Nigerian parents and caregivers knowledge, attitude and willingness to vaccinate their children against COVID-19.
In order to achieve herd immunity against COVID-19, a significant proportion of the population will need to be vaccinated. Experts have recommended that African children be allowed to get vaccinated to protect them from emerging variants of COVID-19 infection. This study investigated Nigerian parents and caregivers' knowledge, attitude, and willingness to vaccinate their children against COVID-19 once the vaccines are made available to them. A cross-sectional online survey of 500 parents/caregivers was conducted in Nigeria. Participants were asked to complete a questionnaire about their sociodemographic characteristics, knowledge of and attitude toward COVID-19 infection and vaccination, willingness to vaccinate their child and factors that could influence their decision to vaccinate their child. A scoring system was used to classify the level of knowledge and attitude of participants into 2 categories, namely poor, and good. We analyzed data obtained using SPSS Version 22. Majority of the participants were females (63.6%). Analysis of responses revealed good knowledge and attitude in 265 (53.0%) and 266 (53.2%) respondents, respectively. Overall, less than half of the parents/caregivers (48.4%) expressed intention to vaccinate their children against COVID-19. Factors associated with willingness to vaccinate children against COVID-19 included age greater than 40 years, male gender, residing in Southern Nigeria, having good knowledge, knowing an infected person or a vaccinated person, feeling they or their child is at risk of contracting COVID-19 infection, willingness to vaccinate self against COVID-19 and good attitude. Significant predictors of willingness to vaccinate their child include age greater than 40 years [AOR: 2.56; 95% CI = (1.14-5.76)], willingness to vaccinate self [AOR: 1016.81; 95% CI = (128.51-8045.60)] and good attitude [AOR: 6.21; 95% CI = (2.83-13.64)]. This study revealed that parental willingness to vaccinate their children against COVID-19 is low and identified factors influencing it. It is important to develop and implement health education programs iterating the risk of children getting infected with SARS-CoV-2 and its emerging variants to ensure optimal uptake of the COVID-19 vaccine in Nigerian children.


The Effect of Educational Intervention on Improvement of Breastfeeding Self-Efficacy: A Systematic Review and Meta-Analysis.
Self-efficacy is an important psychological and motivational factor in breastfeeding, and it is a valuable framework that predicts breastfeeding outcomes and demonstrates maternal confidence in breastfeeding. The meta-analysis evaluated the effectiveness of educational interventions on improving breastfeeding self-efficacy (BSE). The English and Persian databases including Medline, Embase, Cochrane Database of Systematic Reviews (CDSR), PubMed, Web of Science, Scopus, CINAHL, Sid, IRANDOC, and Marg-Iran were systematically searched for studies published from January 2005 to December 2020. The quality of studies was evaluated using the Cochrane risk of bias tool and the heterogeneity by I 2 statistic. The extracted data were analyzed using RevMan 5 statistical software and presented using random effects standardized mean difference (SMD). The funnel plot was used for evaluating publication bias. Results from 40 RCTs showed that educational intervention had a positive effect on the BSE compared with the usual/standard care (pooled SMD = 1.20; 95% CI = 0.75-1.64, p value <0.001). The subgroup analysis indicated that the educational intervention was based on theory, group class format, direct method education, during the first week of postpartum, doing during pregnancy, on primiparous women, and health center setting, and the Asian region has a more effect on BSE than the others. Breastfeeding education is considered an influential factor in the improvement of BSE. It is recommended that breastfeeding education should be continued for several weeks after childbirth for gaining its benefit. The Asian region has a more effect on BSE than the others. Therefore, it is important to add the values in content of education in each country.


Integrated environmental health assessment: Proposed approaches to exposure during chemical incidents.
An integrated environmental health exposure assessment (IEHA) refers to the integration of human biomonitoring data (HBM) and environmental measurements and aims to optimize the exposure assessment process. Due to lack of data, this approach remains an issue during chemical incidents. This study aims to explore integrated exposure approaches for assessing human health risks during chemical incidents. Based on the Preferred Reporting Items of Systematic reviews and Meta-Analyses statement, a literature analysis was performed. A level of confidence ranging from 1 to 4 was established to define the quality and strength of data used to undertake an IEHA approach. Twenty-seven articles (n = 18) and texts (n = 9) from Europe (41%) and the United States (37%) were analyzed. Among the 18 scientific articles, 61% (n = 11) presented a quantitative approach and 17% (n = 3) presented a qualitative approach. Quantitative approaches must be based on accurate data, coupled with predictive models. Of all the scientific papers, 40% (n = 7) responded to a confidence level greater than or equal to 2. Uncertainties detected through the integrated exposure approaches were related to input data, analytical methods, and HBM reference value interpretations. During chemical incidents, direct measurements were the most relevant data. Few scientific studies have developed an integrated approach during emergency situations. However, when this was used, they presented a high level of confidence by defining levels of exposure that support decision-making processes. Despite the multiple approaches, there was a lack of guidelines allowing an integrated risk assessment to be performed during an emergency chemical exposure. Integr Environ Assess Manag 2023;00:1-17. © 2023 SETAC.


AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin.
The A kinase-anchoring protein AKAP79/150 is a postsynaptic scaffold molecule and a key regulator of signaling events. At the postsynapse it coordinates phosphorylation and dephosphorylation of receptors via anchoring kinases and phosphatases near their substrates. Interactions between AKAP79 and two Ca(2+) -binding proteins caldendrin and calmodulin have been investigated here. Calmodulin is a known interaction partner of AKAP79/150 that has been shown to regulate activity of the kinase PKC in a Ca(2+) -dependent manner. Pull-down experiments and surface plasmon resonance biosensor analyses have been used here to demonstrate that AKAP79 can also interact with caldendrin, a neuronal calcium-binding protein implicated in regulation of Ca(2+) -influx and release. We demonstrate that calmodulin and caldendrin compete for a partially overlapping binding site on AKAP79 and that their binding is differentially dependent on calcium. Therefore, this competition is regulated by calcium levels. Moreover, both proteins have different binding characteristics suggesting that the two proteins might play complementary roles. The postsynaptic enrichment, the complex binding mechanism, and the competition with calmodulin, makes caldendrin an interesting novel player in the signaling toolkit of the AKAP interactome.


Neurotoxic Anatoxin-a Can Also Exert Immunotoxicity by the Induction of Apoptosis on Carassius auratus Lymphocytes in vitro When Exposed to Environmentally Relevant Concentrations.
Hazardous anatoxin-a (ANTX-a) is produced by freshwater algal blooms worldwide, which greatly increases the risk of consumer exposure. Although ANTX-a shows widespread neurotoxicity in aquatic animals, little is known about its mechanism of action and biotransformation in biological systems, especially in immunobiological models. In this study, transmission electron microscopy results showed that ANTX-a can destroy lymphocytes of Carassius auratus in vitro by inducing cytoplasmic concentration, vacuolation, and swollen mitochondria. DNA fragmentations clearly showed a ladder pattern in agarose gel electrophoresis, which demonstrated that the apoptosis of fish lymphocytes was caused by exposure to ANTX-a. Flow cytometry results showed that the apoptotic percentage of fish lymphocytes exposed to 0.01, 0.1, 1, and 10 mg/L of ANTX-a for 12 h reached 18.89, 22.89, 39.23, and 35.58%, respectively. ANTX-a exposure induced a significant increase in reactive oxygen species (ROS) and malonaldehyde (MDA) in lymphocytes. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and the glutathione (GSH) content of the 0.01 mg/L ANTX-a-treated group decreased significantly by about 41, 46, 67, and 54% compared with that of the control group (p < 0.01), respectively. Although these observations were dose-dependent, these results suggested that ANTX-a can induce lymphocyte apoptosis via intracellular oxidative stress and destroy the antioxidant system after a short exposure time of only 12 h. Besides neurotoxicity, ANTX-a may also be toxic to the immune system of fish, even when the fish are exposed to environmentally relevant concentrations, which clearly demonstrated that the potential health risks induced by ANTX-a in aquatic organisms requires attention.


Effect of veneering technique on the fracture resistance of zirconia fixed dental prostheses.
To compare the fracture resistance of zirconia 3-unit posterior fixed dental prostheses (FDPs) frameworks veneered with different veneering materials and techniques before and after artificial ageing. Forty-eight zirconia 3-unit FDPs, representing a missing first molar, were adhesively cemented on human teeth. The zirconia frameworks were randomly distributed according to the veneering materials and techniques into three groups, each containing 16 samples: group LV (layering technique/Vintage ZR), group LZ (layering technique/ZIROX) and group PP (CAD/CAM and press-over techniques/PressXZr). Half of each group was artificially aged through dynamic loading and thermocycling to simulate 5 years of clinical service. Afterwards, all specimens were tested for fracture resistance using compressive load. An analysis of variance (anova) was used to assess the effect of veneering ceramic and artificial ageing on fracture resistance (P < 0·05). Except for one minor cohesive chipping in group LV1, all specimens survived artificial ageing. The mean fracture resistance values (in Newton) of different non-aged (± s.d.)/aged (± s.d.) groups were as follows: LV0 2034 (± 401)/LV1 1625 (± 291); LZ0 2373 (± 718)/LZ1 1769 (± 136); and PP0 1959 (± 453)/PP1 1897 (± 329). Artificial ageing significantly reduced the fracture resistance in groups veneered with the layering technique (P < 0·05), whereas no significant effect was found in specimens veneered with the CAD/CAM and press-over techniques. All tested systems have the potential to withstand occlusal forces applied in the posterior region. The combination of the CAD/CAM and press-over techniques for the veneering process improved the overall stability after artificial ageing, relative to the layering technique.


Caffeine and theobromine levels in chocolate couverture and coating products.
Thirty-two samples of chocolate products were analysed by HPLC for caffeine and theobromine contents. Defatted residues of samples were extracted with 80% aqueous acetone. After extraction into boiling water, the methylxanthines were identified and quantified with the use of μ-Bondapak column and mobile phase of methanol:water:acetic acid (20:79:1). Levels of caffein and theobromine in 32 samples of chocolate products averaged 0.62-1.14 mg/g and 0.026-0.153 mg/g respectively. Mean values for theobromine and caffeine content for chocolate coating were 0.82 and 0.07 mg/g respectively. The chocolate coating made from fat substitute had theobromine and caffeine levels ranging from 0.36-0.70 mg/g and 0.027-0.061 mg/g respectively, with mean values of 0.49 mg theobromine/g and 0.039 mg caffeine/g. In local chocolate, the mean theobromine and caffeine levels respectively were 0.72 mg/g and 0.04 mg/g in milk chocolate, and 0.85 mg/g and 0.06 mg/g in dark chocolate. Meanwhile, for imported chocolate, the mean theobromine and caffeine levels respectively were 1.05 mg/g and 0.12 mg/g in dark chocolate; 0.76 mg/g and 0.04 mg/g in milk chocolate; and 0.74 mg/g and 0.03 mg/g in white chocolate. Compared with the local chocolates, imported chocolates had higher levels of theobromine and caffeine at 1.141 mg/g and 0.1533mg/g. The average theobromine and caffeine concentrations in local chocolate were 0.082mg/g and 0.066mg/g. Theobromine concentration in chocolate samples is within the range of 0.62mg/g-1.141mg/g and the range of caffeine concentration is 0.026mg/g-0.153mg/g respectively. Bittersweet chocolates were found to have higher theobromine and caffeine concentrations than normal sweet chocolates and milk chocolates.


Glycerol-3-phosphate acyltransferase 6 (GPAT6) is important for tapetum development in Arabidopsis and plays multiple roles in plant fertility.
Glycerol-3-phosphate acyltransferase (GPAT) mediates the initial synthetic step for the formation of glycerolipids, which act as the major components of biological membranes and the principal stored forms of energy. GPAT6 is a member of the Arabidopsis GPAT family, which is crucial for cutin biosynthesis in sepals and petals. In this work, a functional analysis of GPAT6 in anther development and plant fertility was performed. GPAT6 was highly expressed in the tapetum and microspores during anther development. The knockout mutant, gpat6, caused a massive reduction in seed production. This report shows that the ablation of GPAT6 caused defective tapetum development with reduced endoplasmic reticulum (ER) profiles in the tapetum, which largely led to the abortion of pollen grains and defective pollen wall formation. In addition, pollen germination and pollen tube elongation were affected in the mutant plants. Furthermore, the double mutant analysis showed that GPAT6 and GPAT1 make joint effects on the release of microspores from tetrads and stamen filament elongation. This work shows that GPAT6 plays multiple roles in stamen development and fertility in Arabidopsis.


Reactivation of immobilized acetylcholinesterase-tabun complex by pralidoxime, its isomers, and homologs.
Reactivation efficacy of three homologous and three isomeric series of pralidoxime-type reactivators with aldoxime group in position 2, 3 and 4 of the heterocycle was tested in reactivation of tabun-inhibited AChE. The experiments were performed with immobilized and stabilized porcine brain AChE. The enzyme activity was measured by Ellman method. Reactivation efficacy was determined by measurement of indicator fabric coloration intensity as a measure of AChE activity. Of the studied group of nine reactivators, isomers with the functional group in position 2 were the most effective. The highest value (30 %) for reactivation of inhibited AChE was found for 2PAE after treatment for 15 min at concentration 0.5 mg/cm(3). The efficacy of the isomers decreased in the order ortho > para > meta. No marked effect on the efficacy of the reactivators was observed on prolongation of the reactivation time. The reactivators efficacy decreased with decreasing concentration of their solutions.


Chicks discriminate human gaze with their right hemisphere.
Domestic chicks were tested for eye use while feeding on the floor in the presence of a dummy mask which could either look at the location where the chicks were feeding or in the opposite direction. Animals completely naïve of visual experience of human eyes and gaze showed a more intense fear response when directly looked at (as shown by higher latency to approach the food) and a preferential use of the left eye (mainly feeding structures in their right hemisphere) to monitor the dummy mask. This response, seemingly predisposed, could be reversed in chicks with experience of human eyes and gaze directed toward them, which showed higher latency to approach the food and preferential left eye use when the dummy mask looked away from them. The results are discussed in relation to evidence for a right hemisphere involvement in fear responses and detection of predators in the vertebrate brain.


Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity.
The present study examined the response of the prostate epithelium of senescent gerbils submitted to orchiectomy and with or without steroidal blockade. Animals were divided into five groups, all surgically castrated except the control group composed of intact animals. In the experimental groups, doses of flutamide and/or tamoxifen were applied for 1, 3, 7 and 30 days postcastration. The structural methods applied reveal that castration, whether associated or not with anti-steroidal drugs, promoted short- and long-term decrease in wet and relative weights of the prostate. The quantitative decline of epithelial compartment proportion observed at the end of treatment was due to the sum of slight changes in the epithelium and lumen. The apoptotic index had risen significantly at 1 day and declined at 7 days postcastration. Androgen receptor (AR) expression decreased after 3 days of hormonal ablation, coinciding with the highest levels of apoptosis and cell proliferation observed in all treated groups. The majority of cells remained differentiated in all groups due to CK 8/18 expression. Some animals remained with injuries such as carcinomas and adenocarcinomas after hormonal ablation. In the latter a mixture of AR-positive and AR-negative cells was identified. Microinvasive carcinomas found in the group treated for 30 days consisted of PCNA-positive, inflammatory and non-proliferating cells. Low apoptosis incidence and bcl-2 positive cells were observed in these lesions. The treatments promoted a reduction of lesions in older gerbils, but treatment-resistant tumours will improve understanding of the events that lead to hormone resistance.


Selection of novel nickel-binding peptides from flagella displayed secondary peptide library.
Nickel (Ni) performs its biological or toxic functions in nickel-protein coordination form. Novel Ni-binding peptides were isolated from a random dodecapeptide library displayed on the flagella of Escherichia coli against immobilized ions. On the basis of isolated sequences rich in histidine residues, two secondary libraries were constructed respectively. By consequent selection, more Ni-chelating peptides were identified and the consensus motif RHXHR (where X was always H) was deduced. The result suggested that not only histidine, but also arginine, play an important role in Ni-binding. Furthermore, two selected clones (1035 and 2022) were chosen for further identification. They exhibited similar relative binding affinity, which was about nine times that of the original library derived clones and statistically much more significant than the positive control with polyhistidine insert. Free nickel ions could almost completely inhibit the binding of the clones 1035 and 2022 to immobilized nickel, implicating that the peptides were able to chelate nickel ions. These studies reveal that bacterial surface displayed peptide libraries may have promising future potential for the development of metal bioadsorbents. Furthermore, novel Ni-binding peptides may provide lead molecules for Ni-chelation and applications thereof.


Pleuroparenchymal Fibroelastosis: A Case Report.
Pleuroparenchymal fibroelastosis (PPFE) is a rare, idiopathic interstitial pneumonia. wherein the first symptom might be dyspnea or a dry cough. The condition can also be manifested with chest pain secondary to pneumothorax. While the definitive diagnosis is based on a histological evaluation (which is not often performed), a computed tomography scan shows findings, such as apical fibrosis and pleural thickening of the apical lobes, which help assess the diagnosis. We describe a case of PPFE diagnosed radiologically in a 69-year-old man. This case highlights that PPFE is a pathology that can go unnoticed for a long time, and patients might neglect the revealing symptoms such as coughing.


The Importance of REST for Development and Function of Beta Cells.
Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are also defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. Among these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators. REST targets include genes encoding transcription factors, proteins involved in exocytosis, synaptic transmission or ion channeling, and non-coding RNAs. REST is expressed in the progenitors of both neurons and beta cells during development, but it is down-regulated as the cells differentiate. Although REST mutations and deregulation have yet to be connected to diabetes in humans, REST activation during both development and in adult beta cells leads to diabetes in mice.


ATG overdose in a kidney-grafted patient. Clinical course and possible implications.
During antirejection treatment with antithymocyte globulin (ATG), a 48-year-old male kidney graft recipient was erroneously given 30 mg/kg ATG on day 5 of the treatment course. Clinically, the patient presented with abdominal pain, profuse diarrhea, and fever. Initially, the platelet count dropped to 94 x 10(3)/microliters and showed a further decrease to 65 x 10(3)/microliters 2 days thereafter. Plasmapheresis carried out about 12 h after the end of ATG infusion resulted in a decrease in serum levels of total rabbit immunoglobulin as well as the antibody fraction reactive with human T lymphocytes. Within 10 days after the discontinuation of ATG treatment, the relative and absolute number of the T-cell subpopulations, which had disappeared from the circulation at the time of antirejection therapy, returned to normal values. In addition, at this time both platelet and lymphocyte counts were again found to be in the normal range. Kidney function had recovered from the rejection crisis such that the patient could be discharged 26 days posttransplantation.


A de novo T73I mutation in PTPN11 in a neonate with severe and prolonged congenital thrombocytopenia and Noonan syndrome.
We observed a neonate with severe congenital thrombocytopenia and features of Noonan syndrome where evaluations were negative for immune-mediated thrombocytopenia, congenital infections, and Fanconi anemia. The marrow findings and a significantly elevated plasma thrombopoietin (Tpo) level were consistent with congenital amegakaryocytic thrombocytopenia; we sought a genetic mutation that could explain this phenotype. No mutations were identified in c-MPL (the Tpo receptor gene). Microarray analysis of peripheral blood did not reveal an abnormality. DNA sequencing of the PTPN11 gene showed a heterozygous C>T nucleotide substitution in exon 3 (c.218C>T) predicted to result in a threonine-to-isoleucine change at residue 73 (T73I). A 6-week trial of eltrombopag (an agonist of the Tpo receptor) failed to increase the platelet count. We propose this specific PTPN11 mutation results in abnormalities of the protein product SHP-2, which, because of its role in signal transduction, results in severe congenital thrombocytopenia refractory to c-MPL agonists.


Life events, social support, coping strategies, and quality of life in attempted suicide: A case-control study.
Though deliberate self-harm encompasses a wide variety of medical and social disciplines some of the important psychosocial variable such as life events, social support, coping strategies, and quality of life have not yet been explored in depth in India. The aim was to analyze and compare the type and severity of life events, coping strategies, social support, and quality of life of suicide attempters versus matched normal controls, and to identify the risk factors leading to suicide. A total of 50 consecutive suicide attempters were compared with same number of age, sex, and martial status matched healthy controls using Presumptive Stressful Life Events Scale, Social Support Questionnaire, AECOM Coping Style Scale, and WHO QOL-Bref. Attempters experienced significantly more life events especially untoward events whereas the control group experienced more desirable and impersonal life events. Social support, positive coping, and of QOL were significantly lower in attempters. Among all risk factors desirable life events, good education, and good social support were protective against suicide. Suicide attempters were differentiated from healthy controls based on more stressful life events, lower social support, less healthy coping, and poor QOL. Positive life events, good education, and good social support were protective factors against suicide. However, it is difficult to pinpoint a single factor responsible for suicidal behavior. It is the complex interplay of various interrelated factors and the resultant buffering effect, which is protecting the individual against deliberate self-harm.


Self-assembly of two hydrophobins from marine fungi affected by interaction with surfaces.
Hydrophobins are amphiphilic fungal proteins endowed with peculiar characteristics, such as a high surface activity and an interface triggered self-assembly. Several applications of these proteins have been proposed in the food, cosmetics and biomedical fields. Moreover, their use as proteinaceous coatings can be effective for materials and nanomaterials applications. The discovery of novel hydrophobins with diverse properties may be advantageous from both the scientific and industrial points of view. Stressful environmental conditions of fungal growth may induce the production of proteins with peculiar features. Two Class I hydrophobins from fungi isolated from marine environment have been recently purified. Herein, their propensity to aggregate forming nanometric fibrillar structures has been compared, using different techniques, such as circular dichroism, dynamic light scattering and Thioflavin T fluorescence assay. Furthermore, TEM and AFM images indicate that the interaction of these proteins with specific surfaces, are crucial in the formation of amyloid fibrils and in the assembly morphologies. These self-assembling proteins show promising properties as bio-coating for different materials via a green process. Biotechnol. Bioeng. 2017;114: 2173-2186. © 2017 Wiley Periodicals, Inc.


Contour adaptation.
It is known that adaptation to a disk that flickers between black and white at 3-8 Hz on a gray surround renders invisible a congruent gray test disk viewed afterwards. This is contrast adaptation. We now report that adapting simply to the flickering circular outline of the disk can have the same effect. We call this "contour adaptation." This adaptation does not transfer interocularly, and apparently applies only to luminance, not color. One can adapt selectively to only some of the contours in a display, making only these contours temporarily invisible. For instance, a plaid comprises a vertical grating superimposed on a horizontal grating. If one first adapts to appropriate flickering vertical lines, the vertical components of the plaid disappears and it looks like a horizontal grating. Also, we simulated a Cornsweet (1970) edge, and we selectively adapted out the subjective and objective contours of a Kanisza (1976) subjective square. By temporarily removing edges, contour adaptation offers a new technique to study the role of visual edges, and it demonstrates how brightness information is concentrated in edges and propagates from them as it fills in surfaces.


Botox injection in treatment of sialorrhea in children with cerebral palsy.
The occurrence of sialorrhea (drooling) in children with cerebral palsy is one of the important complications of this disease, which is associated with the impaired quality of life of patients and also the dissatisfaction of their parents. Botox injection in the salivary glands is one of the treatment methods that has recently received special attention in these patients, but there are still many challenges regarding its effectiveness and safety. We aimed to test the effectiveness and safety of botulinum toxin type A in reducing sialorrhea in children with cerebral palsy. This semi-experimental before-after study was performed on 12 children who suffering from sialorrhea. The ethics code of this project is IR.MUI.MED.REC.1400.774 and the clinical trial registry code is IRCT20220516054868N1 (https://www.irct.ir/trial/64393). In each of the parotid and submandibular glands, an amount of 0.5 U/kg of botulinum toxin type A was injected by ultrasound guidance under general anesthesia. Before and 6 months after the intervention, the severity and frequency of drooling were tested by Drooling Frequency and Severity Scale. We found a decreasing trend in the severity and frequency scores for drooling within one month; however, after that time, until the end of the 24th week, we saw an increasing trend in the intensity and frequency of this complication. Only two-thirds of parents were satisfied with the therapeutic protocol. Side effects related to botox injection were revealed in 25.0% mostly as dysphagia. Botox injection in salivary glands is not a definitive and stable treatment in the treatment of sialorrhea in children with cerebral palsy.


Vitamin E administration erases an enhanced oxidation in multiple sclerosis.
Systemic peroxidation status has been reported as a pathogenic factor for multiple sclerosis (MS). Systemically elevated oxidation levels are associated with serum lipid peroxidation and somatic telomere length (TL) shortening. We investigated whether vitamin E (VE) administration suppresses peroxidation and improves clinical symptoms in 34 MS patients. We analyzed serum lipid peroxidation and degree of TL in circulating leukocytes of MS patients before and after VE treatment. The oxidation level was enhanced and TL was shortened in MS. The MS population treated with VE 400 mg/day for 3 months showed significantly reduced serum lipid oxidation level with maintenance of TL. These findings showed that systemic peroxidation is associated with the development of MS. Antioxidants such as vitamin E can be candidates for supplementary therapeutic agents for MS.


Establishing a Policy Framework for the Primary Prevention of Occupational Cancer: A Proposal Based on a Prospective Health Policy Analysis.
Despite our knowledge of the causes of cancer, millions of workers are involuntarily exposed to a wide range of known and suspected carcinogens in the workplace. To address this issue from a policy perspective, we developed a policy framework based on a prospective health policy analysis. Use of the framework was demonstrated for developing policies to prevent cancers associated with diesel engine exhaust (DEE), asbestos, and shift work, three occupational carcinogens with global reach and large cancer impact. An environmental scan of existing prospective health policy analyses was conducted to select and describe our framework parameters. These parameters were augmented by considerations unique to occupational cancer. Policy-related resources, predominantly from Canada, were used to demonstrate how the framework can be applied to cancers associated with DEE, asbestos, and shift work. The parameters of the framework were: problem statement, context, jurisdictional evidence, primary prevention policy options, and key policy players and their attributes. Applying the framework to the three selected carcinogens illustrated multiple avenues for primary prevention, including establishing an occupational exposure limit for DEE, banning asbestos, and improving shift schedules. The framework emphasized the need for leadership by employers and government. To our knowledge, this is the first proposal for a comprehensive policy framework dedicated to the primary prevention of occupational cancer. The framework can be adapted and applied by key policy players in Canada and other countries as a guide of what parameters to consider when developing policies to protect workers' health.


Chronic headache as a sequela of rigid fixation for craniosynostosis.
Rigid fixation has been used over the past 20 years for the long-lasting correction of traumatic and congenital craniofacial defects. It has been noted that the use of plates and screws can result in the migration of the hardware through the skull to the inner cerebral cortex where it embeds in the dura. In addition, there is controversy concerning the safety of using titanium plates in the pediatric population. We report here on an 8-year-old boy who presented to our clinic with a chronic headache after rigid craniofacial fixation using titanium plates 7 years before.


Exosomal DEK removes chemoradiotherapy resistance by triggering quiescence exit of breast cancer stem cells.
Tumor therapeutics often target the primary tumor bulk but fail to eradicate therapy-resistant cancer stem cells (CSCs) in quiescent state. These can then become activated to initiate recurrence and/or metastasis beyond therapy. Here, we identified and isolated chemoradiotherapy-resistant CSCs in quiescent state with high capacity of tumor-initiation and tumorsphere formation from three types of breast tumors in mice. Experiments of knockdown and rescue revealed DEK, a nuclear protein, as essential for CSC activation. Exogenous DEK was then used to trigger quiescence exit of CSCs. ChIP-seq and ATAC-seq showed that DEK directly binds to chromatin, facilitating its genome-wide accessibility. The resulting epigenetic events upregulate the expression of cellular activation-related genes including MYC targets, whereas cellular quiescence-related genes including the p53 signaling pathway are silenced. However, twinned with DEK-induced activation, formerly resistant CSCs were then destroyed by chemotherapy in vitro. In mice, traditional chemoradiotherapy concurrent with the injection of DEK-containing exosomes resulted in eradication of primary tumors together with formerly resistant CSCs without recurrence or metastasis. Our findings advance knowledge of the mechanism of quiescent CSC activation and may provide novel clinical opportunities for removal of quiescence-linked therapy resistance.


How can free energy component analysis explain the difference in protein stability caused by amino acid substitutions? Effect of three hydrophobic mutations at the 56th residue on the stability of human lysozyme.
To elucidate the molecular mechanism of thermal stability, it is essential to determine what are the major free energy components that contribute significantly to the total free energy difference caused by amino acid mutations. In this work, we carried out free energy calculations based on all-atom molecular dynamics simulations to investigate the effect of three hydrophobic mutations at the same position, I56A, I56V and I56F of human lysozyme. The calculated free energy differences are in good agreement with the experimental values in all cases. From free energy component analysis, we found that small changes in stability in the I56A and I56V mutants originate from the short-range Lennard-Jones interactions, whereas the I56F mutant is largely destabilized owing to the changes in the long-range electrostatic interactions. The calculated results are also compared with the free energy components determined by an empirical relationship based on the native-state structure and thermodynamic data. Although this relationship has been shown to be very successful in reproducing the stability changes caused by various amino acid substitutions in several proteins, the changes of stability in I56V and I56F mutants are not reproduced very well. By comparing the free energy components calculated by these two approaches, we showed that the effect of the long-range interaction on the stability changes may be underestimated in the empirical relationships when the structural change caused by mutation is relatively small, as in I56F. It is also suggested that estimation of the change in accessible surface area, deltadeltaASA, may be overestimated if the structure around the mutation site in the denatured state is native-like, which would cause overestimation of the free energy change as in the case of I56V. Our results clearly show that the combined approach of the free energy calculation based on the all-atom molecular dynamics simulation and the empirical relationships is very useful for understanding the detailed mechanism of protein stability.


Hexachlorobenzene as hormonal disruptor--studies about glucocorticoids: their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis.
In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC) normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of this work was to investigate, in a time-course study, the effects of HCB on plasma GC, its adrenal synthesis and stimulation, and the kinetic parameters of its hepatic receptors (GR) in relation to the gluconeogenic blockage produced by HCB. Plasma corticosterone (CORT) concentration, urinary porphyrins and hepatic PEPCK were determined after 2, 4, 6 and 8 weeks of HCB-treatment. The effect of HCB on kinetic parameters of GR was studied in adrenalectomized porphyric rats after 2, 4 and 8 weeks of treatment. Additionally, adrenal CORT synthesis in the same weeks was measured with or without ACTH. Results show that plasma CORT in intoxicated animals dropped significantly after 2 and 4 weeks of treatment (23% and 58%, respectively), and then remained constant until the 8th week. HCB also promoted a reduction in the number of hepatic GR (50-55%) without modifying affinity. After 8 weeks, when porphyria was well established (40-50-fold increase in urinary porphyrins), a reduction (52%) in hepatic GR number, as well as a decrease in PEPCK activity (56%) were observed. Moreover, CORT biosynthesis in adrenals from intoxicated animals significantly decreased (60%) without changes in ACTH effect. Briefly, this paper shows that HCB causes a disruption in GC and GR. This disturbance could contribute to the negative effect on glucose synthesis through PEPCK regulation, thus modulating porphyria. These results enhance the knowledge about the hormonal disruption produced by chlorinated xenobiotics.


Insight into the invasion process and immune-protective evaluation of Tp0971, a membrane lipoprotein from Treponema pallidum.
Treponema pallidum (T. pallidum), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of T. pallidum remain a mystery. In this study, we established a T. pallidum infection model in New Zealand rabbits, and the T. pallidum burden in various tissues and organs was detected to investigate the dynamic spread of T. pallidum in different organs. Our results indicated that the T. pallidum burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of T. pallidum. The immune-protective effect of the T. pallidum infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of T. pallidum in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of T. pallidum. IMPORTANCE The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation "the stealth pathogen." There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.


Why can't we fund supported employment?
Work is one of the most valued social rules in modern society, contributing to a person's sense of economic well-being, self-esteem, personal identity, and social status. Conversely, the inability to work or sustain employment due to a psychiatric condition is the primary factor in determining eligibility for disability benefits, such as Social Security Disability Income or Social Security Supplemental Income. Just as work is valued strongly by society, it is also important to people with serious mental illness. In this editorial, we contemplate why we cannot "do the right thing" and fully fund supported employment for persons with serious mental illness. (PsycINFO Database Record


CareFusion 3100B high-frequency oscillatory ventilator diaphragms require pre-use inspection.
A rubber diaphragm in the driver assembly of the CareFusion 3100B high-frequency oscillatory ventilator may fail before its scheduled replacement at 4,000 hours of use, rendering the unit incapable of ventilation. CareFusion is in the process of revising the suggested replacemen schedule and adding user guidance to the device's operator's manual to address the problem. Users should thoroughly inspect the diaphragm each time they connect a breathing circuit and should remove from service any 3100B whose diaphragm shows signs of degradation.


Risk factors and oncological impact of positive resection margins in gastrectomy for cancer: are they salvaged by an additional resection?
The situation of positive resection margins (PRMs) varies notably between Western and Asian countries. In the West, PRMs are associated with advanced disease and R1, whereas in Asia, PRMs are also considered in early disease because stomach preservation was recently prioritized. Furthermore, PRMs are usually resected to obtain R0. However, the oncological impact of PRMs and additional resection remains unclear. The aim of this study is to evaluate the oncological impact of PRMs in laparoscopic gastrectomy (LG) for clinical stage (cStage) I gastric cancer. A total of 2121 patients who underwent LG for cStage I gastric cancer between 2007 and 2015 were enrolled. Survival outcomes were compared between patients with PRMs (group P) and those without (group N). Furthermore, prognostic factors were analyzed using multivariate analysis. Twenty-seven patients (1.3%) had PRMs. Patients in group P had upper and more advanced disease, and the 5-year relapse-free survival (RFS) rate was worse in group P compared with group N (76.3% vs. 95.1%, P = 0.003). The 5-year RFS of patients with pT2 or deeper (pT2-4) disease in group P was significantly worse than that of patients in group N (66.7% vs. 89.5%, P = 0.030) although that of patients with pT1 was not. Likelihood ratio tests showed that there was a significant interaction between pT status and PRM (P = 0.005). PRM in cStage I gastric cancer is associated with advanced upper disease. It remains an independent prognostic factor in pT2-4 disease even after an additional resection to obtain R0.


Lectins as probes of membrane carbohydrates in mesothelial cells in vitro.
Carbohydrates present on the surface of cells have been implicated in such processes as bacterial adherence, surfactant secretion and reutilization, and cell-cell recognition. In this study, fluorescein isothiocyanate (FITC) conjugated lectins were used to probe for such carbohydrates on the surface and interior regions of rabbit peritoneal mesothelial cells propagated in vitro. A cell permeabilization technique employing treatment with formalin and saponin provided the greatest presentation of surface membrane structure and lectin binding. FITC-lectins derived from C. ensiformis (Concanavalin A; mannose specific), T. vulgaris, A. hypogaea, E. cristagalli, B. simplicifolia, and M. pomifera bound to the cell surface. When two strains of Edwarsiella tarda were exposed to the mesothelial cells, only the mannose-specific strain (ET-4) demonstrated substantial adherence to the cell surface.


Design and Functional Characterization of a Novel Abscisic Acid Analog.
The phytohormone abscisic acid (ABA) plays a crucial role in mediating plant growth and development by recruiting genetically redundant ABA receptors. To overcome its oxidation inactivation, we developed a novel ABA analog named 2',3'-benzo-iso-ABA (iso-PhABA) and studied its function and structural characterization with A. thaliana ABA receptors. The (+)-iso-PhABA form showed much higher ABA-like activities than (+)-ABA including inhibitory effects on the seed germination of lettuce and A. thaliana, wheat embryo germination and rice seedling elongation. The PP2C (protein phosphatases 2C) activity assay showed that (+)-iso-PhABA acted as a potent and selective ABA receptor agonist, which is preferred to PYL10. In some cases, (-)-iso-PhABA showed moderate to high activity for the PYL protein inhibiting PP2C activity, suggesting different mechanisms of action of iso-PhABA and ABA. The complex crystal structure of iso-PhABA with PYL10 was determined and elucidated successfully, revealing that (+)-iso-PhABA was better coordinated in the same binding pocket compared to (+)-ABA. Moreover, the detailed interaction network of iso-PhABA/PYL10 was disclosed and involves hydrogen bonds and multiple hydrophobic interactions that provide a robust framework for the design of novel ABA receptor agonists/antagonists.


Heterogeneity of congenital retinal non-attachment, falciform folds and retinal dysplasia. A guide to genetic counselling.
The heritable falciform folds and congenital retinal non-attachment reported in the literature are here divided into monosymptomatic and complex types. Of the former, autosomal dominant and recessive disorders are known. The complex types comprise several syndromes, both autosomal recessive and X-linked. Retinal dysplasia is sometimes seen in histological sections from these affections, but it is an unspecific histological reaction, and not a disease sui generis. Attention is drawn to the syndrome with microcephaly, microphthalmia and falciform detachment which, though previously described, has not so far been delineated. It is hypothesized that hydrocephaly and congenital retinal non-attachment with or without microphthalmia and persistent hyperplastic primary vitreous constitute yet another 'new' syndrome, mainly seen in females.


Acute and chronic lithium treatments influence agonist and depolarization-stimulated inositol phospholipid hydrolysis in rat cerebral cortex.
The ability of acute and chronic Li treatment to influence agonist and depolarization-induced phosphoinositide metabolism was examined in rat cerebral cortex slices. After acute treatment (6.75 mEq/kg, 18 hr), [3H]inositol phosphates accumulating in the presence of 100 microM carbachol (muscarinic), 31 mM K+, 300 microM histamine (H1) and 300 microM 5-hydroxytryptamine (5-hydroxytryptamine2) were reduced significantly even after preincubation of slices with 2.5 mM myo-inositol. However, the response to noradrenaline (100 microM) (alpha-1) was unaffected. In the absence of a drug-free period, chronic Li (2 weeks) maintained the reduced phosphoinositide response to receptor agonists and K+, and now even noradrenaline responses were reduced significantly. Dose-response curves revealed that reduction in the response to carbachol was due to a fall in maximal response and not in EC50. When rats were withdrawn from chronic treatment for 18 hr, the responses to carbachol were enhanced significantly with respect to untreated controls. Neither acute nor chronic Li treatments altered significantly the overall incorporation of [3H]inositol into phospholipids. Furthermore, Li treatment did not influence the activity of phospholipase C assayed in crude homogenates of cerebral cortex. In conclusion, acute and chronic Li treatments producing less than [1 mM] in cerebral tissue, severely disrupts phosphoinositide metabolism. Although such effects may well be secondary to inhibition of inositol-monophosphatase, they are not reversed by inositol and therefore do not appear to result from depleted phosphoinositides.


Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?
Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.


Bio-based and compostable polyesters in food contact: analysis of monomers and (in)organic fillers.
Polyesters labelled as bio-based or compostable are increasingly common among the 'bioplastics' in use as food contact materials (FCM). The knowledge of material composition is mandatory to predict potential leachable oligomers as well as to partly evaluate the correctness of the label 'bioplastic', which is used for promotional purposes. The composition of (bio)polyesters can be determined by alkaline hydrolysis of the entire material and subsequent analysis of the monomers via high-performance liquid chromatography with diode array detection and GC-MS detection. Thirty-three frequently used monomers (polycarboxylic acids, hydroxy carboxylic acids, polyols) including highly polar monomers such as lactic acid were analysed with detection limits below 10 g/kg of the material. Lactic acid enantiomer elucidation was performed using an enzyme assay. The content of non-hydrolysable residue was determined gravimetrically after hydrolysis, and the inorganic residue after washing. The composition of 12 polyesters mostly in food contact, labelled as bio-based or compostable and sampled from the market was elucidated recovering 92-101% of the total mass by summing up the determined monomers and non-polyester contents. Seven different monomers were detected in the 12 samples (up to four different monomers per sample), lactic acid being the most common (9 samples) with contents ranging from a minor component (about 11 mol%) up to the only monomer found in the material. The ratio of d- to l-lactic acid ranged from 0.3:99.7 to 4.7:95.3 (w/w). The non-hydrolysable (in)organic residue was quantified in amounts of up to 390 g/kg. Overall, the presented analytical protocol is a fundamental tool helping both to verify the appropriateness of labelling as biopolyesters as well as to predict potential leachables such as oligomers during an FCM risk assessment.


Use of older patients as cadaveric kidney donors.
We have no fixed upper age limit for cadaveric kidney donors and donors over the age of 50 provided kidneys for 22 per cent of our adult transplant recipients between 1983 and 1986. Immediate function following transplantation occurred in 17 per cent of these kidneys compared with 58 per cent for kidneys from donors under the age of 50. The 1-year actuarial graft survival rate for transplants from donors over 50 was 52 per cent, compared with 70 per cent for transplants from donors under 50 (P less than 0.05). Thus kidneys from older donors make an important contribution to the total pool of organs available for transplantation, but their use leads to inferior results in comparison with kidneys from younger donors.


The Alma-Ata Decade: the crisis of development and international health.
The paper analyzes formulations in the area of international health at the time of the International Conference on Primary Health Care, held in Alma Ata, Kazakhstan, in 1978. It is set within the context of the broader debate on development and international cooperation throughout the 1970s. Three sets of concepts and prescriptive formulations were examined namely: the New International Economic Order (NIEO), the Dag Hammarskjöld Report (DHR) and the Basic Human Needs Approach (BHN). They were compared with the proposals in documents from the World Health Organization and in the statements from Halfdan Mahler, its director. As a whole, this set of formulations and proposals share a broad spectrum of terms and notions, as well as much of the expectations for change and tensions that existed in the classic period of development during the later years of the post-war era.


Advanced oxidation protein products as a biomarker of cutaneous lupus erythematosus complicated by nephritis: a case-control study.
Oxidative stress is involved in the pathogenesis of lupus nephritis (LN). The current study investigated the significance of advanced oxidation protein products (AOPPs) as a biomarker of LN in patients with cutaneous lupus erythematosus. Ninety-two patients who initially presented with systemic lupus erythematosus were divided into the LN- and LN+ groups. Serum AOPP levels were determined, and the association between AOPP levels and LN was investigated in a case-control study. In the LN+ group, patients with higher AOPP levels exhibited higher levels of dsDNA and proteinuria but lower levels of eGFR and complement C3 compared to those in patients with lower AOPP levels. A multivariable logistic regression model showed that the AOPP level was an independent risk factor for LN. The risk of nephritis specifically increased 24% for each 10 μM increase in AOPP (95% confidence interval, 1.166-1.915, P = 0.030). In contrast, neither elevated dsDNA level nor decreased complement C3 level was an independent risk factor for LN. Higher serum AOPP levels were associated with an increased risk of LN. Therefore, future studies are warranted to determine the potential clinical value of this novel biomarker.


Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis.
To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol)/poly(propylene glycol)(PEG/PPG) ophthalmic solution. The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test. No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005) and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001).The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events occurred. The 5% glycyrrhizin ophthalmic solution was well tolerated in healthy volunteers and in patients with chronic moderate/severe blepharitis, and in association with eyelid hygiene showed good clinical anti-inflammatory activity that lasted after instillation suspension.


Clinical outcomes of secondary prevention strategies for young patients with cryptogenic stroke and patent foramen ovale.
Background The aim of this study was to compare the immediate and long-term clinical outcomes of medical therapy and percutaneous patent foramen ovale (PFO) closure as secondary prevention strategies in patients younger than 55 years of age presenting with cryptogenic stroke and PFO. Methods Between January 2006 and April 2015, all patients with the diagnosis of cryptogenic stroke and PFO were analysed and prospectively followed. Stroke was confirmed in 159 out of 309 patients (51%). In the remaining cases, other neurological conditions were found and therefore excluded from further analysis. Patients received PFO closure or medical therapy on the basis of a pre-specified algorithm. Primary outcome was the assessment of recurrent ischaemic events at follow-up. Results Percutaneous PFO closure was performed in 77 patients (48%) and 82 (52%) were treated medically. Mean follow-up was 51.6 ± 34.8 months. Two ischaemic strokes occurred in the medical group only (2.4% vs 0%; P = 0.16) and no complications related to the invasive procedure were observed. Conclusions The diagnosis of stroke in patients with PFO could be confirmed in 50% of cases only, underlining the importance of a multidisciplinary evaluation of these patients. A very low ischaemic recurrence rate was observed in the medical therapy group, suggesting that a personalized treatment based on a prespecified diagnostic algorithm yields good clinical results irrespective of the treatment modality. Given the low number of recurrences, larger cohorts may be needed to prove significant differences.


Association of provider HPV vaccination training with provider assessment of HPV vaccination status and recommendation of HPV vaccination.
The delivery of strong HPV vaccine recommendations hinges on the expertise of healthcare providers (HCPs) in assessing patients' status and recommending HPV vaccination. We conducted a population-based cross-sectional study of HCPs practicing in Texas to examine the relationship between HPV vaccination training of HCPs and HPV vaccination status assessment and recommendation. Logistic regression analyses were used to assess the association between HCPs' formal training and recency of training in HPV vaccination promotion or counseling with HPV vaccination status assessment and recommendation. Of the 1,283 HCPs who completed the online survey, 43% had received training in HPV vaccination promotion or counseling, 47% often/always assess HPV vaccination status, and 59% often/always recommend HPV vaccination. Compared with HCPs who received no training, those who received training had over four times higher odds (adjusted odds ratio [AOR]: 4.32; 95% CI: 3.06-6.10) of often/always assessing HPV vaccination status and over three and half times higher odds (AOR: 3.66; 95% CI: 2.73-4.90) of often/always recommending HPV vaccination. Furthermore, HCPs who recently received HPV vaccination training had higher odds of HPV vaccination status assessment and recommendations than those without training. Hispanic HCPs had higher odds of often/always assessing HPV vaccination status and recommending vaccination than did non-Hispanic White HCPs. Also, nurses and physician assistants had lower odds of often/always assessing HPV vaccination status and recommending HPV vaccination than did physicians. Targeted and continuous training of HCPs in HPV vaccination promotion or counseling is needed to increase HPV vaccination status assessment, recommendation, and uptake rates.


Irpexolidal Represents a Class of Triterpenoid from the Fruiting Bodies of the Medicinal Fungus Irpex lacteus.
Irpexolidal (1), a triterpenoid with an unprecedented carbon skeleton, along with its biogenetic-related compound irpexolide A (2), were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus. Irpexolidal features a 6/5/6/5/6/5-fused polycyclic skeletal system which arises from the eburicane-type triterpene by a 6,7- seco-6,8- cyclo pattern. The structures of 1 and 2 were established by means of extensive spectroscopic techniques, ECD calculation, and DP4+ probability based on GIAO NMR chemical shift calculations. The plausible biosynthetic pathways for compounds 1 and 2 were proposed. Their biological activities were evaluated.


Evaluation and modification of existing CETP.
For the development of small and medium scale industries in various Gujarat industrial development corporation (GIDC) areas and in clusters of industrial areas, the common effluent treatment plant (CETP) has always been found advantageous in view of cost of treatment, operation and maintenance and disposal of residues being produced. In small scale industrial units due to market requirement, product changes and quantity enhancement are taking place. Due to such changes, the effluent characteristics are continuously changing which affects performance of CETP. Hence it has been found necessary to study continuously the performance, evaluation and modification in the working of the CETP. This paper contains a case study of one of the existing CETP near Baroda which is facing the problem of disposal of treated effluent in which the important parameters like COD, BOD, Suspended Solid, NH3-N and oil and grease were analyzed. Based on the characterization of wastewater, the various treatability studies were carried out on CETP wastewater. To comply with disposal standard prescribed by Effluent Channel Project Ltd.(ECPL)* and Gujarat Pollution Control Board (GPCB) for discharge of industrial effluent into channel, various treatments in form of ammonia stripping, coagulation and flocculation, biological treatment, filtration and chlorination are suggested.


A CT based radiomics nomogram for differentiation between focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma.
The purpose of this study was to develop and validate an CT-based radiomics nomogram for the preoperative differentiation of focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma. 96 patients with focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma have been enrolled in the study (32 and 64 cases respectively). All cases have been confirmed by imaging, clinical follow-up and/or pathology. The imaging data were considered as: 70% training cohort and 30% test cohort. Pancreatic lesions have been manually delineated by two radiologists and image segmentation was performed to extract radiomic features from the CT images. Independent-sample T tests and LASSO regression were used for feature selection. The training cohort was classified using a variety of machine learning-based classifiers, and 5-fold cross-validation has been performed. The classification performance was evaluated using the test cohort. Multivariate logistic regression analysis was then used to develop a radiomics nomogram model, containing the CT findings and Rad-Score. Calibration curves have been plotted showing the agreement between the predicted and actual probabilities of the radiomics nomogram model. Different patients have been selected to test and evaluate the model prediction process. Finally, receiver operating characteristic curves and decision curves were plotted, and the radiomics nomogram model was compared with a single model to visually assess its diagnostic ability. A total of 158 radiomics features were extracted from each image. 7 features were selected to construct the radiomics model, then a variety of classifiers were used for classification and multinomial logistic regression (MLR) was selected to be the optimal classifier. Combining CT findings with radiomics model, a prediction model based on CT findings and radiomics was finally obtained. The nomogram model showed a good sensitivity and specificity with AUCs of 0.87 and 0.83 in training and test cohorts, respectively. The areas under the curve and decision curve analysis showed that the radiomics nomogram model may provide better diagnostic performance than the single model and achieve greater clinical net benefits than the CT finding model and radiomics signature model individually. The CT image-based radiomics nomogram model can accurately distinguish between focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma patients and provide additional clinical benefits.


Zinc-Based Biodegradable Materials for Orthopaedic Internal Fixation.
Traditional inert materials used in internal fixation have caused many complications and generally require removal with secondary surgeries. Biodegradable materials, such as magnesium (Mg)-, iron (Fe)- and zinc (Zn)-based alloys, open up a new pathway to address those issues. During the last decades, Mg-based alloys have attracted much attention by researchers. However, the issues with an over-fast degradation rate and release of hydrogen still need to be overcome. Zn alloys have comparable mechanical properties with traditional metal materials, e.g., titanium (Ti), and have a moderate degradation rate, potentially serving as a good candidate for internal fixation materials, especially at load-bearing sites of the skeleton. Emerging Zn-based alloys and composites have been developed in recent years and in vitro and in vivo studies have been performed to explore their biodegradability, mechanical property, and biocompatibility in order to move towards the ultimate goal of clinical application in fracture fixation. This article seeks to offer a review of related research progress on Zn-based biodegradable materials, which may provide a useful reference for future studies on Zn-based biodegradable materials targeting applications in orthopedic internal fixation.


Development of tympanosclerosis: can predicting factors be identified?
The etiological hypothesis is that there might be factors triggering an immunological chain reaction that eventually leads to tympanosclerosis formation. Tympanosclerosis is a condition leading to a calcification process in the middle ear and, occasionally, also to the lining of the inner ear. This sometimes leads to hearing loss due to fixation of the middle ear ossicles. In severe cases. deafness may occur as a result of the inner ear impairment. Surgery is the treatment offered, often with poor long-term results, and, alternatively, prescription of hearing aids. Some patients develop tympanosclerosis after mild inflammatory otitis media processes whereas some heal without tympanosclerosis after more aggressive infections. This difference may be due to individual variations in the inflammatory response. The biological mechanism of calcification in tympanosclerosis is probably similar to that occurring in other calcifying tissues due to diseases. The present investigation was performed to develop methods for immunohistochemical analyses of this delicate tissue consisting of both hard bone and the very thin tympanic membrane. Sprague-Dawley rats were inoculated with a suspension of Streptococcus pneumoniae, type 3, into the middle ear and sacrificed after 1 week up to 6 months. A new technique was elaborated where the whole specimen was prefixed briefly and then en bloc incubated with the primary antibodies and after that decalcified in edetic acid (EDTA). Primary antibodies against macrophages were used for the immunohistochemical staining. Acute otitis media was successfully induced in the rats and myringosclerosis was seen in 30% of the animals, often localized close to the bony frame where macrophages could also be detected. Acute otitis media and myringosclerosis were introduced in the animals. Conventional immunological techniques were tested on this delicate tissue. A new method for immunohistochemical staining was elaborated in which specimens were stained en bloc before decalcification and sectioning were performed. Expression of macrophages was demonstrated in the tympanic membrane.


Role of district and community nurses in bereavement care: a qualitative study.
The district nurse is one of the main providers of palliative care, which includes bereavement care. However, previous evidence shows a lack of education and training, as well as time management, as important factors in the delivery of bereavement care. This qualitative study aimed to explore the provision of bereavement care from a district nurse's perspective. Data were collected from five participants using semi-structured interviews, and thematically analysed to produce the findings. The interviews were conducted within the author's and participants' working environments to maintain a professional stance between both parties. The results suggest an awareness of bereavement care, but a lack of training and education into the theoretical aspects of the care. Knowing the types and stages of bereavement would be beneficial, both in the delivery and the identification of the most effective time to refer on. Bereavement care was understood to be part of the district nurse role, but the findings suggest that some nurses get too involved and no end date could be standardised, as each case is dependent on need. More experience of bereavement care and exposure increased awareness to its importance and improved confidence toward its delivery.


Role of smooth muscle cells in coronary artery bypass grafting failure.
Atherosclerosis is the underlying pathology of many cardiovascular diseases. The formation and rupture of atherosclerotic plaques in the coronary arteries results in angina and myocardial infarction. Venous coronary artery bypass grafts are designed to reduce the consequences of atherosclerosis in the coronary arteries by diverting blood flow around the atherosclerotic plaques. However, vein grafts suffer a high failure rate due to intimal thickening that occurs as a result of vascular cell injury and activation and can act as 'a soil' for subsequent atherosclerotic plaque formation. A clinically-proven method for the reduction of vein graft intimal thickening and subsequent major adverse clinical events is currently not available. Consequently, a greater understanding of the underlying mechanisms of intimal thickening may be beneficial for the design of future therapies for vein graft failure. Vein grafting induces inflammation and endothelial cell damage and dysfunction, that promotes vascular smooth muscle cell (VSMC) migration, and proliferation. Injury to the wall of the vein as a result of grafting leads to the production of chemoattractants, remodelling of the extracellular matrix and cell-cell contacts; which all contribute to the induction of VSMC migration and proliferation. This review focuses on the role of altered behaviour of VSMCs in the vein graft and some of the factors which critically lead to intimal thickening that pre-disposes the vein graft to further atherosclerosis and re-occurrence of symptoms in the patient.


Validation and Field Performance of the Italian Version of the Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire.
Psoriatic arthritis (PsA) is a potentially severe inflammatory condition (entheso-arthro-osteopathy), and early diagnosis is important to guide treatment choices in patients with psoriasis. The objective of this study is to further validate the PsA Screening and Evaluation (PASE) questionnaire, and to assess its field performance. Data were collected in 10 Italian centres, and the PASE was administered at baseline, after 3 days and after 3 months. The Skindex-29 was also administered. To determine the best cut-off value to identify patients with PsA we produced receiver operating characteristic (ROC) curves using the rheumatologist's diagnosis as outcome. Of the 298 patients that were enrolled, 28% were classified as having PsA according to the CASPAR criteria, while 19% had received a diagnosis of PsA from a rheumatologist. PASE score were always significantly different in patients with or without PsA, while Skindex-29 scores never were. The internal consistency of the PASE was very good (Cronbach's α of 0.90-0.95), the test-retest reliability was also very high (intraclass correlation coefficients 0.91-0.93), and the PASE scores showed good responsiveness to clinical change over time. The optimal cut-off identified through the ROC curves was ≥ 48 on the total PASE score, which was able to distinguish PsA from non-PsA patients with a 73.2% sensitivity and a 76.1% specificity. Our results confirm the good psychometric properties of the PASE, and indicate that it may be a useful tool for the dermatologists, both to screen for PsA and to obtain a standardized patient-reported measure to monitor and evaluate the health status of the patients with PsA.


Mediastinal compression due to tension hydrothorax.
We describe a patient in whom a malignant pleural effusion accumulated with sufficient pressure to cause mediastinal compression resulting in acute respiratory distress, dysphagia, and massive edema of the lower extremities. Emergency thoracocentesis produced immediate relief to respiratory symptoms and dysphagia, with gradual disappearance of the edema and a weight loss of 6.8 kg (15 lb) without adjunctive medications. It is suggested that thoracocentesis is a life-saving measure in this circumstance and should be done immediately in patients with similar initial clinical findings, as further diagnostic evaluation or other therapy directed to the mediastinum will not releive the tension and will only delay removal of the fluid.


Targeting mitochondrial degradation by chimeric autophagy-tethering compounds.
The ability to regulate mitophagy in a living system with small molecules remains a great challenge. We hypothesize that adding fragments specific to the key autophagosome protein LC3 to mitochondria will mimic receptor-mediated mitophagy, thus engaging the autophagy-lysosome pathway to induce mitochondrial degradation. Herein, we develop a general biochemical approach to modulate mitophagy, dubbed mito-ATTECs, which employ chimera molecules composed of LC3-binding moieties linked to mitochondria-targeting ligands. Mito-ATTECs trigger mitophagy via targeting mitochondria to autophagosomes through direct interaction between mito-ATTECs and LC3 on mitochondrial membranes. Subsequently, autophagosomes containing mitochondria rapidly fuse with lysosomes to facilitate the degradation of mitochondria. Therefore, mito-ATTECs circumvent the detrimental effects related to disruption of mitochondrial membrane integrity by inducers routinely used to manipulate mitophagy, and provide a versatile biochemical approach to investigate the physiological roles of mitophagy. Furthermore, we found that sustained mitophagy lead to mitochondrial depletion and autophagic cell death in several malignant cell lines (lethal mitophagy). Among them, apoptosis-resistant malignant melanoma cell lines are particularly sensitive to lethal mitophagy. The therapeutic efficacy of mito-ATTECs has been further evaluated by using subcutaneous and pulmonary metastatic melanoma models. Together, the mitochondrial depletion achieved by mito-ATTECs may demonstrate the general concept of inducing cancer cell lethality through excessive mitochondrial clearance, establishing a promising therapeutic paradigm for apoptosis-resistant tumors.


Describing and visualizing the patient and caregiver experience of cancer pain in the home context using ecological momentary assessments.
Pain continues to be a difficult and pervasive problem for patients with cancer, and those who care for them. Remote health monitoring systems (RHMS), such as the Behavioral and Environmental Sensing and Intervention for Cancer (BESI-C), can utilize Ecological Momentary Assessments (EMAs) to provide a more holistic understanding of the patient and family experience of cancer pain within the home context. Participants used the BESI-C system for 2-weeks which collected data via EMAs deployed on wearable devices (smartwatches) worn by both patients with cancer and their primary family caregiver. We developed three unique EMA schemas that allowed patients and caregivers to describe patient pain events and perceived impact on quality of life from their own perspective. EMA data were analyzed to provide a descriptive summary of pain events and explore different types of data visualizations. Data were collected from five (n = 5) patient-caregiver dyads (total 10 individual participants, 5 patients, 5 caregivers). A total of 283 user-initiated pain event EMAs were recorded (198 by patients; 85 by caregivers) over all 5 deployments with an average severity score of 5.4/10 for patients and 4.6/10 for caregivers' assessments of patient pain. Average self-reported overall distress and pain interference levels (1 = least distress; 4 = most distress) were higher for caregivers (x¯ 3.02, x¯2.60,respectively) compared to patients (x¯ 2.82, x¯ 2.25, respectively) while perceived burden of partner distress was higher for patients (i.e., patients perceived caregivers to be more distressed, x¯ 3.21, than caregivers perceived patients to be distressed, x¯2.55). Data visualizations were created using time wheels, bubble charts, box plots and line graphs to graphically represent EMA findings. Collecting data via EMAs is a viable RHMS strategy to capture longitudinal cancer pain event data from patients and caregivers that can inform personalized pain management and distress-alleviating interventions.


Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6.
To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.


Ethics and forensic psychiatry: translating principles into practice.
Twenty-five years ago, Alan Stone expressed his skepticism that forensic psychiatry could be practiced ethically. His remarks have proven a useful goad to the field, focusing attention on the importance of an ethics framework for forensic practice. But Stone remains dubious that any system of ethics--including the "Standard Position" on which he focuses his critique--could be of much value in practice. In contrast, I suggest that Stone's pessimism is not well founded. Immanent in forensic practice itself is a reasonable set of ethics principles, based on truth-telling and respect for persons. Psychiatrists can offer reliable and valid testimony, while resisting seduction into an advocacy role. Indeed, with new structured approaches to assessment, the potential utility of forensic testimony is probably greater than ever. Though problematic behavior still exists, forensic psychiatry offers the factual background and interpretive context to allow legal decision-makers to make better choices than they otherwise would.


Effect of Adenotonsillectomy on Ambulatory Blood Pressure in Pediatric Obstructive Sleep Apnea: 6-Month Follow-up Study.
To investigate 24-hour ambulatory blood pressure changes 6 months after surgery among children with obstructive sleep apnea. Prospective interventional study. Tertiary medical hospital. Children aged 4 to 16 years with symptoms of obstructive sleep apnea (apnea-hypopnea index >1) were recruited. All children underwent adenotonsillectomy and postoperative polysomnography overnight. The 24-hour ambulatory blood pressure was measured before and 6 months after surgery. The study cohort enrolled 124 children: mean (SD) age, 7.3 (3.1) years; 73% boys. After surgery, the apnea-hypopnea index significantly decreased from 13.3 (18.1) to 3.3 (7.2) events per hour ( P < .001). Overall systolic blood pressure and diastolic blood pressure were not significantly different following surgery, while daytime systolic blood pressure was slightly increased (114.3 to 117.3 mm Hg, P < .01) postoperatively. The hypertensive group (n = 43) exhibited significantly decreased levels of overall diastolic, nighttime systolic, and nighttime diastolic blood pressure ( P < .05), and 54% of hypertensive children became nonhypertensive after surgery. The nonhypertensive group (n = 81) showed slightly increased levels of nocturnal overall systolic, daytime systolic, and nighttime systolic blood pressure. A generalized linear mixed model revealed that children with hypertension had a greater decrease in systolic and diastolic ambulatory blood pressure during the daytime and nighttime (all P < .05) than those without hypertension. Ambulatory blood pressure changes after adenotonsillectomy among children with obstructive sleep apnea are minimal. The decrease in ambulatory blood pressure after surgery is more prominent for hypertensive children than nonhypertensive children.


X/XYq - mosaicism and mixed gonadal dysgenesis.
A non-fluorescent Y chromosome was observed in a phenotypic male with 45,X/46,XYq-mosaicism and mixed gonadal dysgenesis. Q-banding of the father's chromosomes showed a normally fluorescent Y. Measurements of the Y chromosomes in the father and the patient showed a significant difference in length. Evidence for translocation of the Y fluorescent segment to another chromosome was lacking in the present case.


[The history of plastic surgery in Israel].
The medical institutions in the country have advanced together with the development of the state of Israel. Plastic surgery, which has progressed significantly during the 20th century, has also grown rapidly in the new state. The arrival of Jewish plastic surgeons from all over the world with the knowledge and experience gained in their countries of origin, as well as the need for reconstructive surgical treatment for many combat injured soldiers, also contributed to the development of plastic surgery. This review tells the story of plastic surgery in Israel, since its foundation until nowadays. This article reviews the work of the founders of plastic surgery in Israel, indicating significant milestones in its development, and clinical and scientific contribution to the international plastic surgery profession. Moreover, the article describes the current condition of the field of plastic surgery in Israel and presents the trends and the future challenges facing the next generation of plastic surgery in Israel.


Attribute-Based Encryption Schemes for Next Generation Wireless IoT Networks: A Comprehensive Survey.
Most data nowadays are stored in the cloud; therefore, cloud computing and its extension-fog computing-are the most in-demand services at the present time. Cloud and fog computing platforms are largely used by Internet of Things (IoT) applications where various mobile devices, end users, PCs, and smart objects are connected to each other via the internet. IoT applications are common in several application areas, such as healthcare, smart cities, industries, logistics, agriculture, and many more. Due to this, there is an increasing need for new security and privacy techniques, with attribute-based encryption (ABE) being the most effective among them. ABE provides fine-grained access control, enables secure storage of data on unreliable storage, and is flexible enough to be used in different systems. In this paper, we survey ABE schemes, their features, methodologies, benefits/drawbacks, attacks on ABE, and how ABE can be used with IoT and its applications. This survey reviews ABE models suitable for IoT platforms, taking into account the desired features and characteristics. We also discuss various performance indicators used for ABE and how they affect efficiency. Furthermore, some selected schemes are analyzed through simulation to compare their efficiency in terms of different performance indicators. As a result, we find that some schemes simultaneously perform well in one or two performance indicators, whereas none shines in all of them at once. The work will help researchers identify the characteristics of different ABE schemes quickly and recognize whether they are suitable for specific IoT applications. Future work that may be helpful for ABE is also discussed.


Leukocyte count and bronchial hyperresponsiveness.
The relationship of total and differential blood leukocyte counts with bronchial methacholine response was studied in a population-based sample of 324 men. Geometric mean total leukocyte counts were significantly higher in reactors (6567 cells/mm3) than in nonreactors (5732 cells/mm3; p = 0.003). After adjusting for smoking habits, a factor contributing to both an elevation in peripheral leukocyte count and an increased level of airway responsiveness, reactor status remained significantly associated with leukocyte count. This association also persisted after controlling, with a logistic model, for atopy and common cold (marker of infection) and after excluding men with a history of asthma, chronic bronchitis, or low FEV1. Study of the differential leukocyte counts has shown that an increase was present for almost every type of leukocyte, and particularly evident for neutrophils. Whether these findings reflect an association between bronchial hyperresponsiveness and cellular inflammation needs more investigation.


Lymph node spread of gallbladder cancer from the perspective of embryologically-based anatomy and significance of the lymphatic basin along the embryonic right hepatic artery.
Lymph node metastasis from gallbladder cancer is often found in the pericholedochal area; however, these regional lymph nodes are not typically accompanied by arteries. We hypothesized that the artery accompanying pericholedochal lymph nodes was either the regressed embryonic right hepatic artery (eRHA) or an aberrant right hepatic artery (aRHA) remaining without regression. This study aimed to determine the artery supplying pericholedochal lymph nodes. We obtained serial tissue sections of resected specimens from 10 patients who underwent pancreaticoduodenectomy with combined resection of the superior mesenteric artery and vein and investigated the association between the distribution of enlarged lymph nodes and the course of blood vessels in each section. In 2 cases with aRHA, enlarged lymph nodes were distributed in the posterosuperior area, pancreaticoduodenal region and retroportal area along this artery. By contrast, no blood vessels accompanied enlarged lymph nodes in 8 patients exhibiting a normal hepatic artery branching pattern, although these nodes exhibited a distribution pattern similar to that of patients with the aRHA. Thus, the artery supplying pericholedochal lymph nodes appears to be either the regressed eRHA or an aRHA persisting without regression.


Measurement of cellular elastic properties by acoustic microscopy.
The acoustic microscope is used to investigate the elastic properties of living biological cells. A quantitative model is developed relating acoustic microscope image contrast to cellular elastic properties. Cytoplasmic acoustic attenuation is measured by focusing the acoustic microscope on the surface of the underlying substrate. Cytoplasmic acoustic impedance is measured by focusing the acoustic microscope on the top surface of the cell. The model allows the acoustic microscope to give quantitative information about cellular elasticity on a subcellular scale.


Continuous hemodiafiltration during cardiopulmonary bypass in infants.
The homologous blood prime in cardiopulmonary bypass circuits contributes a significant electrolyte and metabolite load in small infants. The efficacy of hemofiltration and continuous hemodiafiltration of the blood prime in preventing metabolic disturbances in small infants was compared in two groups of 60 patients each. Blood pH, base excess, and calcium concentrations decreased during cardiopulmonary bypass in the hemofiltration group. The acid-base balance was well preserved during cardiopulmonary bypass by continuous hemodiafiltration. This therapeutic strategy may confer an advantage in maintaining more physiological conditions during cardiopulmonary bypass in small infants.


Vestibular hair cell pathology in the dancer mouse mutant.
The morphogenetic type of inner ear defect in the dancer (Dc/+) mouse mutant affects primarily the vestibular part of the labyrinth. The animals show a circling-waltzing behaviour. The inner ears from 7-day to 12-month-old Dc/+ mutants have been analysed. Apart from gross malformations, the gene caused changes in fine structure which were found primarily in the cuticular plate and the stereocilia. As the cuticle gradually disintegrated, the sensory hairs became disarrayed and later showed hair fusion. The combination of the gross malformations and the specific ultrastructural changes in the hair cells probably interferes with both posture and behaviour and, probably together with a dysfunction of the central nervous system, is the cause of the animal's behaviour.


A treatable cause of recurrent severe hypoglycemia.
To see if glucocorticoid deficiency might explain increased insulin sensitivity causing severe brittle diabetes in two type I diabetic patients. We describe two patients who developed brittle diabetes characterized by recurrent severe hypoglycemia on small daily insulin doses with severe hyperglycemia on further insulin dose reduction. In both patients, insulin requirements had fallen markedly. Both patients were found to have glucocorticoid deficiency. In one patient, this was a result of hypopituitarism, in which hypoglycemia was aggravated by growth hormone deficiency. In the other patient, glucocorticoid deficiency was the result of primary adrenal failure. Resolution of brittle diabetes and restoration of normal insulin doses followed steroid replacement therapy in both patients. These patients emphasize the importance of seeking an organic cause for recurrent severe hypoglycemia. Increasing insulin sensitivity in type I diabetic patients should alert clinicians to the possibility of glucocorticoid deficiency.


The ultrastructure of contact lens induced changes.
The endothelium of 15 human corneas was studied with specular and electron microscopy after exposure to a thick, low water content, soft contact lens (SCL). Five control corneas (no lens wear) were studied using the same methods. SCL wear produced obvious changes in endothelial morphology in 12 of the 15 eyes. With specular microscopy, the changes consisted of an apparent increase in separation of cells and development of areas of loss of membrane reflectivity (blebs). When viewed with electron microscopy, the changes in the same corneas consisted of oedema in the nuclear area of the cells and bulging of the posterior endothelial surface, in some cases over an area of several cells. In 4 cases, the cellular oedema was marked showing both intracellular and intercellular vacuoles. It was concluded that the transient endothelial changes seen with specular microscopy following SCL lens wear were produced by alterations in the contour of the posterior endothelial surface resulting from disturbance to the endothelial environment.


Placental melatonin production and melatonin receptor expression are altered in preeclampsia: new insights into the role of this hormone in pregnancy.
The melatonin system in preeclamptic pregnancies has been largely overlooked, especially in the placenta. We have previously documented melatonin production and expression of its receptors in normal human placentas. In addition, we and others have shown a beneficial role of melatonin in placental and fetal functions. In line with this, decreased maternal blood levels of melatonin are found in preeclamptic compared with normotensive pregnancies. However, melatonin production and expression of its receptors in preeclamptic compared with normotensive pregnancy placentas has never been examined. This study compares (i) melatonin-synthesizing enzyme expression and activity, (ii) melatonin and serotonin, melatonin's immediate precursor, levels and (iii) expression of MT1 and MT2 melatonin receptors in placentas from preeclamptic and normotensive pregnancies. Protein and mRNA expression of aralkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), the melatonin-synthesizing enzymes, as well as MT1 and MT2 receptors were determined by RT-qPCR and Western blot, respectively. The activities of melatonin-synthesizing enzymes were assessed by radiometric assays while melatonin levels were determined by LC-MS/MS. There is a significant inhibition of AANAT, melatonin's rate-limiting enzyme, expression and activity in preeclamptic placentas, correlating with decreased melatonin levels. Likewise, MT1 and MT2 expression is significantly reduced in preeclamptic compared with normotensive pregnancy placentas. We propose that reduced maternal plasma melatonin levels may be an early diagnostic tool to identify pregnancies complicated by preeclampsia. This study indicates a clinical utility of melatonin as a potential treatment for preeclampsia in women where reduced maternal plasma levels have been identified.


Practice uncertainty: changing perceptions.
Practice uncertainty is inevitable in health care, and there are many contextual factors that can lead to either good or bad outcomes for patients and health care providers. Practice uncertainty is not a well-established concept in the literature, perhaps because of the predominant empirical paradigm and the high value placed on certainty within current health care culture. This study was conducted to explore practice uncertainty and bring this topic into the foreground as a first step toward practice evolution. A shift in the perception of practice uncertainty may change the way in which practitioners experience this phenomenon. This process must start with nursing educators recognizing and acknowledging this phenomenon when it occurs.


Complete Genome Sequence of Isolate Bari 1, a Mild Strain of Cauliflower Mosaic Virus.
We present here the complete genome sequence of isolate Bari 1, a mild strain of cauliflower mosaic virus (CaMV). The isolate was collected from Diplotaxis tenuifolia (perennial wall-rocket) in Bari, Italy. The genome was 8,020 nucleotides long and shared ≤85.4% nucleotide identity with other CaMV isolates.