Epidemiology of Sepsis Syndrome among Intensive Care Unit Patients at a Tertiary University Hospital in Palestine in 2019.
Sepsis syndrome is an emerging healthcare problem, especially in critically ill patients, regardless whether it's community- or hospital-acquired sepsis. This study evaluates the characteristics of these patients, in addition to the type, source, and outcome of sepsis and septic shock, in a university tertiary hospital in Palestine. It also studies the most common organisms encountered in these patients. This is retrospective observational chart review study of all adult admissions to the intensive care unit over a period of 2 years. The presence of sepsis and septic shock was assessed and documented based on the Third International Consensus Definitions (Sepsis-3). Data regarding demographics, severity, comorbidities, source of infection, microbiology, length of stay, and outcomes (dead/alive at discharge from ICU) were recorded. A total number of 174 patients were included. The mean age was 57.4 years, with cardiovascular diseases and diabetes being the leading comorbidities encountered in them. Respiratory infections were the most common site of sepsis, found in around 71% of patients, followed by urinary tract infections. More than 70% of cases were due to hospital-acquired infections (HAIs). Acinetobacter species were the most common gram-negative organisms encountered, while Enterococcus was the most common gram-positive organisms. Around 54% of patients had multidrug-resistant organisms. The average length of stay in the ICU was 8 days. The average mortality rate was 39.7%, which is higher among septic shock patients. Both sepsis and septic shock carry high morbidity and mortality rates, and they are very frequent among critically ill patients. Special care and developing management bundles are crucial in controlling and preventing this threat. Rabee HA, Tanbour R, Nazzal Z, Hamshari Y, Habash Y, Anaya A, et al. Epidemiology of Sepsis Syndrome among Intensive Care Unit Patients at a Tertiary University Hospital in Palestine in 2019. Indian J Crit Care Med 2020;24(7):551-556.


Saliency, switching, attention and control: a network model of insula function.
The insula is a brain structure implicated in disparate cognitive, affective, and regulatory functions, including interoceptive awareness, emotional responses, and empathic processes. While classically considered a limbic region, recent evidence from network analysis suggests a critical role for the insula, particularly the anterior division, in high-level cognitive control and attentional processes. The crucial insight and view we present here is of the anterior insula as an integral hub in mediating dynamic interactions between other large-scale brain networks involved in externally oriented attention and internally oriented or self-related cognition. The model we present postulates that the insula is sensitive to salient events, and that its core function is to mark such events for additional processing and initiate appropriate control signals. The anterior insula and the anterior cingulate cortex form a "salience network" that functions to segregate the most relevant among internal and extrapersonal stimuli in order to guide behavior. Within the framework of our network model, the disparate functions ascribed to the insula can be conceptualized by a few basic mechanisms: (1) bottom-up detection of salient events, (2) switching between other large-scale networks to facilitate access to attention and working memory resources when a salient event is detected, (3) interaction of the anterior and posterior insula to modulate autonomic reactivity to salient stimuli, and (4) strong functional coupling with the anterior cingulate cortex that facilitates rapid access to the motor system. In this manner, with the insula as its integral hub, the salience network assists target brain regions in the generation of appropriate behavioral responses to salient stimuli. We suggest that this framework provides a parsimonious account of insula function in neurotypical adults, and may provide novel insights into the neural basis of disorders of affective and social cognition.


Largely intact memory for spatial locations during navigation in an individual with dense amnesia.
Spatial navigation and event memory (termed episodic memory) are thought to be heavily intertwined, both in terms of their cognitive processes and underlying neural systems. Some theoretical models posit that both memory for places during navigation and episodic memory depend on highly overlapping brain systems. Here, we assessed this relationship by testing navigation in an individual with severe retrograde and anterograde amnesia; the amnesia stemmed from bilateral lesions in the medial temporal lobes from two separate strokes. The individual with amnesia and age-matched controls were tested on their memories for the locations of previously seen objects relative to distal mountain cues in an immersive virtual environment involving free ambulation. All participants were tested from both repeated and novel start locations and when a single distal mountain cue was unknowingly moved to determine if they relied on a single (beacon) cue to a greater extent than the collection of all distal cues. Compared to age-matched controls, the individual with amnesia showed no significant deficits in navigation from either the repeated or novel start points, although both the individual with amnesia and controls performed well above chance at placing objects near their correct locations. The individual with amnesia also relied on a combination of distal cues in a manner comparable to age-matched controls. Despite largely intact memory for locations using distal cues, the individual with amnesia walked longer paths, rotated more, and took longer to complete trials. Our findings suggest that memory for places during navigation and episodic memory may involve partially dissociable brain circuits and that other brain regions outside of the medial temporal lobe partially support some aspects of navigation. At the same time, the fact that the individual with amnesia walked more circuitous paths and had dense amnesia for autobiographic events supports the idea that the hippocampus may be important for binding information as part of a larger role in memory.


[Two-layer adhesive film Diplen-denta C--a new compound containing polymer base and active component Solcoseryl].
Characteristics of the main components of a new effective long-lasting dosage form--biopolymer two-layer adhesive solcoseryl containing film Diplen-denta C--are presented. It has a potent wound-healing action on oral mucosa, retains therapeutic properties during long time, is self dissolving and can be easily fixed on oral mucous membrane.


Factors associated with body mass index in children and adolescents: An international cross-sectional study.
The increasing prevalence of overweight and obesity in childhood has implications for their future health. There are many potential contributors to overweight and obesity in childhood. The aim was to investigate the association between postulated risk factors and body mass index (BMI) in children and adolescents. Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6-7 years completed a questionnaire about their child's current height and weight, and the postulated risk factors. Adolescents aged 13-14 years reported their own height and weight and answered questions about the postulated risk factors. A general linear mixed model was used to determine the association between BMI and the postulated risk factors. Imputation was used if there were missing responses for 3 or fewer explanatory variables. 65,721 children (27 centres, 15 countries) and 189,282 adolescents (70 centres, 35 countries) were included in the final analyses. Many statistically significant associations were identified, although for most variables the effect sizes were small. In children birth weight (for each kg increase in birth weight the BMI increased by +0.43 kg/m2, p<0.001), television viewing (5+ hours/day +0.33 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week +0.16 kg/m2 vs. never, p<0.001) vigorous physical activity (3+ hours/week 0.071 kg/m2 vs. never, p = 0.023) and maternal smoking in the first year of life (+0.13 kg/m2, p<0.001) were associated with a higher BMI in the adjusted model. Nut consumption (≥3 times/week -0.11 kg/m2 vs. never, p = 0.002) was associated with a lower BMI. Early life exposures (antibiotics, paracetamol and breast feeding) were also associated with BMI. For adolescents statistically significant associations with BMI and were seen with maternal smoking (+0.25 kg/m2, p<0.001), television viewing (5+ hours/day +0.23 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week -0.19 kg/m2 vs. never, p<0.001), vigorous physical activity (3+ hours/week 0.047 kg/m2 vs. never, p<0.001) and nuts (≥3 times/week -0.22 kg/m2 vs. never, p<0.001). Although several early life exposures were associated with small differences in BMI, most effect sizes were small. Larger effect sizes were seen with current maternal smoking, television viewing (both with higher BMI) and frequent nut consumption (lower BMI) in both children and adolescents, suggesting that current behaviours are more important than early exposures. Although many variables may influence BMI in childhood, the putative factors studied are not of sufficient magnitude to support major public health interventions.


Systematic review of orthoses for stroke-induced upper extremity deficits.
Background: Orthoses for individuals with stroke is considered an integral part of the neurorehabilitation process. However, there are no universal guidelines to determine the initiation period, duration, or type of orthosis for stroke patients. Objectives: For this study, we systematically reviewed the evidence surrounding the use of orthoses for stroke-related upper extremity deficits. Methods: Medical librarians searched MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Health Technology Assessment Database, Physiotherapy Evidence Database, and OTSeeker using subject headings and keywords related to upper extremities, orthoses, and stroke. The resulting articles were evaluated for inclusion by the systematic review team. Articles that met the inclusion criteria were appraised for content and quality using the "Evaluation Guidelines for Rating the Quality of an Intervention Study" (EQIS). Results: 14 studies were included, with the mean score of 31.29 (out of 48) for the EQIS using an ordinal scale with a range of 23-43.6 studies produced significant outcomes with effect sizes ranging from d = .52 (wrist flexion PROM) to d = 9.02 (patient satisfaction with orthosis). Conclusion: Future studies should aim to utilize homogenous outcome measures while exploring variability in dosage and level of upper extremity impairment upon initiation. Additionally, universal guidelines for initiation period, duration, and type of orthosis for patients post-stroke need to be established.


The population genetic structure of a large temperate pollinator species, Bombus pascuorum (Scopoli) (Hymenoptera: Apidae)
The genetic population structure of the bumble bee Bombus pascuorum was studied using six microsatellite loci and a partial sequence of the mitochondrial gene cytochrome b. Eighteen populations from central and northern Europe were included in the analysis. Observed levels of genetic variability and heterozygosity were high. Estimates of population differentiation based on F- and phi-statistics revealed significant genetic differentiation among B. pascuorum populations and suggest that two partially isolated gene pools, separated by the Alps, do exist. The distribution of mtDNA haplo-types supports this view and presents direct evidence for gene flow across the Alps. Estimates of the number of migrants exchanged among populations north of the Alps suggest that historical events may have left a strong imprint on population structure.


Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model.
Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model. A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis. Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P = .015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P = .022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14. This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant.


Comparative study of the hygienic behavior of Carniolan and Africanized honey bees directed towards grouped versus isolated dead brood cells.
In Apis mellifera, hygienic behavior involves recognition and removal of sick, damaged or dead brood from capped cells. We investigated whether bees react in the same way to grouped versus isolated damaged capped brood cells. Three colonies of wild-type Africanized honey bees and three colonies of Carniolan honey bees were used for this investigation. Capped worker brood cells aged 12 to 14 days old were perforated with the pin-killing method. After making holes in the brood cells, the combs were placed back into the hives; 24 h later the number of cleaned cells was recorded in areas with pin-killed and control brood cells. Four repetitions were made in each colony. Isolated cells were more frequently cleaned than grouped cells, though variance analysis showed no significant difference (P = 0.1421). Carniolan bees also were somewhat, though not significantly more hygienic than Africanized honey bees (P = 0.0840). We conclude that honey bees can detect and remove both isolated and grouped dead brood. The tendency towards greater hygienic efficiency directed towards grouped pin-killed brood may be a consequence of a greater concentration of volatiles emanating from the wounds in the dead pupae.


Control of midline glia development in the embryonic Drosophila CNS.
The midline glial cells are required for correct formation of the axonal pattern in the embryonic ventral nerve cord of Drosophila. Initially, six midline cells form an equivalence group with the capacity to develop as glial cells. By the end of embryonic development three to four cells are singled out as midline glial cells. Midline glia development occurs in two steps, both of which depend on the activation of the Drosophila EGF-receptor homolog and subsequent ras1/raf-mediated signal transduction. Nuclear targets of this signalling cascade are the ETS domain transcription factors pointedP2 and yan. In the midline glia pointedP2 in turn activates the transcription of argos, which encodes a diffusible negative regulator of EGF-receptor signalling.


The pH dependence of quantitative ristocetin-induced platelet aggregation: theoretical and practical implications-a new device for maintenance of platelet-rich plasma pH.
Quantitative ristocetin-induced platelet aggregation of normal platelet-rich plasma (PRP) decreased with time after PRP preparation. An increase in p H of the PRP with time proved to be responsible for this finding. Diffusion of CO2from the plasma is the prime determinant of the change in pH. Since a complex combination of factors influences CO2 diffusion (surface area-to-volume relationship, capping, mixing, etc.) The change in pH is variable with time. Thus, quantitative ristocetin aggregation should be pH controlled. A simple device for maintaining PRP pH constant by control of the ambient pCO2 was designed and found effective in keeping both pH and quantitative ristocetin aggregation constant over a prolonged period of time. It can be adapted for use in platelet aggregation studies employing other reagents. The pH dependence of ristocetin-induced platelet aggregation is consistent with other data supporting an elctrostatic interaction between the platelet, von Willebrand factor, and ristocetin. We favor a model wherein ristocetin neutralizes some of the platelet's negative change and permits the von Willebrand factor to bridge sites on separate platelets to induce agglutination.


Alzheimer's disease: pathological mechanisms and recent insights.
Amyloidopathies cause neurodegeneration in a substantial portion of the elderly population. Improvements in long term health care have made elderly individuals a large and growing demographic group, marking these diseases as a major public health concern. Alzheimer's Disease (AD) is the most studied form of neurodegenerative amyloidopathy. Although our understanding of AD is far from complete, several decades of research have advanced our knowledge to the point where it is conceivable that some form of disease modifying therapy may be available in the near future. These advances have been built on a strong mechanistic understanding of the disease from its underlying genetics, molecular biology and clinical pathology. Insights derived from the study of other neurodegenerative diseases, such as some forms of frontotemporal dementia, have been critical to this process. This knowledge has allowed researchers to construct animal models of the disease process that have paved the way towards the development of therapeutics. However, what was once thought to be a straightforward problem has evolved into a series of disappointing outcomes. Examination of pathways common to all neurodegenerative diseases, including the cellular mechanisms that clear misfolded proteins and their regulation, may be the best way to move forward.


Making financial uncertainty count: Unit-linked insurance, investment and the individualisation of financial risk in British life insurance.
While most scholarship in the sociology of insurance has focused on the making of insurance risk by investigating mechanisms of pooling and spreading, this article examines insurers' management of financial uncertainty. Based on a large corpus of written sources and 44 semi-structured oral history interviews, this article seeks to describe and explain a shift in how financial uncertainty is dealt with in British life insurance, away from traditional multipolar arrangements revolving around actuarial prudence and discretion, towards bipolar arrangements that rely on explicit risk quantification and the logic of risk-based capital to "individualise" financial risk. The article identifies two factors that were key in bringing about this shift: first, the competitive dynamics that unfolded with the emergence of challenger "unit-linked" insurers in the 1960s, and, second, changes in the professional ecology, as manifested by the changing relations between the actuarial profession and insurance supervisors.


Modulations in the light of the firefly.
Continuous light could be produced from the firefly by making it inhale vapours of ethyl acetate. Here we perform such a control experiment on the Indian species of the firefly Luciola praeusta Kiesenwetter 1874 (Coleoptera : Lampyridae : Luciolinae), and analyse the light in the microsecond time scale. The amplitude of the continuous train of triangular pulses is apparently altered in accordance with the instantaneous values of a hypothetical signal, which exhibits pulse amplitude modulation (PAM). In addition to sampling in amplitude, this scheme apparently provides sampling in time, representing pulse width modulation (PWM). A Fourier transform spectrum of this waveform shows the 'carrier' frequency and the accompanying 'side bands'.


The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context.
The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, DNA polymerase β [Polβ] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context. We constructed nucleosome core particles with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polβ and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees depending on the enzyme. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner. On the basis of the obtained and literature data, we suggest a hypothetical model of the contribution of PARP1 and PARP2 to BER.


Intrinsic Magnetic (EuIn)As Nanowire Shells with a Unique Crystal Structure.
In the pursuit of magneto-electronic systems nonstoichiometric magnetic elements commonly introduce disorder and enhance magnetic scattering. We demonstrate the growth of (EuIn)As shells, with a unique crystal structure comprised of a dense net of Eu inversion planes, over InAs and InAs1-xSbx core nanowires. This is imaged with atomic and elemental resolution which reveal a prismatic configuration of the Eu planes. The results are supported by molecular dynamics simulations. Local magnetic and susceptibility mappings show magnetic response in all nanowires, while a subset bearing a DC signal points to ferromagnetic order. These provide a mechanism for enhancing Zeeman responses, operational at zero applied magnetic field. Such properties suggest that the obtained structures can serve as a preferred platform for time-reversal symmetry broken one-dimensional states including intrinsic topological superconductivity.


An overview of cytidine deaminases.
Enzymes that deaminate cytidine to uridine play an important role in a variety of pathways from bacteria to man. Ancestral members of this family were able to deaminate cytidine only in a mononucleotide or nucleoside context. Recently, a family of enzymes has been discovered with the ability to deaminate cytidines on RNA or DNA. The first member of this new family is APOBEC1, which deaminates apolipoprotein B messenger RNA to generate a premature stop codon. APOBEC1 has the conserved active site motif found in Escherichia coli cytidine deaminase. In addition, APOBEC1 has a unique motif containing 2 phenylalanine residues and an insert of 4 amino acid residues across the active site motif. This motif is present in APOBEC family members including activation-induced cytidine deaminase (AID), APOBEC2, and APOBEC3A through APOBEC3G. AID is essential for initiating class-switch recombination, somatic hypermutation, and gene conversion. The APOBEC3 family is unique to primates. APOBEC3G is able to protect cells from human immunodeficiency virus and other viral infections. This function is not unique to APOBEC3G; other APOBEC3 family members also have this ability. Overexpression of enzymes in this family can cause cancer, suggesting that the genes for the APOBEC family of proteins are proto-oncogenes. Recent advances in the understanding of the mechanism of action of this family are summarized in this review.


Meaningful everyday life situations from the perspective of children born preterm: A photo-elicitation interview study with six-year-old children.
The aim of the study was to explore meaningful everyday life situations as perceived by six-year-old children born preterm. The study had a descriptive qualitative design with an inductive approach. Ten, six-year-old children born preterm, not diagnosed with any disabilities, participated. Data was collected by photo-elicitation interviews to stimulate and help the children to describe their meaningful everyday life situations. A qualitative content analysis according to Elo and Kyngäs was applied. The children's descriptions of meaningful everyday life situations can be understood as being in an active and dynamic process, representing the core category. The analysis resulted in three generic categories, as the children described the significance of having significant circumstances and doing things. The experiences the children gain when they do things create their desire for further development. The results reveal that children born preterm are able to reflect on and give detailed descriptions of situations of importance to them. The study suggests that if six-year-old children born preterm are given the opportunity to share their views they can take an active role e.g. in planning and carrying through of interventions by health care services.


A joint alignment and reconstruction algorithm for electron tomography to visualize in-depth cell-to-cell interactions.
Electron tomography allows one to obtain 3D reconstructions visualizing a tissue's ultrastructure from a series of 2D projection images. An inherent problem with this imaging technique is that its projection images contain unwanted shifts, which must be corrected for to achieve reliable reconstructions. Commonly, the projection images are aligned with each other by means of fiducial markers prior to the reconstruction procedure. In this work, we propose a joint alignment and reconstruction algorithm that iteratively solves for both the unknown reconstruction and the unintentional shift and does not require any fiducial markers. We evaluate the approach first on synthetic phantom data where the focus is not only on the reconstruction quality but more importantly on the shift correction. Subsequently, we apply the algorithm to healthy C57BL/6J mice and then compare it with non-obese diabetic (NOD) mice, with the aim of visualizing the attack of immune cells on pancreatic beta cells within type 1 diabetic mice at a more profound level through 3D analysis. We empirically demonstrate that the proposed algorithm is able to compute the shift with a remaining error at only the sub-pixel level and yields high-quality reconstructions for the limited-angle inverse problem. By decreasing labour and material costs, the algorithm facilitates further research directed towards investigating the immune system's attacks in pancreata of NOD mice for numerous samples at different stages of type 1 diabetes.


[Mechanism of action of glucose on L-asparaginase synthesis by Escherichia coli bacteria].
The synthesis of L-asparaginase in Escherichia coli W and E. coli K-12 was almost completely supressed if glucose was added at a concentration of 0.5 per cent to a growth medium. The level of L-asparaginase synthesis decreased by ca. 75 per cent as a result of cyamutations when the bacteria could not produce cyclo-3',5'-AMP (cAMP). Apparently, a decrease in the intracellular content of cAMP caused by glucose could not be the only factor inhibiting L-asparaginase synthesis. Lactate was found to stimulate L-asparaginase synthesis. Glucose caused the catabolite repression and catabolite inhibition of the components of a system involved in lactate transport. The inhibition of L-asparaginase synthesis by glucose seems to be due, at least partly, to the fact that it prevents the assimilation of lactate by the cells, as well as the utilization of some other compounds which stimulate synthesis of this enzyme.


Gastrooesophageal reflux disease in preterm infants: current management and diagnostic dilemmas.
Gastrooesophageal reflux disease (GORD) provides a diagnostic and therapeutic challenge to many neonatologists. Reflux of gastric contents is common in preterm infants but usually not pathological. GORD is frequently diagnosed despite the lack of a fully identified clinical syndrome and of a truly valid diagnostic test. Treatment modalities, for which there is little convincing evidence regarding efficacy, are commonly instigated for troublesome symptoms attributed to GORD. Diagnosis is so problematic in preterm infants that GORD is starting to be described as the clinical syndrome that responds to anti-reflux treatment. We discuss the dilemmas facing us when dealing with this condition, summarise the best available evidence regarding diagnosis and management, and use it to inform a suggested treatment pathway. We introduce the concept of a clinical scoring system to aid the diagnosis and monitoring of GORD in preterm infants and highlight areas where further research would be beneficial.


Socioeconomic and other predictors of colonoscopy preparation quality.
Suboptimal bowel preparation prior to colonoscopy is a common occurrence, with a deleterious impact on colonoscopy effectiveness. Established risk factors for suboptimal bowel preparation have been proposed, but social factors, such as socioeconomic status and marital status, have not been investigated. The aim of this study was to evaluate sociodemographic factors, including insurance status and marital status, as predictive of suboptimal preparation. We analyzed a database of 12,430 consecutive colonoscopies during a 28-month period at Columbia University Medical Center. We collected the following variables: age, gender, indication for colonoscopy, location (inpatient vs. outpatient), race, marital status, and Medicaid status. Preparation quality was recorded and dichotomized as optimal or suboptimal. We employed multivariate regression to determine independent risk factors for suboptimal bowel preparation. Among the 10,921 examinations in which bowel preparation was recorded, suboptimal preparation occurred in 34% of Medicaid patients versus 18% of non-Medicaid patients (P < 0.0001); this remained significant in the multivariate analysis (odds ratio (OR) 1.84, 95% CI 1.61-2.11). Married patients had decreased rates of suboptimal preparation (OR 0.89, 95% CI 0.80-0.98). Other variables associated with suboptimal preparation included increased age (OR per 10 years 1.09, 95% CI 1.05-1.14), male gender (OR 1.44, 95% CI 1.31-1.59), inpatient status (OR 1.51, 95% CI 1.26-1.80), and later time of day (OR 1.89, 95% CI 1.71-2.09). Unmarried status and Medicaid status are predictive of suboptimal bowel preparation. Future studies are warranted to identify how these social conditions predict bowel preparation quality and to implement interventions to optimize bowel preparation in vulnerable populations.


Political Philosophies and Positive Political Psychology: Inter-Disciplinary Framework for the Common Good.
This manuscript explores the relationship between positive psychology and political philosophy, revealing an inter-disciplinary approach that speaks to the concerns of the common good. Since positive psychology has been expanding its reach into social and political spheres, its relationship to philosophical arguments has been worthy of exploration. Positive psychology is associated with utilitarianism, and aspects of hedonic psychology. However, an alternative concept of eudaimonic well-being has enabled this psychology to have links to other political philosophies. Therefore, this manuscript provides an overview of contemporary political philosophies: first, it discusses the debate between liberalism and communitarianism, and secondly, it summarizes the subsequent developments of liberal perfectionism, capability approach, and deliberative democracy. Then, the configuration of these political philosophies is indicated by the figure of two axes of "individual/collective" and "ethical/non-ethical." The following section compiles the inter-relationships between the conceptions of citizenship, justice, and well-being, regarding the main political philosophies: egoism, utilitarianism, libertarianism, liberalism, communitarianism, and conservatism. Utilitarianism is associated with happiness, while liberalism and libertarianism rely on the concept of rights, which is almost equal to the idea of justice. Accordingly, utilitarianism is a philosophy of well-being, while liberalism and libertarianism are philosophies of justice. However, there is little connection between well-being and justice in these philosophies because the two kinds of philosophies are incompatible. The latter kind criticizes the former because the maximization of happiness can infringe on people's rights. Moreover, these philosophies do not particularly value citizenship. In contrast, communitarianism is intrinsically the political philosophy of citizenship most attuned to increasing well-being, and it can connect an idea of justice with well-being. The final part offers a framework to develop an inter-disciplinary collaboration. Positive psychology can provide the empirical basis of the two axes above concerning political philosophies. On the other hand, the correspondence makes the character of political philosophies clearer. While libertarianism and liberalism correspond to psychology as usual, utilitarianism and communitarianism correspond to positive psychology, and the latter can be regarded as positive political philosophies. This recognition leads to the interdisciplinary framework, enabling multi-disciplinary collaboration, including work with the social sciences, which could benefit the common good.


PET-Guided Surgery - High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours.
Positron emission tomography (PET) with 11C-labeled 5-hydroxytryptophane (5-HTP) is a sensitive technique to visualize neuroendocrine tumours (NETs), due to high intracellular uptake of amine-precursors like L-dihydroxyphenylalanine (L-DOPA) and 5-HTP. NETs are often small and difficult to localize in spite of overt clinical symptoms due to hormonal excess. In our study, 38 consecutive NET patients underwent 11C-5-HTP-PET and morphological imaging by CT within 12 weeks prior to surgery. Surgical, histopathological and 5-HTP PET findings were correlated. 11C-5-HTP-PET corresponded to the surgical findings in 31 cases, was false negative in six, and true negative in one case resulting in 83.8% sensitivity and 100% specificity. Positive predicted value was 100%. In 11 patients 11C-5-HTP-PET was the only imaging method applied to localize the tumour. Thus, we could demonstrate that functional imaging by 11C-5-HTP-PET in many cases adds vital preoperative diagnostic information and in more than every fourth patient was the only imaging method that will guide the surgeon in finding the NET-lesion. Although the present results demonstrates that 11C-5-HTP may be used as an universal NET tracer, the sensitivity to visualize benign insulinomas and non functioning pancreatic NETs was lower.


Misuse of drugs act 1971.
An attempt is made to explain the provisions of the Misuse of Drugs Act 1971 stressing, where possible, those portions of the Act which affect members of the medical profession.


GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons.
The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders.


[Microinvasive CT-controlled tumor therapy of soft tissue and skeletal metastases].
Micro-invasive CT-guided intratumoral therapy (MIC-ITT) when used in combination with sympathectomy can be an excellent palliative treatment with little impairment of the patient. Rapid as well as complete reduction of pain without systemic side effects can be achieved under local anesthesia in patients in advanced tumor stages by the direct instillation of 50 to 96% alcohol and/or a locally efficacious low toxic cytostatic (Mitoxantron) under CT guidance. CT enables not only exact puncture without injuring endangered structures but also a controlled application of medication. The interventions can be performed with special probes with a diameter of 18 to 25 G. The study population consisted of 145 patients who received a total of 434 treatments. Repeated micro invasive intratumoral treatment was performed on 110 patients with bone and soft tissue metastases (Group I, 335 single treatments) and on 35 patients with vertebral metastases (Group II, 109 single treatments). In all patients conventional therapeutic strategies had been exhausted or were no longer applicable on the basis of a reduced Karnofsky Index. Treatment was performed in combination with sympathetic neurolysis at the upper tumor pole in all cases. The maximum follow-up time was 30 months. Pain reduction was estimated on a visual analogic scale. In Group I up to time of death a pain reduction of 75% or better was achieved in 88 patients (80%). A reduction in tumor size concomitant with a stabilization of the tumor region could be shown in 25% in this group, no change in 62% and progression in 13%. In Group II a pain reduction greater than 75% was achieved in 84% as well as a reduction in tumor size (< 50%) in 18% of the patients. Necrotic zones could be shown in 27% and calcification of tumor area in 35%. No change in tumor size was found in 66% of the patients, progression in 16%. All treatments were free of complications. On the whole the results of this therapeutic approach are encouraging. In particular one aspect should be mentioned: with respect to palliative treatment the reduction of tumor size is not crucial. The decisive factor is the improvement in quality of life of the patient using an intervention which impairs the patient only minimally. Furthermore this micro invasive approach should always involve the combination of local tumor treatment with treatment or lysis of the autonomic sympathetic nervous system in tumor vicinity.(ABSTRACT TRUNCATED AT 400 WORDS)


Expanding harm reduction to include fentanyl urine testing: results from a pilot in rural British Columbia.
Harm reduction has been at the forefront of the response to the opioid overdose public health emergency in British Columbia (BC). The unprecedented number of opioid overdose deaths in the province calls for an expansion of harm reduction services. The purpose of this study was to determine the acceptability of a fentanyl urine drug test among people who use drugs (PWUD) and explore whether testing introduced any changes in participants' attitudes and behaviors towards their drug use. A pilot of fentanyl urine testing was implemented in partnership with an outreach harm reduction program in rural BC. Participants were PWUD who had consumed within the last 3 days prior to the test. Participants filled out a semi-structured questionnaire at the time of the test and were invited for a follow-up interview 2 to 4 weeks after the test. Urine samples were tested with BNTX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/ml norfentanyl. Of the 24 participants who completed the urine test and first interview, 4 had a positive fentanyl urine test. Fifteen clients completed the second questionnaire, 10 of whom reported introducing a behavior change after testing and the remaining 5 indicated being already engaged in harm reduction practices. All four clients who tested positive completed the second questionnaire; all but one indicated adopting behaviors towards overdose prevention. Fentanyl urine testing appealed to illicit opioid users and may have contributed to adopting behaviors towards safer drug use. A relationship of trust between tester and client seemed important for clients who expressed concerns with privacy of the urine test results. Post-consumption urine testing could complement the use of pre-consumption drug checking in the context of harm reduction services.


A management model for Hospital Hygiene Unit: evidence-based proactive surveillance of potential environmental sources of infection in order to prevent patient's risk.
The aim of this study is to describe a proactive surveillance system of food, water and environmental surfaces, in order to avoid Healthcare-Associated Infections (HAIs) from hospital environment. It is a retrospective descriptive study. The surveillance system consists of two integrated phases: pre-analytic and post-analytic. The activities are distinguished in ordinary control activities, performed after scheduled and shared surveys, and compliance activities, performed when it is necessary to establish the adequacy of the destination use, for example opening a new ward. A total of 1,470 Samples were collected and 539 Reports were generated across the five-year study period. Water for human consumption procedure: a statistically significant trend was found only in the total number of Samples collected (p < 0.001). Legionella spp. infection water risk procedure: all Samples and Reports, with the exception of Compliance Report Samples, showed a statistically significant trend (p < 0.001). Pseudomonas aeruginosa water risk procedure: only Ordinary Reports and Compliance Report Samples trend were statistically significant (p = 0.002 and p = 0.028 respectively). Effectiveness of surface sanitization procedure: no trend was statistically significant (p < 0.05). Hospital catering and food surfaces procedure: Samples and Reports yearly number was constant, no trend analysis was performed. HAIs prevalence was never over 5% in the hospital under study. This surveillance system of water, food and environmental surfaces represents an innovative way of approaching hospital safety for patients and personnel because it overcomes the limitations due to a classic approach limited to a laboratory analytic phase only, according to the best available scientific evidence.


Efficacy of Continuous-Wave Transscleral Cyclophotocoagulation Post-Pars Plana Vitrectomy in Glaucoma Patients: A Retrospective Study from Poland.
BACKGROUND Glaucoma, a vision-threatening condition, results from optic nerve damage and affects millions of people worldwide. Often asymptomatic, it is hereditary, with risk factors like hypertension, diabetes, and steroid use. Despite its link with intraocular pressure (IOP), not everyone with high IOP develops glaucoma. After pars plana vitrectomy (PPV), patients face increased IOP risks. Traditional treatment includes pharmacotherapy, and, when ineffective, surgical interventions. Continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) is an alternative for refractory glaucoma but can have complications. Our study compares the efficacy and safety of CW-TSCPC after PPV. MATERIAL AND METHODS The study group consisted of 18 patients diagnosed with glaucoma who underwent the CW-TSCP procedure as the first-choice therapy after conservative treatment of glaucoma proved ineffective. The comparison group consisted of 12 patients who underwent the CW-TSCP procedure after conservative drug treatment and in whom surgical treatment of glaucoma had been unsuccessful. All patients had inadequate control of IOP after PPV. RESULTS Study and comparison group patients showed a decrease in IOP during the follow-up, independent of the type of endotamponade used (P<0.05). When the indication for PPV was retinal detachment hemorrhage into the vitreous chamber, a significant decrease in IOP between 0 days and 180 days was only found in the study group (P<0.05). In contrast, when the indication for PPV was the state after uveitis or proliferative diabetic retinopathy, a significant decrease in IOP was found at 180 days in the study and comparison groups (P<0.05). CONCLUSIONS The analysis showed that the CW-TSCPC procedure can be recommended as the first-choice invasive treatment in patients with increased IOP after PPV.


Detection of NG,NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody.
Two endogenous inhibitors of nitric oxide synthesis, NG-monomethylarginine (MMA) and NG,NG-dimethylarginine (DMA), are broken down by NG,NG-dimethylarginine dimethylaminohydrolase (DDAH) [EC 18.104.22.168]. This enzymatic activity is widely distributed in rat tissues, and is correlated with the distribution of free MMA and DMA, and the production of nitric oxide. In this study, immunoblotting analyses with a monoclonal antibody directed towards rat kidney DDAH showed that immunoreactive proteins exist in human pancreas, kidney, and liver. Enzyme activity was definitely detected in these tissues, but the specific activity was lower than that in the corresponding rat tissue. These results are interesting in connection with the idea that the enzyme might play a role as a regulator of nitric oxide generation in human tissues.


Engineered human Diamond-Blackfan anemia disease model confirms therapeutic effects of clinically applicable lentiviral vector at single-cell resolution.
Diamond-Blackfan anemia is a rare genetic bone marrow failure disorder which is usually caused by mutations in ribosomal protein genes. In the present study, we generated a traceable RPS19-deficient cell model using CRISPR-Cas9 and homology-directed repair to investigate the therapeutic effects of a clinically applicable lentiviral vector at single-cell resolution. We developed a gentle nanostraw delivery platform to edit the RPS19 gene in primary human cord bloodderived CD34+ hematopoietic stem and progenitor cells. The edited cells showed expected impaired erythroid differentiation phenotype, and a specific erythroid progenitor with abnormal cell cycle status accompanied by enrichment of TNFα/NF-κB and p53 signaling pathways was identified by single-cell RNA sequencing analysis. The therapeutic vector could rescue the abnormal erythropoiesis by activating cell cycle-related signaling pathways and promoted red blood cell production. Overall, these results establish nanostraws as a gentle option for CRISPR-Cas9- based gene editing in sensitive primary hematopoietic stem and progenitor cells, and provide support for future clinical investigations of the lentiviral gene therapy strategy.


Anatomy education in a changing medical curriculum.
How we educate students in the first two years of medical school is changing at many institutions. Effective medical education should be viewed as a continuum, integration of the basic sciences and clinical medicine should occur throughout the curriculum, and self-directed, life-long learning should be emphasized. Curricular revision may be appropriate if these fundamental concepts are absent. The principles of three curricular models are discussed: traditional, problem-based, and systems-oriented. The ideal curriculum may draw from each of these: A truly integrated curriculum. However, the curricular model chosen must meet the needs of the institution and its students. As anatomists we should not shy away from this process of change. With progressive educational approaches, we can be leaders in this climate of curricular reform. Anatomy courses are laboratory based and the laboratory is an outstanding small group, faculty/student interactive opportunity. However, we must show flexibility and innovation in our educational approaches whatever the curricular design being proposed.


Treatment of non union of humerus using G. A. Ilizarov technique.
The management of the non union of humerus is one of the most challenging problems that the surgeon confronts in his practice. The procedures traditionally used are: I.M. Nailing, interlocking, plating, transplantation of allograft. In our series, 36 cases with non union has been treated by G.A. Ilizarov technique. The age range were: 21-62 years with an average of 32 years. The initial treatment were done by DCP, rush nails & plates with screw fixation. The duration of treatment ranged from 5-11 months (average 8 months). With the application of Ilizarov fixator a good range of elbow & shoulder motion were achieved. The average follow up period was 5 years with a range of 1-8 years. Union was achieved in all the 36 cases.


Between and within-woman differences in the association between menstruation and migraine days.
To investigate between and within-woman differences in the association between menstruation and migraine days. Prior diary studies have shown that at the population level, aggregating across individuals, the odds of migraine increase during the perimenstrual window (from day -2 to day +3, where +1 is the first day of bleeding). These studies have been neither long nor large enough to assess the association between migraine and menses from an individual perspective. Consequently, existing research on menstrual-related migraine has largely overlooked between and within-woman variation that is critical for progressing clinical understanding and practice. Intensive longitudinal data for the current study were collected in a digital platform (N1-Headache® ) that tracks individual migraine-related factors daily. Participants for the current study were actively menstruating adult (18+ years old) women who used the platform. Two variables were of primary interest, migraine day (no/yes) and menstrual status (inside or outside the 5-day perimenstrual window). The sample consisted of 203 women with a mean age of 35.6 (SD = 8.7) years. At baseline, the women reported an average of 30.6 (SD = 23.6) headache days over the last 3 months. Analyses were based on a total of 53,302 days (median of 150 per person), 18,520 of which were migraine days (median of 44 per person), and a total of 2,126 menstrual cycles (median of 7 per person). Results showed that the 5-day perimenstrual window was associated with a 34% increase in odds of a migraine day compared to other days (OR = 1.34, 95% CI: 1.23-1.45, p < 0.0001). Importantly, there was between and within-woman variability in the association between menses and migraine days (between-woman variability: p = 0.002; within-woman [between-cycles] variability: p < 0.0001). Exploration of these individual differences demonstrated that relationship between menses and migraine days varied more within-person across cycles than between women. This study supports previous research and demonstrates that the odds of migraine days are elevated from day -2 to day +3 of the menstrual cycle. We also show that the effect of menses on migraine days varies more within-woman than between-women. This work provides an initial foundation for better understanding menstrual-related migraine from the perspective of the individual patient.


Regional variation in the incidence of hip fracture in New Zealand.
To determine the regional incidence of hip fracture among individuals aged 60 years or older in New Zealand. New Zealand Health Information Service inpatient morbidity data for the years 1988-92 were examined by area health board region to identify all hip fractures (ICD N820) among individuals aged 60 years or older. Substantial regional variation exists in the incidence of hip fractures among older people in New Zealand. Among both men and women, similar regional variations were observed with the age-standardised rates being consistently highest in the West Coast (790 per 100,000 for women and 360 per 100,000 in men) and lowest in Northland (540 per 100,000 in women and 185 per 100,000 in men). These findings have implications for resource allocation, both in terms of targeting prevention initiatives and in providing acute and long term management of hip fracture patients. In addition, they raise questions as to why such variations in hip fracture incidence exist in New Zealand.


Admission and mid-stay MedisGroups scores as predictors of hospitalization charges.
This study examines the ability of MedisGroups, a severity measure based on clinical data abstracted from the medical record, to predict hospitalization charges. MedisGroups measures severity both on admission and approximately 1 week into the hospital stay. The data base contained 23,361 admissions of Medicare beneficiaries in six conditions from 836 hospitals in seven states between January 1985, and May 1986. In all six conditions, higher admission and mid-stay severity scores were generally associated with higher charges. Across the six conditions, the R2 values for predicting charges using diagnosis-related group (DRG) class ranged from 0.06 to 0.32 using trimmed data. Adding admission MedisGroups scores to DRG class produced R2 values ranging from 0.09 to 0.33, while adding mid-stay scores yielded R2 values from 0.15 to 0.41, and adding both admission and mid-stay scores produced R2 levels ranging from 0.17 to 0.42. Very little of the superior predictive power of the mid-stay score could be attributed to its serving as a proxy for length of stay.


Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes.
Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene expression, protein content and biodistribution.


Ionizing radiation induces caspase-dependent but Chk2- and p53-independent cell death in Drosophila melanogaster.
Ionizing radiation (IR) can induce apoptosis via p53, which is the most commonly mutated gene in human cancers. Loss of p53, however, can render cancer cells refractory to therapeutic effects of IR. Alternate p53-independent pathways exist but are not as well understood as p53-dependent apoptosis. Studies of how IR induces p53-independent cell death could benefit from the existence of a genetically tractable model. In Drosophila melanogaster, IR induces apoptosis in the imaginal discs of larvae, typically assayed at 4-6 hr after exposure to a LD(50) dose. In mutants of Drosophila Chk2 or p53 homologs, apoptosis is severely diminished in these assays, leading to the widely held belief that IR-induced apoptosis depends on these genes in Drosophila. In this article, we show that IR-induced apoptosis still occurs in the imaginal discs of chk2 and p53 mutant larvae, albeit with a delay. We demonstrate that this phenomenon is a true apoptotic response because it requires caspase activity and the chromosomal locus that encodes the pro-apoptotic genes reaper, hid, and grim. We also show that Chk2- and p53-independent apoptosis is IR dose-dependent and is therefore probably triggered by a DNA damage signal. We conclude that Drosophila has Chk2- and p53-independent pathways to activate caspases and induce apoptosis in response to IR. This work establishes Drosophila as a model for p53-independent apoptosis, which is of potential therapeutic importance for inducing cell death in p53-deficient cancer cells.


Ion recombination corrections for the NACP parallel-plate chamber in a pulsed electron beam.
The NACP electron chamber is one of three parallel-plate chambers recommended for use in the UK. Measurements with this chamber type have indicated a problem in determining the recombination correction. This is due to a variation of the ionization current I with polarizing voltage V which deviates from the accepted Boag theory. It is shown that there is a chamber-dependent threshold voltage below which the NACP chamber follows the Boag theory. Above this voltage the chamber should be used with caution, although it is still possible to correct for the dependence of the chamber response on the dose per pulse. The existence of such deviations from theory demonstrates the usefulness of the 1/I against 1/V plot and the limitations of the Boag two-voltage analysis. Values for the initial recombination and the coefficient of general recombination are measured for several NACP chambers. It is shown that from these one can derive a value for the effective plate separation and the collector radius of each chamber. Differences in the behaviour of NACP chambers manufactured by Scanditronix and Dosetek are discussed and the implications of free-electron collection are considered.


Innovation in sexually transmitted disease and HIV prevention: internet and mobile phone delivery vehicles for global diffusion.
Efficacious behavioral interventions and practices have not been universally accepted, adopted, or diffused by policy makers, administrators, providers, advocates, or consumers. Biomedical innovations for sexually transmitted disease (STD) and HIV prevention have been embraced but their effectiveness is hindered by behavioral factors. Behavioral interventions are required to support providers and consumers for adoption and diffusion of biomedical innovations, protocol adherence, and sustained prevention for other STDs. Information and communication technology such as the Internet and mobile phones can deliver behavioral components for STD/HIV prevention and care to more people at less cost. Recent innovations in STD/HIV prevention with information and communication technology-mediated behavioral supports include STD/HIV testing and partner interventions, behavioral interventions, self-management, and provider care. Computer-based and Internet-based behavioral STD/HIV interventions have demonstrated efficacy comparable to face-to-face interventions. Mobile phone STD/HIV interventions using text-messaging are being broadly utilized but more work is needed to demonstrate efficacy. Electronic health records and care management systems can improve care, but interventions are needed to support adoption. Information and communication technology is rapidly diffusing globally. Over the next 5-10 years smart-phones will be broadly disseminated, connecting billions of people to the Internet and enabling lower cost, highly engaging, and ubiquitous STD/HIV prevention and treatment support interventions.


Association between parent-infant interactions in infancy and disruptive behaviour disorders at age seven: a nested, case-control ALSPAC study.
Effective early intervention to prevent oppositional/conduct disorders requires early identification of children at risk. Patterns of parent-child interaction may predict oppositional/conduct disorders but large community-based prospective studies are needed to evaluate this possibility. We sought to examine whether the Mellow Parenting Observational System (MPOS) used to assess parent-infant interactions at one year was associated with psychopathology at age 7. The MPOS assesses positive and negative interactions between parent and child. It examines six dimensions: anticipation of child's needs, responsiveness, autonomy, cooperation, containment of child distress, and control/conflict; these are summed to produce measures of total positive and negative interactions. We examined videos from the Avon Longitudinal Study of Parents and Children (ALSPAC) sub-cohort who attended the 'Children in Focus' clinic at one year of age. Our sample comprised 180 videos of parent-infant interaction: 60 from infants who received a psychiatric diagnostic categorisation at seven years and 120 randomly selected controls who were group-matched on sex. A negative association between positive interactions and oppositional/conduct disorders was found. With the exception of pervasive developmental disorders (autism), an increase of one positive interaction per minute predicted a 15% (95% CI: 4% to 26%) reduction in the odds of the infant being case diagnosed. There was no statistically significant relationship between negative parenting interactions and oppositional/conduct disorders, although negative interactions were rarely observed in this setting. The Mellow Parenting Observation System, specifically low scores for positive parenting interactions (such as Responsiveness which encompasses parental warmth towards the infant), predicted later psychiatric diagnostic categorisation of oppositional/conduct disorders.


Ursolic Acid, a Novel Liver X Receptor α (LXRα) Antagonist Inhibiting Ligand-Induced Nonalcoholic Fatty Liver and Drug-Induced Lipogenesis.
Nonalcoholic fatty liver disease (NAFLD) is a very common liver disease, and its incidence has significantly increased worldwide. The liver X receptor α (LXRα) is a multifunctional nuclear receptor that controls lipid homeostasis. Inhibition of LXRα transactivation may be beneficial for NAFLD and hyperlipidemia treatment. Ursolic acid (UA) is a plant triterpenoid with many beneficial effects; however, the mechanism of its action on LXRα remains elusive. We evaluated the effects of UA on T0901317 (T090)-induced LXRα activation and steatosis. UA significantly decreased the LXR response element and sterol regulatory element-binding protein-1c ( SREBP-1c) gene promoter activities, mRNA, protein expression of LXRα target genes, and hepatic cellular lipid content in a T090-induced mouse model. A molecular docking study indicated that UA bound competitively with T090 at the LXRα ligand binding domain. UA stimulated AMP-activated protein kinase (AMPK) phosphorylation in hepatic cells and increased corepressor, small heterodimer partner-interacting leucine zipper protein (SMILE) but decreased coactivator, steroid receptor coactivator-1 (SRC-1) recruitment to the SREBP-1c promoter region. In contrast, UA induced SRC-1 binding but decreased SMILE binding to reverse cholesterol transport-related gene promoters in intestinal cells, increasing lipid excretion from intestinal cells. Additionally, UA reduced valproate-induced LXRα mediated and rifampin-induced pregnane X receptor mediated lipogenesis, offering potential treatments for drug-induced hepatic steatosis. Thus, UA displays liver specificity and can be selectively repressed while RCT stimulation by LXRα is preserved and enhanced. This is a novel therapeutic option to treat NAFLD and may be helpful in developing LXR agonists to prevent atherosclerosis.


[The role of government in the control of technology research and development].
It is obvious that government cannot afford to refuse support to precommercial general research and development because they would thus deprive their national industry of a very important source. The new administration of President Clinton emphasized particularly the role of the government in the control of technological research and development. The United States wil in future not rely on the action of market forces in the commercialization of new innovating technologies and shy away from their responsibility. In a recent document Technology for America's Economic Growth President Clinton said: "Investing in technology is investing into America's future. The traditional support of basic science and defence-oriented research only was a strategy suited for previous generations, but not for coping with the complicated problems of today. Therefore we must focus attention on these new and difficult tasks, being aware that the Government can play a key role in the help given to private firms with their innovation."


A Behavioral and Biological Analysis of Aesthetics: Implications for Research and Applications.
Seeking to identify the common and distinguishing attributes of effects one might call "aesthetic," I examined hundreds of examples in music, visual arts, poetry, literature, humor, performance arts, architecture, science, mathematics, games, and other disciplines. I observed that all involve quasi-emotional reactions to stimuli that are composites of multiple elements that ordinarily do not occur together and whose interaction, when appropriately potentiated, is transformative-different in kind from the effects of the separate constituent elements. Such effects, termed synergetic, can evoke surprise-tinged emotional responses. Aesthetic reactions, unlike many other kinds of emotional reactions, are never evoked by biologically urgent action-demanding events, such as threats or opportunities. The examined effects were created by various concept manipulation devices: class expansion, identification of new relations, repetition, symmetry, parsimony, and emotional displays for the audience to mirror (I identified a total of 16 such devices). The effects would occur only for individuals with the necessary priming, in circumstances that include effective potentiating factors. Synergetic stimuli that evoke aesthetic responses tend to be reinforcing, via mechanisms related to their biological utility during our evolution. I offer a theory as to how aesthetics may have evolved from its primordial pre-aesthetic roots, with examples of how consideration of those roots often explains aesthetic and related effects. The article suggests that aesthetic phenomena are a special case of a more pervasive aspect of behavior and proposes research approaches involving laboratory models and fMRI technology.


Thiopurines in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring and clinical recommendations.
There is a growing interest in the use of thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) for the management of inflammatory bowel disease. The genetically controlled thiopurine (S)-methyltransferase enzyme is involved in the metabolism of these agents and is hypothesised to determine the clinical response to thiopurines. Diminished activity of this enzyme decreases the methylation of thiopurines, theoretically resulting in potential overdosing, while high thiopurine (S)-methyltransferase status leads to overproduction of toxic metabolites and ineffectiveness of azathioprine and 6-mercaptopurine. In practice, controversies exist regarding the utility of standard thiopurine (S)-methyltransferase pheno- and genotyping. Current pharmacogenetic insights suggest that another enzyme system may participate in the efficacy and toxicity of thiopurines; inosine triphosphate pyrophosphatase. Other topics discussed in this review are the utilisation of therapeutic drug monitoring and the experimental use of 6-thioguanine in the treatment of inflammatory bowel disease. 6-Thioguanine has a less genetically controlled metabolism and skips genetically determined metabolic steps. On theoretical basis, 6-thioguanine might therefore have a more predictable profile than azathioprine and 6-mercaptopurine. However, the use of 6-thioguanine has been associated with an increased risk of nodular regenerative hyperplasia of the liver and veno-occlusive disease. Further research is warranted before 6-thioguanine can be considered as a treatment option for inflammatory bowel disease.


Imaging addiction with PET: is insight in sight?
Neurochemical imaging studies can identify molecular targets of abused drugs and link them to the underlying pathology associated with behaviors such as drug dependence, addiction and withdrawal. positron emission tomography (PET) is opening new avenues for the investigation of the neurochemical disturbances underlying drug abuse and addiction and the in vivo mechanisms by which medications might ameliorate these conditions. PET can identify vulnerable human populations, treatment strategies and monitor treatment efficacy. Thus, with this tool and the knowledge it provides, the potential for developing novel drugs and treatment strategies for drug addiction is now close at hand.


A hedgehog survival pathway in 'undead' lipotoxic hepatocytes.
Ballooned hepatocytes in non-alcoholic steatohepatitis (NASH) generate sonic hedgehog (SHH). This observation is consistent with a cellular phenotype in which the cell death program has been initiated but cannot be executed. Our aim was to determine whether ballooned hepatocytes have potentially disabled the cell death execution machinery, and if so, can their functional biology be modeled in vitro. Immunohistochemistry was performed on human NASH specimens. In vitro studies were performed using HuH-7 cells with shRNA targeted knockdown of caspase 9 (shC9 cells) or primary hepatocytes from caspase 3(-/-) mice. Ballooned hepatocytes in NASH display diminished expression of caspase 9. This phenotype was modeled using shC9 cells; these cells were resistant to lipoapoptosis by palmitate (PA) or lysophosphatidylcholine (LPC) despite lipid droplet formation. During lipid loading by either PA or LPC, shC9 cells activate JNK which induces SHH expression via AP-1. An autocrine hedgehog survival signaling pathway was further delineated in both shC9 and caspase 3(-/-) cells during lipotoxic stress. Ballooned hepatocytes in NASH downregulate caspase 9, a pivotal caspase executing the mitochondrial pathway of apoptosis. Hepatocytes engineered to reduce caspase 9 expression are resistant to lipoapoptosis, in part, due to a hedgehog autocrine survival signaling pathway.


Beta subunit phosphorylation selectively increases fast desensitization and prolongs deactivation of alpha1beta1gamma2L and alpha1beta3gamma2L GABA(A) receptor currents.
We studied the effects of phosphorylation by protein kinase A (PKA) on GABA(A) receptors (alpha1beta1gamma2L andalpha1beta3gamma2L) transiently expressed in HEK 293T cells. Under conditions favorable for PKA activation, currents obtained using whole-cell patch clamp of lifted cells displayed increased rate and extent of the fast phases of desensitization, decreased rate of current deactivation after GABA removal, and prolongation of brief IPSC-like currents. Mutation of serine residues (beta1 S409, beta3 S407, beta3 S408) revealed that only beta1 S409 and beta3 S408 were critical for the modulatory effect of PKA on GABA(A) receptor currents. Additionally, repeated pulse inhibition was increased in receptors after mutation of the critical serine to glutamate and decreased when the serine was mutated to alanine. These data demonstrate that PKA phosphorylation modulated GABA(A) receptor currents by increasing fast phases of macroscopic desensitization and suggest a role for PKA in regulating GABAergic IPSC duration.


Diffusion tensor imaging predicts motor outcome in children with acquired brain injury.
Rehabilitation in children with acquired brain injury is a challenging endeavour. There is a large variability in motor recovery between patients, and a need to optimize therapies by exploiting cerebral plasticity and recovery mechanisms. This retrospective study aims to identify tract-based markers that could serve as predictors of functional outcome following rehabilitation. Twenty-nine children with traumatic brain injury (n = 14) or stroke (n = 15) underwent a 3 T Magnetic Resonance Imaging (MRI) measurement, including Diffusion Tensor Imaging (DTI) between admission to the Hospital and onset of rehabilitation therapy at the Rehabilitation Centre. The Functional Independence Measure for Children (WeeFIM) was routinely applied at admission and discharge from the Rehabilitation Centre. Distinguishing between children with good versus poor functional independence was performed using ROC-analysis. A non-parametric partial correlation analysis between the DTI and WeeFIM motor scores was performed with age, time in rehabilitation, and time of MRI scan after injury as covariates. Mean fractional anisotropy (FA) from the DTI in the ipsilesional corticospinal-tract provided the highest predictive accuracy (sensitivity = 95 %, specificity = 78 %, Youden Index = 0.73, Area under the curve = 0.9), in comparison to the lesion volume or other clinical variables. Mean FA of the ipsilesional corticospinal-tract correlated positively with the WeeFIM discharge motor scores (ρ = 0.547, p = 0.004). Prediction was poorer for the lesion volume or Glasgow Coma Scale. The results suggest that DTI data could improve the prediction of functional outcome after rehabilitation in children and adolescents with stroke or traumatic brain injury. Specifically, mean FA shows the highest predictive accuracy in comparison to lesion volume or clinical scales.


A study on the contribution of body vibrations to the vibratory sensation induced by high-level, complex low-frequency noise.
To investigate the contribution of body vibrations to the vibratory sensation induced by high-level, complex low-frequency noise, we conducted two experiments. In Experiment 1, eight male subjects were exposed to seven types of low-frequency noise stimuli: two pure tones [a 31.5-Hz, 100-dB(SPL) tone and a 50-Hz, 100-dB(SPL) tone] and five complex noises composed of the pure tones. For the complex noise stimuli, the sound pressure level of one tonal component was 100 dB(SPL) and that of another one was either 90, 95, or 100 dB(SPL). Vibration induced on the body surface was measured at five locations, and the correlation with the subjective rating of the vibratory sensation at each site of measurement was examined. In Experiment 2, the correlation between the body surface vibration and the vibratory sensation was similarly examined using seven types of noise stimuli composed of a 25-Hz tone and a 50-Hz tone. In both the experiments, we found that at the chest and the abdomen, the rating of the vibratory sensation was in close correlation with the vibration acceleration level (VAL) of the body surface vibration measured at each corresponding location. This was consistent with our previous results and suggested that at the trunk of the body (the chest and the abdomen), the mechanoreception of body vibrations plays an important role in the experience of the vibratory sensation in persons exposed to high-level low-frequency noise. At the head, however, no close correlation was found between the rating of the vibratory sensation and the VAL of body surface vibration. This suggested that at the head, the perceptual mechanisms of vibration induced by high-level low-frequency noise were different from those in the trunk of the body.


Development of a test battery (NPM-X) for neuropsychological and neuromotor examination of children with developmental disabilities or mental retardation. A theoretical and clinical study.
Biological and behavioural diagnosis often do not provide information on functional competence. This is, however, of utmost importance in planning services as well as in research on treatment effects for children with developmental disorders. For school-aged children neuropsychological assessment has proved its value in this respect. For children of chronological age (CA) below 5-7 with specific developmental disabilities, and for children with severe mental retardation there has been a lack of applicable test batteries. This thesis presents a new test battery for neuropsychological and neuromotor examination, NPM-X, for these two groups of children. The first part of the thesis reviews available medical and psychological tests and assessment procedures with respect to applicability and relevance for neuropsychological assessment to children with mental retardation and mental age (MA) below 7. The second part describes the theoretical background and the content of the new test battery. The methodology for testing these children, who due to their age and/or their developmental disabilities often co-operate poorly, is described. Scoring categories, specifically developed to enable a detailed and differentiated description of the child, are presented. Because of the instability of the behavioural function in early age as well as in cases of severe disability, the scoring system records both the child's optimal functional capacity and inconsistencies in behaviour. For the purpose of planning treatment and training according to the child's resources as well as dysfunctions, two different functional profiles are provided. In the normative functional profile the child's functional level is compared to normal expectations for the child's CA, and in the ideographic functional profile the child's function in each area is compared to the child's average functional level. In the third part of the thesis the reliability results are presented and discussed. A pair of trained M.D.s, or psychology or special education Ph.D.s examined 110 children in a blind design. The study showed satisfactory interrater and test-retest reliability. In the fourth part current validation theory is reviewed before content and construct validity for the test battery is discussed. A concurrent criterion validation study is presented as well. Assessments available in the psychological and psychiatric records (PPR) of 35 children with CA below 7 were compared to test results obtained with NPM-X. The comparison showed high agreement in areas of function assessed both by PPR and NPM-X. In addition, NPM-X provided more information about the child's functional capacity, of relevance for the diagnostic appraisal as well as for the treatment of the child. It is concluded that a reliable and valid test battery for neuropsychological and neuromotor developmental assessment has showed its applicability and clinical utility for children with specific developmental disabilities and CA < 7 and for children with general developmental disabilities up to CA 12-13 but with MA < 7.


The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases.
Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder involving motor and cognitive dysfunction. Currently, there is no effective treatment either for symptomatic relief or disease modification. This relates, in part, to a lack of knowledge of the underlying neurochemical abnormalities, including cholinergic receptor status in the basal ganglia. To measure muscarinic M2 and M4 receptors in the basal ganglia in PSP. The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex were autoradiographically measured in pathologically confirmed cases of PSP (n = 18), and compared with cases of Lewy body dementias (LBDs; n = 45), Alzheimer's disease (AD; n = 39) and controls (n = 50). In cases of PSP, there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to controls, but no significant changes in the pallidum. Cases with AD showed lower M2 receptors in the posterior striatum. Groups with LBD and AD showed higher M2 binding in the insular cortex compared with controls. The results suggest loss of posterior striatal cholinergic interneurones in PSP, and reduction in medium spiny projection neurones bearing M4 receptors. These results should be taken in the context of more widespread pathology in PSP, but may have implications for future trials of cholinergic treatments.


Pavlovian conditioning of morphine-induced alterations of immune status: evidence for peripheral beta-adrenergic receptor involvement.
The present studies examined the involvement of peripheral beta-adrenergic receptor activity in the establishment and expression of conditioned morphine-induced alterations of immune status. Previous work in our laboratory has shown that morphine's immunomodulatory effects can become conditioned to environmental stimuli which predict drug administration. These immune alterations include conditioned changes in natural killer cell activity, interleukin-2 production, and mitogen-induced lymphocyte proliferation. During the training phase of these experiments, Lewis rats received two conditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment. On the test day, rats were reexposed to the conditioned stimulus prior to sacrifice. Saline or nadolol (0.002, 0.02, 0.2, or 2.0 mg/kg) was administered either prior to the training sessions or prior to the test session. Administration of nadolol prior to training did not affect the development of conditioned alterations of immune status. Conversely, nadolol administration prior to testing completely attenuated the expression of a subset of the conditioned morphine-induced changes in immune status. Taken together, these studies suggest that whereas peripheral beta-adrenergic receptor activity is not required for the establishment of conditioned morphine-induced alterations of immune status, it is involved in the expression of a subset of these conditioned immunomodulatory effects.


Purified proteins from Leishmania amastigotes-induced delayed type hypersensitivity reactions and remission of collagen-induced arthritis in animal models.
A treatment preparation composed of purified Leishmania (L) antigenic fractions (AS210) induced linear delayed type hypersensitivity (DTH) reactions over a 1-40 microg dose range, in guinea pigs. When a DBA-1 mouse collagen induced arthritis (CIA) model was used to compare AS210 treatment against: a polyvalent vaccine (AS110-1), a monovalent vaccine (AS110-2) and placebo, the AS210 treated mice had the least amount of forepaw inflammation and the lowest mean arthritis scores (MAS). When MAS for day(s) 1-40 were analyzed using one way ANOVA, statistically significant (P < 0.05) differences were seen for the following study groups: PBS versus Dexamethasone and PBS versus AS210. Subsequently, the ANOVA analysis results were corroborated by the Mann-Whitney test: analysis of the first group (P < 0.001) and analysis of the second group (P < 0.001). Comparison between dexamethasone and AS210 at different time intervals by Mann-Whitney test were as follows: day 0-day 5 both treatments had equal values (P = 1.00), from day-7 to 20 AS210 treatment had lower MAS values than dexamethasone (P = 0.037), and from day-21 to 30, AS210 MAS were similar to dexamethasone values (P = 0.319). No statistical difference was observed between AS110-1, AS110-2, and placebo groups.


Valve-preserving surgery of the proximal aorta.
Surgical treatment of proximal aortic disease currently offers a variety of surgical options. Traditionally, replacement of the proximal aorta has been performed with a composite graft in most cases; supracommissural aortic replacement was the only alternative if preservation of the native aortic valve was attempted. Valve-preserving root operations currently allow us to avoid the disadvantages of prosthetic heart valves and completely eliminate aortic root pathology. Between 10/95 and 5/99, 219 patients were treated for proximal aortic disease. The diagnoses included degenerative disease (n=158), acute dissection (n=48), and chronic dissection (n=13). Composite replacement of valve and root (n=99) was used only in patients with significant degeneration or stenosis of the aortic valve. For near-normal root dimensions supracommissural aortic replacement (n=44) was chosen. Root remodeling (n=60) and reimplantation of the valve within a vascular graft (n=16) were performed for aortic valve regurgitation and root dilatation. Overall hospital mortality was 5.7%; in elective operations, mortality was expectedly lower compared to emergency interventions (2.4% vs 16.3%; p<0.05). Hospital mortality for valve preserving procedures was similar (elective procedures 1.9%, emergency operations 9.5%). Two-year freedom from aortic regurgitation grade II or higher was 89% for remodeling and 92% for reimplantation. Freedom from reoperation for secondary and increasing regurgitation at two years was 96% for remodeling and 100% after reimplantation. Using current techniques of valve preserving surgery, combined disease of the aortic valve, root, and extended segments of the aorta can be corrected without the disadvantages of prosthetic heart valves in the majority of patients. Further experience will define the relative role of the different operative modifications.


Static autoregulation in humans: a review and reanalysis.
Cerebral autoregulation (CA) is a theoretical construct characterized by the relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). We performed a comprehensive literature search to provide an up-to-date review on the static relationship between MAP and CBF. The results are based on 40 studies (49 individual experimental protocols) in healthy subjects between 18 and 65 years. Exclusion criteria were: a ΔMAP <5%, hypoxia/hyperoxia or hypo/hypercapnia, and unstable levels (<2 min stages). The partial pressure of arterial CO2 (PaCO2) was measured in a subset of the included studies (n=28); therefore, CBF was also adjusted to account for small changes in PaCO2. The linear regression coefficient between MAP and CBF (or velocity) of 0.82±0.77%ΔCBF/%ΔMAP during decreases in MAP (n=23 experiments) was significantly different than the relationship of 0.21±0.47%ΔCBF/%ΔMAP during increases (n=26 experiments; p<0.001). After correction for increases/decreases in PaCO2, the slopes were not significantly different: 0.64±1.16%ΔCBF/%ΔMAP (n=16) and 0.39±0.30%ΔCBF/%ΔMAP (n=12) for increased vs. decreased MAP changes, respectively (p=0.60). The autoregulatory ability of the cerebral circulation appears to be more active in buffering increases in MAP as compared to reductions in MAP. However, the statistical finding of hysteresis is lost following an attempt to correct for PaCO2.


Prevalence, Severity, and Clinical Management of Brain Incidental Findings in Healthy Young Adults: MRi-Share Cross-Sectional Study.
Background and Objectives: Young adults represent an increasingly large proportion of healthy volunteers in brain imaging research, but descriptions of incidental findings (IFs) in this age group are scarce. We aimed to assess the prevalence and severity of IFs on brain MRIs of healthy young research participants aged 18-35 years, and to describe the protocol implemented to handle them. Methods: The study population comprised 1,867 participants aged 22.1 ± 2.3 years (72% women) from MRi-Share, the cross-sectional brain MRI substudy of the i-Share student cohort. IFs were flagged during the MRI quality control. We estimated the proportion of participants with IFs [any, requiring medical referral, potentially serious (PSIFs) as defined in the UK biobank]: overall, by type and severity of the final diagnosis, as well as the number of IFs. Results: 78/1,867 participants had at least one IF [4.2%, 95% Confidence Interval (CI) 3.4-5.2%]. IFs requiring medical referral (n = 38) were observed in 36/1,867 participants (1.9%, 1.4-2.7%), and represented 47.5% of the 80 IFs initially flagged. Referred IFs were retrospectively classified as PSIFs in 25/1,867 participants (1.3%, 0.9-2.0%), accounting for 68.4% of anomalies referred (26/38). The most common final diagnosis was cysts or ventricular abnormalities in all participants (9/1,867; 0.5%, 0.2-0.9%) and in those with referred IFs (9/36; 25.0%, 13.6-41.3%), while it was multiple sclerosis or radiologically isolated syndrome in participants with PSIFs (5/19; 26.3%, 11.5-49.1%) who represented 0.1% (0.0-0.4%) and 0.2% (0.03-0.5%) of all participants, respectively. Final diagnoses were considered serious in 11/1,867 participants (0.6%, 0.3-1.1%). Among participants with referred IFs, 13.9% (5/36) required active intervention, while 50.0% (18/36) were put on clinical surveillance. Conclusions: In a large brain imaging study of young healthy adults participating in research we observed a non-negligible frequency of IFs. The etiological pattern differed from what has been described in older adults.


[Estimation of antihypertension efficiency and use of fixed combination perindopril+amlodipin by uncontrollable hypertension patients within the limits of routine treatment].
The results of observational investigation by prescription of the fixed combination perindopril + amlodipin produced by to the uncontrollable hypertension patients by the previous therapy are described in the given article. In Kazan population 50 patients at the age of 32 to 92 with essential hypertension having blood pressure level of 140/90 mm/hg. Were included into the investigation. Before these patients took different groups of antihypertension preparation (including perindopril). The preparation was prescribed in different fixed dosage depending on duration of hypertension, quantity of taken hypertension groups of preparations and blood pressure level. Then during 1, 2, 3 months of treatment the physician had the possibility to determine the dosage necessary to prescribe. The prescription of perindopril in combination with amlodipin during 3 months led to certain lowering of systolic and diastolic arterial pressure for 38.2 and 11.6 mm/hg accordingly and 80% of patients had the required pressure level of (<140/90 mm/hg). Moreover, the frequency of heart beat reduced and necessary increase of patient compliance for treatment took place. Taking the preparation only 31% of patients had unwilling effects but it didnt require the abolition of the antihypertension therapy till the end of observation. As a result, the investigation confirmed the high efficiency, good perception, improvement of patient compliance for treatment by prescribing the fixed combination perindopril + amlodipin.


Observed positive parenting behaviors and youth genotype: evidence for gene-environment correlations and moderation by parent personality traits.
Gene-environment correlations (rGE) have been demonstrated in behavioral genetic studies, but rGE have proven elusive in molecular genetic research. Significant gene-environment correlations may be difficult to detect because potential moderators could reduce correlations between measured genetic variants and the environment. Molecular genetic studies investigating moderated rGE are lacking. This study examined associations between child catechol-O-methyltransferase genotype and aspects of positive parenting (responsiveness and warmth), and whether these associations were moderated by parental personality traits (neuroticism and extraversion) among a general community sample of third, sixth, and ninth graders (N = 263) and their parents. Results showed that parent personality traits moderated the rGE association between youths' genotype and coded observations of positive parenting. Parents with low levels of neuroticism and high levels of extraversion exhibited greater sensitive responsiveness and warmth, respectively, to youth with the valine/valine genotype. Moreover, youth with this genotype exhibited lower levels of observed anger. There was no association between the catechol-O-methyltransferase genotype and parenting behaviors for parents high on neuroticism and low on extraversion. Findings highlight the importance of considering moderating variables that may influence child genetic effects on the rearing environment. Implications for developmental models of maladaptive and adaptive child outcomes, and interventions for psychopathology, are discussed within a developmental psychopathology framework.


Clinicopathological and immunohistochemical analysis of spindle cell squamous cell carcinoma of the tongue: a rare case.
Spindle cell squamous cell carcinoma of the tongue is a rare variant of squamous cell carcinoma. This paper reports the case of a spindle cell squamous cell carcinoma of the tongue, in a 64-year-old male patient, and presents a review of the etiopathogenesis, clinicopathological and immunohistochemical features and treatment of the malignancy. The patient presented for evaluation of a painful swelling on his tongue. Extraoral examination revealed palpable submandibular and superior cervical lymph nodes. Based on the presumptive diagnoses of squamous cell carcinoma or malignant salivary gland neoplasm, an incisional biopsy was performed. Histopathological analysis showed a proliferation of atypical spindle cells, exhibiting extensive pleomorphism. Tumor cells were positive for vimentin, P53 and alpha-smooth muscle actin, focally positive for epithelial membrane antigen and P63, and negative for pan-cytokeratin (AE1/AE3), CK7, CD138, CD34, CD56, and S-100. The positivity index for Ki-67 was approximately 40%. The diagnosis of spindle cell squamous cell carcinoma was established and the patient was referred to a head and neck surgery service. In the oral cavity, spindle cell squamous cell carcinoma of the tongue is an aggressive variant of squamous cell carcinoma, which usually presents as an exophytic mass located on the tongue of elderly males. Due to its distinct histopathological characteristics, immunohistochemistry is a valuable and helpful tool to establish the diagnosis of spindle cell squamous cell carcinoma of the tongue.


Profiling FLT3 Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients: Impact on Overall Survival.
Background: Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The FLT3 gene participates in hematopoietic stem cell proliferation. FLT3 mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated. Aim of the study: This study aimed to identify the profile of FLT3 mutations in pediatric patients with de novo AML and to assess their possible influence on overall survival (OS) and other clinical features. Methods: Massive parallel target sequencing of FLT3 was performed in 80 patients. Results: FLT3 mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in FLT3 POS cases than in FLT3 NEG (p = 0.03). The average OS for FLT3 POS was 1.2 vs. 2.2 years in FLT3 NEG. There were no significant differences in the children's sex, age, percentage of blasts in bone marrow aspirate, or white blood cell count in peripheral blood at diagnosis between both groups. No differences were identified stratifying by the mutational load (high > 0.4) or type of mutation. The negative effect of FLT3 mutations was also observed in patients with acute promyelocytic leukemia (APL). Conclusions: FLT3 mutational profile is described in Mexican pediatric AML patients for the first time. Mutated FLT3 negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the FLT3 POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients.