Haemocompatibility of segmented polyurethanes investigated in vivo.
Samples of segmented polyurethanes differing in composition and in surface morphology were introduced into the left ventricles of hearts of goats for 72 h. After removal of the samples, their surface and the surface of the heart endothelium were evaluated visually with respect to the formation of thrombi. Differences in the interaction of the individual polyurethanes with blood were examined by XPS photoelectron spectroscopy, SEM, and by infrared (i.r.) reflexion spectroscopy. The results suggest ways for improving the haemocompatibility of the surfaces of polyurethanes used as parts of the total artificial heart.


Ontogenetic Shifts in Body Morphology of Demersal Sharks' Species (Order: Squaliformes) Inhabiting the Western-Central Mediterranean Sea, with Implications for Their Bio-Ecological Role.
Several elasmobranch species undergo shifts in body proportions during their ontogenetic growth. Such morphological changes could reflect variation in diet, locomotion, or, more broadly, in the species' interactions with their environment. However, to date, only a few studies have been conducted on this topic, and most of them focused on particular body regions. In the present study, the ontogenetic growth of five different demersal shark species was investigated by using both traditional linear morphometry of the entire body and shape analysis of the caudal fin. A total of 449 sharks were analysed: 95 little gulper sharks, 80 longnose spurdogs, 103 kitefin sharks, 124 velvet belly lanternsharks, and 47 angular roughsharks. From each specimen, 36 linear morphometric measurements were taken. While a first canonical analysis of principal coordinates ruled out the possibility of different growth patterns between males and females, the same analysis statistically discriminated between small and large individuals in every species based on their morphology. A Similarity Percentage analysis revealed that the most important measurements in distinguishing these two groups were those related to body lengths, indicating that large individuals are more elongated than small individuals. The shape analysis of caudal fins revealed allometric growth during ontogenetic development, with adult individuals having a wider fin (discriminant analysis, p < 0.05). These findings could be related to changes in predatory skills, supporting the hypothesis of a shift in the ecological role that these sharks play in their environment, thus providing new essential information for their conservation.


Advanced Glycation End Products (AGEs), Glutathione and Breast Cancer: Factors, Mechanism and Therapeutic Interventions.
Advanced Glycation End products (AGEs) are basically the end result of glycation of proteins and/or lipids in the presence of sugars. Specific cases of hyperglycemia have been reported with increased propensity of generation of AGEs. Many chronic and deadly diseases such as diabetes, cancer and neurodegenerative disorders have been known to be caused as a result of generation of AGEs. The role of glutathione (GSH) metabolism and its intricate association with AGEs have also been well established in breast cancer prognosis and treatment. To understand the etiology, mechanism and production of AGEs along with clinical relevance of Receptors for Advanced Glycation End-products (RAGE) and RAGE ligands, their interplay with GSH is of paramount importance especially in relation to breast cancer. The available literature using PubMed, National Library of Medicine database, Web of Science and SCOPUS indexed, Science Direct and other prestigious journals have been systematically reviewed using the keywords: advanced glycation end-products, breast cancer, glutathione RAGE, and AGEs inhibitors. This narrative review of all the relevant papers with significant citations has led us to have greater insight into the action mechanism and potential therapeutic significance of AGEs inhibitors. Targeting breast cancer with the specific immunoglobulins and with other therapeutic interventions is needed to inhibit the generation of AGEs and manage glutathione expression, thus having strong implications in the management of breast cancer. Many RAGE ligands such as HMGB1, S100P, S100A8, S100A9 etc. have been known to enhance RAGE expression which may further lead to increased proliferation, migration and metastatic nature of tumor cells. Hence, RAGE and RAGE ligands in a close linkup with GSH may prove to be effective therapeutic markers of severity of breast cancer and for angiogenesis of tumor. This review provides a strong platform to comprehend the etiology, mechanism and production of AGEs and glutathione along with the agents which can block their production, paving a way for the therapeutic intervention and an amicable solution to treat and manage breast cancer.


A succinct review of the general and immunological pharmacologic effects of proton pump inhibitors.
Proton pump inhibitors (PPI) are a group of anti-ulcer agents. PPI have selective anti-cancer effects via apoptosis of tumour, sensitization of cancer cell to chemotherapy and radiotherapy. Also PPI have anti-malarial and anti-leishmanial activity. Rising of endosomal (P)H inhibits the presentation of antigens that enter cell through endocytosis. PPI can affect transmigration of leucocytes from vessels to inflammatory sites and also can mitigate neutrophile adherence to endothelial cell. PPI increase the intralysosomal (P)H and decrease the expression of intracellular adhesion molecules. Therefore PPI can exert immunomodulation in immunological diseases through hampering antigen processing, antigen presentation, and leucocytes transmigration.


Effects of tetrodotoxin, elevated calcium and calcium antagonists on electrically induced 3H-noradrenaline release from brain slices.
Electrically induced release of 3H-noradrenaline from superfused rat brain cortex slices was completely inhibited by tetrodotoxin (1 microgram/ml) if 0.5 or 1 V stimuli were used, while inhibition was 97% with 2 V, and nil with 12 V stimuli. 20 mM calcium depressed noradrenaline release at all applied potentials, and shifted the release versus voltage curve to higher potentials. Manganese (5 mM) and D-600 (10-100 microgram/ml) also considerably inhibited release. This suggests that stimuli of up to 2 V induce transmitter release by exciting intracortical noradrenergic axons in their non-terminal regions.


X-ray absorption spectroscopy of metal site speciation in the metallo-β-lactamase BcII from Bacillus cereus.
Cobalt and zinc binding by the subclass B1 metallo-β-lactamase BcII from Bacillus cereus is examined by X-ray absorption spectroscopy, at various levels of metal loading. The data show that a significant amount of the dinuclear enzyme is formed, even at substoichiometric levels of metal loading, whether the added metal is Zn(II) or Co(II). Increasing metal addition, from 0.5 to 1.0 to 2.0eq/mol of enzyme, are shown to result in a more ordered active site. While Zn(II) appears to show no preference for the Zn(1) (3H) or Zn(2) (DCH) sites, the extended X-ray absorption fine structure (EXAFS) suggests that Co(II) shows a slight preference for the DCH site at low levels of added Co(II). The results are discussed in the context of similar metal-binding studies of other B1 metallo-β-lactamases.


Tuning chromosomal gene expression in Escherichia coli by combining single-stranded oligonucleotides mediated recombination and kil counter selection system.
Extensively modulating gene expression to achieve optimal flux is a critical step in metabolic engineering. Gene expression is usually modulated at the transcriptional level by controlling the strength of a promoter. However, this type of modulation is often hampered by its inability to fully sample the complete continuum of transcriptional control. In Escherichia coli, this limitation can be solved by constructing promoters with a wide range of strengths. In this study, a highly efficient method was developed to modulate a particular chromosomal gene of E. coli at a wide range of expression levels. This was achieved by combining highly efficient single-stranded oligonucleotide-mediated recombination and a stringent counter selection system kil. Using this strategy, a chromosomal library, with a range from 0.3% to 388% relative to the wild lac promoter, was easily obtained. The strength of our chromosomal promoter library was approximately 5-60 times wider in range than those of libraries reported before.


Crossbridge head detachment rate constants determined from a model that explains the behavior of both weakly- and strongly-binding crossbridges.
Experimentally it is observed that the head regions of weakly-binding myosin crossbridges (crossbridges with ATP or ADP.Pi at the nucleotide binding site) are mobile while attached to actin, while strongly-binding crossbridge heads, such as those with PPi or AMP-PNP at the nucleotide binding site, are immobile (Pate and Cooke, Biophys. J., 1988; Fajer et al., Biophys. J., 1988). I postulate that the fundamental difference between weakly- and strongly-binding crossbridges is not their difference in affinity for actin, but the difference in mobility of the myosin heads attached to actin. Because the heads of weakly-binding crossbridges are mobile while attached to actin, the heads function independently and their behavior can be described by a simple independent-head model. With strongly-binding crossbridges, when one head detaches, it cannot re-attach in a position of lesser strain while the other is attached immobile; both heads must be detached concurrently before the crossbridge can relocate to a position of less strain and relax any tension it supports. This makes the heads appear to act cooperatively. A double-headed crossbridge model is presented which takes into account the difference between weakly- and strongly-binding crossbridges. The model is quite successful at describing the experimental data. In particular, for weakly-binding crossbridges the time constant of the response to stretch is shown to be relatively insensitive to ionic strength and for strongly-binding crossbridges, the model predicts with great accuracy the large ionic strength dependence of the rate constant for force decay. When the experimental results are interpreted according to the model, an important conclusion that emerges is that in all cases (for both weakly- and strongly-binding crossbridges) unstrained crossbridge heads in the muscle fiber detach from actin with approximately the same rate constant as myosin subfragment-1 detaches from actin in solution.


Reducing Neonatal Hypothermia in Premature Infants in an Israeli Neonatal Intensive Care Unit.
Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality. To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit. The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia. The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures. Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia.


Experimental investigation of egg ovalbumin scaling on heated stainless steel surface and scale-removal compared with that of whey protein.
Fouling and cleaning on a heat exchanger surface during milk processing have been studied extensively in the past due to their great importance in energy, product quality, and safety. However, little information is available for egg ovalbumin (OVA) fouling and cleaning behavior. In the present work, fouling and cleaning behaviors of OVA were investigated using a real-time monitoring system for heat transfer coefficient. A comparison was made between the behavior of whey protein concentrate (WPC) and that of OVA. WPC has been well studied which can be used as a benchmark. Ultrasonic cleaning was also applied to investigate the cleaning behavior of OVA fouling. Results have shown that OVA created more thermal resistance than WPC in the 2 h fouling process. It was also much more difficult to remove the OVA deposit than the WPC fouling. Different from what were observed from WPC deposit, there was no optimal cleaning rate for OVA deposit in the NaOH concentration range tested (0-2.0 wt%), while WPC fouling is known to have the highest cleaning rate around 0.5 wt% NaOH concentration at moderate temperatures.


A Trial-Based Predictive Microsimulation Assessing the Public Health Benefits of Nalmefene and Psychosocial Support for the Reduction of Alcohol Consumption in Alcohol Dependence.
Alcohol dependence causes considerable harm to patients. Treatment with nalmefene, aiming to reduce consumption rather than maintain complete abstinence, has been licensed based on trials demonstrating a reduction in total alcohol consumption and heavy drinking days. Relating these trial outcomes to harmful events avoided is important to demonstrate the clinical relevance of nalmefene treatment. A predictive microsimulation model was developed to compare nalmefene plus brief psychosocial intervention (BRENDA) versus placebo plus BRENDA for the treatment of patients with alcohol dependence and a high or very high drinking risk level based on three pooled clinical trials. The model simulated patterns and level of alcohol consumption, day-by-day, for 12 months, to estimate the occurrence of alcohol-attributable diseases, injuries and deaths; assessing the clinical relevance of reducing alcohol consumption with treatment. The microsimulation model predicted that, in a cohort of 100,000 patients, 971 (95 % confidence interval [CI] 904-1038) alcohol-attributable diseases and injuries and 133 (95 % CI 117-150) deaths would be avoided with nalmefene versus placebo. This level of benefit has been considered clinically relevant by the European Medicines Agency. This microsimulation model supports the clinical relevance of the reduction in alcohol consumption, and has estimated the extent of the public health benefit of treatment with nalmefene in patients with alcohol dependence and a high or very high drinking risk level.


Imaging of the opacified middle ear.
Middle ear opacification on imaging studies performed in a non-traumatic setting mostly reflects chronic inflammatory/infectious disease. In some of these patients an underlying cholesteatoma will be found. High-resolution computed tomography examinations and magnetic resonance imaging are often used in the work-out of the disease. High-resolution computed tomography of the opacified middle ear serves to describe the status of the ossicular chain, and its suspensory apparatus, as well as the status of the tympanic and mastoid wall. When ossicular erosions are visualized, the probability of a present cholesteatoma is about 90%. Whereas high-resolution computed tomography is not able to differentiate cholesteatoma from other types of opacification, magnetic resonance imaging is. The combined use of delayed post-Gd T1-weighted images and non-EPI based DWI seems to be the actual best option on this matter.


Analysis of ECG data, for data compression.
A number of papers on the subject of data reduction techniques applied to ECG Data have recently been published; however, the authors found that most of these articles did not consider quantization techniques, which can be effectively applied to ECG data without any complex parameter extraction procedures. In this paper the authors have looked at the effects of quantization on ECG data and techniques of reducing the amount of data needed to represent these signals. Basically, 3 data reduction techniques, linear prediction using differential pulse code modulation, spectral analysis and slope change detection are investigated and a relative assessment of their performance is presented. This analysis revealed that a slope change detection, as applied to prefiltered data, can be used to represent ECG data at a rate of 2 bits/sample, while maintaining the mean squared error and peak error below 1% and 5% respectively. This technique therefore gives an effective 3 to 1 reduction over the original sampled data, since it was found that the original data could be quantized to 6 bits without significant loss of waveform information.


Studies on the pathogenesis and survival of different culture forms of Listeria monocytogenes to pulsed UV-light irradiation after exposure to mild-food processing stresses.
The effects of mild conventional food-processing conditions on Listeria monocytogenes survival to pulsed UV (PUV) irradiation and virulence-associated characteristics were investigated. Specifically, this study describes the inability of 10 strains representative of 3 different culture forms or morphotypes of L. monocytogenes to adapt to normally lethal levels of PUV-irradiation after exposure to sub-lethal concentrations of salt (7.5% (w/v) NaCl for 1 h), acid (pH 5.5 for 1 h), heating (48 °C for 1 h) or PUV (UV dose 0.08 μJ/cm(2)). Findings showed that the order of increasing sensitivity of L. monocytogenes of non-adapted and stressed morphotypes to low pH (pH 3.5 for 5 h, adjusted with lactic), high salt (17.5% w/v NaCl for 5 h), heating (60 °C for 1 h) and PUV-irradiation (100 pulses at 7.2 J and 12.8 J, equivalent to UV doses of 2.7 and 8.4 μJ/cm(2) respectively) was typical wild-type smooth (S/WT), atypical filamentous rough (FR) and atypical multiple-cell-chain (MCR) variants. Exposure of L. monocytogenes cells to sub-lethal acid, salt or heating conditions resulted in similar or increased susceptibility to PUV treatments. Only prior exposure to mild heat stressing significantly enhanced invasion of Caco-2 cells, whereas subjection of L. monocytogenes cells to combined sub-lethal salt, acid and heating conditions produced the greatest reduction in invasiveness. Implications of these findings are discussed. This constitutes the first study to show that pre-exposure to mild conventional food-processing stresses enhances sensitivity of different culture morphotypes of L. monocytogenes to PUV, which is growing in popularity as an alternative or complementary approach for decontamination in the food environment.


[Psychodynamic aspects of behavioral disorders in the senescent patient and their psychodynamic approach].
Melanie Klein's therapy is comprised of elements likely to be transposed to senescence for a better understanding of certain disorders in pathological aging. To this day, several clinical states that appear for the first time at an advanced stage in life, such as certain forms of depression, deliria or intellectual deficiency, have not been satisfactorily explained psychodynamically. The author attempts to create a new approach with a Kleinien perspective.


Cosmetic correction of the mild or partially corrected pectus excavatum utilizing silastic implant.
The alternative approach to the cosmetic problem of mild or partially corrected pectus excavatum is presented. A case report with a discussion of the use of silicone in this problem is undertaken. An extremely simple method of implant casting is demonstrated.


Use of intra- and extra-amniotic prostaglandins for the termination of pregnancies--report of multicentric trial in India.
The Indian Council of Medical Research initiated a multicentric trial with prostaglandins in 1976 to assess the safety and efficacy of their use in midtrimester abortions. PGF2 alpha and 15-Me-PGF2 alpha were compared using the intra-amniotic (I.A.) route. 15-Me-PGF2 alpha was also evaluated by extra-amniotic (E.A.) route. With intra-amniotic instillation, success rate was 88.1 per cent with PGF2 alpha and 93.0 per cent with 15-Me-PGF2 alpha within 48 hours and by the extra-amniotic route it was 78.1 per cent within 36 hours. The mean induction-abortion interval was 19 hours with I.A. and 14.8 hours with E.A. Abortions were complete in 48.8 per cent of the women following I.A. PGF2 alpha, 56.0 per cent following I.A. 15-Me-PGF2 alpha and only 23.0 per cent following E.A. administration. Vomiting and diarrhoea were the most commonly reported side effects. Cervical injuries were 4.7 per cent with I.A. PGF2 alpha, 1.4 per cent with I.A. 15-Me-PGF2 alpha and only 0.6 per cent with E.A. route.


The SGK1 inhibitor EMD638683, prevents Angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation.
Inflammation has emerged as a critical biological process contributing to hypertensive cardiac remodeling. Effective pharmacological treatments targeting the cardiac inflammatory response, however, are still lacking. Prior studies suggested that the serum- and glucocorticoid-inducible kinase (SGK1) plays a key role in inflammation and cardiac remodeling. Recently, a highly selective SGK1 inhibitor, EMD638683, was developed, though whether EMD638683 can prevent hypertension-induced cardiac fibrosis and the mechanisms by which this inhibitor may alter the disease process remain unknown. Using a murine Angiotension II (Ang II) infusion-induced hypertension model we found that EMD638683 treatment inhibited cardiac fibrosis and remodeling, with significant abatement of cardiac inflammation. EMD638683 was shown to suppress Ang II infusion-induced interleukin (IL)-1β release, and substantially reduce nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) expression and caspase-1 activation in cardiac tissues. In vitro experiments revealed that EMD638683 ameliorated Ang II-stimulated IL-1β secretion in macrophages by blocking NLRP3 inflammasome activation. By reducing IL-1β production in macrophages, the transformation of fibroblasts to myofibroblasts was inhibited. The effects of EMD638683 on cardiac fibrosis were abolished by supplementation with exogenous IL-1β. Administration of the NLRP3 inflammasome inhibitor MCC950 indicated that EMD638683 attenuated Ang II-induced cardiac inflammation and fibrosis by inhibiting the NLRP3 inflammasome/IL-1β secretion axis. These findings indicate that the SGK1 inhibitor EMD638683 can negatively regulate NLRP3 inflammasome activation, and may represent a promising approach to the treatment of hypertensive cardiac damage.


Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.
The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi.


Psychometric properties of the HRQOLISP-40: a novel, shortened multiculturally valid holistic stroke measure.
A recent review showed that no existing instrument measured the entire spectrum of health-related quality of life (HRQOL) in stroke patients. However, the HRQOL in stroke patients (HRQOLISP) questionnaire is valid and exceptionally comprehensive. Founded on a holistic model of human life, it comprises both physical and spiritual spheres. However, its 102-item length may discourage routine use. Therefore, the aim was to determine the psychometric attributes of a shortened version based on a multicultural transnational study. HRQOLISP was administered to 100 stroke patients in Ibadan, 103 in Berlin, and control groups of 100 apparently healthy adults in Ibadan and 50 in Berlin. Analyzing data from both cities, items were reduced to 40. Construct validity of the resulting HRQOLISP-40 was assessed by comparison with the National Institutes of Health Stroke Scale (NIHSS), Stroke Levity Scale (SLS), modified Rankin Scale (mRS), and Short Form 36 (SF-36) Health Survey. In multicultural settings, the HRQOLISP-40 showed good internal consistency (α = .76, .86) and test-retest reliability. It retained its discriminant validity between stroke and healthy participants and demonstrated good "known-groups" validity in its relationship to the SLS, NIHSS, and mRS in the physical sphere. The physical sphere showed good convergent validity with corresponding facets of the SF-36. Despite item reduction, the HRQOLISP-40 demonstrated excellent psychometric properties and is valid for routine use and clinical trials in stroke. The relative preservation of the spiritual sphere demonstrated the concept of disability disparity. Its ability to simultaneously assess the physical and spiritual spheres may be beneficial in studies aimed at potentiating internal adaptation in stroke patients.


Prevalence of physical violence in a forensic psychiatric hospital system during 2011-2013: Patient assaults, staff assaults, and repeatedly violent patients.
Introduction We examined physical violence in a large, multihospital state psychiatric system during 2011-2013, and associated demographic and clinical characteristics of violent patients to better understand issues of patient and staff safety. Acts of physical violence committed by patients against other patients (n=10,958) or against staff (n=8429) during 2011-2013 were collected and analyzed for all hospitalized patients during the same time period to derive prevalence rates and associated odds ratios. Overall, 31.4% of patients committed at least 1 violent assault during their hospitalization. Differential risk factor patterns were noted across patient and staff assault. Younger age was associated with a higher prevalence of both patient and staff assault, as was nonforensic legal status. Females had a higher prevalence of staff assault than patient assault. Ethnic groups varied on rates of patient assault, but had no significant differences for staff assault. Schizoaffective disorder was associated with higher prevalence and odds of patient (OR 1.244, 95% CI 1.131 to 1.370) and staff (OR 1.346, 95% CI 1.202 to 1.507) assault when compared to patients diagnosed with schizophrenia. Most personality disorder diagnoses also had a higher prevalence and odds of physical violence. One percent of patients accounted for 28.7% of all assaults. Additionally, violent patients had a significantly longer length of hospitalization. Discussion Implications of these findings to enhance patient safety and inform future violence reduction efforts, including the need for new treatments in conjunction with the use of violence risk assessments, are discussed.


Neuropsychological and behavioral abnormalities in an adolescent with frontal lobe seizures.
A 13-year-old girl had a reversible frontal syndrome secondary to partial complex seizures. She developed sudden and dramatic behavioral changes including sexual disinhibition, loss of concern for personal hygiene, physical and verbal aggression, and pressured and tangential speech. Although the basic neurologic examination was normal, neuropsychological testing revealed selective impairment on tasks sensitive to frontal dysfunction with relatively normal performance on other tests. This case demonstrates that a frontal syndrome can be caused by partial complex seizures and that behavior comparable to that observed in adults with frontal dysfunction may occur in young adolescents.


Immobilization of horseradish peroxidase on nonwoven polyester fabric coated with chitosan.
The immobilization of horseradish peroxidase (HRP) on composite membrane has been investigated. This membrane was prepared by coating nonwoven polyester fabric with chitosan glutamate in the presence of glutraldehyde as a crosslinking agent. The physicochemical properties of soluble and immobilized HRP were evaluated. The soluble HRP lost 90% of its activity after 4 weeks of storage at 4 degrees C, whereas the immobilized enzyme retained 85% of its original activity at the same time. A reusability study of immobilized HRP showed that the enzyme retained 54% of its activity after 10 cycles of reuse. Soluble and immobilized HRP showed the same pH optima at pH 5.5. The immobilized enzyme had significant stability at different pH values, where it had maximum stability at pH 3.0 and 6.0. The kinetic properties indicated that the immobilized enzyme had more affinity toward substrates than soluble enzyme. The soluble and immobilized enzymes had temperature optima at 30 and 40 degrees C and were stable up to 40 and 50 degrees C, respectively. The stability of HRP against metal ion inactivation was improved after immobilization. Immobilized HRP exhibited high resistance to proteolysis by trypsin. The immobilized HRP was more resistant to inactivation induced by urea, Triton X-100, and organic solvents compared to its soluble counterpart. The immobilized HRP showed very high yield of immobilization and markedly high stabilization against several forms of denaturants that offer potential for several applications.


The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.
The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.


Integration of Nanographenes and Organic Chemistry - Toward Nanographene-based Two-dimensional Materials.
The front cover artwork is provided by Takeharu Haino's group. The image shows the fragmentation of a graphene sheet by chemical oxidation, producing nanographenes. The quantum size effect opens the band gap of nanographenes, allowing them to emit photoluminescence in the visible region. Read the full text of the Concept at 10.1002/cphc.202200311.


Improvements in medicated tulle dressings.
The antibacterial activity of four new medicated tulle dressings was determined by a modified zone inhibition method. Six different test organisms were used and from the results of the investigation, it was concluded that although the dressings differed in their duration of action and the rate at which the medicaments were released from their individual formulations, they all possessed significant antimicrobial activity.


Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake.
The neuropeptides orexin-A and orexin-B are produced in neurons of the lateral hypothalamic area and have been implicated to be involved in the regulation of food/water intake and sleep-wake control. The orexins act at two different G-protein-coupled orexin receptors (OX-R1 and OX-R2) that are derived from separate genes and expressed differentially throughout the central nervous system. In the present study, we have used a polyclonal antipeptide antiserum to analyse in detail the distribution of OX-R1-immunoreactive neurons in the rat hypothalamus. In order to identify the chemical mediators of orexin action in the hypothalamus, the OX-R1-containing neurons were characterized with regard to the content of peptides shown previously to affect ingestive and drinking behaviour. Neurons containing OX-R1 immunoreactivity were widely distributed in the hypothalamus with cell bodies located in the suprachiasmatic, periventricular, paraventricular (both magno- and parvocellular division), supraoptic, arcuate, ventromedial, dorsomedial and tuberomammillary nuclei and the lateral hypothalamic area. In magnocellular neurons of the paraventricular and supraoptic nuclei, OX-R1 immunoreactivity was seen in both vasopressin- and oxytocin-containing neurons. OX-R1 immunoreactivity was demonstrated in vasopressin and vasoactive intestinal polypeptide (VIP) neurons of the suprachiasmatic nucleus, in somatostatin neurons of the periventricular nucleus and in corticotropin-releasing hormone (CRH) neurons of the parvocellular paraventricular nucleus. In the arcuate nucleus, OX-R1 immunoreactivity was present in neuropeptide Y (NPY) and agouti-related peptide (AGRP) neurons of the ventromedial part as well as in proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) neurons of the ventrolateral division. In the lateral hypothalamic area, OX-R1 immunoreactivity was demonstrated in melanin-concentrating hormone (MCH)- and orexin-containing neurons. In the hypothalamic tuberomammillary nucleus, OX-R1-immunoreactivity was shown in many histamine-containing neurons. The results support the idea that orexins have important actions on hypothalamic neurons that control food intake and fluid balance, but also that orexins may regulate other neuroendocrine systems.


Electrical stimulation of abdominal muscles for control of blood pressure and augmentation of cough in a C3/4 level tetraplegic.
Evaluation of a FES (Functional Electrical Stimulation) device for the relief of postural hypertension and augmentation of cough in a C3 ventilator-dependent tetraplegic. A single case study. A supra regional spinal unit in the UK. A dual channel stimulator was designed that allowed selection and initiation of two predetermined stimulation intensities using a chin controlled joystick. Two sets of 70 mm diameter electrodes were placed either side of the abdomen. Approximately 80 mA, 300 micros, 40 Hz was required for assisted cough while about 40 mA was required for maintenance of blood pressure. After eating, the lower level stimulus is self-administered every 3 to 5 min gradually increasing the time between groups of burst to once every hour after 90 min. Following eating, a blood pressure of 60/45 mmHg was recorded. After five 1 s bursts of stimulation in quick repetition, this was increased to 133/92 mmHg. After 2 min blood pressure had fallen to 124/86 mmHg and to 93/66 after a further 4 min. The electrical stimulation was then repeated, returning the blood pressure to the previous higher level. Measurement of peak expiratory flow showed an increase from 275 l/min for an unassisted cough to 425 l/min when using the device. The device is used every day. The user is now independent in coughing function and no longer requires suction or manual assistance. Maintenance of blood pressure has significantly improved his quality of life.


Interaction between exercise training and cold acclimation in rats.
Five groups of 10 rats were used. Group A included sedentary rats kept at 24 degrees C, group B exercised-trained rats and group C rats exposed at -15 degrees C for 2 h every day and kept at 24 degrees C for the remaining time. These 3 groups were kept on this regimen for 10 weeks. In addition group D was acclimated to cold (2 h.d-1 at -15 degrees C) for 6 weeks and subsequently deacclimated at 24 degrees C for 4 weeks. Group E was also acclimated to cold for 6 weeks and during the deacclimation, at 24 degrees C period which lasted 4 weeks, the animals were exercised 2 h per day. Following the 10 week experimental period all animals were sacrificed and DNA and protein content of the IBAT as well as its total mass were measured. The results show significant increases in the cold adapted group. Exercise training which had no effect on brown adipose tissue IBAT at room temperature, caused an accelerated reduction in weight, DNA and protein content of the BAT in rats previously acclimated to cold. In spite of this, the thermogenic response to noradrenaline was significantly enhanced in the group which exercised during the deacclimation period. It is suggested that tissues other than IBAT may explain this enhanced heat production capacity.


The evaluation of neutron and gamma ray dose equivalent distributions in patients and the effectiveness of shield materials for high energy photons radiotherapy facilities.
In this study, the MCNP5 code was used to model radiotherapy room of a medical linear accelerator operating at 18 MV and to evaluate the neutron and the secondary gamma ray fluences, the energy spectra and the dose equivalent distributions inside a liquid tissue-equivalent (TE) phantom. The obtained results were compared with measured data published in the literature. Moreover, the shielding effects of various neutron material shields on the radiotherapy room wall were also investigated. Our simulation results showed that paraffin wax containing boron carbide presents enough effectiveness to reduce both neutron and secondary gamma ray doses.


Prevalence of lower urinary tract symptoms in individuals with Down syndrome.
Down syndrome (DS), which is caused by the trisomy of chromosome 21, is the most frequent of all genetic syndromes. The current study aims to estimate the prevalence of lower urinary tract symptoms (LUTS) in individuals with DS buy using the Dysfunctional Voiding Symptom Score (DVSS) and correlate with functional constipation, age, and gender, as well as determine the most sensitive and specific factors associated with LUTS. LUTS was assessed in individuals with DS using a cross-sectional study through the application of a validated and adapted version of the DVSS for the Brazilian population. The presence of functional constipation was evaluated according to the Rome III criteria. Of the 114 individuals assessed, 84 were included in the study (median age 16 ± 5.0 years, 66.7% female). The prevalence of LUTS was 27.3%. The symptoms were more frequent in males (OR 3.0, 95% CI 1.1-8.3, p = 0.03) and in individuals younger than 10 years of age (OR 5.2, 95% CI 1.8-14, p = 0.001). Functional constipation was observed in 50% of subjects. It was detected in 95.65% of the individuals with LUTS and 32.78% without LUTS (OR 45.1, 95% CI 5.66-301, p = 0.001). The symptom listed in question 8 ("push to pee") was the most specific indicator. When present, this symptom indicated a higher probability of LUTS (LR+ = 6.3), while the symptom listed in question 4 ("push for bowel movements to come out") showed high sensitivity and, when absent, indicated a lower probability of LUTS (LR- = 0.1). LUTS was more prevalent in young males with DS and appeared to improve with age. Functional constipation was strongly associated with LUTS. These findings will contribute to raising the awareness of professionals involved in the follow-up of individuals with DS regarding the clinical manifestations and the need for a standardized investigation of LUTS.


Patchy fur, a mouse coat mutation associated with X-Y nondisjunction, maps to the pseudoautosomal boundary region.
Patchy fur is a semidominant X-linked mutation in the mouse, resulting in a sparse coat. The Paf mutation also alters the normal segregation of the X and the Y chromosomes during male meiosis by causing nondisjunction at anaphase I. Analysis of 1139 female meioses from an intersubspecific backcross using 15 PCR-based markers localizes Paf to an approximately 0.2-cM interval that includes the pseudoautosomal boundary. The meiotic nondisjunction phenotype may result from a chromosomal rearrangement that includes pseudoautosomal sequences and affects XY pairing.


Drivers of medical spending behaviour amid the COVID-19 pandemic: Heuristic or systematic.
The COVID-19 pandemic has been creating unprecedented chaos and it could forever alter the way people live and work. Experiencing multiple waves of pandemic attacks could make people evolve their perceived risks about the health crisis, change their healthcare behaviours and medical spending to deal with the changing threats over time. Even though there has been a great dealt of research on personal healthcare behaviours during the COVID-19 pandemic, the individual decision on medical spending has not been well explored. This study uses the health belief model and heuristic-systematic information processing theory to study the key drivers of medical spending behaviour as the COVID-19 pandemic evolved in Vietnam. Two surveys were conducted during the first (April 2020) and second waves (August 2020) of the COVID-19 pandemic resulted in a sample size of 1037 cases. The partial least square structural equation modeling (PLS-SEM) technique was employed to explore the structural relationships between health-seeking behaviours, pandemic perceived risks, panic buying, and demographic factors and how these sets of factors drive medical spending behaviours over time. Comparing the two pandemic waves, this study finds significant distinctions in how people evaluate the risks of the pandemic and process information to make decisions about their medical spending. People were primarily influenced by the heuristic processes of panic buying patterns (β = 0.313, p < 0.001) and the health-related established habits in the first wave. Only in the second wave of the pandemic, the impact of the COVID-19 pandemic perceived risk has been recognized as a significant factor on medical spending via the comparison between perceived risks of the first and second pandemic waves (β = 0.262, p < 0.001). This study explores how individuals formulate their spending decisions in extreme conditions and provide valuable insights to help governments and institutions plan their policies to combat the COVID-19 pandemic more effectively.


Physical modification of biochar to expose the inner pores and their functional groups to enhance lead adsorption.
Biochars have been successfully used to treat wastewater and contaminated soils. The efficiency of biochar as a biosorbent of heavy metals can be increased by reducing the particle size, exposing the inner pores and their functional groups. In this study, the empty fruit bunch biochar (EFBB) of oil palm was separated into three particle sizes, fine (F-EFBB < 50 μm), medium (M-EFBB 250-500 μm) and coarse (C-EFBB > 2000 μm) to compare their physical and chemical characteristics and their adsorption capacity for lead. Results revealed that the F-EFBB had greater surface area and exposed more micropores compared to the other particle sizes. Similarly, the F-EFBB had the most oxygen containing functional groups, CEC, and negative charges as measured by the zeta potential. The F-EFBB had the highest adsorption capacity for Pb, followed by M-EFBB and C-EFBB with the lowest. Therefore, the F-EFBB are able to adsorb more heavy metals as compared to M-EFBB and C-EFBB, as suggested by the more favourable physical and chemical characteristics.


Solution-Phase Chemical Synthesis of Modified RNA Dinucleotides.
This article describes a simple, reliable, efficient, and improved solution-phase method for the gram-scale chemical synthesis of RNA dinucleotides such as pAm pA, pAm pG, and pAm pU that utilizes phosphoramidite chemistry. The overall synthetic strategy involves three steps. The first step involves the coupling reaction between 5'-O-MMT protected nucleoside-3'-O-phosphoramidite and a protected nucleoside containing a free 5'-OH group in the presence of tetrazole, followed by the oxidation of phosphite triester using tert-butyl hydroperoxide to give the corresponding protected Nm pN. Next, the 5'-O-MMT is cleaved under 3% trichloroacetic acid in dichloromethane conditions. Finally, the 5'-hydroxyl group is phosphorylated by the use of an activated bis(2-cyanoethyl)-N,N-diisopropyl phosphoramidite using tetrazole, followed by the oxidation of trivalent to pentavalent phosphorus using tert-butyl hydroperoxide and subsequent deprotection using ammonium hydroxide to afford the corresponding RNA dinucleotide, pNm pN, in good yields with high purity (>99.5%). © 2022 Wiley Periodicals LLC.


Experience with Tofacitinib in Patients with Ulcerative Colitis: Data from a United States Claims Database.
Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). To evaluate real-world data in US patients with UC receiving tofacitinib. Characteristics and outcomes of patients with UC initiating tofacitinib between 2018 and 2019 were assessed using data from the IBM® MarketScan® claims database. The index date was the first tofacitinib claim; pre- and post-index periods were 12 months. Outcomes included tofacitinib adherence/persistence, oral corticosteroid (OCS) use, and healthcare resource utilization (HCRU) and costs. Of 276 patients with UC who initiated tofacitinib, 68 (24.6%) were bio-naïve, and 208 (75.4%) bio-experienced. At month 12, overall median tofacitinib adherence (proportion of days covered) was 0.82 (mean 0.68); 43.8% of patients discontinued tofacitinib (90-day gap). Of patients receiving OCS during the post-index 16-week tapering period, 40.4% discontinued OCS up to 12 months post-index. OCS use decreased in patients continuing tofacitinib versus those discontinuing tofacitinib (29.7% vs 59.5%, respectively). Reductions in all-cause and UC-related outpatient visits were observed for bio-naïve (- 1.34 and - 0.88, respectively) and bio-experienced (- 4.72 and - 5.16, respectively) patients, post-index. Decreased UC-related costs per year were observed for bio-experienced patients (difference in post-index vs pre-index, - US$12,448; driven by changes in pharmacy costs), but not for bio-naïve patients (US$47,152). In this real-world analysis in a mostly bio-experienced population, the majority of US patients with UC initiating tofacitinib remained on therapy at 12 months, and OCS use was reduced with tofacitinib treatment. HCRU (all patients) and UC-related costs were reduced in bio-experienced patients. The majority of patients with ulcerative colitis starting tofacitinib in this real-world study continued therapy at 12 months; there was a reduction in the use of steroids, and a decrease in healthcare resournce utilization and costs.


Some Characteristics and Arguments in Favor of a Science of Machine Behavior Analysis.
Researchers and practitioners recognize four domains of behavior analysis: radical behaviorism, the experimental analysis of behavior, applied behavior analysis, and the practice of behavior analysis. Given the omnipresence of technology in every sphere of our lives, the purpose of this conceptual article is to describe and argue in favor of a fifth domain: machine behavior analysis. Machine behavior analysis is a science that examines how machines interact with and produce relevant changes in their external environment by relying on replicability, behavioral terminology, and the philosophical assumptions of behavior analysis (e.g., selectionism, determinism, parsimony) to study artificial behavior. Arguments in favor of a science of machine behavior include the omnipresence and impact of machines on human behavior, the inability of engineering alone to explain and control machine behavior, and the need to organize a verbal community of scientists around this common issue. Regardless of whether behavior analysts agree or disagree with this proposal, I argue that the field needs a debate on the topic. As such, the current article aims to encourage and contribute to this debate.


Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma.
To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma.


Being devastated by critical illness journey in the family: A grounded theory approach of post-intensive care syndrome-family.
This study aimed to explore the meaning and structure of postintensive care syndrome experienced by families of critically ill patients. This qualitative study applied the constructivist grounded theory approach and conducted one or two interviews with eight participants with postintensive care syndrome-family for a total of 12 interviews. The contents of the interviews were analysed through line-by-line coding, focused coding, and categorisation. Data collection and analysis were iterative, to enable continuous comparative analysis. The core category of postintensive care syndrome experienced by families was 'being devastated by the critical illness journey in the family' and comprised the interactions of four categories: 'overwhelming intensive care experience', 'taking responsibility for the recovery trajectory of critical illness', 'life devastated by the trauma of intensive care and family caregiving', and 'balancing and compromising'. Based on this grounded theory approach, postintensive care syndrome experienced by families is a complex and ongoing phenomenon that arises from the recovery trajectory of a critical illness. It involves mental, physical, social and familial aspects, particularly the impact on the patient's family. The findings can guide critical care nurses to understand postintensive care syndrome experienced by families in providing patient or family-centred care. To improve the long-term outcomes and quality of life for families, it is necessary to assess their unique needs within the continuum of post-intensive care syndrome experienced by the family and to propose interventions to satisfy those needs.


MACC chemotherapy for adenocarcinoma and epidermoid carcinoma of the lung: low response rate in a Cooperative Group Study. Eastern Cooperative Oncology Group.
The MACC (methotrexate, adriamycin, cyclophosphamide, CCNU) regimen was administered to 43 patients with advanced epidermoid and adenocarcinoma of the lung. Only 5 patients (12%), all of whom were ambulatory responded with partial remissions. Median time to progression for the 5 responders was 20 weeks from start of treatment. Median survival was 15.5 weeks for patients with epidermoid cancer and 14.4 weeks for those with adenocarcinoma. Hematologic toxicity was severe, with 2 treatment-related deaths during profound myelosuppression. White blood counts below 2000/microliter were reported in 47%, and below 1,000/microliter in 26%. Since the activity of this regimen, given as it was in full doses, is not superior to that achieved with standard doses of single agents which are less toxic, further employment of the MACC regimen is not recommended, either for advanced disease or as a surgical adjuvant.


Interaction of lectins with human platelets. Effects on platelet stimulation by thrombin and ristocetin.
Wheat germ agglutinin induced aggregation and secretion of fresh platelets. Aggregation, but not secretion of serotonin by platelets in plasma, by the lectin was inhibited by 5 mM EDTA. Further, the lectin-induced stimulation of fresh platelets was blocked by prostaglandin E1. Thus, this lectin stimulates platelets by a mechanism which closely mimics thrombin activation and is independent of intercellular crosslinking. Lentil lectin did not stimulate platelets. Each platelet contained about 6 . 10(-5) binding sites for the lectins with an apparent dissociation constant of 3.0 . 10(-7) M. Wheat germ agglutinin, which binds mainly to glycoprotein I (Mr 150 000), increased the subsequent binding of thrombin to fixed platelets while lentil lectin was without effect. It appears that thrombin and wheat germ agglutinin bind to independent but interacting sites. Wheat germ agglutinin, but neither thrombin nor lentil lectin, inhibited the agglutination of platelets by ristocetin. Further, rat platelets were not aggregated by either ristocetin or wheat germ agglutinin. It appears that the interaction sites of ristocetin and wheat germ agglutinin on platelets are overlapping.


Assessment of HCC response to Yttrium-90 radioembolization with gadoxetate disodium MRI: correlation with histopathology.
Transarterial 90Y radioembolization (TARE) is increasingly being used for hepatocellular carcinoma (HCC) treatment. However, tumor response assessment after TARE may be challenging. We aimed to assess the diagnostic performance of gadoxetate disodium MRI for predicting complete pathologic necrosis (CPN) of HCC treated with TARE, using histopathology as the reference standard. This retrospective study included 48 patients (M/F: 36/12, mean age: 62 years) with HCC treated by TARE followed by surgery with gadoxetate disodium MRI within 90 days of surgery. Two radiologists evaluated tumor response using RECIST1.1, mRECIST, EASL, and LI-RADS-TR criteria and evaluated the percentage of necrosis on subtraction during late arterial, portal venous, and hepatobiliary phases (AP/PVP/HBP). Statistical analysis included inter-reader agreement, correlation between radiologic and pathologic percentage of necrosis, and prediction of CPN using logistic regression and ROC analyses. Histopathology demonstrated 71 HCCs (2.8 ± 1.7 cm, range: 0.5-7.5 cm) including 42 with CPN, 22 with partial necrosis, and 7 without necrosis. EASL and percentage of tumor necrosis on subtraction at the AP/PVP were independent predictors of CPN (p = 0.02-0.03). Percentage of necrosis, mRECIST, EASL, and LI-RADS-TR had fair to good performance for diagnosing CPN (AUCs: 0.78 - 0.83), with a significant difference between subtraction and LI-RADS-TR for reader 2, and in specificity between subtraction and other criteria for both readers (p-range: 0.01-0.04). Radiologic percentage of necrosis was significantly correlated to histopathologic degree of tumor necrosis (r = 0.66 - 0.8, p < 0.001). Percentage of tumor necrosis on subtraction and EASL criteria were significant independent predictors of CPN in HCC treated with TARE. Image subtraction should be considered for assessing HCC response to TARE when using MRI. • Percentage of tumor necrosis on image subtraction and EASL criteria are significant independent predictors of complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization. • Subtraction, mRECIST, EASL, and LI-RADS-TR have fair to good performance for diagnosing complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization.


Barriers to cancer pain management: home-health and hospice nurses and patients.
Undertreatment of cancer pain remains a major health-care problem. We utilized focus groups of hospice and home-health nurses and patients to elucidate factors contributing to inadequate pain management and to generate solutions for closing the gap between the current reality and optimal pain management. Focus groups were conducted among hospice and home-health-care nurses (two groups; n=22) and patients (six groups; n=54) using a standardized question guide. Audiotapes were transcribed and analyzed using NUD*IST software. Themes discovered among patients and nurses were analyzed for similarities and differences. Of 22 participants in the two home-health and hospice nurses focus groups, all were white women, the average age was 43 (range 29-64) years, and the average number of years in nursing was 21 (range 8-47) years. Of 54 participants in the six cancer patient focus groups, 80% were women, the average age was 54 (range 25-76) years, and 76% were white. Fifty-four percent of patients reported a history of pain associated with their cancer, and almost 30% had pain that they rated as 8 or higher on the pain scale. Barriers to adequate pain management fell into four categories: fears; attitudes, beliefs, and values; patient and provider behaviors; and structural barriers. Patients and nurses reported similar barriers to pain management; however, patients identified more barriers related to provider behavior and structure of the health care system. This study identified several barriers to cancer pain control not previously identified in the literature. Strategies to improve cancer pain control are suggested.


New protocol for simplified reduction and fixation of subcondylar fractures of the mandible: a technical note.
The dilemma regarding the management of condylar fractures generally revolves around the surgical approach, implant design, and the surgeon's experience. Zide and Kent's guidelines streamlined the decision making process for condylar fractures. However, there exists no standardized protocol for reduction and fixation of condylar fractures. Here, we have described a detailed and stepwise protocol, common to any surgical approach, that would lead to predictable, reproducible, and repeatable results in every surgeon's hands.


Mannitol in neonatal cerebral oedema.
Twenty-five full term severely asphyxiated newborn babies with cerebral oedema were divided into 2 groups and treated on a randomised basis with either Mannitol or no Mannitol. We report our findings and conclude that Mannitol is of no benefit in the management of cerebral oedema in severely asphyxiated term infants.


Task-switching abilities in pre-manifest Huntington's disease subjects.
Huntington's Disease (HD) cognitive dysfunction occurs before unequivocal motor signs become apparent. The predominant early cognitive abnormal domains may include deficits in psychomotor speed, negative emotion recognition and executive functioning. Our study is aimed to investigate the executive control of cognition in pre-manifest (pre) HD subjects, by means of a task-switching protocol. We recruited 30 pre-HD subjects and 18 age-, sex- and education-matched Healthy Controls (HC). Subjects were assigned to two experimental groups: 15 pre-HD1 with a Total Motor Score (TMS) ≤4 (far from onset) and 15 pre-HD2 with a 5 ≤ TMS≤9 (near to onset and Diagnostic Confidence Level (DCL) still<4). Two different tasks were performed in rapid and random succession, so that the task was either changed from one trial to the next one (switch trials) or repeated (repetition trials). Switch trials are usually slower than repetitions, causing a so-called Switch Cost (SC). Pre-HD subjects had worse performance than HC in the switch and repetition trials, as indicated by increased SC and reaction times. In particular, pre-HD2 showed impaired switching abilities with reaction times slower than pre-HD1 and HC. Our study highlighted a task-switching impairment since HD was still at a pre-manifest stage. Such abnormalities worsen when pre-HD subjects start to show subtle motor manifestations, still nonspecific and insufficient to define the clinical diagnosis of HD (DCL<4). Considering that such abilities have obvious implications for activities of daily living, early cognitive rehabilitation programs addressing such deficits might be useful in the premanifest stage of the disease.


The effect of semiconditional dorsal penile nerve electrical stimulation on capacity and compliance of the bladder with deformity in spinal cord injury patients: a pilot study.
Bladder capacity, bladder compliance, the volume of the first overactive contraction, maximal volume during cystometry (CMG) and the vesicoureteral reflux, bladder wall deformity before and after semiconditional stimulation on DPN. To evaluate the effect of the semiconditional electrical stimulation on dorsal penile nerve (DPN) to improve the complicated bladder function in male with spinal cord injury (SCI). Semiconditional stimulation system and urodynamic laboratory in a university hospital. Six men (age, 33-59 years) with SCI incurred from 38 to 156 months before this study. semiconditional stimulation parameters were set during CMG and semiconditional stimulation on DPN by surface electrodes via Empi Focus stimulator was applied from 14 to 28 days, at home. Parameters about bladder function were measured before and after stimulation applied. All parameters for bladder after semiconditional stimulation were increased. Also, the vesicoureteral reflux and bladder wall deformity was improved in five of six patients. Semiconditional electrical stimulation on DPN effectively suppresses neurogenic detrusor overactivity and distend the bladder physiologically in the SCI patient with a complicated bladder. The bladder capacity and compliance as well as the bladder wall deformity were improved as a result of this treatment.


A bioluminescence reporter mouse model for visualizing and quantifying CD8+ T cells in vivo.
Cytotoxic CD8+ T cells are the primary effector cells mediating anti-tumor responses. In vivo monitoring of CD8+ T cells has broad implications for the development of novel cancer therapies. Here we describe the development of a genetically engineered mouse model (GEMM) in which CD8+ T cells are labeled with an optical reporter, enabling in vivo, longitudinal monitoring using bioluminescence imaging (BLI). Firefly luciferase (Luc2), human diphtheria toxin receptor (DTR), and enhanced green fluorescence protein (eGFP) cDNAs are engineered under the CD8α promoter to generate a transgenic mouse line. Luciferase mRNA and CD8α mRNA were generally correlated in various tissues from these mice. Sorted splenic CD8+ T cells, CD4+ T cells and CD3- non-T cells verified that the luciferase signal is specific to CD8+ T cells. In vivo imaging showed that luciferase signal was detected in various immune organs, such as lymph nodes, thymus, and spleen, and the detection was confirmed by ex vivo examination. Administration of diphtheria toxin markedly reduced luciferase signal systemically, confirming the function of the DTR. In the MC38 mouse syngeneic model, we observed significant increases in CD8+ T cells with mDX400 treatment, an anti PD-1 mouse monoclonal antibody that correlated with tumor growth inhibition. This novel reporter GEMM is a valuable drug discovery tool for profiling compounds and understanding mechanisms of action in immunotherapy of cancer.


Dose-effect relationship and molecular mechanism by which BMSC-derived exosomes promote peripheral nerve regeneration after crush injury.
The development of new treatment strategies to improve peripheral nerve repair after injury, especially those that accelerate axonal nerve regeneration, is very important. The aim of this study is to elucidate the molecular mechanisms of how bone marrow stromal cell (BMSC)-derived exosomes (EXOs) participate in peripheral nerve regeneration and whether the regenerative effect of EXOs is correlated with dose. BMSCs were transfected with or without an siRNA targeting Ago2 (SiAgo2). EXOs extracted from the BMSCs were administered to dorsal root ganglion (DRG) neurons in vitro. After 48 h of culture, the neurite length was measured. Moreover, EXOs at four different doses were injected into the gastrocnemius muscles of rats with sciatic nerve crush injury. The sciatic nerve functional index (SFI) and latency of thermal pain (LTP) of the hind leg sciatic nerve were measured before the operation and at 7, 14, 21, and 28 days after the operation. Then, the number and diameter of the regenerated fibers in the injured distal sciatic nerve were quantified. Seven genes associated with nerve regeneration were investigated by qRT-PCR in DRG neurons extracted from rats 7 days after the sciatic nerve crush. We showed that after 48 h of culture, the mean number of neurites and the length of cultured DRG neurons in the SiAgo2-BMSC-EXO and SiAgo2-BMSC groups were smaller than that in the untreated and siRNA control groups. The average number and diameter of regenerated axons, LTP, and SFI in the group with 0.9 × 1010 particles/ml EXOs were better than those in other groups, while the group that received a minimum EXO dose (0.4 × 1010 particles/ml) was not significantly different from the PBS group. The expression of PMP22, VEGFA, NGFr, and S100b in DRGs from the EXO-treated group was significantly higher than that in the PBS control group. No significant difference was observed in the expression of HGF and Akt1 among the groups. These results showed that BMSC-derived EXOs can promote the regeneration of peripheral nerves and that the mechanism may involve miRNA-mediated regulation of regeneration-related genes, such as VEGFA. Finally, a dose-effect relationship between EXO treatment and nerve regeneration was shown.


Use of Volatile Anesthetic Agent in Extracorporeal Circuit as a Cause of Break in Polycarbonate Connector-Lessons Learnt.
Mishaps, near misses, and lethal incidents are known to occur during cardiopulmonary bypass. We share one such rare case of break in polycarbonate connector because of the use of isoflurane in extracorporeal circuit and its successful management.


Combined mitochondrial and nuclear data enhance resolution of a rapid radiation of Australian rainbow skinks (Scincidae: Carlia).
In contrast to low diversity seen in many Australian rainforest squamate genera, sclerophyll adapted groups--such as Carlia--show signs of faster diversification. Here we expand upon a previous single-locus mitochondrial DNA phylogenetic study of Carlia which described a major polytomy at an intermediate level of divergence. With additional mtDNA data, two nuclear intron loci and comprehensive taxonomic coverage, we provide support, congruent across loci, for the existence of three major clades. In doing so we recognise three genera for the 'Carlia group of skinks': clade 1, Carlia Gray, 1845; 2, Lygisaurus De Vis, 1884 (includes all species formerly known as Lygisaurus, and also includes C. parrhasius); 3, Liburnascincus Wells and Wellington, 1984 (consisting of three boulder-dwelling species). Remaining regions of low bootstrap and posterior probability support are associated with short internodes and apparent conflict among loci, as inferred by Partition Branch Support. Likelihood-based diversification-rate analysis rejects constant rate models, and indicates that Carlia underwent a period of relatively rapid diversification early in the evolution of the group, a rate 3-4 times faster than subsequent rates, and faster than comparable wet forest skinks.


Controlled growth of a single carbon nanotube on an AFM probe.
Carbon nanotubes (CNTs) can be used as atomic force microscopy (AFM) tips for high-resolution scanning due to their small diameter, high aspect ratio and outstanding wear resistance. However, previous approaches for fabricating CNT probes are complex and poorly controlled. In this paper, we introduce a simple method to selectively fabricate a single CNT on an AFM tip by controlling the trigger threshold to adjust the amount of growth solution attached to the tip. The yield rate is over 93%. The resulting CNT probes are suitable in length, without the need for a subsequent cutting process. We used the CNT probe to scan the complex nanostructure with a high aspect ratio, thereby solving the long-lasting problem of mapping complex nanostructures.


Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice.
Regulation of adhesion and degranulation of mast cells plays an important role in allergy and inflammation. We investigated a possible role of Bruton's tyrosine kinase (Btk) in the regulation of adhesion and degranulation by using bone marrow-derived mast cells from X-linked immunodeficiency (Xid) and Btk-deficient mice. Cross-linking of the high affinity IgE receptor (Fc epsilonRI) and steel factor (SLF) induced indistinguishable adhesive responses of mast cells to fibronectin in kinetics, and these adhesive responses were comparable among wild type, Xid, and Btk-deficient mast cells. Cross-linking of Fc epsilonRI, but not SLF triggered degranulation of bone marrow-derived mast cells. However, Fc epsilonRI-induced degranulation was impaired in Xid and Btk-deficient mast cells. Calcium influx induced by Fc epsilonRI cross-linking and SLF were also reduced in Xid and Btk-deficient mast cells. Degranulation and calcium influx were reduced more severely in Btk-deficient than in Xid mast cells. Consistently, cross-linking Fc epsilonRI and SLF augmented Btk kinase activities transiently. Inositol triphosphate (IP3) production was also severely reduced in Btk-deficient mast cells, indicating Btk play a critical role of Fc epsilonRI-induced IP3 production. The differential sensitivity of wortmannin on calcium influx in wild type and Xid mast cells suggested that the activation of phosphatidylinositol 3 kinase (PI 3-kinase) was required in calcium influx. Furthermore, abnormal secretory granules with translucent contents and variable in size were observed both in Xid and Btk-deficient mast cells. Our study demonstrated a critical role of Btk in regulating intracellular calcium and granule exocytosis.


The paradoxical flow hypothesis of the carotid artery: supporting evidence from phase-contrast magnetic resonance imaging.
Narrowing of the poststenotic internal carotid artery (ICA) has been found to be associated with reduced risk of ipsilateral stroke. A paradoxical mechanism has been hypothesized to explain this finding: narrowing of the distal-normal (reference) ICA is associated with low blood flow rates (Q) in the stenotic ICA, and lower Q causes lower risk of ipsilateral stroke, perhaps by an associated reduction in mechanical stress on the atherosclerotic plaque. The purpose of this study was to confirm that the reference ICA diameter (RICAD) is indeed predictive of Q, a finding that would indirectly support the hypothesis of a relationship between lower Q and lower risk of ipsilateral stroke. Magnetic resonance imaging from 38 patients was included in the study. The study included 17 stenotic carotid arteries and 59 normal carotid arteries. All patients underwent contrast-enhanced magnetic resonance angiography from which measurements were obtained of the RICAD and the internal-common carotid diameter ratio. Patients underwent cardiac-gated, velocity-encoded phase-contrast magnetic resonance imaging for measurement of Q. Mean flow rates differed between stenotic (4.3 +/- 1.7 mL/s) and normal (5.4 +/- 1.7 mL/s) arteries (P = .02). RICAD was found to be a predictor of Q for stenotic arteries (P = .009) and for all arteries (P = .025) but not for the group of normal arteries (P = .162). Right-left differences in RICAD were highly predictive of right-left differences in Q in the subgroup of individuals with normal arteries (P < .001) and in the group of all participants (P < .001). Internal-common carotid diameter ratio was not found to be a statistically significant predictor of Q in the subgroup of stenotic arteries (P = .156). This study demonstrated that, as hypothesized, RICAD is correlated with Q.


Structural insights into the redox regulation of Oncomelania hupensis TRP14 and its potential role in the snail host response to parasite invasion.
The freshwater amphibious snail Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum, but little attention has been paid to the interaction between the two. In snails, the production of reactive oxygen species (ROS) by hemocytes has been shown to be vital for snail immune defense against schistosome infection. However, excessive ROS accumulation could lead to oxidative damage, requiring the antioxidant system for maintaining the cellular redox homeostasis. Previously we identified a thioredoxin-related protein of 14 kDa from O. hupensis (OhTRP14), and showed that it was involved in the scavenging of ROS in circulating hemocytes. Here, we confirmed that OhTRP14 plays a potential role in the snail host response to parasite challenge and determined the crystal structures of OhTRP14 in two different states (oxidized and transition state). The overall structure revealed a typical Trx fold and is similar to that of human TRP14 (hTRP14), but there were significant structural differences between the two states. Noticeably, there was a different pair of thiol groups from Cys30 and Cys44 in the transition state of OhTRP14, were with the similar separation of 2.9 Å as that (2.6 Å) between Cys41 and Cys44, but in a different orientation, suggesting that the Cys30 is likely to function as an important molecular switch involved in the oxidoreductase activity of OhTRP14. Comparative studies between OhTRP14 and hTRP14 by analyzing the surface characteristics, charge distribution and oxidoreductase activity toward insulin demonstrated they might have similar substrates. The results are expected to provide structural insights into the redox regulation of OhTRP14 and contribute to better understanding of TRP14 family. DATA DEPOSITION: The atomic coordinates of the structure and the structure factors were deposited in Protein Data Bank with PDB ID codes 7XQ3 and 7XPW.


Juvenile proximal spinal muscular atrophy with early hypertrophy of calves.
The clinical, electrophysiological, histological and ultrastructural features of a patient with chronic spinal muscular atrophy of adolescent onset associated with hypertrophied calf-muscle are described. This recently recognised entity must be distinguished from other types of spinal muscular atrophy.


Trans-encapsidation of hepatitis C virus subgenomic replicon RNA with viral structure proteins.
A trans-packaging system for hepatitis C virus (HCV) subgenomic replicon RNAs was developed. HCV subgenomic replicon was efficiently encapsidated by the HCV structural proteins that were stably expressed in trans under the control of a mammalian promoter. Infectious HCV-like particles (HCV-LPs), established a single-round infection, were produced and released into culture medium in titers of up to 10(3) focus forming units/ml. Expression of NS2 protein with structural proteins (core, E1, E2, and p7) was shown to be critical for the infectivity of HCV-LPs. Anti-CD81 treatment decreased the number of infected cells, suggesting that HCV-LPs infected cells in a CD81-dependent manner. The packaging cell line should be useful both for the production of single-round infectious HCV-LPs to elucidate the mechanisms of HCV assembly, particle formation and infection to host cells, and for the development of HCV replicon-based vaccines.


Clinical and economic implications of epilepsy management across treatment lines in Spain: a real-life database analysis.
Epilepsy is a chronic brain disease characterized by recurrent seizures. We investigated real-world management of epilepsy across treatment lines in Spain, including healthcare resource use (HRU) and associated costs. This was a retrospective study of real-life data from epilepsy patients prescribed antiseizure medication (ASM) between January 2016 and December 2021. Patients were grouped according to their line of treatment (1st, 2nd, 3rd and 4th +) during the recruitment period. Demographic and clinical characteristics, comorbidities and concomitant medications were analyzed during the baseline period (6 months before starting treatment line); antiepileptic treatments, concomitant medications, HRU and associated costs were analyzed during follow-up. The study included 5006 patients. Treatment duration decreased as treatment lines progressed (mean ± SD progression time: 523.2 ± 279.1 days from 1st to 2nd line, 351.6 ± 194.4 days from 2nd to 3rd line; 272.7 ± 139.3 days from 3rd to 4th + line). Significant HRU differences were found with subsequent treatment lines, including an increase in hospital admissions and patients on sick leave. Mean (95% CI) adjusted total costs per patient were €2974/year (2773-3175) in the 1st line and €5735/year (5043-6428) in the 4th + line. There was an increase in adjusted direct and total costs with subsequent treatment lines; the mean difference in total costs between cohorts was €2761 (p < 0.001). The highest direct costs were associated with epilepsy medication, days at the hospital and specialist visits. Our data revealed a progressive increase in the use of resources and associated costs across subsequent epilepsy treatment lines.


A comprehensive survey of cancer risks in extended families.
Cancer is familial; yet known cancer predisposition genes, as well as recognized environmental factors, explain only a small percentage of familial cancer clusters. This population-based description of cancer clustering describes patterns of cancer coaggregation suggestive of a genetic predisposition. Using a computerized genealogy of Utah families linked to a statewide cancer registry, we estimated the relative risks for 36 different cancer sites in first-, second-, and third-degree relatives of cancer cases, for each cancer site individually, and between cancer sites. We estimated the sex- and birth-year-specific rates for cancer using 1 million individuals in the resource. We applied these rates to groups of cases or relatives and compared the observed and expected numbers of cancers to estimate relative risks. Many cancer sites show significantly elevated relative risks among distant relatives for cancer of the same site, strongly supporting a heritable contribution. Multiple combinations of cancer sites were observed among first-, second-, and third-degree relatives, suggesting the existence of heritable syndromes involving more than one cancer site. This complete description of coaggregation of cancer by site in a well-defined population provides a set of observations supporting heritable cancer predispositions and may support the existence of genetic factors for many different cancers.


Modeling factors critical for implementation of precision medicine at health systems-level: an IRT approach.
Through recent advances in omics technologies, precision medicine (PM) promises to fundamentally change the way we approach health, disease and illness. Imperative applications of omics-based biomarkers are gradually moving from research to clinical settings, with huge long-term clinical and public health implications. Whereas much of research in PM is mainly focused on basic biomedical discoveries, currently there is little research on the clinical implementation of omics biomarkers, especially at health systems level. This study investigated the application of multidimensional item response theory (IRT) models to validate a hypothesized PM implementation measurement model. This is a contribution to PM implementation at health systems level. Data obtained through an item-sort procedure involving 496 observations from 124 study participants formed the basis of a 22-item PMI measurement model. Statistical significance of the bifactor model suggests PM implementation may have to be examined using factors that reflect a single common underlying implementation construct, as well as factors that reflect unique variances for the identified four content-specific factors.


Modulating activity of B lymphocytes on haemopoiesis (II)--the purification of proliferation amplifying factor (PAF).
In recent years we have done a series of observations on the haemopoietic modulation effects of lymphocytes. Now we report here, for the first time, the purification of a modulating factor (proliferation amplifying factor, PAE) with affinity chromatography and HPLC from supernatant conditioned by a lymphoma cell line M12.4.1. RAF exhibits on SDS-PAGE only one band, the molecular weight is about 31,000, the specific activity is 20,000 times that in the conditioned medium. It may provide a direct evidence that the B lymphocyte also possesses some haemopoietic modulation effects.


[Importance of the surgical phase in treatment with osseointegrated implants].
In this article the authors explain extensively the importance of diagnosis before any operation. The authors explain in detail the surgical's phases in general and they go in the depth in many facets of different patients to be treated, differentiating the lower jaw from the upper maxillar and also patients that are totally or partially edentulous. They underline the importance of surgical's templates in order to place fixtures in right places.


What does a "face cell" want?'
In the 1970s Charlie Gross was among the first to identify neurons that respond selectively to faces, in the macaque inferior temporal (IT) cortex. This seminal finding has been followed by numerous studies quantifying the visual features that trigger a response from face cells in order to answer the question; what do face cells want? However, the connection between face-selective activity in IT cortex and visual perception remains only partially understood. Here we present fMRI results in the macaque showing that some face patches respond to illusory facial features in objects. We argue that to fully understand the functional role of face cells, we need to develop approaches that test the extent to which their response explains what we see.


Arsenic species and their transformation pathways in marine plants. Usefulness of advanced hyphenated techniques HPLC/ICP-MS and UPLC/ESI-MS/MS in arsenic species analysis.
The growing popularity of algae as a foodstuff around the world raises concern for the safety of this food type with respect to arsenic content in algae. The need for determination of total arsenic content and arsenic speciation in algae food has become an important issue. In this paper we have developed a complete analytical procedure for arsenic determination in algae products comprised of 1) total arsenic (tAs) determination in native algae samples after digestion, 2) extraction of As species with the use of two extraction methods with three extracting agents, 3) extracted total arsenic (extracted tAs) determination in algae extracts, 4) bespoke As speciation, 4) mass balance estimation based on extracted tAs and bespoke As speciation results, 5) unknown arsenic (uAs) species identification. Two advanced hyphenated techniques, HPLC/ICP-MS and UPLC/ESI-MS/MS, were employed along with the HPLC/ICP-MS method validation. Total As content in edible algae samples was found to range from (19.28 ± 0.45) mg kg-1 up to (72.6 ± 2.7) mg kg-1. Bespoke arsenic speciation of edible algae samples has revealed the presence of some known inorganic and simple organic As compounds such as As(III) from <LOD to (8.97 ± 0.59) mg kg-1, As(V) from <LOD to (5.95 ± 0.29) mg kg-1 and DMA from <LOD to (0.766 ± 0.040) mg kg-1. Mass balance calculation carried out on the basis of tAs and bespoke As speciation results has shown that the amount of unknown As species in edible algae samples varied from 28% to 100% of extracted tAs. Identification of uAs species in edible algae samples has shown the presence of a high variety of As-sugars (12 compounds) and confirmed the presence of simple inorganic and organic As species such as As(V) and DMA along with 8 more simple organic As compounds. The results obtained in this study have confirmed that the high amounts of tAs do not correspond to the toxicity of algae based food due to the lack of the inorganic As in the tested samples.


Synthesis, characterization and in vitro antibacterial activity of new steroidal 5-en-3-oxazolo and thiazoloquinoxaline.
Steriodal heterocyclic systems namely cholest-5-en-3-oxazolo and thiazoloquinoxaline have been synthesized via the reaction of cholest-5-en-3-one semicarbazone/thiosemicarbazone with 2,3-dichloroquinoxaline at 80 degrees C in high yield. Cholest-5-en-3-one semicarbazone is obtained by the condensation of cholest-5-en-3-one with semicarbazide in the presence of AcONa in ethanol and cholest-5-en-one thiosemicarbazone is obtained by the condensation of cholest-5-en-3-one with thiosemicarbazide in ethanol in the presence of a few drops of HCl. The structures of these compounds were evident by elemental analysis, IR, 1H NMR and FAB mass spectral analysis. These synthesized compounds were investigated for antibacterial activity first by the disk-diffusion assay against two Gram-positive and two Gram-negative bacteria and then the minimum inhibitory concentration (MIC) of these compounds were determined and the results were compared with the standard drug Amoxicillin. The results showed that these compounds oxazolo/thiazoloquinoxaline are better antibacterial agents as compared to the standard drug Amoxicillin.


Portrayals of overweight and obese individuals on commercial television.
This study examined the distribution and individual characteristics of body types on prime-time television. Five episodes of each of the 10 top-rated prime-time fictional programs on 6 broadcast networks during the 1999-2000 season were quantitatively analyzed. Of 1018 major television characters, 14% of females and 24% of males were overweight or obese, less than half their percentages in the general population. Overweight and obese females were less likely to be considered attractive, to interact with romantic partners, or to display physical affection. Overweight and obese males were less likely to interact with romantic partners and friends or to talk about dating and were more likely to be shown eating. Overweight and obese television characters are associated with specific negative characteristics.


High frequency oscillatory ventilation in children: experience of a medical center in Taiwan.
Data about the effectiveness of high frequency oscillatory ventilation (HFOV) in children with respiratory failure are limited. This study investigated the efficacy and prognostic factors of this treatment. Children between 2 months and 18 years of age who received HFOV between January 2000 and September 2006 in a tertiary care center were enrolled in this retrospective study. Thirty-six HFOV treatments were given to 33 patients (twice in one patient and three times in another patient) at a mean age of 5.4 +/- 5.0 years. HFOV was used as a rescue after conventional mechanical ventilation (CMV) for 4.4 +/- 4.2 days. The mean duration of HFOV was 7.6 +/- 7.9 days. The most common indication for HFOV was oxygenation failure, which was due to pneumonia with acute respiratory distress syndrome in 15 (45.5%), severe lobar pneumonia in nine (27.3%), pulmonary hemorrhage in eight (24.2%) and pneumothorax in one (3%). PaCO2 was significantly improved 4 hours after HFOV and the PaO2/FiO2 ratio increased significantly 12 hours later. The oxygenation index and alveolar-arterial oxygen difference P(A-a)O2, however, did not change markedly. Four (12%) patients needed further extracorporeal life support and two of these survived. The overall survival rate was 45.5%. Patients with heavier body weight (p less than 0.05) and of the male gender (p less than 0.05) had a higher risk of mortality. As a relatively late rescue therapy after failure of CMV, HFOV may improve PaCO2 and PaO2/FiO2 in children with respiratory failure. However, it carries an increased mortality rate in patients with heavier body weight and male gender.


Cohort Changes and Sex Differences After Age 50 in Cognitive Variables in the English Longitudinal Study of Ageing.
This paper models cognitive aging, across mid and late life, and estimates birth cohort and sex differences in both initial levels and aging trajectories over time in a sample with multiple cohorts and a wide span of ages. The data used in this study came from the first 9 waves of the English Longitudinal Study of Ageing, spanning 2002-2019. There were n = 76,014 observations (proportion male 45%). Dependent measures were verbal fluency, immediate recall, delayed recall, and orientation. Data were modeled using a Bayesian logistic growth curve model. Cognitive aging was substantial in 3 of the 4 variables examined. For verbal fluency and immediate recall, males and females could expect to lose about 30% of their initial ability between the ages of 52 and 89. Delayed recall showed a steeper decline, with males losing 40% and females losing 50% of their delayed recall ability between ages 52 and 89 (although females had a higher initial level of delayed recall). Orientation alone was not particularly affected by aging, with less than a 10% change for either males or females. Furthermore, we found cohort effects for initial ability level, with particularly steep increases for cohorts born between approximately 1930 and 1950. These cohort effects generally favored later-born cohorts. Implications and future directions are discussed.


The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism: A Randomized Controlled Trial.
Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited. Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea? This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire). A total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ISWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7-88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, -4%; 95% CI, -0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention. In patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation. ClinicalTrials.gov; No.: NCT03405480; URL: www. gov.


Intraperitoneal stability of alginate-polyornithine microcapsules in rats: an FTIR and SEM analysis.
Alginate-polycation microcapsule systems have been used over decades as delivery vehicles for cell and protein therapy. These systems have been unpredictable across a range of indications with questions resulting around the inherent stability of the alginate polysaccharide and failure mode of the delivery system. The current study focuses on such a system using 5 different alginates, 2 of which are commercially purified, which are crosslinked by polyornithine. Capsules formed by frequency-generated droplet formation were studied in the peritoneal cavity of Long-Evans rats over the course of 3 months by morphometry, Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy of the surface. Individual capsule components were also investigated on FTIR and a relative stability index was generated by titration for comparison to explanted samples over time. Using these techniques, a distinct degradation pattern was noted and is compared between the 5 alginate sources.


Italian pilot version of DEMOQL-PROXY: Content and Face validity: a methodological bridge for a future Italian validation.
The assessment of Quality of Life through validated tools allow to improve level of assistance for people suffering from Dementia. To our Knowledge in Italian language seem to be absent a tool to evaluate mild and moderate dementia, consequently underestimating and underrating needs of this specific target. We show an Italian pilot version of the DEMQOL-PROXY (specific for mild and moderate Dementia) testing some psychometric properties as: back-translation, content validity and face validity in Italian language. A back-translation by two bilingual authors was presented. Was enrolled an expert panel to test Content Validity composed by eight Medical Doctor and a panel of six participants was recruited to assess Face Validity (three professional caregivers and three family caregivers) related to patients with moderate Dementia (with 10 to 20 MMSE, mild and moderate Dementia). Each item has a degree of agreement between experts of more than 70% and the Total CVI score is .90 (90% of agreement). So, in line with these results we can accept the version of items proposed. As regard Face Validity, the items of the instrument seem to be clear, without difficulty and there are no questions consiedered offensive or irritating. The Italian version of the DEMQOL-PROXY showed good psychometric properties: its structure and the results it leads to are similar to the original version and to the other translations produced so far. For this reason, we consider this paper as a methodological bridge for a future complete Italian Validation.


Receiving treatment and labor force activity in a community survey of people with anxiety and affective disorders.
Standard treatments for depression and anxiety disorders are generally expected to benefit individuals, employers, and the wider community through improvements in work-functioning and productivity. Although some evidence supports expectations of treatment benefits, these are rarely examined at a population level. We investigated receiving treatment, labor force activity, and self-reported work performance among people with ICD-10 affective and anxiety disorders. Data were collected by the Australian Bureau of Statistics using representative multistage sampling strategies. This large household probability sample consisted of 37,580 working age individuals. A secondary analysis was conducted using multiple binary logistic regression. After statistically controlling for eight covariates: extent of employment restrictions; mental health status; age; sex; partner status; country of birth; age left school; and educational attainment; receiving treatment was consistently associated with non-participation in the labor force, and was negatively associated with work performance. At a population level, receiving treatment for anxiety and depression was negatively associated with being employed or looking for work. This could be an unintended side effect of treatment, although other explanations are also possible. These results justify more specific longitudinal investigations into how different forms of mental health treatment influence labor force activity among working age community residents with anxiety and affective disorders.