foci can present a transient neglect phenomenon on the line-bisection task in the postictal period, even in the absence of overt clinical neglect signs. These findings might be useful in establishing the laterality and even localization of epileptic foci based on the postictal neuropsychological evaluation.


Screening of Lipases with Unusual High Activity in the sn-2 Esterification of 1,3-Dicaprin under Mild Operating Conditions.
In this work, the synthesis of acylglycerides with high nutritional value was carried out by enzymatic esterification at sn-2 position of 1,3-dicaprin with palmitic acid. A comparative study of the performance of several biocatalysts according to the obtained products was carried out. The results obtained with several of the biocatalysts evaluated are very interesting, and it would be possible to use them to obtain a mixture of acylglycerides to act as a fat substitute. The final product was composed of about 90% of nutritionally attractive glycerides. These glycerides were medium-chain length triglycerides, medium-long chain triglycerides (mainly triglycerides with medium chain fatty acids at sn-1 and sn-3 positions and long chain fatty acid at sn-2 position), and 1,3-diglycerides. Pseudomonas fluorescens lipase and Burkholderia cepacia lipase immobilized on chitosan demonstrated unusual high activity in the sn-2 esterification of 1,3-dicaprin with palmitic acid at 45 °C and 12 h with 33% yield to 1,3-dicaproyl-2-palmitoyl glycerol. Burkholderia cepacia lipase has the advantage of being immobilized; however, BCL/chitosan has the advantages of being immobilized and therefore its easy recovery from the reaction media.


Using Neutron Reflectometry to Characterize Antimicrobial Protein Surface Coatings.
Understanding the interaction of adsorbed or covalently immobilized proteins with solid substrates at the molecular level guides the successful design of functionalized surfaces used in biomedical applications. In this report, neutron reflectometry (NR) was used to characterize the structure of surface-attached antimicrobial protein films, with antimicrobial activity assessed using an adaption of the Japanese Industrial Standard Test JIS Z 2801. NR allowed parameters influencing bioactivity to be measured at nanometer resolution and for conclusions about structural characteristics relating to bioactivity to be drawn. Hydramacin-1 (HM-1) and lysozyme were covalently attached to poly(methyl methacrylate) (PMMA) and 3-aminopropyltriethoxysilane (APTES) films in the presence and absence of a four-unit poly(ethylene glycol) PEG-based spacer and measured using NR, followed by antimicrobial assays. APTES-PEG-protein films were structurally unique, with a layer of 80% water directly beneath the protein layer, and were the only films that displayed antimicrobial activity against Escherichia coli and Bacillus subtilis. The hydration content of these films combined with the subtle difference in the PEG layer thickness of APTES versus PMMA films played a role in defining antimicrobial activity of the prepared surface coatings.


[Comparison of the biological properties of various strains of Aujeszky's disease viruses].
We compared three strains of Aujeszky's disease virus that had been isolated from slaughter pigs from the dormant foci of Aujeszky's disease, with the known virulent strain CVOS and TOP. No significant differences were found out in the following characters: titer value on tissue cultures from chick embryonal cells (KEB) and cellular line MDBK at the temperatures of 37 degrees C and 40 degrees C, cytopathogenic effect (CPE) in the HeLa cells, plaque formation in the KEB tissue culture, pruritus rise and the time of rabbit death after infection. Assessing the results of the comparison, the three new-isolated strains of Aujeszky's disease virus can be evaluated as strongly virulent.


[The facial expression says more than words. Is emotional "contagion" via facial expression the first step toward empathy?].
The hypotheses of this investigation were based on the conception of automatic mimicking being an early component involved in the formation of emotional empathy. The parameters compared were facial mimicry reactions, as represented by electromyographic (EMG) activity when subjects were exposed to pictures of angry or happy faces, and the degree of correspondence between facial EMG reactions and their own reported feelings. The subjects in the high-empathy group were found to have a higher degree of mimicking behaviour, while the low-empathy group showed inverse zygomaticus muscle reactions; they "smiled" when exposed to angry faces.


[Comparative study between tobramicin and tobramicin plus ciprofloxacin in transrectal prostate biopsy prophylaxis].
To compare the efficacy of tobramicin and tobramicin + ciprofloxacin for prevention of transrectal prostatic biopsy infectious complications. We revised our complications, microorganism most common in the infectious complications, and their sensibility. Prospective and randomized study in 153 patients with 157 prostatic biopsies. The 71 patients in group A were treated with intramuscular tobramicin 100 mg, one dose 30 minutes before biopsy and another one 8 hours afterwards. The 85 patients in group B were treated with the same tobramicin doses and oral ciprofloxacin 500 mg, one dose 30 minutes before biopsy and afterwards they continue with the ciprofloxacin every 12 hours during 3 days. we did 71 biopsies in group A and 86 in group B. 50 (31,8%) patients had hematuria, 20 (12,7%) fever, 15 (9,5%) hemospermia, 7 (4,4%) perineal pain, one (1,2%) orchiepididymitis and another one (1,2%) urinary retention. The patients who had fever were 15 of the group A and 5 of the group B (p=0,004). A total of 15 (21,1%) patients with fever of the group A needed to be treated in the hospital and 3 patients (3,5%) of the group B (p=0,0006). E. coli growthed in 67% of the blood cultures and amoxicillin-clavulanic, tobramicin and third generation of cephalosporins were the antibiotics more eficacious. Prophylaxis scheme with tobramicin plus ciprofloxacin was more efficacy that tobramicina alone in transrectal prostatic biopsy. Hematuria was the most common complication. E. coli was the microorganism most frequent in infectious complications after prostatic biopsy and amoxicillin-clavulanic, tobramicin and third generation of cephalosporins the most effective antibiotics in our hospital.


Cloning of novel isoforms of the human Gli2 oncogene and their activities to enhance tax-dependent transcription of the human T-cell leukemia virus type 1 genome.
The expression of human T-cell leukemia virus type 1 (HTLV-1) is activated by interaction of a viral transactivator protein, Tax, and cellular transcription factor, CREB (cyclic AMP response element binding protein), which bind to a 21-bp enhancer in the long terminal repeats (LTR). THP (Tax-helping protein) was previously determined to enhance the transactivation by Tax protein. Here we report novel forms of the human homolog of a member of the Gli oncogene family, Gli2 (also termed Gli2/THP), an extended form of a zinc finger protein, THP, which was described previously. Four possible isoforms (hGli2 alpha, beta, gamma, and delta) are formed by combinations of two independent alternative splicings, and all the isoforms could bind to a DNA motif, TRE2S, in the LTR. The longer isoforms, alpha and beta, were abundantly expressed in various cell lines including HTLV-1-infected T-cell lines. Fusion proteins of the hGli2 isoforms with the DNA-binding domain of Gal4 activated transcription when the reporter contained a Gal4-binding site and one copy of the 21-bp sequence, to which CREB binds. This activation was observed only in the presence of Tax. The 21-bp sequence in the reporter was also essential for the activation. These results suggest that simultaneous binding of hGli2 and CREB to the respective sites in the reporter seems to be critical for Tax protein to activate transcription. Consequently, it is probable that the LTR can be regulated by two independent signals through hGli2 and CREB, since the LTR contains the 21-bp and TRE2S sequences in the vicinity.


mRNA Engineering for the Efficient Chaperone-Mediated Co-Translational Folding of Recombinant Proteins in Escherichia coli.
The production of soluble, functional recombinant proteins by engineered bacterial hosts is challenging. Natural molecular chaperone systems have been used to solubilize various recombinant proteins with limited success. Here, we attempted to facilitate chaperone-mediated folding by directing the molecular chaperones to their protein substrates before the co-translational folding process completed. To achieve this, we either anchored the bacterial chaperone DnaJ to the 3' untranslated region of a target mRNA by fusing with an RNA-binding domain in the chaperone-recruiting mRNA scaffold (CRAS) system, or coupled the expression of DnaJ and a target recombinant protein using the overlapping stop-start codons 5'-TAATG-3' between the two genes in a chaperone-substrate co-localized expression (CLEX) system. By engineering the untranslated and intergenic sequences of the mRNA transcript, bacterial molecular chaperones are spatially constrained to the location of protein translation, expressing selected aggregation-prone proteins in their functionally active, soluble form. Our mRNA engineering methods surpassed the in-vivo solubilization efficiency of the simple DnaJ chaperone co-overexpression method, thus providing more effective tools for producing soluble therapeutic proteins and enzymes.


A Uranyl Peroxide Dimer in the Gas Phase.
The gas-phase uranyl peroxide dimer, [(UO2)2(O2)(L)2]2+ where L = 2,2'-trifluoroethylazanediyl)bis(N,N'-dimethylacetamide), was synthesized by electrospray ionization of a solution of UO22+ and L. Collision-induced dissociation of this dimer resulted in endothermic O atom elimination to give [(UO2)2(O)(L)2]2+, which was found to spontaneously react with water via exothermic hydrolytic chemisorption to yield [(UO2)2(OH)2(L)2]2+. Density functional theory computations of the energies for the gas-phase reactions are in accord with observations. The structures of the observed uranyl dimer were computed, with that of the peroxide of particular interest, as a basis to evaluate the formation of condensed phase uranyl peroxides with bent structures. The computed dihedral angle in [(UO2)2(O2)(L)2]2+ is 145°, indicating a substantial deviation from the planar structure with a dihedral angle of 180°. Energies needed to induce bending in the most elementary gas-phase uranyl peroxide complex, [(UO2)2(O2)]2+, were computed. It was found that bending from the lowest-energy planar structure to dihedral angles up to 140° required energies of <10 kJ/mol. The gas-phase results demonstrate the inherent stability of the uranyl peroxide moiety and support the notion that the uranyl-peroxide-uranyl structural unit is intrinsically planar, with only minor energy perturbations needed to form the bent structures found in studtite and uranyl peroxide nanostructures.


From acute care to home care: the evolution of hospital responsibility and rationale for increased vertical integration.
The responsibility of hospitals is changing. Those activities that were once confined within the walls of the medical facility have largely shifted outside them, yet the requirements for hospitals have only grown in scope. With the passage of the Patient Protection and Affordable Care Act (ACA) and the development of accountable care organizations, financial incentives are focused on care coordination, and a hospital's responsibility now includes postdischarge outcomes. As a result, hospitals need to adjust their business model to accommodate their increased need to impact post-acute care settings. A home care service line can fulfill this role for hospitals, serving as an effective conduit to the postdischarge realm-serving as both a potential profit center and a risk mitigation offering. An alliance between home care agencies and hospitals can help improve clinical outcomes, provide the necessary care for communities, and establish a potentially profitable product line.


Communication: Structure, formation, and equilibration of ensembles of Ag-S complexes on an Ag surface.
We have utilized conditions of very low temperature (4.7 K) and very low sulfur coverage to isolate and identify Ag-S complexes that exist on the Ag(111) surface. The experimental conditions are such that the complexes form at temperatures above the temperature of observation. These complexes can be regarded as polymeric chains of varying length, with an Ag4S pyramid at the core of each monomeric unit. Steps may catalyze the formation of the chains and this mechanism may be reflected in the chain length distribution.


Pyrene-excimers-based antenna systems.
A series of dendrimeric compounds bearing pyrene units were synthesized to afford light-harvesting antennae based on the formation of intramolecular excimers. The synthetic plan profited from the efficiency of the Huisgen reaction, the 1,3-dipolar cycloaddition of azides and terminal alkynes, which allowed ready assembly of the different building blocks. The three molecular antennae obtained, of increasing generation, revealed efficient energy transfer both in solution and in the solid state.


Trends in population blood pressure and determinant factors for population blood pressure.
Strategies to reduce the burden of blood pressure attributable diseases require knowledge of secular trend in PBP and its determinants. The issues were investigated in the Copenhagen City Heart Study. The design of CCHS is a repeated measures study. Such designs are uniquely suited to studying changes of an outcome and what risk factors may be associated with that outcome. Repeated measures studies are very well suited for trend analysis by using mixed effect analyses. SBP decreased about 2 mmHg in 25 years. The risk factors age, gender and BMI were found valid as determinant factors for secular trends in SBP. In addition, the following factors were identified: household income and the interactions ''gender*age'' and ''survey*age''. The interaction ''gender*age'' stated that the difference between SBP in the two genders was great in the young individuals and diminished by age. The interaction ''survey*age'' stated that SBP in the young individuals decreased more with survey than SBP in the older individuals. Thus, the 20 years old subjects in survey 2, 3 and 4 have lower SBP than the 20 years old subjects in preceding surveys. The slopes were less steep in higher ages. In the group of elderly and old subjects the trend is partly explained by treatment bias because more and more subjects leave the untreated group and start treatment. The factor ''household income'' was significant only in the female population and stated that high-income women had lower SBP and a more beneficial secular trend in SBP than low-income women. Marital status, self-reported physical exercise and alcohol intake were not significant factors. A number of factors, that are interesting in relation to SBP, were not included in the CCHS and therefore not investigated. Among them are salt intake, childhood factors, genetic factors and the DASH diet. A survival study was performed to investigate the mortality rate in relation to SBP changes during the observation period. A Cox regression analysis was used in this study. The survival study demonstrated that SBP was a significant variable in survival models for all age groups. There was a decrease in mortality rate in young to middle-aged individuals. The mortality rate that is associated with a particular value of SBP did not change. Thus, it was concluded that SBP was as dangerous as it has always been and that the reduction in mortality rate was most pronounced in the age classes that also experienced the greatest reduction in blood pressure. During the observation period the number of treated individuals in the population increased from 6.5% to 18.1%. About 50% of the population was hypertensive (SBP ≥ 140 mmHg or treated with antihypertensive medication). The value of SBPtreated was used as an indicator for hypertension control in the treated population. Hypertension control is a collection of topics that includes guidelines, available medicine, physicians attitude towards hypertension treatment, systematic control, patient awareness and patient compliance. The analysis of trends in SPB in treated hypertensives showed that SBPtreated decreased 9.2 mmHg in 25 years. The result may be ascribed to improvements in treatment but may also be caused by a change in start-to-treat practice: If hypertensives start treatment at an increasingly lower SBPthreshold then SBPtreated will decrease without improvements in treatment. Therefore the start-to-treat practice was evaluated by SBPthreshold. A change in SBPthreshold was not observed. Thus, the 9.2 mmHg decrease in SBPtreated may represent improvements in treatment. ''Age'' was a significant factor for SBPtreated. This result demonstrated that elderly and old individuals were treated less successful than young and middle-aged individuals. Subjects diagnosed with ischemic heart disease constitute a group with a more advantageous slope than subjects with other diagnoses (stroke, IHD in combination with stroke, and hypertension alone). Self-reported physical exercise, gender, alcohol intake, household income and family structure were not significant as variables in the decreasing SBP among treated hypertensives. Thus, the papers in this thesis described SBP trends in the untreated and in the treated part of a population. Different patient-related factors were identified as determinant factors for trends in the two groups. The determinant factors are the explanatory variables most associated with trends in SBP. The determinant factors were different for the two groups (except for age).


Trifluridine/tipiracil and regorafenib: new weapons in the war against metastatic colorectal cancer.
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Approximately 20% of patients have metastatic disease at diagnosis, and a vast number of these patients die within 5 years. The advent of modern chemotherapeutics has improved median overall survival for these patients; nonetheless, we must keep striving for better outcomes. Trifluridine/tipiracil (TAS-102) and regorafenib are agents newly approved by the US Food and Drug Administration that show promise in the treatment of metastatic colorectal cancer. These drugs have the benefit of being formulated for oral administration and have different side effect profiles. These differences are important in the selection of the best therapy for each patient, especially if the patient is prone to a side effect that is unique to just one of the treatments. In this review, we discuss the mechanism of action, side effect profile, and clinical efficacy of trifluridine/tipiracil, and compare them with those of regorafenib. Future trials will evaluate the use of these drugs in earlier lines of therapy, alone and in combination with other agents. We now have 2 more agents in the arsenal against metastatic colorectal cancer and the future is looking brighter for patients, although we still have a long way to go.


Evaluation of an emergency department falls pathway for older people: A patient chart review.
The number of older adults presenting to EDs following a fall continues to rise, yet falls management often ignores opportunities for secondary falls risk reduction. Advanced Nurse Practitioners (ANPs) in EDs have an important clinical leadership role in improving outcomes for this group of patients. This study describes the development of an ANP led falls pathway in an ED to improve safe discharge. It evaluates compliance with the pathway and referrals to community falls prevention services. It also draws comparison with baseline practice as recorded in 2014. The Falls Pathway involves four steps: 1) screening at triage (3 questions), 2) risk stratification (low, medium, high), 3) risk assessment (lying and standing blood pressure (B/P), timed-up and go (TUG), 4-AT for delirium screening, polypharmacy), and 4) referral to community falls services. We undertook a 12-month chart review of all patients aged 65 years or older presenting following a fall to the ANP service in 2018. We compared data to a baseline audit in 2014; descriptive and Chi squared statistics were used to examine the data. The 2018 audit involved 77 patients representing 27% of ANP caseload. A repeat fall occurred in 42% (32/77) of cases and 35% (22/77) reported a fear of falling. The Falls Pathway was initiated in nearly 80% (62/77) of patients and compliance with falls risk assessment ranged from 42% for lying and standing B/P to 75% for TUG. In 2014, a review of 59 patient charts showed 27% (16/59) experienced a repeat fall, but other risk factors such as fear of falling were not recorded. In 2018, the majority of patients (88%) discharged home were referred to community falls prevention services compared to 22% in 2014. The Falls Pathway improved falls risk assessment in the ED, identified opportunities for risk reduction and optimised referral to community falls services. The pathway continues to be a valuable tool but requires resources for ongoing implementation among the wider ED team.


Vulvar syringoma aggravated by pregnancy.
Syringoma is a benign tumors of eccrine sweat gland. They appear as multiple, tiny, firm, skin-colored papules. Vulvar involvement of syringoma is rare. Only 24 cases with vulvar syringoma have been previously reported in the literature. The majority of patients with vulvar syringomas are asymptomatic. A case of syringoma of the vulva exacerbated during pregnancy is presented. The case appears remarkable for the experienced aggravated pruritic symptoms of the patient during her pregnancy.


User comments on a clinical event monitor.
Columbia-Presbyterian Medical Center's health care providers have access to alerts and interpretations generated by an Arden Syntax-based clinical event monitor. They have the opportunity to send comments to the clinical information services staff. Over a period of 26 months, they sent 126 comments. The comments were analyzed using the critical incident technique, resulting in a hierarchy of categories that summarizes user concerns. The majority of comments (65) indicated that the messages were actually (8) or at least potentially useful (57). A minority (28) indicated that they were unhelpful (27) or actually harmful (1). Another group (27) made suggestions or asked questions. The comments have been very helpful for the maintenance of Medical Logic Modules (MLMs) and the clinical event monitor itself.


Trends and Clinical Characteristics of HIV and Cerebrovascular Disease in Low- and Middle-Income Countries (LMICs) Between 1990 and 2021.
To describe trends and clinical characteristics of HIV and cerebrovascular disease between 1990 and 2021 in LMICs and identify the gaps in our understanding. In the era of antiretroviral therapy (ART), people living with HIV (PLWH) live longer and risk excess cerebrovascular events due to ageing and HIV-driven factors. Despite the highest burden of HIV infection in low-to-middle income countries, there is underreporting in the literature of cerebrovascular events in this population. We systematically reviewed published literature for primary clinical studies in adult PLWH and cerebrovascular disease in LMICs. The clinical phenotype of cerebrovascular disease among PLWH over the last three decades in LMICs has evolved and transitioned to an older group with overlapping cerebrovascular risk factors. There is an important need to increase research in this population and standardise reporting to facilitate understanding, guide development of appropriate interventions, and evaluate their impact.


The Benefits of Culture Change in Nursing Homes-Obtaining Nationally Representative Evidence.
Despite face validity and regulatory support, empirical evidence of the benefit of culture change practices in nursing homes (NHs) has been inconclusive. We used rigorous methods and large resident-level cohorts to determine whether NH increases in culture change practice adoption in the domains of environment, staff empowerment, and resident-centered care are associated with improved resident-level quality outcomes. We linked national panel 2009-2011 and 2016-2017 survey data to Minimum Data Set assessment data to test the impact of increases in each of the culture change domains on resident quality outcomes. The sample included 1584 nationally representative US NHs that responded to both surveys, and more than 188,000 long-stay residents cared for in the pre- and/or postsurvey periods. We used multivariable logistic regression with robust standard errors and a difference-in-differences methodology. Controlling for the endogeneity between increases in culture change adoption and NH characteristics that are also related to quality outcomes, we tested whether pre-post quality outcome differences (ie, improvements in outcomes) were greater for residents in NHs with culture change increases vs in those without such increases. NH performance on most quality indicators improved, but improvement was not significantly different by whether NHs increased or did not increase their culture change domain practices. This study found that increases in an NH's culture change domain practices were not significantly associated with improved resident-level quality. It describes a number of potential limitations that may have contributed to the null findings.


Hepatitis B virus markers, alpha-fetoprotein and survival in fulminant viral hepatitis.
The serological markers of hepatitis B virus and serum alpha-fetoprotein (AFP) levels have been studied in 28 consecutive cases of fulminant hepatitis, correlating the data with survival. On admission, 20 patients were found to be positive for HBsAg and eight for anti-HBs. All anti-HBs-positive cases showed high titers of anti-HBc, and six patients were positive for specific anti-HBc-IgM. DNA polymerase activity was detected in serum of 11 HBsAg-positive (55%) and four anti-HBs-positive (50%) patients. HBeAg was detected in six (21.4%) subjects (five HBsAg-positive and one anti-HBs-positive), whereas anti-HBe was present in nine (32.1%) subjects (six HBsAg-positive and three anti-HBs-positive). AFP levels greater than 60 ng/ml were found in sera of 14 patients (50%). No significant difference was evidenced in the survival rate between HBsAg-positive and anti-HBs-positive and between HBeAg-positive and HBe Ag-negative patients. However, a statistically significant difference (P less than 0.05) in the survival rate was found in patients positive and negative for DNA polymerase activity and in those with AFP levels higher and lower than 60 ng/ml (P less than 0.005). Pathogenetic and prognostic significance of these findings are discussed.


Liquid-microjet photoelectron imaging spectrometry for liquid aqueous solutions.
A new liquid-microjet photoelectron imaging (PEI) spectrometer has been constructed that combines the liquid-microjet technique with velocity-map imaging. This novel method enables us to simultaneously measure the energy and angular distributions of the photoelectrons produced from highly volatile liquid solutions. The capability of the spectrometer has been demonstrated by recording the photoelectron image of the aqueous 2-furfural. To our knowledge, this is the first time that the PEI of liquid aqueous solutions has succeeded.


Half-metallic ferromagnetism and large negative magnetoresistance in the new lacunar spinel GaTi3VS8.
The lacunar spinel compounds GaTi(4-x)V(x)S(8) (0 < x < 4), consisting of Ti(4-x)V(x) tetrahedral clusters, were prepared and their structures were determined by powder X-ray diffraction. The electronic structures of GaTi(4-x)V(x)S(8) (x = 0, 1, 2, 3) were examined by density functional calculations, and the electrical resistivity and magnetic susceptibility of these compounds were measured. Our calculations predict that GaTi(3)VS(8) is a ferromagnetic half-metal, and this prediction was confirmed by magnetotransport experiments performed on polycrystalline samples of GaTi(3)VS(8). The latter reveal a large negative magnetoresistance (up to 22% at 2 K), which is consistent with the intergrain tunnelling magnetoresistance expected for powder samples of a ferromagnetic half-metal and indicates the presence of high spin polarization greater than 53% in GaTi(3)VS(8).


The phacoemulsification procedure. II. Corneal endothelial changes.
The effect of phacoemulsification, with the Cavitron-Kelman instrument, on the corneal endothelium of rabbit and cats was studied by scanning electron microscopy and nitroblue tetrazolium staining. The various steps of the procedure were examined separately. Irrigation of the anterior chamber of the eye with balanced salt solution (Plasma-Lyte) for ten minutes caused no cell damage. Ultrasound and irrigation alone for four to six minutes caused increased permeability to NBT. Edema of endothelial cells and cell junction disruption occurred after eight minutes of anterior chamber irrigation with Plasma-Lyte. Uncomplicated phacoemulsification produced moderate cellular edema with scattered loss of endothelial cells. Destruction of endothelial cells was frequent after phacoemulsification, it appeared to be due to lens nucleus manipulation in the anterior chamber, instrumentation, and needle contact. From two to five days postoperatively, intercellular edema, altered cell morphology, and mosaic pattern were seen. However, it gradually recovered and seven to ten days later the endothelium appeared normal.


Electrochemical Healing of Fractured Metals.
Repairing fractured metals to extend their useful lifetimes advances sustainability and mitigates carbon emissions from metal mining and processing. While high-temperature techniques are being used to repair metals, the increasing ubiquity of digital manufacturing and "unweldable" alloys, as well as the integration of metals with polymers and electronics, call for radically different repair approaches. Herein, a framework for effective room-temperature repair of fractured metals using an area-selective nickel electrodeposition process refered to as electrochemical healing is presented. Based on a model that links geometric, mechanical, and electrochemical parameters to the recovery of tensile strength, this framework enables 100% recovery of tensile strength in nickel, low-carbon steel, two "unweldable" aluminum alloys, and a 3D-printed difficult-to-weld shellular structure using a single common electrolyte. Through a distinct energy-dissipation mechanism, this framework also enables up to 136% recovery of toughness in an aluminum alloy. To facilitate practical adoption, this work reveals scaling laws for the energetic, financial, and time costs of healing, and demonstrates the restoration of a functional level of strength in a fractured standard steel wrench. Empowered with this framework, room-temperature electrochemical healing can open exciting possibilities for the effective, scalable repair of metals in diverse applications.


Recurrent leg ulcers in a young man with hyperhomocysteinemia, factor V Leiden and impaired fibrinolysis.
We present a young male patient referred to our hospital with leg ulcers on both legs that were more than 3 years refractory to standard treatment with compression therapy. By thrombophilia screening factor V Leiden mutation, hyperhomocysteinemia and evidence for impaired fibrinolysis were found. Treatment with folic acid in combination with long-term oral anticoagulant therapy was added to non-elastic compression therapy. The leg ulcers showed slow improvement and complete healing within 3 years. During a 6-year follow-up period neither new thrombo-embolic events occurred nor recurrence of ulcerations. This case suggests a potential synergistic pathogenic role of factor V Leiden, hyperhomocysteinemia and impaired fibrinolysis in the development of postthrombotic syndrome and his sequelae. We postulate that increased formation of thrombi in the microcirculation of the skin in combination with ambulatory venous hypertension due to recurrent deep venous thrombosis might explain our observation.