Sleep patterns of cyclic parenteral nutrition, a pilot study: are there sleepless nights?
Cyclic home parenteral nutrition (HPN) is 1 of the few medical therapies given during normal nocturnal sleep hours, and it is possible that infusion may alter normal sleep patterns. The aim of this pilot study was to evaluate the sleep patterns of 5 patients receiving HPN. An Epworth sleep questionnaire was completed and wrist Actigraph data were collected before admission to the sleep laboratory. Formal overnight polysomnography was then preformed for 3 consecutive nights. The first night served as the acclimatization period. On the second and third nights, patients were randomized to receive either no infusion or infusion of their standard parenteral nutrition. Results were reported as the median and range and were compared with historical aged-matched controls. Five patients (3 women and 2 men) with a mean age of 61 years (40 to 73 years) were studied. Patients had been HPN-dependent for a median of 23 months (4 to 60 months). Patients were receiving HPN because of short bowel syndrome (2), chronic pancreatitis (2), and intestinal pseudoobstruction (1). A 1.5-liter HPN formula, infused over 10 hours, included approximately 25 kcal/kg/d with 30% lipid and 1.0 to 1.5 g/kg/d of protein. All solutions included multiple trace elements and standard multivitamins. During total parenteral nutrition (TPN) infusion, the percent of sleep efficiency was higher than without infusion, 81% versus 72%. Sleep efficiency in age-matched controls was approximately 88%. Sleep latency was longer in patients compared with controls, and longer in patients during infusion than without infusion, 35 versus 28 minutes. During TPN infusion, the percent of stage-1 (2%), stage-2 (52%), slow-wave (24%) and random eye movement (REM) sleep (21%) was similar to values during the night without infusion. Controls had lower slow-wave and REM times. The median Epworth sleep score was 3, which is the normal reported range. Although sleep quality is reduced in patients receiving HPN compared with aged-matched controls, sleep quality does not seem to be negatively effected by cyclic HPN infusion.


Induction of the autolytic system of Escherichia coli by specific insertion of bacteriophage MS2 lysis protein into the bacterial cell envelope.
Bacterial lysis induced by the expression of the cloned lysis gene of the RNA bacteriophage MS2 in Escherichia coli was shown to be under the same regulatory control mechanisms as penicillin-induced lysis. It was controlled by the stringent response and showed the phenomenon of tolerance when E. coli was grown at pH 5. Changes in the fine structure of the murein were found to be the earliest physiological changes in the cell, taking place 10 min before the onset of cellular lysis and inhibition of murein synthesis. Both the average length of the glycan strands and, with a time lag, the degree of cross-linkage were altered, indicating that a lytic transglycosylase and a DD-endopeptidase had been triggered. After extensive separation of the membranes by isopycnic sucrose gradient centrifugation, the lysis protein was present predominantly in the cytoplasmic membrane and in a fraction of intermediate density and, to a lesser degree, in the outer membrane, irrespective of the conditions of growth. However, only under lysis-permissive conditions could a 17% increase in the number of adhesion sites between the inner and outer membranes be observed. Thus, a casual relationship between lysis and the formation of lysis protein-induced adhesion sites seems to exist.


Antisense ribosomes: rRNA as a vehicle for antisense RNAs.
Although rRNA has a conserved core structure, its size varies by more than 2000 bases between eubacteria and vertebrates, mostly due to the size variation of discrete variable regions. Previous studies have shown that insertion of foreign sequences into some of these variable regions has little effect on rRNA function. These properties make rRNA a potentially very advantageous vehicle to carry other RNA moieties with biological activity, such as "antisense RNAs." We have explored this possibility by inserting antisense RNAs targeted against one essential and two nonessential genes into a site within a variable region in the Tetrahymena thermophila large subunit rRNA gene. Expression of each of the three genes tested can be drastically reduced or eliminated in transformed T. thermophila lines containing these altered rRNAs. In addition, we found that only antisense rRNAs containing RNA sequences complementary to the 5' untranslated region of the targeted mRNA were effective. Lines containing antisense rRNAs targeted against either of the nonessential genes grow well, indicating that the altered rRNAs fulfill their functions within the ribosome. Since functional rRNA is extremely abundant and stable and comes into direct contact with translated mRNAs, it may prove to be an unparalleled vehicle for enhancing the activity of functional RNAs that act on mRNAs.


Combining visual information from the two eyes: the relationship between isthmotectal cells that project to ipsilateral and to contralateral optic tectum using fluorescent retrograde labels in the frog, Rana pipiens.
The frog nucleus isthmi (homolog of the mammalian parabigeminal nucleus) is a visually responsive tegmental structure that is reciprocally connected with the ipsilateral optic tectum; cells in nucleus isthmi also project to the contralateral optic tectum. We investigated the location of the isthmotectal cells that project ipsilaterally and contralaterally using three retrograde fluorescent label solutions: Alexa Fluor 488 10,000 mw dextran conjugate; Rhodamine B isothiocyanate; and Nuclear Yellow. Dye solutions were pressure-injected into separate sites in the superficial optic tectum. Following a 6-day survival, brains were fixed, sectioned, and then photographed. Injection of the different labels at separate, discrete locations in the optic tectum result in retrograde filling of singly labeled clusters of cells in both the ipsilateral and contralateral nucleus isthmi. Generally, ipsilaterally projecting cells are dorsal to the contralaterally projecting cells, but there is a slight overlap between the two sets of cells. Nonetheless, when different retrograde labels are injected into opposite tecta, there is no indication that individual cells project to both tecta. The set of cells that project to the ipsilateral tectum and the set of cells that project to the contralateral tectum form a visuotopic map in a roughly vertical, transverse slab. Our results suggest that nucleus isthmi can be separated into two regions with cells in the dorsolateral portion projecting primarily to the ipsilateral optic tectum and cells in the ventrolateral nucleus isthmi projecting primarily to the contralateral optic tectum.


[Age dynamics of cell reaction in the preoptic hypothalamic nucleus during melatonin administration with a special reference to blockade and activation of the kisspeptinergic system].
Kisspeptin activates neurocytes and astrocytes of the preoptic hypothalamic nucleus of 1-, 3- and 24-month-old male rats. Kisspeptin antagonist (P-234) depresses the neurocytes, but not the astrocytes of the preoptic nucleus. Melatonin at a dose of 100 mkg/100 g b.w. inhibits the neurons of old male rats. During combined administration of melatonin and kisspeptin, as well as melatonin and P-234, the state of the kisspeptinergic system is crusial for the activity of the neurons in the preoptic nucleus of 1- and 3-month-old animals. However, in old rats melatonin significantly changes the neuron response of the preoptic nucleus to kisspeptin and its antagonist administration, while it's observed the neuron stimulation. Generally, the state of the kisspeptinergic system has a determining influence on the preoptic hypothalamic nucleus of the immature and young mature male rats. In old rats the cell functional state of the preoptic nucleus depends on the interaction of the kisspeptinergic system and melatonin level.


Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets.
The specific effects of U 46619 (9,11-dideoxy,9 alpha-11 alpha-methanoepoxyprostaglandin F2 alpha), thromboxane A2-prostaglandin H2 (TxA2/PGH2) analogue, on human platelet shape change, myosin light-chain phosphorylation, serotonin release, fibrinogen receptor exposure, and platelet aggregation were measured and compared with binding of [3H]U 46619 to platelets. Shape change and myosin light-chain phosphorylation were found to be saturable and dose dependent, having effective concentration producing 50% of the maximum response (EC50) values of 0.035 +/- 0.005 and 0.057 +/- 0.021 microM, respectively (mean +/- SE). These two effects were competitively inhibited by specific antagonists of TxA2/PGH2 receptors (BM 13177, PTA-OH, and 1.PTA-OH) indicating that they are receptor mediated. Binding of [3H]U 46619 showed two components. Occupancy of high-affinity binding sites [dissociation constant (Kd) = 0.041 +/- 0.009 microM, maximum binding site (Bmax) = 19.4 +/- 5.3 fmol/10(7) platelets, with 1,166 +/- 310 sites/platelet; n = 12] correlated with platelet shape change and myosin light-chain phosphorylation. We propose that a second component with an apparent Kd of 1.46 +/- 0.47 microM (n = 12) represents a second, low-affinity site. Mean EC50 values for U 46619-induced serotonin release, platelet aggregation, and fibrinogen receptor exposure were 0.54 +/- 0.13. 1.31 +/- 0.34 and 0.53 +/- 0.21 microM, respectively. Therefore, the platelet release reaction was not directly correlated with occupancy of high-affinity receptors but could be related to the second binding component of U 46619. Fibrinogen receptor exposure and platelet aggregation caused by U 46619 appeared to be events mediated by the release of adenosine diphosphate from platelet-dense granules.


Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients.
The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.


Surgical aspects of pulmonary paragonimiasis.
Pulmonary paragonimiasis is caused by the presence of the oriental lung fluke, Paragonimus westermani, within the lung parenchyma. The disease is indigenous to Korea. In a retrospective review of operative cases from 1972 through July 1979 at the National Medical Center in Seoul, Korea, eleven cases were analyzed. The mean age of the patients was 27 years, and all had a history of ingesting raw crustaceans. Diagnosis was based on history, positive skin test, and radiographic findings. The patients were treated with bithionil before undergoing surgery for severe pleural or pleuroparenchymal lung disease. There was one operative death. Long-term follow-up from 6 to 84 months indicated satisfactory results in ten patients. Our experience with this clinical entity forms the basis of this report.


Necrotising fasciitis of the left leg caused by perforated caecal adenocarcinoma.
An 82-year-old man presented with abdominal pain and a painful and swollen left thigh. On examination there was oedema, tenderness and crepitus with skin discoloration of the left thigh. Computed tomography showed retroperitoneal perforation of the caecum and necrotising fasciitis of the left thigh. A right hemicolectomy and repeated fasciotomies of the left thigh with debridement of necrotic tissue were performed but the patient died of multi-organ failure. Histology showed a pT4aN2c caecal adenocarcinoma. This is a unique presentation of a retroperitoneal caecal perforation and acts as a reminder that unexplained severe fasciitis of the thigh may be caused by an intra-abdominal pathology.


Histochemical studies with an estrogen receptor-related protein in human breast tumors.
The histochemical characteristics of a Mr 29,000 phosphoprotein related to estradiol receptor are described in a large series of human breast tumors. The antigen was detected with a monoclonal antibody (D5) raised against partially purified human myometrial estradiol receptor. An indirect immunoperoxidase method was used with methacarn-fixed, wax-embedded sections. Quantitation of staining and its reproducibility are described. Results with trucut biopsies agree with those obtained with larger tumor sections. Normal breast is infrequently positive. Histochemical staining is higher in invasive carcinoma than in normal breast with ductal carcinoma in situ adjacent to infiltrating tumors exhibiting intermediate values. Furthermore, most in situ carcinomas have a heterogeneous staining pattern. About 20% of invasive tumors also exhibit heterogeneity. No simple correlation is seen between staining and histological grade. There are more low-staining tumors in young (less than 50 yr old) patients than in older women. Staining correlates with levels of cytosol estradiol receptor but not cytosol progesterone receptor. However, cytosol estradiol receptor-negative, cytosol progesterone receptor-positive tumors tend to have positive Mr 29,000 phosphoprotein levels. Positive staining is associated with a higher response rate to hormone therapy (50%). None of the negative tumors responded to hormone treatment. With these patients, comparison of histochemical assay for Mr 29,000 phosphoprotein and [3H]estradiol binding assays indicated that the former was at least as good as the latter assay in predicting hormone response. About 20% of cytosol estradiol receptor-positive tumors have low Mr 29,000 phosphoprotein, and such tumors have poor response to hormone treatment.


Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?
Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled "Epilepsy as a Network Disorder." This was the fourth in a series of conferences, the "Fourth International Halifax Conference and Retreat". This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy.


A reassessment of the assay for the asialoglycoprotein receptor and its use in the quantification of receptor distribution in hepatocytes.
The assay for the fucose-binding protein described by Lehrman & Hill [(1983) Methods Enzymol. 98, 309-319] was adapted for the measurement of the asialoglycoprotein receptor in rat liver. The amount of ligand bound to the plasma-membrane-associated or affinity-purified receptor was acutely sensitive to the concentrations of Triton X-100 and NaCl in the assay: 0.02% (v/v) Triton X-100 increased ligand binding to the two preparations by 100% and 40% respectively. Higher concentrations of detergent progressively decreased binding, and in 0.32% Triton X-100 it was about 30% of the value obtained in detergent-free buffer. The addition of increasing concentrations of NaCl to the assay progressively inhibited ligand binding to the membrane-associated receptor, whereas there was a 60% increase in binding to the pure receptor in the presence of 0.1-0.2 M-NaCl. These effects could not be identified in the original assay procedure described by Hudgin, Pricer, Ashwell, Stockert & Morell [(1974) J. Biol. Chem. 249, 5536-5543]. Using optimal assay conditions the binding of 125I-beta-D-galactosyl-bovine serum albumin to both the membrane-associated and purified receptor was inhibited by 50% by 1 nM-beta-D-galactosyl-bovine serum albumin and -asialoorosomucoid and by approx. 100 microM-beta-L-fucosyl-bovine serum albumin, whereas beta-D-galactose, lactose and beta-L-fucose had no effect on ligand binding up to concentrations of 1 mM, 500 microM and 5 mM respectively. KD values of 0.94 and 1.25 nM and Bmax. values of 40 and 1660 pmol of D-galactosyl-bovine serum albumin bound/mg of receptor were obtained for the membrane-bound and purified receptor respectively. Hill-plot analysis of the same data gave slopes of 0.96 and 1.01. Scatchard analysis of saturation-binding studies with other subcellular fractions indicated that the receptor was distributed in the proportions 72:23:2.5:2.5 between total microsomal fractions, plasma membrane, Golgi and canalicular membrane respectively. The receptor was about 1% of the total protein in each compartment and was estimated to be about 0.3% of the total liver protein.


Longitudinal analysis of colon crypt stem cell dynamics in sulindac treated Familial Adenomatous Polyposis patients.
The non-steroidal anti-inflammatory drug sulindac decreases size and number of adenomas after 4-6 months of treatment for familial adenomatous polyposis (FAP) patients. However, the underlying mechanism remains unknown. As stem cells are thought to be the tumor precursor cells, visualizing their behavior is crucial for monitoring tumor progression. Increased tag diversity in inactive genes is indicative of a protracted clonal evolution and consequently, increased risk for tumor formation. Therefore, the effect of sulindac on stem cell dynamics was studied. Normal appearing single crypts were laser microdissected in placebo- and sulindac- treated FAP patient tissue after which the methylation patterns were visualized by Next Generation Sequencing. A significant difference in tag diversity over time was found in the sulindac group compared to the placebo group (*p = 0.018), indicative of a shortened clonal evolution treated sulindac. The rate of change in tag diversity over time was correlated with polyp number change over time. No significant difference over time was observed in the percent methylation when comparing placebo vs sulindac. In conclusion, daily sulindac administration in FAP patients significantly altered colorectal stem cell dynamics, which might explain the chemopreventive action of this drug indicating that tag diversity may be used as a predictive biomarker.


Optimum design of a moderator system based on dose calculation for an accelerator driven Boron Neutron Capture Therapy.
An accelerator based BNCT has been desired because of its therapeutic convenience. However, optimal design of a neutron moderator system is still one of the issues. Therefore, detailed studies on materials consisting of the moderator system are necessary to obtain the optimal condition. In this study, the epithermal neutron flux and the RBE dose have been calculated as the indicators to look for optimal materials for the filter and the moderator. As a result, it was found that a combination of MgF2 moderator with Fe filter gave best performance, and the moderator system gave a dose ratio greater than 3 and an epithermal neutron flux over 1.0×10(9)cm(-2)s(-1).


Longitudinal changes in microperimetry and low luminance visual acuity in age-related macular degeneration.
There is a need for more sensitive measures of disease in intermediate age-related macular degeneration (AMD) to evaluate novel interventions more effectively and expediently. To determine if microperimetry and low luminance visual acuity can detect functional changes over a short duration of follow-up. Prospective longitudinal examination of 49 participants with consecutive AMD and 10 healthy participants in a research clinic from May 1, 2012, to December 31, 2013. Forty-one participants had intermediate AMD, 8 had nonfoveal geographic atrophy due to AMD. Participants underwent microperimetry examinations in 1 eye during a 12-month period at 6-month intervals for participants with AMD and at baseline and 12 months for control participants; low luminance visual acuity was performed at baseline and at 12 months for all participants. Changes in pathological features of intermediate AMD eyes were determined using side-by-side comparisons of color fundus photographs from the initial and final visit as remaining stable, progressed, or improved. Microperimetric sensitivity and low luminance visual acuity. A reduction in mean (SE) microperimetric pointwise sensitivity was identified at 12 months compared with the baseline for intermediate AMD eyes graded as stable (-0.31 dB [0.10 dB]; P = .003) or worsened (-0.42 dB [0.12 dB]; P < .001) and an improvement in mean (SE) pointwise sensitivity was identified in eyes graded as improved (1.13 dB [0.23 dB]; P < .001). A reduction in mean (SE) pointwise sensitivity was identified in eyes with nonfoveal geographic atrophy at both 6 months (-1.41 dB [0.22 dB]; P < .001) and 12 months compared with the baseline (-2.56 dB [0.22 dB]; P < .001) while a change in mean (SE) pointwise sensitivity was not identified over the 12-month period for control participants (-0.11 dB [0.11 dB]; P = .34). No changes in best-corrected visual acuity or low luminance visual acuity were identified in all groups over the 12-month period (P ≥ .07). Microperimetry detected subtle changes in visual function over a 12-month period in eyes with intermediate AMD but visual acuity measures did not identify any such changes. These findings suggest that microperimetry is worth exploring as a method for assessing the efficacy of novel interventions for intermediate AMD potentially requiring a shorter duration of follow-up.


Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload?
Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production.


Laparoscopic Gastric Banding: preliminary series.
Gastric banding as a laparoscopic procedure was performed on 40 morbidly obese patients. This operation matches the advantages of the gastric banding (efficacy, reversibility and low invasivity) with the advantages of the laparoscopic procedure (low surgical risk, short hospital stay and less complications in the short and long term). The maximum follow-up is 6 months and so far the weight loss results are the same as we obtained by the vertical banded gastroplasty of Mason. The greatest problem of laparoscopic gastric banding is to get the right tightness of the band for a stoma of 12-13 mm. In three patients the band was replaced due to stenosis, in two of them by a laparoscopic procedure. The adjustable band of Kuzmak should exclude the risk of stenosis and its use will be tried by the laparoscopic procedure.


Src and caveolin-1 reciprocally regulate metastasis via a common downstream signaling pathway in bladder cancer.
In bladder cancer, increased caveolin-1 (Cav-1) expression and decreased Src expression and kinase activity correlate with tumor aggressiveness. Here, we investigate the clinical and functional significance, if any, of this reciprocal expression in bladder cancer metastasis. We evaluated the ability of tumor Cav-1 and Src RNA and protein expression to predict outcome following cystectomy in 257 patients enrolled in two independent clinical studies. In both, high Cav-1 and low Src levels were associated with metastasis development. We overexpressed or depleted Cav-1 and Src protein levels in UMUC-3 and RT4 human bladder cancer cells and evaluated the effect of this on actin stress fibers, migration using Transwells, and lung metastasis following tail vein inoculation. Cav-1 depletion or expression of active Src in metastatic UMUC-3 cells decreases actin stress fibers, cell migration, and metastasis, while Cav-1 overexpression or Src depletion increased the migration of nonmetastatic RT4 cells. Biochemical studies indicated that Cav-1 mediates these effects via its phosphorylated form (pY14), whereas Src effects are mediated through phosphorylation of p190RhoGAP and these pathways converge to reduce activity of RhoA, RhoC, and Rho effector ROCK1. Treatment with a ROCK inhibitor reduced UMUC-3 lung metastasis in vivo, phenocopying the effect of Cav-1 depletion or expression of active Src. Src suppresses whereas Cav-1 promotes metastasis of bladder cancer through a pharmacologically tractable common downstream signaling pathway. Clinical evaluation of personalized therapy to suppress metastasis development based on Cav-1 and Src profiles seems warranted.


[Fecal examination of Shami goats from Damascus with respiratory syndrome].
This study was carried out in order to determine the prevalence of helminth species and their relation to the respiratory syndrome in Damascus goats bred in Hatay, Turkey. Fecal samples obtained from 130 Shami goats with respiratory signs including coughing, growling respiration and mucopurulent discharge were examined using the Fulleborne's salt saturated flotation, Benedek sedimentation and Baerman Wetzel methods. Helminth invasions were commonly observed in the goats. Of these goats, 68.46% were found to be infected by various helminth species. Besides this, 30% of the goats were infected with Eimeria species. The percentage of lung nematodes causing respiratory syndrome in goats was found to be 18.46. In conclusion, the goats with respiratory syndrome should also be examined for lung nematodes.


A rite of passage: The White Coat Ceremony for advanced practice registered nursing students.
Since 1993, when the Gold Foundation held its first White Coat Ceremony (WCC) to highlight humanism in medicine, many health professions have launched these ceremonies. In 2021, the University of Colorado College of Nursing hosted its first WCC. Postevent, a seven-question survey was sent to all faculty, staff, and student participants. The analytic question driving this program evaluation was as follows: "What is the significance of the White Coat Ceremony to APRN students?" Quantitative data from survey items were overwhelmingly positive; qualitative analysis of open-ended survey text reinforced the central WCC concept of Being/Becoming an APRN and elicited four themes: recognition, transition, symbolism, and connection. A detailed analysis of these themes is presented.


Effect of antispastic drugs on rapid force generation of spastic muscle.
The effect of antispastic drugs, dantrolene sodium and baclofen, on the initiation of rapid knee extension was examined in 8 normal subjects and 8 patients with spastic hemiparesis. Three biomechanical variables, the latency between EMG onset of the rectus femoris and rise of tension (TLT), that between the rise of tension and the maximum tension of knee extension (FTmax) and the maximum tension attained (Fmax), were measured before and after administration of one of the drugs. Dantrolene sodium increased TLT, but did not change FTmax or Fmax. The increase of TLT was remarkable in the normal subjects and the non-affected side, compared to the affected side of the patients. Baclofen did not modify TLT or FTmax, but decreased Fmax. The decrease of Fmax was definite in the normal subjects while it was negligible in the affected side of the patients. Clinical implications and pathophysiological mechanisms of these results were discussed.


Distinct Roles of Interferon Alpha and Beta in Controlling Chikungunya Virus Replication and Modulating Neutrophil-Mediated Inflammation.
Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation.IMPORTANCE Type I interferons (IFNs) possess a range of biological activity and protect against a number of viruses, including alphaviruses. Despite signaling through a shared receptor, there are established biochemical and functional differences among the IFN subtypes. The significance of our research is in demonstrating that IFN-α and IFN-β both have protective roles during acute chikungunya virus (CHIKV) infection but do so by distinct mechanisms. IFN-α limits CHIKV replication and dissemination, whereas IFN-β protects from CHIKV pathogenesis by limiting inflammation mediated by neutrophils. Our findings support the premise that the IFN subtypes have distinct biological activities in the antiviral response.


Quantum pressure focusing in solids: a reconstruction from experimental electron density.
Here an approach is presented for reconstructing the distribution of electronic internal quantum pressure in the electronic continuum of solids from the experimental electron density. Using the formalism of the density functional theory, the spatial inner-crystal map of the quantum pressure is obtained. The results are visualized via the indicator of quantum pressure focusing (IQPF) which reveals the regions where the pressure is concentrated or depleted due to quantum effects. IQPF contains all quantum electron-shell structure-forming contributions resulting from kinetic, exchange and correlation effects, and presents a clear picture of the chemical bond features in crystals with different type of bonding mechanisms.


Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease.
The American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol treatment guidelines have wide-scale implications for treating adults without history of atherosclerotic cardiovascular disease (ASCVD) with statins. To estimate the cost-effectiveness of various 10-year ASCVD risk thresholds that could be used in the ACC/AHA cholesterol treatment guidelines. Microsimulation model, including lifetime time horizon, US societal perspective, 3% discount rate for costs, and health outcomes. In the model, hypothetical individuals from a representative US population aged 40 to 75 years received statin treatment, experienced ASCVD events, and died from ASCVD-related or non-ASCVD-related causes based on ASCVD natural history and statin treatment parameters. Data sources for model parameters included National Health and Nutrition Examination Surveys, large clinical trials and meta-analyses for statin benefits and treatment, and other published sources. Estimated ASCVD events prevented and incremental costs per quality-adjusted life-year (QALY) gained. In the base-case scenario, the current ASCVD threshold of 7.5% or higher, which was estimated to be associated with 48% of adults treated with statins, had an incremental cost-effectiveness ratio (ICER) of $37,000/QALY compared with a 10% or higher threshold. More lenient ASCVD thresholds of 4.0% or higher (61% of adults treated) and 3.0% or higher (67% of adults treated) had ICERs of $81,000/QALY and $140,000/QALY, respectively. Shifting from a 7.5% or higher ASCVD risk threshold to a 3.0% or higher ASCVD risk threshold was estimated to be associated with an additional 161,560 cardiovascular disease events averted. Cost-effectiveness results were sensitive to changes in the disutility associated with taking a pill daily, statin price, and the risk of statin-induced diabetes. In probabilistic sensitivity analysis, there was a higher than 93% chance that the optimal ASCVD threshold was 5.0% or lower using a cost-effectiveness threshold of $100,000/QALY. In this microsimulation model of US adults aged 45 to 75 years [corrected], the current 10-year ASCVD risk threshold (≥7.5% risk threshold) used in the ACC/AHA cholesterol treatment guidelines has an acceptable cost-effectiveness profile (ICER, $37,000/QALY), but more lenient ASCVD thresholds would be optimal using cost-effectiveness thresholds of $100,000/QALY (≥4.0% risk threshold) or $150,000/QALY (≥3.0% risk threshold). The optimal ASCVD threshold was sensitive to patient preferences for taking a pill daily, changes to statin price, and the risk of statin-induced diabetes.


A backbone lever-arm effect enhances polymer mechanochemistry.
Mechanical forces along a polymer backbone can be used to bring about remarkable reactivity in embedded mechanically active functional groups, but little attention has been paid to how a given polymer backbone delivers that force to the reactant. Here, single-molecule force spectroscopy was used to directly quantify and compare the forces associated with the ring opening of gem-dibromo and gem-dichlorocyclopropanes affixed along the backbone of cis-polynorbornene and cis-polybutadiene. The critical force for isomerization drops by about one-third in the polynorbornene scaffold relative to polybutadiene. The root of the effect lies in more efficient chemomechanical coupling through the polynorbornene backbone, which acts as a phenomenological lever with greater mechanical advantage than polybutadiene. The experimental results are supported computationally and provide the foundation for a new strategy by which to engineer mechanochemical reactivity.


Genetic and biochemical characterization of field-evolved resistance to Bacillus thuringiensis toxin Cry1Ac in the diamondback moth, Plutella xylostella.
The long-term usefulness of Bacillus thuringiensis Cry toxins, either in sprays or in transgenic crops, may be compromised by the evolution of resistance in target insects. Managing the evolution of resistance to B. thuringiensis toxins requires extensive knowledge about the mechanisms, genetics, and ecology of resistance genes. To date, laboratory-selected populations have provided information on the diverse genetics and mechanisms of resistance to B. thuringiensis, highly resistant field populations being rare. However, the selection pressures on field and laboratory populations are very different and may produce resistance genes with distinct characteristics. In order to better understand the genetics, biochemical mechanisms, and ecology of field-evolved resistance, a diamondback moth (Plutella xylostella) field population (Karak) which had been exposed to intensive spraying with B. thuringiensis subsp. kurstaki was collected from Malaysia. We detected a very high level of resistance to Cry1Ac; high levels of resistance to B. thuringiensis subsp. kurstaki Cry1Aa, Cry1Ab, and Cry1Fa; and a moderate level of resistance to Cry1Ca. The toxicity of Cry1Ja to the Karak population was not significantly different from that to a standard laboratory population (LAB-UK). Notable features of the Karak population were that field-selected resistance to B. thuringiensis subsp. kurstaki did not decline at all in unselected populations over 11 generations in laboratory microcosm experiments and that resistance to Cry1Ac declined only threefold over the same period. This finding may be due to a lack of fitness costs expressed by resistance strains, since such costs can be environmentally dependent and may not occur under ordinary laboratory culture conditions. Alternatively, resistance in the Karak population may have been near fixation, leading to a very slow increase in heterozygosity. Reciprocal genetic crosses between Karak and LAB-UK populations indicated that resistance was autosomal and recessive. At the highest dose of Cry1Ac tested, resistance was completely recessive, while at the lowest dose, it was incompletely dominant. A direct test of monogenic inheritance based on a backcross of F1 progeny with the Karak population suggested that resistance to Cry1Ac was controlled by a single locus. Binding studies with 125I-labeled Cry1Ab and Cry1Ac revealed greatly reduced binding to brush border membrane vesicles prepared from this field population.


Interaction in cyberspace: an online focus group.
This paper reports a study that explored whether active engagement and group interaction could be captured in an online environment. Focus groups have become a common means of capitalizing on group interaction to collect rich responses to questions posed. Whilst their use is well established in the repertoire of qualitative researchers, with changing technology there is the opportunity to use a computer program that facilitates online engagement and interaction to bring together a group of people to explore issues, attitudes and perceptions. Using a qualitative descriptive method and purposive sampling, 38 Australian Enrolled Nurses participated in an online focus group. WebCT, a program that facilitates online engagement and interaction, was used to enable participants to interact from any computer, from any location, at any time. The experience of conducting an online focus group was a positive one. Advantages such as cost savings and convenience for both researcher and participants were identified. This study demonstrated that participants could be actively engaged over a 2-month period and that group interaction could be achieved to collect richly detailed research data. Whilst online focus groups may not be suitable in every situation, the potential exists to capitalize on technology to bring together a group of people separated by distance in an online environment that encourages interactive discussion.


Crossover from vibrational to rotational collectivity in heavy nuclei in the shell-model Monte Carlo approach.
Heavy nuclei exhibit a crossover from vibrational to rotational collectivity as the number of neutrons or protons increases from shell closure towards midshell, but the microscopic description of this crossover has been a major challenge. We apply the shell model Monte Carlo approach to families of even-even samarium and neodymium isotopes and identify a microscopic signature of the crossover from vibrational to rotational collectivity in the low-temperature behavior of ⟨J(2)⟩(T), where J is the total spin and T is the temperature. This signature agrees well with its values extracted from experimental data. We also calculate the state densities of these nuclei and find them to be in very good agreement with experimental data. Finally, we define a collective enhancement factor from the ratio of the total state density to the intrinsic state density as calculated in the finite-temperature Hartree-Fock-Bogoliubov approximation. The decay of this enhancement factor with excitation energy is found to correlate with the pairing and shape phase transitions in these nuclei.


Elucidating the Effect of a Brief Drinking Intervention Using Neuroimaging: A Preliminary Study.
Brief interventions have empirical support for acutely reducing alcohol use among non-treatment-seeking heavy drinkers. Neuroimaging techniques allow for the examination of the neurobiological effect of behavioral interventions, probing brain systems putatively involved in clinical response to treatment. Few studies have prospectively evaluated whether psychosocial interventions attenuate neural cue reactivity that in turn reduces drinking in the same population. This study aimed to examine the effect of a brief intervention on drinking outcomes, neural alcohol cue reactivity, and the ability of neural alcohol cue reactivity to prospectively predict drinking outcomes. Non-treatment-seeking heavy drinking participants were randomized to receive a brief interview intervention (n = 22) or an attention-matched control (n = 24). Immediately following the intervention or control, participants underwent a functional magnetic resonance imaging scan comprised of the alcohol taste cues paradigm. Four weeks after the intervention (or control), participants completed a follow-up visit to report on their past-month drinking. Baseline and follow-up percent heavy drinking days (PHDD) were calculated for each participant. There was no significant effect of the brief intervention on PHDD at follow-up or on modulating neural activation to alcohol relative to water taste cues. There was a significant association between neural response to alcohol taste cues and PHDD across groups (Z > 2.3, p < 0.05), such that individuals who had greater neural reactivity to alcohol taste cues in the precuneus and prefrontal cortex (PFC) had fewer PHDD at follow-up. This study did not find an effect of the brief intervention on alcohol use in this sample, and the intervention was not associated with differential neural alcohol cue reactivity. Nevertheless, greater activation of the precuneus and PFC during alcohol cue exposure predicted less alcohol use prospectively suggesting that these neural substrates subserve the effects of alcohol cues on drinking behavior.


Quantitative wear particle analysis for osteoarthritis assessment.
Osteoarthritis is a degenerative joint disease that affects millions of people worldwide. The aims of this study were (1) to quantitatively characterise the boundary and surface features of wear particles present in the synovial fluid of patients, (2) to select key numerical parameters that describe distinctive particle features and enable osteoarthritis assessment and (3) to develop a model to assess osteoarthritis conditions using comprehensive wear debris information. Discriminant analysis was used to statistically group particles based on differences in their numerical parameters. The analysis methods agreed with the clinical osteoarthritis grades in 63%, 50% and 61% of particles for no osteoarthritis, mild osteoarthritis and severe osteoarthritis, respectively. This study has revealed particle features specific to different osteoarthritis grades and provided further understanding of the cartilage degradation process through wear particle analysis - the technique that has the potential to be developed as an objective and minimally invasive method for osteoarthritis diagnosis.


Associations between serum taurine concentrations in mothers and neonates and the children's anthropometrics and early neurodevelopment: Results from the Seychelles Child Development Study, Nutrition Cohort 2.
High concentrations of taurine are present in the developing human brain and maternal breast milk. Taurine is thought to influence fetal growth and brain development based on experimental rodent studies. As fish is an important dietary source of taurine, we investigated associations between taurine concentrations and child outcomes in a high fish consuming population. To examine associations between maternal and cord serum taurine concentrations and birth anthropometric measures and cognitive development in children at 20 months of age. Pregnant women were recruited between 2008 and 2011 as part of Nutrition Cohort 2 (NC2) of the Seychelles Child Development Study (SCDS). Maternal taurine serum concentrations were measured at 28 week's gestation and in cord serum. Child weight, length and head circumference were measured at birth and neurodevelopment was assessed using Bayley Scales of Infant Development II (BSID-II) at 20 months of age. Associations between taurine status, birth measures and neurodevelopmental outcomes were examined (n = 300) using regression models and adjusted for relevant covariates. Mean (SD) maternal and cord taurine concentrations were 124.9 (39.2) µmol/L (range 28.2-253.9 µmol/L) and 187.6 (60.0) µmol/L (range 55.0-417.4 µmol/L) respectively. We found no associations between maternal taurine concentrations and child anthropometric and neurodevelopmental measures (weight β = -0.001, SE=0.001; length β = -0.006, SE=0.006; head circumference β = -0.002, SE=0.002; MDI β = -0.005, SE=0.015; PDI β = -0.004, SE=0.016; all P > 0.05), or between cord taurine concentrations and outcomes (weight β = -0.001, SE<0.000; length β = -0.001, SE=0.004; head circumference β < 0.000, SE=0.002; MDI β = 0.004, SE=0.010; PDI β = -0.015, SE=0.012; all P > 0.05). The Seychellois population have high maternal and cord taurine concentrations owing to their high fish intake and may be considered taurine replete compared to individuals who consume a Westernised diet. This high taurine status may explain why there were no significant associations between maternal and cord taurine concentrations and outcomes after adjusting for covariates.


Leptin receptor signaling in T cells is required for Th17 differentiation.
The hormone leptin plays a key role in energy homeostasis, and the absence of either leptin or its receptor (LepR) leads to severe obesity and metabolic disorders. To avoid indirect effects and to address the cell-intrinsic role of leptin signaling in the immune system, we conditionally targeted LepR in T cells. In contrast with pleiotropic immune disorders reported in obese mice with leptin or LepR deficiency, we found that LepR deficiency in CD4(+) T cells resulted in a selective defect in both autoimmune and protective Th17 responses. Reduced capacity for differentiation toward a Th17 phenotype by lepr-deficient T cells was attributed to reduced activation of the STAT3 and its downstream targets. This study establishes cell-intrinsic roles for LepR signaling in the immune system and suggests that leptin signaling during T cell differentiation plays a crucial role in T cell peripheral effector function.


Autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED)--a diagnostic and therapeutic challenge.
Autoimmune polyendocrinopathy - candidosis - ectodermal dystrophy (APECED), also known as autoimmune polyendocrine/polyglandular syndrome type 1 (APS1), is a rare disease caused by mutations in the autoimmune regulator (AIRE) gene pair resulting in absence of active AIRE protein, which is essential for both central and peripheral self-tolerance. The phenotype is widely variable. Apart from the classical triad of mucocutaneous candidosis, hypoparathyroidism and adrenal failure, several other components, some of which are potentially life-threatening, may develop. Due to the unpredictable clinical course, the patients need regular follow-up by a clinician familiar with the disease. Diagnosis is often possible by clinical diagnostic criteria, but in many cases the early clinical picture does not bring it to mind. A novel tool, search for autoantibodies against interferon-omega, enables proof or exclusion of APECED with more certainty than gene analysis. It is highly specific and sensitive for APECED if thymoma and myasthenia gravis are excluded.


Differences in cross-protection in rats immunized with the B subunits of cholera toxin and Escherichia coli heat-labile toxin.
Although cholera toxin (CT), Escherichia coli heat-labile toxin (LT), and their B subunits are known to be immunologically related, the ability of each to raise an antitoxin response that provides equally strong cross-protection against active challenge with pure heterologous toxin has not been examined previously. We immunized rats with pure preparations of the B subunits of human LT, porcine LT, and CT. Immunization with either of the LT B subunits raised greater than or equal to fourfold increases in specific mucosal immunoglobulin A antitoxin titers to homologous and heterologous LT and CT B subunits, thereby providing strong protection against active challenge in ligated ileal loops with all three respective holotoxins and with a viable LT-producing E. coli strain. In contrast, immunization with the CT B subunit raised a greater than or equal to fourfold increase in antitoxin titers only to itself and provided strong protection only against challenge with the CT holotoxin. Conjugation of the CT B subunit with the E. coli heat-stable toxin by the carbodiimide reaction yielded a cross-linked immunogen with equal antigenicity for both components; immunization with this conjugate raised greater than or equal to fourfold increases in antitoxin titers to both components, but it provided significant protection only against challenge with a viable heat-stable toxin-producing E. coli strain and not to an LT-producing E. coli strain. These observations indicate that immunization with the LT B subunits raises a heterologous antitoxin response that extends to the CT B subunit, thereby providing equally strong protection against LT and CT; however, immunization with the CT B subunit raises principally a homologous antitoxin response, so that this immunogen provides strong protection only against CT.


A systematic review of reviews of neurocognitive functioning in eating disorders: The state-of-the-literature and future directions.
In recent years there has been increasing clinical and empirical interest in neurocognitive functioning in eating disorders (EDs), which has resulted in numerous quantitative and qualitative reviews. However, there has yet to be a comprehensive synthesis or critical review of this literature to identify future directions to advance the field in this area. Therefore the aim of this systematic review of systematic reviews was to (a) characterize the existing literature on neurocognitive functioning in EDs based on recent reviews (i.e., published since 2010), (b) describe related limitations, and (c) suggest avenues for future research to address gaps in the current literature. Electronic databases were queried for reviews of neurocognitive domains (i.e., inhibitory control, decision-making, central coherence, set-shifting, working memory, and attention bias) in EDs, which identified 28 systematic and meta-analytic reviews. Broadly, the literature indicates deficits across these neurocognitive domains in EDs, though heterogeneity was noted in the magnitude of these effects, which varied to some extent across ED subtypes, sample characteristics, and methodological approaches. While these reviews have generally suggested varying patterns of neurocognitive deficits across EDs, there remain critical limitations regarding the methodological quality of these studies (e.g., the lack of prospective designs, consideration of confounding influences, or examination of interrelationships between neurocognitive domains and relationships between neurocognition and other relevant behavioral constructs). Specifically, we outline 10 key areas that are imperative to address in future research in this area in order to move our field forward.


A prospective, randomized, parallel group, controlled study of the effect of intensity of speech and language therapy on early recovery from poststroke aphasia.
To examine whether the amount of speech and language therapy influences the recovery from poststroke aphasia. A hospital stroke unit and community. A prospective, randomized controlled trial. Aphasic stroke patients were randomly allocated to receive 5 hours (intensive therapy group, n=51) or 2 hours (standard therapy group) of speech and language therapy per week for 12 consecutive weeks starting as soon as practicable after the stroke. Another 19 patients were recruited for 2 hours per week of therapy and were treated by National Health Service (NHS) staff (NHS group). OUTCOME MEASURE AND ASSESSMENT: The Western Aphasia Battery. Assessments were made blind to randomization at baseline and 4, 8, 12 and 24 weeks after the start of therapy. Data were analysed by intention to treat. The mean (SD) Western Aphasia Battery score at week 12 for the intensive, standard and NHS groups was 70.3 (26.9), 66.2 (26.2) and 58.1 (33.7), respectively. There was no treatment effect of intensive therapy (P > 0.05), but there was a statistically significant difference between the standard study and the NHS groups (P = 0.002 at week 12 and 0.01 at week 24). Intensive speech and language therapy (as delivered in this study) did not improve the language impairment significantly more than the ;standard' therapy which averaged 1.6 hours/week. The improvement in aphasia was least in patients who were in the NHS group. These patients received 0.57 (0.49) hours of therapy per week.


microRNA159-targeted SlGAMYB transcription factors are required for fruit set in tomato.
The transition from flowering to fruit production, namely fruit set, is crucial to ensure successful sexual plant reproduction. Although studies have described the importance of hormones (i.e. auxin and gibberellins) in controlling fruit set after pollination and fertilization, the role of microRNA-based regulation during ovary development and fruit set is still poorly understood. Here we show that the microRNA159/GAMYB1 and -2 pathway (the miR159/GAMYB1/2 module) is crucial for tomato ovule development and fruit set. MiR159 and SlGAMYBs were expressed in preanthesis ovaries, mainly in meristematic tissues, including developing ovules. SlMIR159-overexpressing tomato cv. Micro-Tom plants exhibited precocious fruit initiation and obligatory parthenocarpy, without modifying fruit shape. Histological analysis showed abnormal ovule development in such plants, which led to the formation of seedless fruits. SlGAMYB1/2 silencing in SlMIR159-overexpressing plants resulted in misregulation of pathways associated with ovule and female gametophyte development and auxin signalling, including AINTEGUMENTA-like genes and the miR167/SlARF8a module. Similarly to SlMIR159-overexpressing plants, SlGAMYB1 was downregulated in ovaries of parthenocarpic mutants with altered responses to gibberellins and auxin. SlGAMYBs likely contribute to fruit initiation by modulating auxin and gibberellin responses, rather than their levels, during ovule and ovary development. Altogether, our results unveil a novel function for the miR159-targeted SlGAMYBs in regulating an agronomically important trait, namely fruit set.


Whole lichen thalli survive exposure to space conditions: results of Lithopanspermia experiment with Aspicilia fruticulosa.
The Lithopanspermia space experiment was launched in 2007 with the European Biopan facility for a 10-day spaceflight on board a Russian Foton retrievable satellite. Lithopanspermia included for the first time the vagrant lichen species Aspicilia fruticulosa from Guadalajara steppic highlands (Central Spain), as well as other lichen species. During spaceflight, the samples were exposed to selected space conditions, that is, the space vacuum, cosmic radiation, and different spectral ranges of solar radiation (λ ≥ 110, ≥200, ≥290, or ≥400 nm, respectively). After retrieval, the algal and fungal metabolic integrity of the samples were evaluated in terms of chlorophyll a fluorescence, ultrastructure, and CO(2) exchange rates. Whereas the space vacuum and cosmic radiation did not impair the metabolic activity of the lichens, solar electromagnetic radiation, especially in the wavelength range between 100 and 200 nm, caused reduced chlorophyll a yield fluorescence; however, there was a complete recovery after 72 h of reactivation. All samples showed positive rates of net photosynthesis and dark respiration in the gas exchange experiment. Although the ultrastructure of all flight samples showed some probable stress-induced changes (such as the presence of electron-dense bodies in cytoplasmic vacuoles and between the chloroplast thylakoids in photobiont cells as well as in cytoplasmic vacuoles of the mycobiont cells), we concluded that A. fruticulosa was capable of repairing all space-induced damage. Due to size limitations within the Lithopanspermia hardware, the possibility for replication on the sun-exposed samples was limited, and these first results on the resistance of the lichen symbiosis A. fruticulosa to space conditions and, in particular, on the spectral effectiveness of solar extraterrestrial radiation must be considered preliminary. Further testing in space and under space-simulated conditions will be required. Results of this study indicate that the quest to discern the limits of lichen symbiosis resistance to extreme environmental conditions remains open.


Acute myopericarditis caused by Salmonella enterica serovar Enteritidis: a case report.
Acute myopericarditis can be caused by a myriad of infectious and non-infectious aetiologies, however, it is often considered to be due to self-limiting viral infection. Salmonella spp. myopericarditis is rare and the few cases in the literature suggest significant associated morbidity and mortality. A 44-year-old man presented with fever, dyspnoea, and chest pain. He was found to have a large pericardial effusion with clinical signs of tamponade and sepsis. Therapeutic pericardiocentesis was performed and ceftriaxone and levofloxacin were administered. Fully sensitive Salmonella enterica serovar Enteritidis (S. Enteritidis) was isolated in his pericardial fluid and he made a full recovery after a 4-week course of ciprofloxacin. A new diagnosis of type 2 diabetes mellitus was made on admission. A follow-up cardiac magnetic resonance (CMR) scan was suggestive of myocarditis which was unexpected given a normal Troponin T level on presentation. We report a rare case of S. Enteritidis myopericarditis. Our case is notable as the patient was immunocompetent apart from newly diagnosed diabetes. This case highlights the value of CMR imaging in assessing for myocarditis and ventricular function.


Assessment of the assessment: evaluation of the model quality estimates in CASP10.
The article presents an assessment of the ability of the thirty-seven model quality assessment (MQA) methods participating in CASP10 to provide an a priori estimation of the quality of structural models, and of the 67 tertiary structure prediction groups to provide confidence estimates for their predicted coordinates. The assessment of MQA predictors is based on the methods used in previous CASPs, such as correlation between the predicted and observed quality of the models (both at the global and local levels), accuracy of methods in distinguishing between good and bad models as well as good and bad regions within them, and ability to identify the best models in the decoy sets. Several numerical evaluations were used in our analysis for the first time, such as comparison of global and local quality predictors with reference (baseline) predictors and a ROC analysis of the predictors' ability to differentiate between the well and poorly modeled regions. For the evaluation of the reliability of self-assessment of the coordinate errors, we used the correlation between the predicted and observed deviations of the coordinates and a ROC analysis of correctly identified errors in the models. A modified two-stage procedure for testing MQA methods in CASP10 whereby a small number of models spanning the whole range of model accuracy was released first followed by the release of a larger number of models of more uniform quality, allowed a more thorough analysis of abilities and inabilities of different types of methods. Clustering methods were shown to have an advantage over the single- and quasi-single- model methods on the larger datasets. At the same time, the evaluation revealed that the size of the dataset has smaller influence on the global quality assessment scores (for both clustering and nonclustering methods), than its diversity. Narrowing the quality range of the assessed models caused significant decrease in accuracy of ranking for global quality predictors but essentially did not change the results for local predictors. Self-assessment error estimates submitted by the majority of groups were poor overall, with two research groups showing significantly better results than the remaining ones.


Online activity and participation in treatment affects the perceived efficacy of social health networks among patients with chronic illness.
The use of online health-related social networks for support, peer-to-peer connections, and obtaining health information has increased dramatically. Participation in an online health-related social network can enhance patients' self-efficacy and empowerment, as they are given knowledge and tools to manage their chronic health condition more effectively. Thus, we can deduce that patient activation, the extent to which individuals are able to manage their own health care, also increases. However, little is known about the effects of participation in online health-related social networks and patient activation on the perceived usefulness of a website across disease groups. The intent of the study was to evaluate the effects and benefits of participation in an online health-related social network and to determine which variables predict perceived site usefulness, while examining patient activation. Data were collected from "Camoni", the first health-related social network in the Hebrew language. It offers medical advice, including blogs, forums, support groups, internal mail, chats, and an opportunity to consult with experts. This study focused on the site's five largest and most active communities: diabetes, heart disease, kidney disease, spinal injury, and depression/anxiety. Recruitment was conducted during a three-month period in which a link to the study questionnaire was displayed on the Camoni home page. Three questionnaires were used: a 13-item measure of perceived usefulness (Cronbach alpha=.93) to estimate the extent to which an individual found the website helpful and informative, a 9-item measure of active involvement in the website (Cronbach alpha=.84), and The Patient Activation Measure (PAM-13, Cronbach alpha=.86), which assesses a patient's level of active participation in his or her health care. There were 296 participants. Men 30-39 years of age scored higher in active involvement than those 40-49 years (P=.03), 50-64 years (P=.004), or 65+ years (P=.01). Respondents 20-29 years of age scored higher in perceived usefulness than those 50-64 years (P=.04) and those 65+ years (P=.049). Those aged 20-29 years scored significantly lower on the PAM-13 scale than those aged 30-39 years (P=.01) and 50-64 years (P=.049). Men and women had similar PAM-13 scores (F9,283=0.17, P=.76). Several variables were significant predictors of perceived usefulness. Age was a negative predictor; younger age was indicative of higher perceived usefulness. Active involvement was a positive predictor. There was a negative relationship found between PAM-13 scores and perceived usefulness, as taking a less active role in one's own medical care predicted higher perceived website usefulness. A trend toward higher frequency of website activity was associated with increased perception of usefulness. Online health-related social networks can be particularly helpful to individuals with lower patient activation. Our findings add information regarding the social and medical importance of such websites, which are gradually becoming an inseparable part of day-to-day chronic disease management in the community.


Plasma neutrophil gelatinase-associated lipocalin predicts renal tubulointerstitial injury in patients with IgA nephropathy.
To investigate the relationship of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) with clinical indicators and pathology in patients with IgA nephropathy (IgAN). Clinical and pathological data of 36 patients with primary IgAN diagnosed by kidney biopsy were selected. The Oxford and Lee classifications were used to rank the pathology of IgAN patients and the particle-enhanced immunoturbidimetric method was adopted to measure pNGAL and uNGAL. Subsequently, the correlations of pNGAL and uNGAL levels with clinical indices and pathology were analyzed to evaluate the diagnostic value. Referring to the comparison group, pNGAL levels were elevated in the women, 24-hour proteinuria ≥ 1 g/day, Lee classification IV - V, and tubular atrophy/interstitial fibrosis (T) score of 1 subgroup of Oxford classification (p < 0.05). The pNGAL was positively correlated with 24-hour proteinuria, urine microalbumin, urine α1 microglobulin, and the score of T (p < 0.05), while uNGAL was negatively correlated with serum albumin (p < 0.05). The occurrence of T1 was evaluated by pNGAL, serum creatinine (Scr), 24-hour proteinuria, and estimated glomerular filtration rate (eGFR), and it was shown that the area under the curve of 24-hour proteinuria, pNGAL, Scr, and eGFR were 0.629, 0.817, 0.919, and 0.799, respectively; in addition, the sensitivity of both pNGAL and eGFR are 100%. The pNGAL levels in patients with IgAN are positively correlated with the Lee and Oxford classifications of T scores. The level of pNGAL in IgAN patients is found to be a prominent indicator for identification of renal tubulointerstitial injury and perhaps this feature may make it a non-invasive predictor for progression of IgAN.


Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center.
Inflammatory bowel diseases (IBDs) are associated with pathologic findings in the liver and biliary tract. Ultrasonography (US) represents a noninvasive means to study hepatobiliary abnormalities. This study evaluated the prevalence of US hepatobiliary changes and their relationship to clinical variables in a large IBD patient population followed in a single center. Five hundred eighty-three consecutive IBD patients were studied with US. After excluding patients with preexisting acute or chronic hepatitis, metabolic disorders, or obesity, 511 patients were investigated for age, duration, site, and severity of the disease, history of surgery, and present medical treatment. At US, liver size, echogenicity (graded as mild-to-moderate or severe indicating a corresponding degree of hepatic steatosis), focal lesions of the liver and gallbladder, and biliary tract abnormalities were recorded. Three hundred eleven patients with Crohn disease (CD) and 200 patients with ulcerative colitis (UC) were recruited for the study. Hepatobiliary abnormalities were found at US in 54.2% and 55.9% of CD and UC patients, respectively. Liver enlargement and mild-to-moderate to severe liver steatosis were found in 25.7% and 39.5% of CD patients and in 25.5% and 35.5% of UC patients, respectively, a higher prevalence than among healthy controls (P < 0.001). The prevalence of gallstones among CD patients was 11%, higher than that among UC patients (7.5%) and controls (5.5%) (P = 0.016). The higher risk of gallbladder stones in CD was related to age, female sex, and previous surgery. The prevalence of liver enlargement and liver steatosis was higher among IBD patients. The prevalence of gallstones was increased in CD patients only. This risk was related to age, female sex, and previous surgery.


Stimulation of collagenase secretion from rheumatoid synovial tissue by human collagen peptides.
Dayer et al. demonstrated that mononuclear cells from human peripheral blood produce a mononuclear-cell factor that stimulates collagenase secretion from adherent rheumatoid synovial cells. The production of this mononuclear-cell factor can be stimulated by phytohemagglutinin, a T-cell mitogen. We have examined immune mechanisms by which collagenase secretion may be stimulated from explants of rheumatoid synovial tissue and from primary monolayer cultures of rheumatoid synovial cells. Conditioned media from cultures of normal peripheral-blood mononuclear cells that had been activated by phytohemagglutinin stimulated collagenase secretion from most explants and from all monolayer cultures that were examined. The direct addition of phytohemagglutinin stimulated collagenase secretion in explants from eight of fourteen patients and in monolayer cultures from three of six patients. These observations indicate the presence of responsive T lymphocytes in rheumatoid synovial tissue and implicate them in the stimulation of collagenase secretion from synovial cells. The direct addition of type-II collagen peptides to rheumatoid explants also stimulated collagenase secretion in explants from six to fifteen patients. Four of five of these patients displayed moderate or severe disease activity. Other patients showed a marginal stimulation of collagenase secretion on addition of type-II collagen peptides (four of fifteen patients) and type-I collagen peptides (three of twelve patients). None of the patients with mild or inactive disease responded to type-II collagen. With one exception, the addition of collagen peptides to monolayer cultures did not stimulate collagenase secretion. An increased production of factors that enhance or inhibit the migration of polymorphonuclear leukocytes was also observed in explant cultures in response to the addition of phytohemagglutinin (in seven of twelve patients), of type-I collagen peptides (in five of ten patients), and of type-II collagen peptides (in five of eleven patients). There was no correlation between production of these factors and stimulation of collagenase secretion in rheumatoid synovial tissue.


Deep stacked support matrix machine based representation learning for motor imagery EEG classification.
Electroencephalograph (EEG) classification is an important technology that can establish a mapping relationship between EEG features and cognitive tasks. Emerging matrix classifiers have been successfully applied to motor imagery (MI) EEG classification, but they belong to shallow classifiers, making powerful stacked generalization principle not exploited for automatically learning deep EEG features. To learn the high-level representation and abstraction, we proposed a novel deep stacked support matrix machine (DSSMM) to improve the performance of existing shallow matrix classifiers in EEG classification. The main idea of our framework is founded on the stacked generalization principle, where support matrix machine (SMM) is introduced as the basic building block of deep stacked network. The weak predictions of all previous layers obtained via SMM are randomly projected to help move apart the manifold of the original input EEG feature, and then the newly generated features are fed into the next layer of DSSMM. The framework only involves an efficient feed-forward rather than parameter fine-tuning with backpropagation, each layer of which is a convex optimization problem, thus simplifying the objective function solving process. Extensive experiments on three public EEG datasets and a self-collected EEG dataset are conducted. Experimental results demonstrate that our DSSMM outperforms the available state-of-the-art methods. The proposed DSSMM inherits the characteristic of matrix classifiers that can learn the structural information of data as well as the powerful capability of deep representation learning, which makes it adapted to classify complex matrix-form EEG data.


DNA aptamers as analyte-responsive cation transporters in fluorogenic vesicles: signal amplification by supramolecular polymerization.
We report that single-stranded (ss) DNA aptamers can be activated by counterions such as dodecylguanidinium (DG) to act as transporters in fluorogenic vesicles. However, their activity is independent of the presence or absence of the analyte. Dimerization into ds-DNA helices increases activity in an overadditive manner. Duplex disassembly in response to analyte binding is thus detectable as inactivation. Shortened and mismatched antiaptamers destabilize the active duplex, reduce activity, and increase the sensitivity for the analyte. Supramolecular polymerization of aptamer/antiaptamer duplexes with "sticky ends" is shown to further increase activity without losses in sensitivity for the analyte. The results demonstrate that the principles of DNA nanotechnology are directly applicable to membrane based sensing systems with high precision and fidelity.


Is income inequality a determinant of population health? Part 2. U.S. National and regional trends in income inequality and age- and cause-specific mortality.
This article describes U.S. income inequality and 100-year national and 30-year regional trends in age- and cause-specific mortality. There is little congruence between national trends in income inequality and age- or cause-specific mortality except perhaps for suicide and homicide. The variable trends in some causes of mortality may be associated regionally with income inequality. However, between 1978 and 2000 those regions experiencing the largest increases in income inequality had the largest declines in mortality (r= 0.81, p < 0.001). Understanding the social determinants of population health requires appreciating how broad indicators of social and economic conditions are related, at different times and places, to the levels and social distribution of major risk factors for particular health outcomes.


[The nurse's role in the rehabilitation of the elderly].
As the elderly people in our country are increasing it becomes more and more frequent the elderly's presence in the services of health and especially of rehabilitation. We bring in this descriptive text the main aspects involved in the elderly's rehabilitation: the referring peculiarities to the rehabilitation in this age group, the functional evaluation as an important indicative of the life quality, the phases of the elderly's rehabilitation and the systematized nursing care through the nurse, inserted in the multidisciplinary team acts with the elderly patient and his family, in an individualized way.


Fingerprinting and profiling in metabolomics of biosamples.
This review focuses on metabolomics from an NMR point of view. It attempts to cover the broad scope of metabolomics and describes the NMR experiments that are most suitable for each sample type. It is addressed not only to NMR specialists, but to all researchers who wish to approach metabolomics with a clear idea of what they wish to achieve but not necessarily with a deep knowledge of NMR. For this reason, some technical parts may seem a bit naïve to the experts. The review starts by describing standard metabolomics procedures, which imply the use of a dedicated 600 MHz instrument and of four properly standardized 1D experiments. Standardization is a must if one wants to directly compare NMR results obtained in different labs. A brief mention is also made of standardized pre-analytical procedures, which are even more essential. Attention is paid to the distinction between fingerprinting and profiling, and the advantages and disadvantages of fingerprinting are clarified. This aspect is often not fully appreciated. Then profiling, and the associated problems of signal assignment and quantitation, are discussed. We also describe less conventional approaches, such as the use of different magnetic fields, the use of signal enhancement techniques to increase sensitivity, and the potential of field-shuttling NMR. A few examples of biomedical applications are also given, again with the focus on NMR techniques that are most suitable to achieve each particular goal, including a description of the most common heteronuclear experiments. Finally, the growing applications of metabolomics to foodstuffs are described.


Temporal switching of an amphiphilic self-assembly by a chemical fuel-driven conformational response.
The spatial and temporal control of self-assemblies is the latest scientific hurdle in supramolecular chemistry which is inspired by the functioning of biological systems fueled by chemical signals. In this study, we work towards alleviating this scenario by employing a unique amphiphilic foldamer that operates under the effect of a chemical fuel. The conformational changes in the foldamer amplify into observable morphological changes in its amphiphilic assembly that are controlled by external molecular cues (fuel). We take advantage of this redox responsive foldamer to affect its conformation in a temporal manner by an enzymatic pathway. The temporal characteristics of the transient conformation/assembly can be modulated by varying the concentrations of the fuel and enzyme. We believe that such a design strategy can have positive consequences in designing molecular and supramolecular systems for future active, adaptive and autonomous materials.


Monoclonal antibodies against a nucleolar protein from differentiating chick muscle cells.
Two monoclonal antibodies, NORM and NORA, bind specifically to a 37 000 molecular weight protein in total protein extracts of chick skeletal muscle cell cultures. They have been used to follow changes in the amount and distribution of this protein during terminal differentiation and the associated cessation of cell division. Immunofluorescence microscopy shows that the antigen is found almost exclusively in the nucleolus in interphase cells and is dispersed in the cytoplasm during mitosis. Low doses of actinomycin D cause segregation of nucleoli into DNA fibrils and ribonucleoprotein granules, and the antigen is clearly associated with the latter. High doses of actinomycin D cause shrinkage of the nucleolus and the antigen is dispersed within the nucleoplasm, but not released into the cytoplasm. The amount and distribution of antigen is similar in all cell types (myoblasts, myotubes and fibroblasts) and there are no major changes during muscle differentiation. From known changes in ribosomal RNA metabolism during myogenesis and after actinomycin D treatment, we suggest that the 37 000 Mr protein is involved in some post-transcriptional aspect of ribosome production and that its concentration and distribution may be related to the concentration of ribosomal RNA in the nucleolus.


The correlation between international prostate symptoms score and sexual health inventory in men with lower urinary tract symptoms.
Lower urinary tract symptoms (LUTS) are common in aging men and are often associated with erectile dysfunction (ED). The International Prostate Symptoms Score (IPSS) and the Sexual Health Inventory for Men (SHIM) are commonly used validated instruments for LUTS and ED, respectively. We explored the correlation between LUTS (assessed by IPSS) and ED (assessed by SHIM) in men over 40 years of age. A total of 585 men, 40 years and above, who presented with LUTS were prospectively enrolled into the study at single tertiary academic center. All patients were evaluated using SHIM and IPSS questionnaires. The self-administered IPSS and SHIM questionnaires were translated in the local language (not validated yet) as well. The data were analyzed using SPSS version 13.0. The correlation coefficient between IPSS and SHIM scores were determined, and the scatter diagram was made. The mean age (SD) of the group was 59.61 ± 11.75 years. The correlation between age and ED was statistically significant (P value < 0.001) with coefficient of 0.376. The correlation between age and LUTS was statistically significant (P value < 0.001) with coefficient of 0.312. Additionally, the correlation between ED and LUTS was statistically significant (P value < 0.001) with coefficient of 0.336. We noted a significant correlation between the severity of LUTS and ED, while confirming the earlier established correlation between age, LUTS, and ED. The exact nature of this relationship and its pathophysiology needs to be determined by further studies.


D-A polymers for fluorescence/photoacoustic imaging and characterization of their photothermal properties.
NIR-II fluorescence imaging has great potential in diagnosis, but the quantum efficiency of contrast agents is an urgent problem to be solved. We synthesized two new multifunctional polymers, P-TT and P-DPP, with a tetrahedral C (sp3) and branched alkyl chains in the main chain, which were beneficial to obtain high quantum efficiency. P-TT and P-DPP showed absorption peaks of 686 nm and 763 nm, respectively, and fluorescence emission peaks of 1071 nm and 1066 nm, respectively. The photothermal effect of P-DPP can reach 52 °C, and the quantum yield reaches 1.5%, which was three times higher than that of nanotube fluorophores (quantum yield 0.4%). P-DPP is used for stable fluorescence imaging of blood vessels and photoacoustic imaging of nude mice, and successfully applied to phototherapy of nude mouse tumours.


Incomplete posterior vitreous detachment: prevalence and clinical relevance.
To investigate the prevalence and clinical relevance of incomplete posterior vitreous detachment (PVD). Prospective, observational cohort study. Institutional. Consecutive patients without previous ocular history who were diagnosed with acute uncomplicated PVD. Baseline kinetic ultrasound evaluation differentiated posterior vitreous separation as complete or incomplete. Prospective follow-up searched for complications related to PVD. Multivariate analysis evaluated associations of baseline demographic and clinical characteristics to incomplete PVD. A Kaplan-Meier analysis evaluated the probability and its standard error of experiencing an adverse outcome. The log-rank test determined whether incomplete PVD modifies the natural history of PVD. Prevalence of incomplete PVD and the estimated incidence of late adverse outcomes such as new retinal tears, epimacular membranes, or both. A total of 54 of 207 patients had incomplete PVD (prevalence, 26.1%). Younger age and lattice degeneration were associated independently with incomplete PVD. After a mean follow-up of 5 years (range, 4 to 8 years), 16 patients (9.7%) experienced some adverse outcome. In 5 patients (2.7%), new retinal tears and 1 retinal detachment developed. In 12 patients (7.6%), epimacular membranes developed. Patients with incomplete PVD at baseline experienced significantly more adverse outcomes than patients with complete PVD (Kaplan-Meier estimated probability and standard error, 19.2% and 0.061 vs 5.4% and 0.02; P = .01, log-rank test). Up to one fourth of symptomatic, acute, and uncomplicated PVDs show incomplete posterior vitreous separation. Delayed complications related to PVD, like retinal tears and epimacular membranes, develop more frequently in patients showing incomplete PVD.


A comparative study on the activity and antigenicity of truncated and full-length forms of streptokinase.
Application of streptokinase (SK) as a common and cost-effective thrombolytic drug is limited by its antigenicity and undesired hemorrhagic effects. Prior structural/functional and epitope-mapping studies on SK suggested that removal of 59 N-terminal residues led to its fibrin dependency and identified SK antigenic regions, respectively. Following in silico analyses two truncated SK proteins were designed and compared for their fibrin specificity and antigenicity with the full-length SK. Computer-based modeling was used to predict the effect of vector (pET41a)-born protein tags on the conformation of SK fragments. SK60-386, SK143-386 and full-length SK (1-414) were separately cloned, expressed in BL21 E. coli cells and confirmed by Western-blotting. Functional activity of the purified proteins was evaluated with chromogenic and clot lysis assays and their antigenicity was tested by ELISA assay using rabbit anti-streptokinase antibody. As expected, chromogenic bioassay showed a major activity decline for SK60-386 and SK143-386 (83 and 91 percent, respectively), compared to SK1-414. However, in clot lysis assay, which is a fibrin-dependent pharmacopoeia-approved test, SK60-386 and SK143-386 were respectively 35 and 31 percent more active though lysed the clots slower than full-length SK. Antigenic analysis also indicated significant decrease in ELISA signals obtained for truncated proteins compared to SK1-414 (45 and 28 percent less reactivity for SK143-386 and SK60-386, respectively, p < 0.0001). The results of this study for the first time pointed to SK143-386 and SK60-386, as improved SK derivatives with increased fibrin-selectivity and decreased antigenicity as well as acceptable bioactivity profiles in a pharmacopoeia-based analysis, which deserve more detailed pharmacological studies.


The Fear of COVID-19 Scale: Psychometric Properties of the Ethiopian Amharic Version.
Fear is an adaptive response that alerts individuals to the presence of a danger or threat. However, in the context of the current novel coronavirus disease 2019 (COVID-19) pandemic, the fear experienced could be intense because the number of victims of the virus is continuously increasing globally and is inducing severe mental health concerns. The seven-item Fear of COVID-19 Scale (FCV-19S) assesses the severity of fear related to COVID-19 and has already been validated in many languages. The present study evaluated the psychometric properties of the Amharic (Ethiopian) version of the FCV-19S. An online survey including the Amharic versions of the FCV-19S and the six-item UCLA Loneliness Scale (ULS-6) was administered to 307 Amharic-speaking participants using convenience sampling. The participants' age ranged between 18 and 70 years. In the evaluation process, confirmatory factor analysis, Item Response Theory, concurrent validity, and reliabilities (Cronbach's alpha, McDonald's omega, Guttman's lambda, and composite reliability) of the Amharic version of the FCV-19S were performed. The uni-dimensional structure of the FCV-19S was confirmed and the Amharic version of the FCV-19S had strong psychometric properties. All reliability coefficients of the Amharic FCV-19S were satisfactory, with sound concurrent validity shown by significant and positive correlations with loneliness. The results indicate that the FCV-19S can be used in research to assess the fear of COVID-19 among Amharic-speaking populations.


Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε.
Increasing evidence suggests that the circadian clock plays an important role in the control of renal function and blood pressure. We previously showed that the circadian clock protein Period (Per)1, positively regulates the expression of the rate limiting subunit of the renal epithelial sodium channel (αENaC), which contributes to blood pressure regulation. Casein kinases 1δ and 1ε (CK1δ/ε) are critical regulators of clock proteins. CK1δ/ε must phosphorylate the circadian clock protein Per1 in order for the latter to enter the nucleus. We used a commercially available CK1δ/ε inhibitor, PF670462, to test the effect of CK1δ/ε blockade and inhibited Per1 nuclear entry on αENaC in a model of the renal cortical collecting duct (mpkCCD(c14) cells). CK1δ/ε blockade prevented Per1 and Clock from interacting with an E-box from the αENaC promoter. CK1δ/ε inhibition reduced αENaC mRNA levels by <60%. A similar decrease in αENaC mRNA was observed following siRNA-mediated CK1δ/ε knock-down. Inhibition of CK1δ/ε effectively prevented the transcriptional response of αENaC to aldosterone, suggesting an interaction between the circadian clock and aldosterone-mediated regulation of αENaC. CK1δ/ε inhibition significantly reduced αENaC but increased Caveolin-1 membrane protein levels; transepithelial current, a measure of ENaC activity, was decreased. Importantly, single channel analysis in amphibian renal cells demonstrated a dramatic decrease in the number of patches with observable ENaC current following CK1δ/ε inhibition. The present study shows for the first time that CK1δ/ε inhibition and impaired Per1 nuclear entry results in decreased αENaC expression and ENaC activity, providing further support for direct control of ENaC by the circadian clock.


Sex differences in symptoms experienced, knowledge about symptoms, symptom attribution, and perceived urgency for treatment seeking among acute coronary syndrome patients in Karachi Pakistan.
Patients' experience of acute coronary syndrome (ACS) symptoms is important in determining their prehospital delay. To explore gender differences in acute symptoms of ACS, knowledge about the symptoms, their attribution, and perception of urgency, among Pakistani ACS patients. Comparative, cross-sectional study design with 249 ACS patients. The most commonly reported symptoms were ghabrahat (fidgetiness), chest pain, and chest heaviness. Most atypical symptoms were experienced more by women, such as nausea/vomiting (p < 0.001), backache (p < 0.001), palpitations (p = 0.004), and epigastric pain (p = 0.005). Chest pain and palpitations were the symptoms most commonly attributed to cardiac causes, whereas epigastric pain was most commonly attributed to non-cardiac causes by both men and women. Significantly more women than men perceived dyspnea (p = 0.026), nausea/vomiting (p = 0.027), sweating (p = 0.014), and palpitations (p = 0.01) as symptoms not at all urgent for treatment. Gender disparity in symptom experience along with the women's perception of non-urgency for their symptoms, could lead to delayed care seeking.


Risk factors and lifelong impact of community-acquired pneumonia in congenital heart disease.
The prevalence of congenital heart disease (CHD) in adults is rising necessitating a greater understanding of acquired diseases such as community-acquired pneumonia, which remains a leading cause of age-related mortality and morbidity in the general population. We hypothesise that the CHD population, given cardiopulmonary mechanics and altered immune function, bears a uniquely high risk for pneumonia-related hospitalisations and mortality. A countrywide cohort study was performed to calculate the relative risk and cumulative incidence of pneumonia hospitalisations and resultant 30-day mortality amongst the adult CHD population, matched 1:10 with non-CHD persons by gender, age, and adjusted for comorbidities. Cox proportional hazard regression quantified the impact of CHD severity and extracardiac defects. The CHD cohort includes 17,162 adults. The majority demonstrate mild/moderate CHD complexity. The cumulative incidence of pneumonia hospitalisation was higher for adults with CHD (hazard ratio 1.90; 95% confidence interval: 1.74-2.06) than the comparison cohort. This risk was increased for those with extracardiac defects or a syndrome (hazard ratio: 4.34; 95% confidence interval: 3.39-5.54). Additionally, CHD individuals with severe/univentricular subtypes demonstrate a heightened risk compared to the non-CHD cohort (hazard ratio: 2.35; 95% confidence interval: 1.94-2.84), as well as compared to those with mild/moderate CHD (hazard ratio: 1.28; 95% confidence interval: 1.07-1.53). In addition, pneumonia hospitalisation mortality was elevated above the comparison population with a 30-day mortality rate ratio of 1.31 (95% confidence interval: 1.00-1.73). Adults with CHD are at elevated risk of pneumonia hospitalisations and pneumonia-associated mortality. This risk is further elevated in those with severe CHD and extracardiac defects.


Tobacco smoke and all-cause mortality and premature death in China: a cohort study.
Tobacco smoke is associated with several diseases, and identified as the second leading risk factor for death from any cause worldwide. The relationship of tobacco smoke to mortality or premature death is not yet available from contemporary cohorts after 2010 in China. This study aimed to investigate the smoking behavior and the relationship of tobacco smoke to mortality and premature death among a nationally representative cohort starting from 2011 in China. The nationally representative datasets (China Health and Retirement Longitudinal Study, CHARLS, 2011-2012) was employed and linked with follow-up data (2013). CHARLS was an ongoing nationally representative survey, which longitudinally followed up subjects aged over 45 years. Smoking status (non-smoker, ex-smoker, smoker, pack-years of smoking, age at starting and ceasing smoking) was used as independent variable, and all-cause mortality, premature death (defined as mortality before age 72.7 years in men and 76.9 years in women) were used as dependent variables. The Cox's proportional hazards regression mode was used to estimate the effect of tobacco smoke and pack-years of smoking on all-cause mortality and premature death. A total of 16,701 subjects were included. The association between tobacco smoker (hazard ratio [HR] = 1.37, 95%CI = 1.02, 1.83) / ex-smoker (HR = 1.75, 95%CI = 1.24, 2.46) and all-cause mortality was significant. Tobacco smoker (HR = 1.58, 95%CI = 1.04, 2.39) and ex-smoker (HR = 2.25, 95%CI = 1.38, 3.66) was associated with increase in the risk of premature death. Pack-years of smoking ≥ 30 was associated with increased risk of premature death compared with non-smokers in total (HR = 1.59, 95%CI = 1.03, 2.43) and women (HR = 3.38, 95%CI = 1.22, 9.38). Additionally, our results also revealed that there was a linear trend between pack-years of smoking and premature death in total (P = 0.002) and women (P = 0.010). This study found a negative effect of smoking status on all-cause mortality and premature death among a contemporary and nationally representative data in China. The correlation between pack-years of smoking and premature death and the trend of pack-years of smoking with premature death was also identified.


[Evaluation of the family focus and community orientation in the Family Health Strategy].
The Family Health Strategy should be focused on the family unit and constructed operationally within the community sphere. The research assessed the family focus and community orientation as attributes of Primary Health Care, comparing if the responses differed among users, professionals and managers. It is an evaluative study of a population-based quantitative approach conducted between January 2010 and March 2011 in São Luís in the state of Maranhão. The study involved a population of 32 managers and 80 professionals with more than six months experience in the Family Health Strategy, and 883 users were selected by means of cluster sampling. Questionnaires validated in Brazil were used based on the components of the Primary Care Assessment Tool (PCATool). The composite index of the family focus was 2.7 for users, 4.9 for professionals and 5.3 for managers. In the posttest phase, differences were detected between users and professionals, and users and managers. The composite index of community orientation was 2.9 for users, 3.9 for professionals and 4.8 for managers (p < 0.001). Managers attributed higher percentages in all indicators, followed by professionals and lastly users. Both attributes were rated as being unsatisfactory in the perception of the users.