Child analysis with a severely disturbed adopted child.
Much of this paper focuses on the psychoanalysis of Bert, a severely disturbed 9-year-old adopted boy. Constitutional factors, parents' personalities and parenting styles, and libidinal and aggressive zonal fixations all played a role in determining Bert's problems. Besides the normal developmental challenges, the adoptive child faces the unique developmental task of becoming the true adoptive child of true adoptive parents. Bert's case shows how this process can be facilitated in psychoanalytic treatment. After a brief introduction to the psychological implications of adoption at various stages of development, the paper elaborates on how and why Bert first came for treatment and describes three phases in the treatment, the first session, the period of transference developments, and the termination phase. The final section outlines special treatment issues and the implications for the psychoanalytic treatment of an adopted child.


No effect of environmental heterogeneity on the maintenance of genetic variation in wing shape in Drosophila melanogaster.
Theory suggests that heterogeneous environments should maintain more genetic variation within populations than homogeneous environments, yet experimental evidence for this effect in quantitative traits has been inconsistent. To examine the effect of heterogeneity on quantitative genetic variation, we maintained replicate populations of Drosophila melanogaster under treatments with constant temperatures, temporally variable temperature, or spatially variable temperature with either panmictic or limited migration. Despite observing differences in fitness and divergence in several wing traits between the environments, we did not find any differences in the additive genetic variance for any wing traits among any of the treatments. Although we found an effect of gene flow constraining adaptive divergence between cages in the limited migration treatment, it did not tend to increase within-population genetic variance relative to any of the other treatments. The lack of any clear and repeatable patterns of response to heterogeneous versus homogeneous environments across several empirical studies suggests that a single general mechanism for the maintenance of standing genetic variation is unlikely; rather, the relative importance of putative mechanisms likely varies considerably from one trait and ecological context to another.


Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells.
Bladder hypertrophy is a general consequence of bladder outlet obstruction (BOO) and a typical phenomenon observed in clinical urologic diseases such as benign prostatic hyperplasia and neurogenic bladder. It is characterized by smooth muscle hyperplasia, altered extracellular matrix composition, and increased contractile function. Various growth factors are likely involved in hypertrophic pathophysiology, but their functions remain unknown. In this report, the role of basic fibroblast growth factor (bFGF) was investigated using a rat bladder smooth muscle cell (BSMC) culture system and an original animal model, in which bFGF was released from a gelatin hydrogel directly onto rat bladders. bFGF treatment promoted BSMC proliferation both in vitro and in vivo. In vitro, bFGF downregulated the expression of type I collagen, but upregulated type III collagen. ERK1/2, but not p38MAPK, was activated by bFGF, whereas inhibition of ERK1/2 by PD98059 reversed bFGF-induced BSMC proliferation, type I collagen downregulation, and type III collagen upregulation. In the in vivo release model, bFGF upregulated type III collagen and increased the contractile force of treated bladders. In parallel with these findings, hypertrophied rat bladders created by urethral constriction showed increased urothelial bFGF expression, BSMC proliferation, and increased type III collagen expression compared with sham-operated rats. These data suggest that bFGF from the urothelium could act as a paracrine signal that stimulates the proliferation and matrix production of BSMC, thereby contributing to the hypertrophic remodeling of the smooth muscle layer.


Creating transient cell membrane pores using a standard inkjet printer.
Bioprinting has a wide range of applications and significance, including tissue engineering, direct cell application therapies, and biosensor microfabrication. Recently, thermal inkjet printing has also been used for gene transfection. The thermal inkjet printing process was shown to temporarily disrupt the cell membranes without affecting cell viability. The transient pores in the membrane can be used to introduce molecules, which would otherwise be too large to pass through the membrane, into the cell cytoplasm. The application being demonstrated here is the use of thermal inkjet printing for the incorporation of fluorescently labeled g-actin monomers into cells. The advantage of using thermal ink-jet printing to inject molecules into cells is that the technique is relatively benign to cells. Cell viability after printing has been shown to be similar to standard cell plating methods. In addition, inkjet printing can process thousands of cells in minutes, which is much faster than manual microinjection. The pores created by printing have been shown to close within about two hours. However, there is a limit to the size of the pore created (~10 nm) with this printing technique, which limits the technique to injecting cells with small proteins and/or particles. A standard HP DeskJet 500 printer was modified to allow for cell printing. The cover of the printer was removed and the paper feed mechanism was bypassed using a mechanical lever. A stage was created to allow for placement of microscope slides and coverslips directly under the print head. Ink cartridges were opened, the ink was removed and they were cleaned prior to use with cells. The printing pattern was created using standard drawing software, which then controlled the printer through a simple print command. 3T3 fibroblasts were grown to confluence, trypsinized, and then resuspended into phosphate buffered saline with soluble fluorescently labeled g-actin monomers. The cell suspension was pipetted into the ink cartridge and lines of cells were printed onto glass microscope cover slips. The live cells were imaged using fluorescence microscopy and actin was found throughout the cytoplasm. Incorporation of fluorescent actin into the cell allows for imaging of short-time cytoskeletal dynamics and is useful for a wide range of applications.


Collaborative Care in Melanoma: The Essential Role of the Nurse .
This article provides perspective from medical oncologists on the importance of this supplement from the Melanoma Nursing Initiative. The authors (a) delineate the challenges inherent in addressing adverse event (AE) management with newer melanoma therapies, particularly in the community setting; (b) illustrate how advanced practice providers with extensive clinical trial experience in melanoma are in a key position to set the agenda and educate colleagues on best practices in AE management; and


Household and familial resemblance in risk factors for type 2 diabetes and related cardiometabolic diseases in rural Uganda: a cross-sectional community sample.
Prevention of type 2 diabetes (T2D) has been successfully established in randomised clinical trials. However, the best methods for the translation of this evidence into effective population-wide interventions remain unclear. To assess whether households could be a target for T2D prevention and screening, we investigated the resemblance of T2D risk factors at household level and by type of familial dyadic relationship in a rural Ugandan community. This cross-sectional household-based study included 437 individuals ≥13 years of age from 90 rural households in south-western Uganda. Resemblance in glycosylated haemoglobin (HbA1c), anthropometry, blood pressure, fitness status and sitting time were analysed using a general mixed model with random effects (by household or dyad) to calculate household intraclass correlation coefficients (ICCs) and dyadic regression coefficients. Logistic regression with household as a random effect was used to calculate the ORs for individuals having a condition or risk factor if another household member had the same condition. The strongest degree of household member resemblances in T2D risk factors was seen in relation to fitness status (ICC=0.24), HbA1c (ICC=0.18) and systolic blood pressure (ICC=0.11). Regarding dyadic resemblance, the highest standardised regression coefficient was seen in fitness status for spouses (0.54, 95% CI 0.32 to 0.76), parent-offspring (0.41, 95% CI 0.28 0.54) and siblings (0.41, 95% CI 0.25 to 0.57). Overall, parent-offspring and sibling pairs were the dyads with strongest resemblance, followed by spouses. The marked degree of resemblance in T2D risk factors at household level and between spouses, parent-offspring and sibling dyads suggest that shared behavioural and environmental factors may influence risk factor levels among cohabiting individuals, which point to the potential of the household setting for screening and prevention of T2D.


Versatile telluracycle synthesis via the sequential electrophilic telluration of C(sp2)-Zn and C(sp2)-H bonds.
We report herein a new approach for the synthesis of tellurium-bridged aromatic compounds based on the sequential electrophilic telluration of C(sp2)-Zn and C(sp2)-H bonds with tellurium(iv) chlorides. A combination of transition metal-catalyzed (migratory) arylmetalation of alkynes and sequential telluration allows for the expedient construction of a library of functionalized benzo[b]tellurophenes. Furthermore, a variety of heteroarene-fused benzotellurophenes and other novel tellurium-embedded polycyclic aromatics can be readily synthesized from the corresponding 2-iodoheterobiaryls.


Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic stellate cells by inhibiting the ubiquitination of p27.
Bone marrow mesenchymal stem cells (BMSCs) have considerable therapeutic potential for the treatment of end-stage liver disease. Previous studies have demonstrated that BMSCs secrete growth factors and cytokines that inactivate hepatic stellate cells (HSCs), which inhibited the progression of hepatic fibrosis. The aim of this study was to determine the mechanism by which BMSCs suppress the function of HSCs in fibrosis. Our results showed that co-culture of BMSCs and HSCs induced cell cycle arrest at the G10/G1 phase and cell apoptosis of HSCs, which finally inhibited the cell proliferation of HSCs. Consistent with the cell cycle arrest, co-culture of BMSCs and HSCs increased the abundance of the cell cycle protein p27. Mechanistically, we further uncovered that following the co-culture with BMSCs, the expression level of the E3 ligase S-phase kinase-associated protein 2 (SKP2) that is responsible for the ubiquitination of p27 was decreased, which attenuated the ubiquitination of p27 and increased the stability of p27 in HSCs. Collectively, our results indicated the potential involvement of the SKP2-p27 axis for the inhibitory effect of BSMCs on the cell proliferation of HSCs.


Alcohol abusers' and social drinkers' responses to alcohol-relevant and general situations.
Responses of alcohol abusers and social drinkers were compared on general and alcohol-specific problem situations using role-play methodology. Multiple responses were assessed including behavioral observational ratings, self-reports and psychophysiologic measures. There were few differences between groups in responses to the general situations. Alcohol abusers had higher urges to drink than did the social drinkers in both the general and the alcohol-specific situations. However, in response to the alcohol-specific situations, the alcohol abusers, compared to the social drinkers, were rated by judges as significantly less skillful, and they displayed more self-reported anxiety, had a higher frequency of occurrence of problem situations in the natural environment and reported greater perceived realism of the alcohol-specific situations. Psychophysiologic measures did not differentiate between the groups. Results are discussed with respect to the importance of situation specificity in understanding the precipitants of drinking and their treatment implications.


Alcohol and indinavir adversely affect protein synthesis and phosphorylation of MAPK and mTOR signaling pathways in C2C12 myocytes.
Alcohol and the antiretroviral drug indinavir (Ind) decrease protein synthesis in skeletal muscle under in vivo and in vitro conditions. The goal of the present study was to identify signaling mechanisms responsible for the inhibitory effect of ethanol (EtOH) and Ind on protein synthesis. C2C12 mouse myocytes were incubated with EtOH, Ind, or a combination of both for 24 hours. The rate of protein synthesis was determined by [35S]methionine/cysteine incorporation into cellular protein. Phosphorylation of eukaryotic initiation and elongation factors were quantitated by Western blot analysis to identify potential mechanisms for regulating translation. Treatment of myocytes with Ind or EtOH for 24 hours decreased protein synthesis by 19 and 22%, respectively, while a 35% decline was observed in cells treated simultaneously with both agents. Mechanistically, treatment with EtOH or Ind decreased the phosphorylation of the S6 ribosomal protein, and this reduction was associated with decreased S6K1 and p90rsk phosphorylation. Ethanol also decreased the phosphorylation of ERK1/2, mTOR, and 4EBP1, while Ind only suppressed ERK1/2 phosphorylation. Both agents inhibited the phosphorylation of Mnk1 and its upstream regulator p38 MAPK, and they decreased the amount of the active eukaryotic initiation factor (eIF) 4G/eIF4E complex. Finally, EtOH and/or Ind increased phosphorylation of the eukaryotic elongation factor (eEF)-2 by 1.6- to 6-fold. The effects of these agents were not additive, although the combination did exert a greater effect on S6K1 and eEF2 phosphorylation. Ethanol and Ind decreased protein synthesis in myocytes and this response was associated with changes in the phosphorylation of proteins that regulate translation initiation and elongation.


Quality of life of residents with dementia in long-term care settings in the Netherlands and Belgium: design of a longitudinal comparative study in traditional nursing homes and small-scale living facilities.
The increase in the number of people with dementia will lead to greater demand for residential care. Currently, large nursing homes are trying to transform their traditional care for residents with dementia to a more home-like approach, by developing small-scale living facilities. It is often assumed that small-scale living will improve the quality of life of residents with dementia. However, little scientific evidence is currently available to test this. The following research question is addressed in this study: Which (combination of) changes in elements affects (different dimensions of) the quality of life of elderly residents with dementia in long-term care settings over the course of one year? A longitudinal comparative study in traditional and small-scale long-term care settings, which follows a quasi-experimental design, will be carried out in Belgium and the Netherlands. To answer the research question, a model has been developed which incorporates relevant elements influencing quality of life in long-term care settings. Validated instruments will be used to evaluate the role of these elements, divided into environmental characteristics (country, type of ward, group size and nursing staff); basic personal characteristics (age, sex, cognitive decline, weight and activities of daily living); behavioural characteristics (behavioural problems and depression); behavioural interventions (use of restraints and use of psychotropic medication); and social interaction (social engagement and visiting frequency of relatives). The main outcome measure for residents in the model is quality of life. Data are collected at baseline, after six and twelve months, from residents living in either small-scale or traditional care settings. The results of this study will provide an insight into the determinants of quality of life for people with dementia living in traditional and small-scale long-term care settings in Belgium and the Netherlands. Possible relevant strengths and weaknesses of the study are discussed in this article. ISRCTN: ISRCTN23772945.


Using XML technology for the ontology-based semantic integration of life science databases.
Several hundred internet accessible life science databases with constantly growing contents and varying areas of specialization are publicly available via the internet. Database integration, consequently, is a fundamental prerequisite to be able to answer complex biological questions. Due to the presence of syntactic, schematic, and semantic heterogeneities, large scale database integration at present takes considerable efforts. As there is a growing apprehension of extensible markup language (XML) as a means for data exchange in the life sciences, this article focuses on the impact of XML technology on database integration in this area. In detail, a general architecture for ontology-driven data integration based on XML technology is introduced, which overcomes some of the traditional problems in this area. As a proof of concept, a prototypical implementation of this architecture based on a native XML database and an expert system shell is described for the realization of a real world integration scenario.


Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development.
The gene expression and protein distribution of matrix metalloproteinase (MMP) -2, -9, membrane type-1 MMP (MT1-MMP), as well as of TIMP-1, -2, and -3 were analyzed during mouse molar development. Immunohistochemical data demonstrated that all the MMPs investigated were expressed in the dental epithelium and mesenchyme. In contrast, gene and protein expression analysis for TIMPs showed that they were differentially expressed. TIMP-1 was expressed in the dental epithelium and mesenchyme between E13 and E16 and was transiently up-regulated at E14, the cap stage. TIMP-1 expression was also detected in differentiating odontoblasts. TIMP-2 RNA transcripts were found in the peridental and dental mesenchyme, odontoblasts, and ameloblasts. Protein analysis revealed high expression on the lingual side of the dental epithelium and underlying mesenchyme together with transient expression in the enamel knot at E14 and expression in the gingival tissue and enamel matrix postnatally. TIMP-3 RNA transcripts were found in discrete regions of the dental epithelium, including at high levels in the cervical loop at E16. Expression was also detected in preodontoblasts at E16 and transiently during ameloblast differentiation. Analysis of the protein distribution revealed a lower level of TIMP-3 on the lingual side of the dental epithelium at E14. MT1-MMP was expressed in the dental mesenchyme between E13 and E16, at relatively high levels in the cervical loop at E14, and in the odontoblasts and ameloblasts. The distinct temporospatial distribution patterns of the TIMPs suggest that these inhibitors play several intrinsic roles during tooth development.


Identification and partial characterization of a parasite antigen in sera from humans infected with Wuchereria bancrofti.
The purpose of this study was to identify and characterize soluble parasite antigens present in sera from humans infected with the filarial nematode Wuchereria bancrofti. Affinity chromatography and immunoblot methods were used to demonstrate a 200,000 m.w. circulating parasite antigen in sera from infected humans which corresponded to an antigen released by adult W. bancrofti during in vitro culture. Two monoclonal antibodies were produced to this antigen by immunizing mice with antigens from Dirofilaria immitis, a filarial parasite that is closely related to W. bancrofti, and screening cell fusion supernatants by enzyme immunoassay and counterimmunoelectrophoresis inhibition. The antibodies bound to a single repeated epitope (not phosphorylcholine) that was resistant to heat, acid, and protease treatments but sensitive to periodate oxidation. Immunoperoxidase studies showed that the epitope was concentrated in the cuticle and reproductive organs in D. immitis, and it was released in relatively large amounts by adult female D. immitis in vitro. The epitope is also present in antigens of other species of filarial and nonfilarial nematodes, but on the basis of preliminary studies, its presence in human serum appears to be specific for W. bancrofti infection.


Linear and nonlinear relations between psychosocial job characteristics, subjective outcomes, and sickness absence: baseline results from SMASH. Study on Musculoskeletal Disorders, Absenteeism, Stress, and Health.
This study investigates the demand-control-support (DCS) model by (a) using a more focused measure of job control, (b) testing for interactive and nonlinear relationships, and (c) further extending the model to the prediction of an objective outcome measure (i.e., company-administrated sickness absence). Hypotheses were tested in a heterogeneous sample of 1,739 employees from a 3-year prospective cohort study called SMASH (Study on Musculoskeletal Disorders, Absenteeism, Stress, and Health). Baseline results showed that a linear additive model was superior for job satisfaction, psychosomatic health complaints, and sickness absence, whereas a curvilinear model was superior for emotional exhaustion and depression. It is concluded that, first, there was no evidence of interactive effects. Second, it seems sensible to pay more attention to curvilinear relationships in future research. Finally, the DCS model was not supported using a more objective outcome measure.


[Molecular and cellular bases of Shigella flexneri virulence].
Shigella flexneri, a Gram negative bacillus, causes bacillary dysentery, an ulcerative disease of the human colon, by invading intestinal epithelial cells. Entry into epithelial cells occurs via an induced phagocytic process which involves the actino-myosin complex. The host-cell receptor and the transmembrane signal which initiate reorganization of the cytoskeleton are under study. Binding to integrins has recently been demonstrated in related models such as the entry of Yersinia pseudotuberculosis and Bordetella pertussis into cells. Bacterial genes necessary to achieve entry are located on five contiguous loci covering 30 kb on a 220 kb virulence plasmid in S. flexneri. Locus 2 has been particularly studied. Six genes organized as an operon encode highly immunogenic proteins among which IpaB (62 kD) and IpaC (48 kD) are the invasins of this microorganism which subsequently grows very rapidly within infected cells due to its capacity to lyse the membrane bound phagocytic vacuole. Once free within the cytoplasm, bacteria interact again with the cell cytoskeleton. They first express Olm (organelle like movement), a phenotype reflecting intracellular movement along actin stress cables. They subsequently express Ics (intracellular spread), a phenotype by which intracellular bacteria induce nucleation and polymerization of actin followed by accumulation of this material at one end of the bacillus. This process causes rapid random movement leading to the formation of protusions which allow passage to adjacent cells. A combination of these two movements achieves bacterial colonization of the epithelium.


Species divergence in sexually selected traits: increase in song elaboration is related to decrease in plumage ornamentation in finches.
Elaborate plumage and complex songs of male birds are two of the best-known examples of sexually selected traits, yet the interaction between these traits is poorly understood. Theory suggests that among a suite of potential displays, animals will emphasize traits that are most conspicuous, least costly, or best signal condition and reduce display of other traits. Here we examined the relationship between song and plumage elaborations in cardueline finches, songbirds that are highly variable in plumage displays and songs, but that share a similar mating system. We statistically controlled for body mass, habitat characteristics, and phylogenetic relationships and found that across species song complexity was strongly negatively related to elaboration of plumage ornamentation. When plumage coloration was partitioned into carotenoid-based and melanin-based components, song complexity was negatively related to elaboration of male carotenoid-based coloration but unrelated to elaboration of melanin-based coloration. These observations support the idea that, for condition-dependent traits, animal species trade off trait expression in response to changes in the costs or the information content of these traits. We discuss several alternative explanations for the observed pattern.


Acute abdominal aortic dissection: insight from the International Registry of Acute Aortic Dissection (IRAD).
Isolated acute dissection of the abdominal aorta is an unusual event that may present with several different clinical scenarios. Because its incidence is low, the natural history is unknown. We report data from the International Registry of Acute Aortic Dissection (IRAD), the largest group of patients treated for acute aortic dissections. The aim of this study was to identify clinical characteristics, therapeutic approaches, risk factors for mortality, in-hospital outcome, and long-term results of this cohort, thus clarifying its natural history. A comprehensive analysis of 290 clinical variables on 18 patients affected by isolated acute abdominal aortic dissection (IAAAD) was performed. Among 1417 patients enrolled in the IRAD from 1996 to 2003, 532 (37.5%) had an acute type B dissection, of which 18 (1.3%) had an IAAAD. Theor mean age was 67.7 +/- 13.3 years, with a male predominance (n = 12, 67%). Aortic aneurysms pre-existed in 5 patients (28%). IAAAD was iatrogenic in 2 cases (11%). Compared with patients with type B aortic dissections, abdominal pain, mesenteric ischemia or infarction, limb ischemia, and hypotension as initial clinical signs were significantly more frequent in patients with IAAAD, whereas chest pain was more typical in patients with type B dissections. No neurologic symptoms, such as ischemic spinal cord damage or ischemic peripheral neuropathy, occurred in the IAAAD cohort. The 18 IAAAD patients were medically, surgically, or percutaneously managed in 12 (66.6%), five (27.8%), and one (5.6%) cases, respectively. The overall in-hospital mortality rate was 5.6% (n = 1). The patient who died was medically managed. No deaths were reported among patients who underwent surgery or had an endovascular procedure, irrespective of their preoperative status. A mean follow-up of 5 years (range, 1 month to 9 years) was completed for 71% (12 of 17) of the patients. Four patients (33.3%) died during the 9-year follow-up period. Overall survival was 93.3% +/- 12.6% at 1 year and 73.3% +/- 27.2% at 5 years. All patients who died during the follow-up period had in-hospital medical management (P = .04). IAAAD is a condition that may present differently compared with classic type B aortic dissections. IAAAD patients treated with surgical or endovascular procedures had a lower unadjusted in-hospital and long-term mortality rate compared with medically managed patients. On the basis of the present natural history report, continued surveillance appears mandatory. To improve the life expectancy of patients with IAAAD, aggressive surgical or endovascular management seems justified.


Symbiosomes: temporary moonlighting organelles.
Symbiosomes are a unique structural entity that performs the role of biological nitrogen fixation, an energy-demanding process that is the primary entryway of fixed nitrogen into the biosphere. Symbiosomes result from the infection of specific rhizobial strains into the roots of an appropriate leguminous host plant forming an organ referred to as a nodule. Within the infected plant cells of the nodule, the rhizobia are encased within membrane-bounded structures that develop into symbiosomes. Mature symbiosomes create an environment that allows the rhizobia to differentiate into a nitrogen-fixing form called bacteroids. The bacteroids are surrounded by the symbiosome space, which is populated by proteins from both eukaryotic and prokaryotic symbionts, suggesting this space is the quintessential component of symbiosis: an inter-kingdom environment with the single purpose of symbiotic nitrogen fixation. Proteins associated with the symbiosome membrane are largely plant-derived proteins and are non-metabolic in nature. The proteins of the symbiosome space are mostly derived from the bacteroid with annotated functions of carbon metabolism, whereas relatively few are involved in nitrogen metabolism. An appreciable portion of both the eukaryotic and prokaryotic proteins in the symbiosome are also 'moonlighting' proteins, which are defined as proteins that perform roles unrelated to their annotated activities when found in an unexpected physiological environment. The essential functions of symbiotic nitrogen fixation of the symbiosome are performed by co-operative interactions of proteins from both symbionts some of which may be performing unexpected roles.


A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism.
Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.


Knee osteoarthritis in a chestnut farmer - Case Report.
Several studies have dealt with the issue of professional risk factors and onset of knee osteoarthritis (OA). In particular, occupational epidemiological studies have provided evidence that activities resulting in biomechanical overload may be linked with an increased risk of knee OA - also among farmers. To our knowledge, no cases of knee OA among chestnut farmers have been reported in the literature. We report the case of a 70-year-old Caucasian male who has worked for more than 50 years on a chestnut farm. In 2007, an X-ray and a MRI, performed after a workplace accident to his left knee, showed the presence of knee OA. His job required a range of repetitive tasks, such as squatting, kneeling, climbing, walking on sloping terrain, assuming uncomfortable postures, and lifting and carrying heavy loads for the great majority of the working day. All the aforementioned tasks are known occupational risk factors for knee OA. Regarding individual risk factors, at the time of the first diagnosis of knee OA, the worker was 64-years-old with a body mass index of 26.5 kg/m2. He reported no cases of arthritis among his relatives and no sports playing on his part. In addition, his medical history revealed the presence of two minor lumbar disc herniations and tendinitis of the long head of the biceps. Considering the lack of major individual risk factors for knee OA, it is reasonable to suppose that five decades of exposure to biomechanical overload as a chestnut farmer was a relevant risk factor for the onset of the disease.


Lewis Acidity Scale of Diaryliodonium Ions toward Oxygen, Nitrogen, and Halogen Lewis Bases.
Equilibrium constants for the associations of 17 diaryliodonium salts Ar2I+X- with 11 different Lewis bases (halide ions, carboxylates, p-nitrophenolate, amines, and tris(p-anisyl)phosphine) have been investigated by titrations followed by photometric or conductometric methods as well as by isothermal titration calorimetry (ITC) in acetonitrile at 20 °C. The resulting set of equilibrium constants KI covers 6 orders of magnitude and can be expressed by the linear free-energy relationship lg KI = sI LAI + LBI, which characterizes iodonium ions by the Lewis acidity parameter LAI, as well as the iodonium-specific affinities of Lewis bases by the Lewis basicity parameter LBI and the susceptibility sI. Least squares minimization with the definition LAI = 0 for Ph2I+ and sI = 1.00 for the benzoate ion provides Lewis acidities LAI for 17 iodonium ions and Lewis basicities LBI and sI for 10 Lewis bases. The lack of a general correlation between the Lewis basicities LBI (with respect to Ar2I+) and LB (with respect to Ar2CH+) indicates that different factors control the thermodynamics of Lewis adduct formation for iodonium ions and carbenium ions. Analysis of temperature-dependent equilibrium measurements as well as ITC experiments reveal a large entropic contribution to the observed Gibbs reaction energies for the Lewis adduct formations from iodonium ions and Lewis bases originating from solvation effects. The kinetics of the benzoate transfer from the bis(4-dimethylamino)-substituted benzhydryl benzoate Ar2CH-OBz to the phenyl(perfluorophenyl)iodonium ion was found to follow a first-order rate law. The first-order rate constant kobs was not affected by the concentration of Ph(C6F5)I+ indicating that the benzoate release from Ar2CH-OBz proceeds via an unassisted SN1-type mechanism followed by interception of the released benzoate ions by Ph(C6F5)I+ ions.


Review of anticancer mechanisms of isoquercitin.
This review was based on a literature search of PubMed and Scielo databases using the keywords "quercetin, rutin, isoquercitrin, isoquercitin (IQ), quercetin-3-glucoside, bioavailability, flavonols and favonoids, and cancer" and combinations of all the words. We collected relevant scientific publications from 1990 to 2015 about the absorption, bioavailability, chemoprevention activity, and treatment effects as well as the underlying anticancer mechanisms of isoquercitin. Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom. The subclass of flavonols receives special attention owing to their health benefits. The main components of this class are quercetin, rutin, and IQ, which is a flavonoid and although mostly found as a glycoside, is an aglycone (lacks a glycoside side chain). This compound presents similar therapeutic profiles to quercetin but with superior bioavailability, resulting in increased efficacy compared to the aglycone form. IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant, antiproliferative, anti-inflammatory, anti-hypertensive, and anti-diabetic. The protective effects of IQ in cancer may be due to actions on lipid peroxidation. In addition, the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway, mixed-lineage protein kinase 3, mitogen-activated protein kinase, apoptotic pathways, as well proinflammatory protein signaling. This review contributed to clarifying the mechanisms of absorption, metabolism, and actions of IQ and isoquercitrin in cancer.


[Level of evidence for therapeutic drug monitoring of cisplatin].
Cisplatin is an anticancer agent widely used in clinical practice. Cisplatin undergoes irreversible protein binding in plasma and presents a major nephrotoxicity. Some studies determined unbound and bound platin concentrations using flameless atomic absorption spectrophotometry or chromatography. These studies showed a relationship between cisplatin exposition, notably its maximal concentration, and nephrotoxicity. However, the relationship between cisplatin exposition and its efficacy is not yet established. The population approach using a nonlinear mixed effects model showed a low variability of drug exposition parameters. In some cases, Bayesian adaptative dosing were proposed. However, some particular populations will have to be taken into account such as children, elderly patients, acute or chronic renal failure. The impact of cisplatin pharmacogenetics on its therapeutic monitoring need to be studied. Therapeutic cisplatin monitoring is today possibly useful measuring maximal concentration and using described adjusted-modelling. Some prospective multicentric validations are required.


Impact of Aspiration Percutaneous Vertebroplasty in Reducing Bone Cement Leakage and Enhancing Distribution-An Ex Vivo Study in Goat Vertebrae.
Osteoporosis-induced vertebral compression fracture (OVCF) occurs commonly in people over the age of 50, especially among menopausal women. Besides conservative therapy, minimally invasive percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used in clinical treatment and achieved good efficacy. However, the leakage of bone cement (CL) during vertebroplasty (PV) is a major risk that can cause (serious) complications such as compression of the spinal cord, pulmonary embolism, or even paraplegia. In this study, we introduced a new aspiration technique with standard PV procedures (APV) to ameliorate the risk of leakage with quantitative verifications of its effectiveness. APV intends to create a differential pressure to guide the direction of cement flow within the vertebrae. To test this technique, Nubian goats' ex vivo vertebral bodies (VBs) were used to simulate the PV surgical process in humans. Results show that the proposed APV has a lower leakage rate of 13% compared to the 53% of conventional PV. Additionally, the APV approach achieves more uniform cement distribution via the 9-score method with a value of 7 ± 1.30 in contrast to 4 ± 1.78 by conventional PV.


Dysregulated signaling, proliferation and apoptosis impact on the pathogenesis of TCRγδ+ T cell large granular lymphocyte leukemia.
TCRγδ+ T-LGL leukemia is a rare form of chronic mature T cell disorders in elderly, which is generally characterized by a persistently enlarged CD3+CD57+TCRγδ+ large granular lymphocyte population in the peripheral blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most patients being largely asymptomatic, although neutropenia, fatigue and B symptoms and underlying diseases such as autoimmune diseases or malignancies are also often observed. The etiology of TCRγδ+ T-LGL proliferations is largely unknown. Here, we aimed to investigate underlying molecular mechanisms of these rare proliferations by performing gene expression profiling of TCRγδ+ T-LGL versus normal TCRγδ+ T cell subsets. From our initial microarray dataset we observed that TCRγδ+ T-LGL leukemia forms a separate group when compared with different healthy control TCRγδ+ T cell subsets, correlating best with the healthy TemRA subset. The lowest correlation was seen with the naive subset. Based on specific comparison between healthy control cells and TCRγδ+ T-LGL leukemia cells we observed up-regulation of survival, proliferation and hematopoietic system related genes, with a remarkable down-regulation of apoptotic pathway genes. RQ-PCR validation of important genes representative for the dataset, including apoptosis (XIAP, CASP1, BCLAF1 and CFLAR), proliferation/development (ID3) and inflammation (CD28, CCR7, CX3CR1 and IFNG) processes largely confirmed the dysregulation in proliferation and apoptosis. Based on these expression data we conclude that TCRγδ+ T-LGL leukemia is likely the result of an underlying aberrant molecular mechanisms leading to increased proliferation and reduced apoptosis.


Functional and molecular reorganization of the nucleolar apparatus in maturing mouse oocytes.
In mammalian preovulatory oocytes, rRNA synthesis is down-regulated until egg fertilization and zygotic genome reactivation, but the underlying regulatory mechanisms of this phenomenon are poorly characterized. We examined the molecular organization of the rRNA synthesis and processing machineries in fully grown mouse oocytes in relation to ongoing rDNA transcription and oocyte progression throughout meiosis. We show that, at the germinal vesicle stage, the two RNA polymerase I (RNA pol I) subunits, RPA116 and PAF53/RPA53, and the nucleolar upstream binding factor (UBF) remain present irrespective of ongoing rDNA transcription and colocalize in stoichiometric amounts within discrete foci at the periphery of the nucleolus-like bodies. These foci are spatially associated with the early pre-rRNA processing protein fibrillarin and in part with the pre-ribosome assembly factor B23/nucleophosmin. After germinal vesicle breakdown, the RNA pol I complex disassembles in a step-wise manner from chromosomes, while UBF remains associated with chromosomes until late prometaphase I. Dislodging of UBF, but not of RNA pol I, is impaired by the phosphatase inhibitor okadaic acid, thus strengthening the idea of a relationship between UBF dynamics and protein phosphorylation. Since neither RNA pol I, UBF, fibrillarin, nor B23 is detected at metaphase II, i.e., the normal stage of fertilization, we conclude that these nucleolar proteins are not transported to fertilized eggs by maternal chromosomes. Together, these data demonstrate an essential difference in the dynamics of the major nucleolar proteins during mitosis and meiosis.


Regenerating Mandibular Bone Using rhBMP-2: Part 1-Immediate Reconstruction of Segmental Mandibulectomies.
To describe a surgical technique using a regenerative approach and internal fixation for immediate reconstruction of critical size bone defects after segmental mandibulectomy in dogs. Prospective case series. Dogs (n = 4) that had reconstruction after segmental mandibulectomy for treatment of malignant or benign tumors. Using a combination of extraoral and intraoral approaches, a locking titanium plate was contoured to match the native mandible. After segmental mandibulectomy, the plate was secured and a compression resistant matrix (CRM) infused with rhBMP-2, implanted in the defect. The implant was then covered with a soft tissue envelope followed by intraoral and extraoral closure. All dogs that had mandibular reconstruction healed with intact gingival covering over the mandibular defect and had immediate return to normal function and occlusion. Mineralized tissue formation was observed clinically within 2 weeks and solid cortical bone formation within 3 months. CT findings at 3 months showed that the newly regenerated mandibular bone had ∼50% of the bone density and porosity compared to the contralateral side. No significant complications occurred. Mandibular reconstruction using internal fixation and CRM infused with rhBMP-2 is an excellent solution for immediate reconstruction of segmental mandibulectomy defects in dogs.


[Pathological findings in pigs affected by the postweaning multisystemic wasting syndrome in Argentina].
Postweaning multisystemic wasting syndrome was first described in Canada in 1991 and at present an increasing number of cases has been diagnosed worldwide. In Argentina the first cases of PMWS were reported recently. Forty eight 5 to 12 week old pigs with signs characteristic of PMWS from 19 farms were studied. Although the real distribution of the virus in our country is not known it was observed an increasing number of farms with PMWS distributed in the major producing provinces. The histopathology was an important tool in diagnosis of suspicious cases of PMWS with the observation of different degrees of lesion. In the studied animals, the secondary infections, either by opportunistic pathogens or secondary bacteria could be important.


Systemic GFP silencing is associated with high transgene expression in Nicotiana benthamiana.
Gene silencing in plants using topical dsRNA is a new approach that has the potential to be a sustainable component of the agricultural production systems of the future. However, more research is needed to enable this technology as an economical and efficacious supplement to current crop protection practices. Systemic gene silencing is one key enabling aspect. The objective of this research was to better understand topically-induced, systemic transgene silencing in Nicotiana benthamiana. A previous report details sequencing of the integration site of the Green Fluorescent Protein (GFP) transgene in the well-known N. benthamiana GFP16C event. This investigation revealed an inadvertent co-integration of part of a bacterial transposase in this line. To determine the effect of this transgene configuration on systemic silencing, new GFP transgenic lines with or without the transposase sequences were produced. GFP expression levels in the 19 single-copy events and three hemizygous GFP16C lines produced for this study ranged from 50-72% of the homozygous GFP16C line. GFP expression was equivalent to GFP16C in a two-copy event. Local GFP silencing was observed in all transgenic and GFP16C hemizygous lines after topical application of carbon dot-based formulations containing a GFP targeting dsRNA. The GFP16C-like systemic silencing phenotype was only observed in the two-copy line. The partial transposase had no impact on transgene expression level, local GFP silencing, small RNA abundance and distribution, or systemic GFP silencing in the transgenic lines. We conclude that high transgene expression level is a key enabler of topically-induced, systemic transgene silencing in N. benthamiana.


Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice.
The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.


The pharmacokinetics of albumin conjugates of D-penicillamine in humans.
D-penicillamine (D-PEN) is incompletely recovered during short-term balance studies, despite rapid elimination of D-PEN and its low molecular weight metabolites. Urinary excretion of metabolites of D-PEN also persists long after cessation of chronic therapy. A study was performed to determine whether the formation and later breakdown of a stable disulfide between D-PEN and plasma albumin could explain these aspects of D-PEN pharmacokinetics. Five human volunteers received D-penicillamine, 250 mg orally, daily for 21 days. Plasma concentration-time profiles for D-PEN and D-PEN-albumin disulfide (D-PEN-albumin) were determined during the first day and pre-dose concentrations were measured on five further occasions. The pharmacokinetics of D-PEN on the first day were similar to those reported previously. No D-PEN was found in any of the pre-dose specimens. The concentration of D-PEN-albumin rose rapidly during the first day, with an estimated 8.6% of the bioavailable D-PEN being transformed to D-PEN-albumin. Pseudo-steady-state concentrations of D-PEN-albumin were achieved in three subjects at between 14 and 21 days. The mean trough concentration of D-PEN-albumin at 21 days (19.5 microM) exceeded the peak concentration of D-PEN (during the first day) by 5.7-fold. The terminal elimination half-life of D-PEN-albumin was 1.65 +/- 0.29 days, which compared with an elimination half-life of 59 +/- 8.4 min for D-PEN.(ABSTRACT TRUNCATED AT 250 WORDS)


[Microcirculatory bed of the injured sciatic nerve (experimental study)].
A morphometric, histochemical and electron microscopic investigation of the sciatic nerve hemomicrocirculatory bed was performed (on 45 dogs) after its small part had been resected and the cut end had been sutured microsurgically. During 2--4 weeks after the operation the microvessel reactions depend mainly on the trauma and the resulted processes of aseptic inflammation, the neural fibre degeneration and vascular denervation. Within the interval of 2--4 weeks up to 6-12 months after the nerve cutting, transformations in the hemomicrocirculatory bed play an important role in the energy and plastic ensurance of the regenerative neuroma elements and the adjoining parts of the nerve. Specific reactions of the peripheral nerve microvessels at their restoration should be taken into account when estimating time of surgical operations for neural trunks and elaborating some new neurosurgical approaches.


C-11 radiochemistry in cancer imaging applications.
Carbon-11 (C-11) radiotracers are widely used for the early diagnosis of cancer, monitoring therapeutic response to cancer treatment, and pharmacokinetic investigations of anticancer drugs. PET imaging permits non-invasive monitoring of metabolic processes and molecular targets, while carbon-11 radiotracers allow a "hot-for cold" substitution of biologically active molecules. Advances in organic synthetic chemistry and radiochemistry as well as improved automated techniques for radiosynthesis have encouraged investigators in developing carbon-11 tracers for use in oncology imaging studies. The short half-life of carbon-11 (20.38 minutes) creates special challenges for the synthesis of C-11 labeled tracers; these include the challenges of synthesizing C-11 target compounds with high radiochemical yield, high radiochemical purity and high specific activity in a short time and on a very small scale. The optimization of conditions for making a carbon-11 tracer include the late introduction of the C-11 isotope, the rapid formation and purification of the target compound, and the use of automated systems to afford a high yield of the target compound in a short time. In this review paper, we first briefly introduce some basic principles of PET imaging of cancer; we then discuss principles of carbon-11 radiochemistry, focus on specific advances in radiochemistry, and describe the synthesis of C-11 radiopharmaceuticals developed for cancer imaging. The carbon-11 radiochemistry approaches described include the N,O, and S-alkylations of [(11)C]methyl iodide/[(11)C]methyl triflate and analogues of [(11)C]methyl iodide and their applications for making carbon-11 tracers; we then address recent advances in exploring a transmetallic complex mediated [(11)C]carbonyl reaction for oncologic targets.


[Military psychiatry in Israel: a 50-year perspective].
The history of military psychiatry in Israel may be divided into 2 main periods. The first extended from the War of Independence in 1948, through the Sinai, Six Day and Yom Kippur Wars. Its outstanding feature was avoidance of the issue of combat stress reaction (CSR). The Yom Kippur War made the recognition of CSR inescapable, assisted in breaking up denial, and served as a stimulus for development of the next phase of the system. This second phase was characterized by impressive progress in all areas of military psychiatry. The rich experience accumulated during the wars, together with the assimilation of a research culture which began blooming, especially in the wake of the Lebanon War, aided the development and crystallization of concepts related to combat and non-combat military psychiatry alike. The build-up of the mental health organization overlapped field deployment of the Medical Corps.


Radiologic Assessment of Cervical Canal Stenosis Using Kang MRI Grading System: Do Clinical Symptoms Correlate with Imaging Findings?
Introduction Magnetic resonance imaging (MRI) is widely used in the evaluation of cervical canal stenosis and spinal cord compression. Kang et al. formulated a new MRI grading system for assessing canal stenosis which takes cord signal change into account. The purpose of the study was to determine the agreement between Kang's grading system and neurological symptoms. Methods A cross-sectional study was conducted at Aga Khan University Hospital between April 2014 and December 2015. Patients meeting inclusion criteria were enrolled. T2 sagittal and T2 axial MRI images were acquired and reported by a consultant neuroradiologist, in accordance with the MRI grading system suggested by Kang et al. Neurologic clinical symptoms were acquired by the history taken by the principal investigator. More than one neurologic symptoms and Kang MRI grade 2 or 3 were taken as positive evidence of cord compression resulting from canal stenosis. Results Amongst 126 subjects, 54% were females. Mean age of patients was 50.3 ± 14.3 years (range 19-83 years). Average disease duration was 4.61 ± 3.73 (range 1-24 months). In the majority of the patients, the findings were found at the C5-C6 level. 65.1% of patients were identified positive for cervical canal stenosis by Kang grading system. Most common neurological symptoms were pain (99%) and numbness (56%). Cohen's Kappa was run to evaluate the agreement between neurological symptoms and Kang grading system. There was a strong agreement between the two methods, K = 0.81 (95% CI 0.70-0.92), p < 0.001. Conclusion There was a substantial agreement between Kang's grading system and the presence of clinical symptoms. The agreement was greatest in females, older patients, and those with longer duration of symptoms.


BAYESIAN INFERENCE AND MODEL CHOICE IN A HIDDEN STOCHASTIC TWO-COMPARTMENT MODEL OF HEMATOPOIETIC STEM CELL FATE DECISIONS.
Despite rapid advances in experimental cell biology, the in vivo behavior of hematopoietic stem cells (HSC) cannot be directly observed and measured. Previously we modeled feline hematopoiesis using a two-compartment hidden Markov process that had birth and emigration events in the first compartment. Here we perform Bayesian statistical inference on models which contain two additional events in the first compartment in order to determine if HSC fate decisions are linked to cell division or occur independently. Pareto Optimal Model Assessment approach is used to cross check the estimates from Bayesian inference. Our results show that HSC must divide symmetrically (i.e., produce two HSC daughter cells) in order to maintain hematopoiesis. We then demonstrate that the augmented model that adds asymmetric division events provides a better fit to the competitive transplantation data, and we thus provide evidence that HSC fate determination in vivo occurs both in association with cell division and at a separate point in time. Last we show that assuming each cat has a unique set of parameters leads to either a significant decrease or a nonsignificant increase in model fit, suggesting that the kinetic parameters for HSC are not unique attributes of individual animals, but shared within a species.


Implementation strategies and outcomes for occupational therapy in adult stroke rehabilitation: a scoping review.
Stroke survivors often encounter occupational therapy practitioners in rehabilitation practice settings. Occupational therapy researchers have recently begun to examine the implementation strategies that promote the use of evidence-based occupational therapy practices in stroke rehabilitation; however, the heterogeneity in how occupational therapy research is reported has led to confusion about the types of implementation strategies used in occupational therapy and their association with implementation outcomes. This review presents these strategies and corresponding outcomes using uniform language and identifies the extent to which strategy selection has been guided by theories, models, and frameworks (TMFs). A scoping review protocol was developed to assess the breadth and depth of occupational therapy literature examining implementation strategies, outcomes, and TMFs in the stroke rehabilitation field. Five electronic databases and two peer-reviewed implementation science journals were searched to identify studies meeting the inclusion criteria. Two reviewers applied the inclusion parameters and consulted with a third reviewer to achieve consensus. The 73-item Expert Recommendations for Implementing Change (ERIC) implementation strategy taxonomy guided the synthesis of implementation strategies. The Implementation Outcomes Framework guided the analysis of measured outcomes. The initial search yielded 1219 studies, and 26 were included in the final review. A total of 48 out of 73 discrete implementation strategies were described in the included studies. The most used implementation strategies were "distribute educational materials" (n = 11), "assess for readiness and identify barriers and facilitators" (n = 11), and "conduct educational outreach visits" (n = 10). "Adoption" was the most frequently measured implementation outcome, while "cost" was not measured in any included studies. Eleven studies reported findings supporting the effectiveness of their implementation strategy or strategies; eleven reported inconclusive findings, and four found that their strategies did not lead to improved implementation outcomes. In twelve studies, at least partially beneficial outcomes were reported, corresponding with researchers using TMFs to guide implementation strategies. This scoping review synthesized implementation strategies and outcomes that have been examined in occupational therapy and stroke rehabilitation. With the growth of the stroke survivor population, the occupational therapy profession must identify effective strategies that promote the use of evidence-based practices in routine stroke care and describe those strategies, as well as associated outcomes, using uniform nomenclature. Doing so could advance the occupational therapy field's ability to draw conclusions about effective implementation strategies across diverse practice settings.


Achieving stable Zn metal anode via a hydrophobic and Zn2+-conductive amorphous carbon interface.
High security and low cost enable aqueous zinc ion batteries (AZIBs) with huge application potential in large-scale energy storage. Nevertheless, the loathsome dendrite and side reactions of Zn anode are harmful to the cycling lifespan of AZIBs. Here, a new type of thin amorphous carbon (AC) interface layer (∼100 nm in thickness) is in-situ constructed on the Zn foil (Zn@AC) via a facile low-temperature chemical vapor deposition (LTCVD) method, which owns a hydrophobic peculiarity and a high Zn2+ transference rate. Moreover, this AC coating can homogenize the surface electric field and Zn2+ flux to realize the uniform deposition of Zn. Consequently, dendrite growth and side reactions are concurrently mitigated. Symmetrical cell achieves a dendrite-free Zn plating/stripping over 500 h with a low overpotential of 31 mV at 1 mA cm-2/1 mAh cm-2. Of note, the full cell with a MnO2/CNT cathode harvests a capacity retention of 70.0 % after 550 cycles at 1 A/g. In addition, the assembled flexible quasi-solid-state AZIBs display a stable electrochemical performance under deformation conditions and maintain a capacity of 76.5 mAh/g at 5 A/g after 300 cycles. This innovative amorphous carbon layer is expected to provide a new insight into stabilizing Zn anode.


[Urticaria as a clinical manifestation of intestinal parasitism].
The main goal of this paper is to call the attention of general practitioners and internists on the different affections which may involve urticaria as a clinical manifestations. A differential diagnosis of the causes of urticaria with an allergic and a nonallergic pathogenesis is made. Intestinal parasitism is among the first causes of urticaria. Six cases studied at the allergy service which had been referred from health areas or other hospital services are reviewed and reported. In these patients, a total regression of the clinical picture was achieved once intestinal parasitism was eradicated.


The development of the metabolic syndrome and insulin resistance after adjuvant treatment for breast cancer.
Adjuvant breast cancer treatment is associated with a number of adverse physical changes, including weight gain, and therefore may represent a critical period for the development of metabolic disturbance. The aim of this study was to evaluate changes in the presentation of the metabolic syndrome (MetSyn) and insulin resistance from breast cancer surgery to postcompletion of adjuvant treatment. Sixty-one participants who had completed metabolic screening, including fasting blood samples and anthropometric measurements, on the morning of breast cancer surgery were recruited. Measures were repeated after completion of adjuvant treatment. Change in the proportion of participants presenting with the MetSyn was evaluated using the related-samples McNemar test, and changes in measures of glucose metabolism (fasting insulin, insulin resistance [homeostatic model assessment index], and glycosylated hemoglobin [HbA1c]) were analyzed using paired t tests. The Kruskal-Wallis test was used to compare differences in changes in metabolic parameters across clinical and lifestyle characteristics. There was a significant (P < .001) increase in fasting insulin (mean [SE] change, 2.73 [0.57] mU/L), homeostatic model assessment index (0.58 [0.14]), and HbA1c level (4.49 [5.63] mmol/mol) from baseline to follow-up along with an increase in the proportion diagnosed with the MetSyn (P = .03). Those with the MetSyn at diagnosis experienced a greater increase in insulin resistance. Premenopausal women experienced greatest increases in HbA1c level. Results demonstrate the development of significant metabolic dysfunction, characterized by glucose dysmetabolism and MetSyn, after adjuvant treatment for breast cancer. Interventions to improve the metabolic profile of breast cancer survivors are warranted.


A fractional Fourier transform analysis of a bubble excited by an ultrasonic chirp.
The fractional Fourier transform is proposed here as a model based, signal processing technique for determining the size of a bubble in a fluid. The bubble is insonified with an ultrasonic chirp and the radiated pressure field is recorded. This experimental bubble response is then compared with a series of theoretical model responses to identify the most accurate match between experiment and theory which allows the correct bubble size to be identified. The fractional Fourier transform is used to produce a more detailed description of each response, and two-dimensional cross correlation is then employed to identify the similarities between the experimental response and each theoretical response. In this paper the experimental bubble response is simulated by adding various levels of noise to the theoretical model output. The method is compared to the standard technique of using time-domain cross correlation. The proposed method is shown to be far more robust at correctly sizing the bubble and can cope with much lower signal to noise ratios.


A quasielastic and inelastic neutron scattering study of the alkaline and alkaline-earth borohydrides LiBH4 and Mg(BH4)2 and the mixture LiBH4 + Mg(BH4)2.
Quasielastic neutron scattering was used to investigate the low energy transfer dynamics of the complex borohydrides Mg(BH4)2 in the α- and β-modifications, LiBH4 in the low and high temperature crystal structure, and an 1 : 1 molar mixture of LiBH4 + α-Mg(BH4)2. All investigated compounds show a rich dynamic behaviour below an energy range of ΔE = 10 meV with the superposition of rotational dynamics of the constituent [BH4]- anions and low lying lattice modes. For Mg(BH4)2, the rotational diffusion of the [BH4] units was found to be much more activated in the metastable β-polymorph compared to the α-phase, and the low lying lattice modes are even softer in the former crystal structure. In Mg(BH4)2, the structural phase transition is mainly governed by the lattice dynamics, while alkaline LiBH4 exhibits a transition of the [BH4] rotations around the phase transition temperature. Ball milled LiBH4 + α-Mg(BH4)2 remains a physical mixture of the parent compounds and each component retains its characteristic dynamic signature up to the melting temperature.


Mendelian Randomization as a Tool for Cardiovascular Research: A Review.
Mendelian randomization (MR) is a statistical approach that has become increasingly popular in the field of cardiovascular disease research. It offers a way to infer potentially causal relationships between risk factors and outcomes using observational data, which is particularly important in cases where randomized clinical trials are not feasible or ethical. With the growing availability of large genetic data sets, MR has become a powerful and accessible tool for studying the risk factors for cardiovascular disease. MR uses genetic variation associated with modifiable exposures or risk factors to mitigate biases that affect traditional observational study designs. The approach uses genetic variants that are randomly assigned at conception as proxies for exposure to a risk factor, mimicking a randomized clinical trial. By comparing the outcomes of individuals with different genetic variants, researchers may draw causal inferences about the effects of specific risk factors on cardiovascular disease, provided assumptions are met that address (1) the association between each genetic variant and risk factor and (2) the association of the genetic variants with confounders and (3) that the association between each genetic variant and the outcome only occurs through the risk factor. Like other observational designs, MR has limitations, which include weak instruments that are not strongly associated with the exposure of interest, linkage disequilibrium where genetic instruments influence the outcome via correlated rather than direct effects, overestimated genetic associations, and selection and survival biases. In addition, many genetic databases and MR studies primarily include populations genetically similar to European reference populations; improved diversity of participants in these databases and studies is critically needed. This review provides an overview of MR methodology, including assumptions, strengths, and limitations. Several important applications of MR in cardiovascular disease research are highlighted, including the identification of drug targets, evaluation of potential cardiovascular risk factors, as well as emerging methodology. Overall, while MR alone can never prove a causal relationship beyond reasonable doubt, MR offers a rigorous approach for investigating possible causal relationships in observational data and has the potential to transform our understanding of the etiology and treatment of cardiovascular disease.


Tooth evolution and dental defects: from genetic regulation network to micro-RNA fine-tuning.
Teeth, like all epithelial appendages, form via a sequential and reciprocal series of inductive signals between the epithelium and the underlying mesenchyme. The genes involved in this signaling network regulating ectodermal organ development have been highly conserved during evolution and are gaining more understanding in great detail. The specific functions of numerous genes during embryogenesis are known, and the involvement of their mutations in the pathogenesis of congenital defects is being extensively studied. Recently, the micro-RNA (miRNA) pathway has been associated with various aspects of embryogenesis including ectodermal organ formation and odontogenesis. In this review, I presented the genetic network involved during tooth formation and evolution, and several mutations that give rise to dental defects. The possible impact of fine-tuning and network regulation by miRNAs on development, evolution of teeth, and defects are, therefore, discussed.


[Ultrastructural studies of the epithelium in Reis-Bückler's corneal dystrophy].
In Reis-Bücklers' dystrophy an unknown pathomechanism in Bowman's layer and the basal cells of the corneal epithelium results in recurrent epithelial erosions. The final stage is characterized by visual impairment due to irregular astigmatism and opacities in the superficial stroma. The treatment is superficial keratectomy, lamellar or perforating keratoplasty. This study presents the electron-microscopic findings in the epithelium and Bowman's layer from samples obtained from 3 generations of the same family. All were diagnosed and treated in the University Eye Clinic of Hamburg.


Interaction-induced quantum phase revivals and evidence for the transition to the quantum chaotic regime in 1D atomic Bloch oscillations.
We study atomic Bloch oscillations in an ensemble of one-dimensional tilted superfluids in the Bose-Hubbard regime. For large values of the tilt, we observe interaction-induced coherent decay and matter-wave quantum phase revivals of the Bloch oscillating ensemble. We analyze the revival period dependence on interactions by means of a Feshbach resonance. When reducing the value of the tilt, we observe the disappearance of the quasiperiodic phase revival signature towards an irreversible decay of Bloch oscillations, indicating the transition from regular to quantum chaotic dynamics.


Appropriateness of bone density measurement in Switzerland: a cross-sectional study.
According to the WHO, osteoporosis is one of the most important non- communicable diseases worldwide. Different screening procedures are controversially discussed, especially concerning the concomitant issues of overdiagnosis and harm caused by inappropriate Dual X-ray Absorptiometry (DXA). The aim of this study was to evaluate the frequency and appropriateness of DXA as screening measure in Switzerland considering individual risk factors and to evaluate covariates independently associated with potentially inappropriate DXA screening. Retrospective cross-sectional study using insurance claim data of 2013. Among all patients with DXA screening, women < 65 and men < 70 years without osteoporosis or risk factors for osteoporosis were defined as receiving potentially inappropriate DXA. Statistics included descriptive measures and multivariable regressions to estimate associations of relevant covariates with potentially inappropriate DXA screening. Of 1,131,092 patients, 552,973 were eligible. Among those 2637 of 10,000 (26.4%) underwent potentially inappropriate DXA screening. Female sex (Odds ratio 6.47, CI 6.41-6.54) and higher age showed the strongest association with any DXA screening. Female gender (Odds ratio 1.84, CI 1.49-2.26) and an income among the highest 5% (Odds ratio 1.40, CI 1.01-1.98) were significantly positively associated with potentially inappropriate DXA screening, number of chronic conditions (Odds ratio 0.67, CI 0.65-0.70) and living in the central region of Switzerland (Odds ratio 0.67, CI 0.48-0.95) negatively. One out of four DXAs for screening purpose is potentially inappropriate. Stakeholders of osteoporosis screening campaigns should focus on providing more detailed information on appropriateness of DXA screening indications (e.g. age thresholds) in order to avoid DXA overuse.


Cloning and characterization of human papillomavirus type 52 from cervical carcinoma in Indonesia.
Human papillomavirus (HPV) type 52 from a cervical carcinoma in Indonesia was molecularly cloned and characterized. By hybridization with cervical carcinoma DNAs from Indonesian patients, HPV 52 was detected in 3 of 52 cases (6%), whereas HPV 16 and 18 were detected in 8 and 7 cases, respectively (15% and 13%). Sequence analysis revealed that the E6-E7 ORFs contained several DNA binding motifs (Cys-X-X-Cys) like previously sequenced HPVs. The E6 ORF also contained splice donor and acceptor signals, which may allow the expression of E6* protein. The E7 ORF encoded an amino acid sequence that is conserved in some DNA tumor viruses and is involved in binding to Rb protein and in cellular transformation. Transfection of a subgenomic fragment of HPV 52 under the control of a heterologous promoter showed that the E7 ORF alone induced anchorage-independent growth of established rodent cells and immortalized primary rat embryo fibroblasts (REF), and that in cooperation with activated ras, it induced malignant transformation of REF. The E6 ORF also induced, less efficiently, anchorage-independent growth. These results strongly suggest that HPV 52, like HPV 16 and 18, has oncogenic potential.


Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production.
One of the main challenges in gene therapy is the issue of delivery, and it is especially relevant for the success of gene therapy in the cornea. In the present work, eye drops containing biocompatible non-viral vectors based on solid lipid nanoparticles (SLNs) as gene delivery systems to induce the expression of interleukin 10 (IL-10) were designed to address the treatment of corneal inflammation. Two kinds of SLNs combined with different ligands (protamine, dextran, or hyaluronic acid (HA)) and formulated with polyvinyl alcohol (PVA) were prepared. SLN-based vectors were characterized in terms of size, adhesiveness, viscosity, and pH, before topical administration to wild type and IL-10 knock out (KO) mice. The formulations showed a homogenous particle size below 400 nm and a positive surface charge to favor bioadhesion; the incorporation of PVA improved the corneal penetration. After three days of treatment by topical instillation, SLN-based vectors mainly transfected corneal epithelial cells, HA-formulations being the most effective ones. IL-10 was capable of reaching even the endothelial layer. Corneal sections showed no histological change and formulations seemed to be well tolerated after repeated topical administration. These promising results highlight the possible contribution of non-viral gene augmentation therapy to the future clinical approach of corneal gene therapy.


Bibliometric analysis of adverse drug reactions and pharmacovigilance research activities in Nepal.
Bibliometric analyses have been used previously to study the measures of quality and impact of research performed in several health-related areas such as adverse drug reactions (ADRs) and pharmacovigilance (PV), etc. This method can assess the research performance of publications quantitatively and statistically. There is no evidence of bibilometric studies analyzing ADRs and PV from Nepal. Therefore, the present study aimed to assess scientific output on ADRs and PV-related research activities in Nepal using a bibliometric analysis of publications from 2004 January to December 2018, that is, 15 years. A systematic search was conducted in PubMed, Web of Science, Google Scholar, Scopus and Nepal Journal Online (NepJOL) databases. 'Adverse Drug Reactions' or 'ADRs' or 'ADR' or 'Adverse drug reaction' or 'AE' or 'Adverse Event' or 'Drug-Induced Reaction' or 'Pharmacovigilance' or 'PV' and 'Nepal'. The search covered 15 years (January 2004 to December 2018) of study on ADRs and PV in Nepal. Only articles retrieved from databases were included, whereas published/unpublished drug bulletins, pharmacy newsletters and thesis were excluded. The articles thus retrieved were recorded, and thereafter analyzed. Word count code was used for the analysis of keywords used in the retrieved articles. A total of 124 articles were retrieved, with the highest rate of publications in 2006 and 2007, with 16 papers each. Among the articles, 10 (8.1%) were published in Kathmandu University Medical Journal (KUMJ). Single papers were published in 38 different journals. Brief reports (1.6%), case reports (31.2%), case series (0.8%), education forums (0.8%), letters to the editor (5.6%), original research articles (41.9%), review articles (9.7%), short communications and short reports (8.1%) on ADRs and PV were recorded. Out of 124 papers, 52 (41.9%) were original research publications. The majority (74.1%) of research was done in the category of ADR incidence, types, prevention, and management, followed by policy and suggestions for strengthening national and regional pharmacovigilance centers of Nepal (14.5%). During the study years, there was an increase in scientific publications on drug safety. A total of 124 published articles were found during bibliometric analysis of ADRs and PV research activities in Nepal.


Critical adsorption on defects in ising magnets and binary alloys
Long-range correlations in a magnet close to its critical point or in a binary alloy close to a continuous order-disorder transition can substantially enhance the effect of local perturbations. It is demonstrated using a position-space renormalization procedure that quasi-one-dimensional defects which break the symmetry of the order parameter have pronounced effects: They cause long-range critical adsorption profiles and give rise to new universal critical exponents, which are identified and calculated using field-theoretical methods.


CD1b-autoreactive T cells contribute to hyperlipidemia-induced skin inflammation in mice.
A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that expresses human CD1b and CD1c molecules (hCD1Tg) as well as a CD1b-autoreactive TCR (HJ1Tg) in the ApoE-deficient background (hCD1Tg HJ1Tg Apoe-/- mice) to determine the role of CD1-autoreactive T cells in hyperlipidemia-associated inflammatory diseases. We found that hCD1Tg HJ1Tg Apoe-/- mice spontaneously developed psoriasiform skin inflammation characterized by T cell and neutrophil infiltration and a Th17-biased cytokine response. Anti-IL-17A treatment ameliorated skin inflammation in vivo. Additionally, phospholipids and cholesterol preferentially accumulated in diseased skin and these autoantigens directly activated CD1b-autoreactive HJ1 T cells. Furthermore, hyperlipidemic serum enhanced IL-6 secretion by CD1b+ DCs and increased IL-17A production by HJ1 T cells. In psoriatic patients, the frequency of CD1b-autoreactive T cells was increased compared with that in healthy controls. Thus, this study has demonstrated the pathogenic role of CD1b-autoreactive T cells under hyperlipidemic conditions in a mouse model of spontaneous skin inflammation. As a large proportion of psoriatic patients are dyslipidemic, this finding is of clinical significance and indicates that self-lipid-reactive T cells might serve as a possible link between hyperlipidemia and psoriasis.


Evidence for multiple sources of diamond from primitive chondrites.
Fine-grained diamonds, the most abundant form of circumstellar dust isolated from primitive meteorites, have elemental and isotopic characteristics that are dependent on the host meteorite type. Carbon isotopic compositions vary from -32 to -38 per mil, and nitrogen associated with the diamond changes in overall abundance by over a factor of four from 0.2 to 0.9 weight percent, between ordinary and CM2-type chondrites. Although the ratio of carbon to nitrogen evolves in a distinctive way during combustion of diamond separates, metamorphic degassing of nitrogen is not the main cause of the differences in nitrogen content. The data suggest that intrinsic differences must have been inherited by the diamonds at the time of their formation and that the diamonds were distributed heterogeneously in the solar nebula during condensation. However, the hypothesis that a distinct nitrogen carrier remains hidden within the diamond cannot be ruled out.


Arterial stiffness and asymptomatic intracranial large arterial stenosis and calcification in hypertensive chinese.
Intracranial large artery disease (ICLAD), such as stenosis and calcification, is common in Chinese patients with stroke. However, little is known about ICLAD and its association with large arterial stiffness in hypertensive patients. We recruited 270 (mean age 61.0 years, 45.6% male) untreated hypertensive patients without stroke from a community in Shanghai, China. ICLAD was detected by computerized tomographic angiography (CTA). Carotid-femoral pulse wave velocity (cf-PWV), office, and 24-h ambulatory pulse pressure (PP) as well as ambulatory arterial stiffness index (AASI) were determined as the measures of arterial stiffness. Among all participants, 26 (9.6%) had concurrent intracranial arterial stenosis and calcification, 11 (4.1%) stenosis only, and 71 (26.3%) calcifications only. After adjustment for age, mean arterial pressure, and other covariables, there was significant difference in cf-PWV (13.1 vs. 13.7 vs. 15.0 m/s; P = 0.0015) and 24-h PP (46.7 vs. 48.8 vs. 55.7 mm Hg; P = 0.0007) between patients with normal vessels (n = 162), with stenosis or calcification (n = 82), and with both lesions (n = 26). Multiple ordinal logistic regression analyses showed that both cf-PWV and 24-h PP were independently associated with ICLAD. Odds ratios (95% confidence interval (CI)) of ICLAD after multivariable and mutually adjustment were 1.51 (1.09-2.10) and 1.46 (1.06-2.01) for 1-s.d. increase in cf-PWV and 24-h PP, respectively. No significant association (P ≥ 0.10) with AASI or office PP was observed in multivariable analysis. Increased arterial stiffness was independently associated with ICLAD. cf-PWV and 24-h PP might be useful in identifying those more likely to have ICLAD among hypertensive patients.


Effects of transient, persistent, and resurgent sodium currents on excitability and spike regularity in vestibular ganglion neurons.
Vestibular afferent neurons occur as two populations, regular and irregular, that provide distinct information about head motions. Differences in spike timing regularity are correlated with the different sensory responses important for vestibular processing. Relative to irregular afferents, regular afferents have more sustained firing patterns in response to depolarizing current steps, are more excitable, and have different complements of ion channels. Models of vestibular regularity and excitability emphasize the influence of increased expression of low-voltage-activated potassium currents in irregular neurons. We investigated the potential impact of different modes of voltage-gated sodium (Na V ) current (transient, persistent, and resurgent) in cell bodies from vestibular ganglion neurons (VGNs), dissociated and cultured overnight. We hypothesized that regular VGNs would show the greatest impact of persistent (non-inactivating) Na V currents and of resurgent Na V currents, which flow when Na V channels are blocked and then unblocked. Whole-cell patch clamp experiments showed that much of the Na V current modes is carried by Na V 1.6 channels. With simulations, we detected little substantial effect in any model VGN of persistent or resurgent modes on regularity of spike timing driven by postsynaptic current trains. For simulated irregular neurons, we also saw little effect on spike rate or firing pattern. For simulated regular VGNs, adding resurgent current changed the detailed timing of spikes during a current step, while the small persistent conductance (less than10% of transient Na V conductance density) strongly depolarized resting potential, altered spike waveform, and increased spike rate. These results suggest that persistent and resurgent Na V current can have a greater effect on the regular VGNs than on irregular VGNs, where low-voltage-activated K conductances dominate.


Abnormal neural oscillatory activity to speech sounds in schizophrenia: a magnetoencephalography study.
Schizophrenia impairs many cognitive functions, and abnormalities in language processing have been proposed as one of the bases for this disorder. Previously, it was reported that different magnetoencephalography (MEG) patterns of the evoked oscillatory activity (eOA) of 20-45 Hz to speech and nonspeech sounds were evidence of a fast mechanism for the representation and identification of speech sounds in humans. The current study tested the hypothesis that the schizophrenics would show abnormal neural oscillatory activity, as measured by eOA, to speech and nonspeech sounds. Twenty patients and 23 control subjects participated in this study. MEG responses to speech and nonspeech sounds were recorded and eOA power and phase locking at 20-45 Hz were analyzed. Patients showed significantly delayed peak latencies of the eOA power and phase locking to speech sounds in the left hemisphere and to nonspeech sounds in the right hemisphere. Patients also showed a significantly reduced eOA power to speech sounds in the left hemisphere in 0-50 ms and a significantly larger eOA power to speech sounds in the left hemisphere in 100-150 ms. In addition, the analyses of the lateralization index revealed the pattern of hemispheric lateralization to be the opposite in patients. These results indicated that patients showed different characteristics of eOA compared with normal controls, probably related to deficits in a fast mechanism for identifying speech sounds. Moreover, the present study suggests that schizophrenia might be characterized by an opposite pattern of hemispheric lateralization in auditory evoked oscillations.


Chronic discrimination and bodily pain in a multiethnic cohort of midlife women in the Study of Women's Health Across the Nation.
A growing literature links discrimination to key markers of biobehavioral health. While racial or ethnic differences in pain are seen in experimental and clinical studies, the authors were interested in how chronic discrimination contributes to pain within multiple racial or ethnic groups over time. Participants were 3056 African American, Caucasian, Chinese, Hispanic, and Japanese women from the Study of Women's Health Across the Nation. The Everyday Discrimination Scale was assessed from baseline through 13 follow-up examinations. The bodily pain subscale of the MOS 36-Item Short-Form Health Survey (SF-36) was assessed annually. There were large racial or ethnic differences in reports of discrimination and pain. Discrimination attributions also varied by race or ethnicity. In linear mixed model analyses, initially adjusted for age, education, and pain medications, chronic everyday discrimination was associated with more bodily pain in all ethnic groups (beta = -5.84; P < 0.002 for Japanese; beta = -6.17; P < 0.001 for African American; beta = -8.74; P < 0.001 for Chinese; beta = -10.54; P < 0.001 for Caucasians; beta = -12.82; P < 0.001 for Hispanic). Associations remained significant in all ethnic groups after adjusting for additional covariates in subsequent models until adding depressive symptoms as covariate; in the final fully-adjusted models, discrimination remained a significant predictor of pain for African American (beta = -4.50; P < 0.001), Chinese (beta = -6.62; P < 0.001), and Caucasian (beta = -7.86; P < 0.001) women. In this longitudinal study, experiences of everyday discrimination were strongly linked to reports of bodily pain for the majority of women. Further research is needed to determine if addressing psychosocial stressors, such as discrimination, with patients can enhance clinical management of pain symptoms.


Treatment and outcomes in adolescents with schizophrenia.
The pharmacologic treatment and assessment of outcomes in adolescents with schizophrenia have been inadequately addressed. Structural brain imaging and brain function studies both point to a continuity between adolescent and adult stages of schizophrenia. Because the teenage population seems to be less tolerant of physical side effects, the advent of atypical antipsychotic medications may offer increased safety and efficacy. Studies support the notion that adolescent illness is associated with a more severe form of schizophrenia and that length of illness before treatment is correlated with long-term outcome. As a consequence, the authors recommend assertive pharmacologic intervention in adolescents with schizophrenia and future research focused on the issues of treatment and outcome in teenagers suffering a psychotic disorder.


Rice mill wastewater treatment in microbial fuel cells fabricated using proton exchange membrane and earthen pot at different pH.
Performance of microbial fuel cells (MFCs), fabricated using an earthen pot (MFC-1) and a proton exchange membrane (MFC-2), was evaluated while treating rice mill wastewater at feed pH of 8.0, 7.0 and 6.0. A third MFC (MFC-3), fabricated using a proton exchange membrane (PEM), was operated as control without pH adjustment of the acidic raw wastewater. Maximum chemical oxygen demand (COD) removal efficiencies of 96.5% and 92.6% were obtained in MFC-1 and MFC-2, respectively, at feed pH of 8.0. MFC-3 showed maximum COD removal of 87%. The lignin removal was 84%, 79%, and 77% and the phenol removal was 81%, 77%, and 76% in MFC-1, MFC-2, and MFC-3, respectively. Maximum sustainable volumetric power was obtained at feed pH of 8.0, and it was 2.3 W/m(3) and 0.53 W/m(3), with 100 ohm external resistance, in MFC-1 and MFC-2, respectively. The power was lower at lower feed pH. MFC-3 generated lowest volumetric power (0.27 W/m(3)) as compared to MFC-1 and MFC-2. More effective treatment of rice mill wastewater and higher energy recovery was demonstrated by earthen pot MFC as compared to MFC incorporated with PEM.


Cooperative Power-Domain NOMA Systems: An Overview.
Interference has been a key roadblock against the effectively deployment of applications for end-users in wireless networks including fifth-generation (5G) and beyond fifth-generation (B5G) networks. Protocols and standards for various communication types have been established and utilised by the community in the last few years. However, interference remains a key challenge, preventing end-users from receiving the quality of service (QoS) expected for many 5G applications. The increased need for better data rates and more exposure to multimedia information lead to a non-orthogonal multiple access (NOMA) scheme that aims to enhance spectral efficiency and link additional applications employing successive interference cancellation and superposition coding mechanisms. Recent work suggests that the NOMA scheme performs better when combined with suitable wireless technologies specifically by incorporating antenna diversity including massive multiple-input multiple-output architecture, data rate fairness, energy efficiency, cooperative relaying, beamforming and equalization, network coding, and space-time coding. In this paper, we discuss several cooperative NOMA systems operating under the decode-and-forward and amplify-and-forward protocols. The paper provides an overview of power-domain NOMA-based cooperative communication, and also provides an outlook of future research directions of this area.


Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study.
Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7-5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6-7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61-1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5-11·5] in the chemotherapy alone group and 9·5 months [7·6-11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69-1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3-4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7-7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1-4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53-1·00; p=0·049). Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. None.


The intention to get COVID-19 booster vaccination and its association with cognitive and emotional factors: A survey of Chinese COVID-19 infected people in Hong Kong.
Although the pandemic has ended officially, COVID-19 remains impactful. Booster COVID-19 vaccination is still needed to protect individuals against COVID-19 and the disease's harmful consequences. This study investigated the prevalence of the intention to get booster COVID-19 vaccination after receiving the COVID-19 diagnosis and its associated factors among people reporting prior COVID-19. A population-based anonymous telephone survey was conducted in Hong Kong, China from June to August 2022 among Chinese people reporting prior COVID-1 between February and August 2022 and having taken up ≥2 doses of COVID-19 vaccines prior to COVID-19 diagnosis. The prevalence of the intention to get booster vaccination was 59.2 %. Older age (>60 years), being currently married, not employed full-time, and having chronic diseases were positively associated with the intention to get booster vaccination. Adjusted for the background factors, higher levels of the cognitive factors of perceived susceptibility to COVID-19, perceived acquired moderate-to-strong immunity against COVID-19, and perceived adequate knowledge of COVID-19 were positively associated with the intention to get booster vaccination; stronger perceived severity of prior infection despite vaccination was negatively associated with the intention outcome. In contrast, stronger mental distress due to COVID-19, illness concern, and emotional representation were positively associated with the intention. Self-perceived long COVID status was not a significant factor. The prevalence of the intention to get booster COVID-19 vaccination was limited, especially among younger people reporting prior COVID-19. Health promotion is still required among people reporting prior COVID-19 and may emphasize the significant cognitive factors positively associated with the intention. Future studies are needed to confirm the findings, clarify the role of emotional factors on booster vaccination, and explore other factors of the intention to get booster vaccination among people reporting prior COVID-19.