[Promotion of Mental Health in Early Childhood Institutions in Disadvantaged Areas]. / Förderung der seelischen Gesundheit in Kitas in Quartieren mit besonderen Problemlagen.

A prevention programme for the promotion of psychological health was implemented in six early childhood education institutions, which caters to four different levels (courses for children, courses and counselling for parents, vocational training and supervision for paedagogic professionals, establishing networks within the social environment). New, low-threshold structures have been created in order to simplify the usage of prevention services and to develop meaningful connections between the support systems of health and education. The effects of the programme have been validated by means of a combination research design.

Effect of case hardening on the wear and hardness properties of medium carbon steel for bone crushing application.

The majority of wear-related problems are connected to crushing machines because hammer failure frequently causes machine failure which eventually leads to machine downtime. Therefore, improving the reliability of crushing materials is necessary for effective production. This research investigation focused on the development of crushing material with appropriate strength properties that can function in critical, impact-prone, corrosive, and abrasive conditions. The current study used palm kernel shell, coconut shell, and sawdust powder as the media for medium carbon steel in order to valorize the agro waste. Carburising media PKS-composition, CS-composition, and SD-composition were changed to 40%: 30%: 30%, PKS-composition 100%, CS-composition 100%, and SD-composition 100%. The process was carried out in 1 h (60 mims), 1 h:30 min (90 min), 2 h (120 min), 2 h:30 (150 min), and 3 h (180 min) soak period with varied carburising temperatures of 900, 950, 1000, and 1050 °C. However, several characterisation and mechanical tests were carried out using an optical microscope, a spark spectrometer, a scanning electron microscope coupled with an energy dispersive spectrometer, wear tester to explore their microstructural features. Vicker's hardness tester, sliding wear tester, and a thermal gravimetric analysis testing machine were also employed. In order to establish reasons for failure other than the cyclic loading on the materials, the results were compared with the properties of as-received un-failed, and carburised medium carbon steel. The results of carburisation show that PKS penetrates carbon at a rate that is noticeably higher than that of other materials at various temperatures and times, indicating that carbon diffuses deeply into the material. Hence, this enhances the wear resistance, and sample's hardness number but decreased its impact toughness respectively.

Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase-4 activity in obese patients with type 2 diabetes.

The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass (GBP) surgery is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10-kg equivalent weight loss by GBP (n = 16) or by caloric restriction (CR,n = 14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p = 0.01), but not after CR. The increased peak glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretin concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined.

A nascent HIV type 1 epidemic among injecting drug users in Kabul, Afghanistan is dominated by complex AD recombinant strain, CRF35_AD.

Injecting drug use (IDU), common in global centers of heroin production, confers significant risk for HIV-1 infection. Once introduced into IDU networks, an explosive rise in HIV-1 infection typically occurs, fueled principally by needle sharing. New HIV-1 epidemics in IDUs have occurred in Russia, China, Thailand, Spain, Iran, and in other countries, and some have spread into other risk groups in their respective countries. In Afghanistan, the introduction of HIV-1 into IDU networks has begun, but a recent report of 3% HIV-1 prevalence suggests that the epidemic is still at an early stage. Here we establish, by complete genome sequencing and phylogenetic analysis of four viral strains from Afghan IDUs, that all are the same complex recombinant strain, combining HIV-1 subtypes A and D and herein termed CRF35_AD. Published partial HIV-1 sequences from an HIV-1 epidemic among IDUs in Iran, already at 23.2% HIV-1 prevalence, are either CRF35_AD or a related recombinant. Voluntary HIV-1 screening and harm reduction programs in Afghanistan, applied now, could limit the spread of HIV-1, both in IDUs and in other social networks.

Virtual vs. optical colonoscopy in symptomatic gastroenterology out-patients: the case for virtual imaging followed by targeted diagnostic or therapeutic colonoscopy.

AIM: To compare virtual colonoscopy with optical colonoscopy findings in symptomatic patients. BACKGROUND: Computer tomographic colonography is an alternative to optical colonoscopy. Studies have shown that two-dimensional computer tomographic colonography does not have sufficient sensitivity. Three-dimensional computerized tomographic virtual colonoscopy compares well with optical colonoscopy for colorectal neoplasia screening in asymptomatic individuals. METHODS: One hundred patients aged 50 and older underwent same day virtual colonoscopy and optical colonoscopy. The endoscopists were unaware of the radiologist's report until the withdrawal phase of the endoscopy when segmental unblinding occurred. The virtual colonoscopy and optical colonoscopy findings were compared by using the unblinded optical colonoscopy as the reference standard. RESULTS: Pancolonic endoluminal virtual colonoscopy was achieved in 99 patients. Optical colonoscopy caecal intubation occurred in 91 patients. Direct comparison was possible in 90 patients. Both techniques revealed the three cancers detected. Virtual colonoscopy revealed 11 polyps > or = 6 mm diameter in nine patients. Optical colonoscopy revealed 10 polyps > or = 6 mm diameter in nine patients with a further 15-mm polyp discovered after segmental unblinding. CONCLUSION: In symptomatic patients, three-dimensional virtual colonoscopy is equivalent to optical colonoscopy for diagnosing colon cancer and clinically significant polyps. A case can be made for three-dimensional virtual colonoscopy as a primary modality followed if necessary by same day-targeted optical colonoscopy.

Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae.

The SIR1 gene is one of four specialized genes in Saccharomyces cerevisiae required for repressing transcription at the silent mating-type cassettes, HMLalpha and HMRa, by a mechanism known as silencing. Silencing requires the assembly of a specialized chromatin structure analogous to heterochromatin. FKH1 was isolated as a gene that, when expressed in multiple copies, could substitute for the function of SIR1 in silencing HMRa. FKH1 (Forkhead Homologue One) was named for its homology to the forkhead family of eukaryotic transcription factors classified on the basis of a conserved DNA binding domain. Deletion of FKH1 caused a defect in silencing HMRa, indicating that FKH1 has a positive role in silencing. Significantly, deletion of both FKH1 and its closest homologue in yeast, FKH2, caused a form of yeast pseudohyphal growth, indicating that the two genes have redundant functions in controlling yeast cell morphology. By several criteria, fkh1Delta fkh2Delta-induced pseudohyphal growth was distinct from the nutritionally induced form of pseudohyphal growth observed in some strains of S. cerevisiae. Although FKH2 is redundant with FKH1 in controlling pseudohyphal growth, the two genes have different functions in silencing HMRa. High-copy expression of CLB2, a G2/M-phase cyclin, prevented fkh1Delta fkh2Delta-induced pseudohyphal growth and modulated some of the fkhDelta-induced silencing phenotypes. Interestingly, deletions in either FKH1 or FKH2 alone caused subtle but opposite effects on cell-cycle progression and CLB2 mRNA expression, consistent with a role for each of these genes in modulating the cell cycle and having opposing effects on silencing. The differences between Fkh1p and Fkh2p in vivo were not attributable to differences in their DNA binding domains.

Drug-sensitivity profile of clinical Mycobacterium tuberculosis isolates--a retrospective study from a chest-disease institute in India.

Multi-drug-resistant tuberculosis (MDR-TB) is a major public-health problem, because treatment is complicated and patients remain infectious for months or years, despite receiving the best available therapy. To gain better understanding of MDR-TB, a retrospective study was initiated to determine the level of drug resistance among patients in a chest-disease institute in India. Two hundred and sixty-three isolates from treatment-failure pulmonary tuberculosis patients (20-70 years) were studied. Drug-sensitivity testing was performed by the modified-proportion method. First- and second-line drugs, along with two quinolone drugs (ofloxacin and ciprofloxacin), were tested. Patients included in this study did not improve with therapy; however, 151 isolates (57.5 %) were susceptible to all four first-line antituberculosis drugs. This study reports low resistance to fluoroquinolones among the strains present in these patients.

Brazil nut effect and excluded volume attraction in vibrofluidized granular mixtures.

A two dimensional bi-disperse vibrofluidized granular mixture is studied in the rapid flow regime, where particle interactions occur due to instantaneous collisions. Both experiments and simulations are carried out, and these show the existence of two phenomena which have been observed only in very dense granular flows or in equilibrium systems. The Brazil nut phenomenon, which involves the rise of larger particles in a granular mixture upon vibration, has been observed in dense systems due to the percolation of small particles though the interstitial spaces between the large particles, or due to convection rolls. In the present case, where neither effect is present, it is observed that the fluidization of the smaller particles by vibration results in an exponentially decaying density profile, at heights large compared to the particle diameter, and thereby a pressure field that decreases with height. The larger particles, suspended in this decaying pressure field, experience a larger pressure at the bottom and a smaller pressure on top, and they rise to a height where the net force caused by the decreasing pressure is balanced by the weight of the particle. An attractive force between the large particles, similar to the entropic attraction effect in mixtures of colloids and polymers, is also observed in this nonequilibrium system, because when the distance between the large particles is less than the small particle diameter, the pressure between the large particles is smaller than that on the outside. Analytical results are derived for each of these effects, and these are in agreement with the experimental and simulation results.

Proinflammatory cytokines can significantly induce human mononuclear phagocytes to produce nitric oxide by a cell maturation-dependent process.

The capacity of three proinflammatory cytokines, interferon-gamma (rhifn-gamma), tumour-necrosis factor-alpha (rHTNF-alpha) and interleukin-1 (rHIL-1), to induce release of nitric oxide (NO) from human mononuclear phagocytes were investigated. Peripheral blood monocytes were either used immediately or after culturing in vitro to develop into monocyte-derived macrophages (macrophages). Lipopolysaccharide (LPS) was used as second signal in all experiments. The three cytokines tested had significantly high enhancing influence on the production of nitric oxide by monocytes as well as by macrophages. However production was significantly higher by the monocytes matured in vitro to macrophages (P < 0.01). In our experimental system LPS had only marginal synergistic influence on production of NO2, and IFN-gamma demonstrated to be the most efficient of the three cytokines tested. Addition of L-arginine in the monocytes/macrophages culture further amplified production of NO2, whereas addition of NG-monomethylarginine abrogated this amplification. We conclude that human mononuclear phagocytes are capable of using inducible nitric oxide synthase pathway to produce nitric oxide.

Dinitrosyl-dithiol-iron complexes, nitric oxide (NO) carriers in vivo, as potent inhibitors of human glutathione reductase and glutathione-S-transferase.

Human glutathione reductase (GR) and rat liver glutathione-S-transferases (GSTs) had been shown to be inhibited by the nitric oxide (NO) carrier S-nitroso-glutathione (GSNO). We have now extended these studies by measuring the effects of dinitrosyl-iron complexed thiols (DNIC-[RSH]2) on human GR, GST and glutathione peroxidase. DNIC-[RSH]2 represent important transport forms of NO but also of iron ions and glutathione in vivo. Human GR was found to be inhibited by dinitrosyl-iron-di-glutathione (DNIC-[GSH]2) and dinitrosyl-iron-di-L-cysteine (DNIC-Cys2) in two ways: both compounds were competitive with glutathione disulfide (GSSG), the inhibition constant (Ki) for reversible competition of DNIC-[GSH]2 with GSSG being approximately 5 microM; preincubating GR for 10 min with 4 microM DNIC-[GSH]2 and 40 microM DNIC-Cys2, respectively, led to 50% irreversible enzyme inactivation. More than 95% GR inactivation was achieved by incubation with 36 microM DNIC-[GSH]2 for 30 min. This inhibition depended on the presence of NADPH. Absorption spectra of inhibited GR showed that the charge-transfer interaction between the isoalloxazine moiety of the prosthetic group flavin adenine dinucleotide (FAD) and the active site thiol Cys63 is disturbed by the modification. Cys2 and FAD could be ruled out as sites of the modification. Isolated human placenta glutathione-S-transferase and GST activity measured in hemolysates were also inhibited by DNIC-[GSH]2. This inhibition, however, was reversible and competitive with reduced glutathione, the Ki being 20 nM. The inhibition of GST induced by GSNO was competitive with reduced glutathione (GSH) (Ki = 180 microM) and with the second substrate of the reaction, 1-chloro-2,4,-dinitrobenzene (Ki = 170 microM). An inhibition of human glutathione peroxidase by GSNO or DNIC-[RSH]2 was not detectable. Inactivation of GR by DNIC-[GSH]2 is by two orders of magnitude more effective than modification by GSNO; this result and the very efficient inhibition of GST point to a role of DNIC-[RSH]2 in glutathione metabolism.

A convergent triflate displacement approach to (alpha-monofluoroalkyl)phosphonates.

[reaction: see text] Treatment of primary alkyl triflates or iodides with the potassium salt of diethyl (alpha-fluoro-alpha-phenylsulfonylmethyl)phosphonate yields (alpha-fluoro-alpha-phenylsulfonylalkyl)phosphonates. These can be cleanly desulfonated, in a matter of minutes, with Na(Hg) in MeOH/THF/NaH(2)PO(4). This two-step procedure complements previously reported triflate displacement approaches to alpha-nonfluorinated and alpha,alpha-difluorinated phosphonates.

Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a phytosiderophore.

Non-compliance by patients and poor clinical management due to the use of incorrect regimens are the main reasons for the development of drug resistance by mycobacterial strains. New strategies for the control of multi-drug-resistant mycobacterial strains have become a necessity for proper management of tuberculosis, which, according to the WHO report (1997), is estimated to remain among the top 10 mortality-causing diseases of the twenty-first century. One of the strategies is the use of iron-sequestering agents like siderophores as active therapeutic agents in the treatment of tuberculosis. This report describes for the first time the inhibition of the growth of Mycobacterium tuberculosis H37Ra in vitro by a phytosiderophore isolated from the root washings of Tephrosia purpurea. This finding may help in the establishment of a new drug regimen which will be more effective in the treatment of tuberculosis.

Private pharmacies in tuberculosis control--a neglected link.

In most settings in India, private pharmacies dispense prescriptions for anti-tuberculosis drugs made out by private practitioners. In a cross-sectional study, we assessed the dispensing practices for tuberculosis and knowledge about the national tuberculosis programme of 300 pharmacies. In all, 2800 prescriptions were dispensed monthly by the pharmacies. Doctors' prescriptions were for durations of several months, but half of the patients bought drugs one dose at a time for self-administration. This practice might promote drug resistance. Although 95% of pharmacists were not aware of the existence of the tuberculosis programme, the majority (97%) were willing to learn and contribute towards tuberculosis control. The need and the potential of private pharmacies for participation in tuberculosis control are highlighted.

Blood, bone marrow and splenic lymphocyte subset profiles in Indian visceral leishmaniasis.

We examined the lymphocyte subsets in peripheral blood, bone marrow and spleen of 11 patients with acute visceral leishmaniasis (VL) and 9 with chronic VL before and after 8 weeks of antileishmanial therapy. On admission, the CD4 cell count was depressed in the peripheral blood of acute and chronic VL cases as compared to the value in 10 normal control subjects. In contrast, CD4 cell counts were higher in the bone marrow in acute and chronic cases, and in splenic aspirates of chronic cases only, compared to normal values. The peripheral blood CD8 cell count, while normal in acute cases, was uniformly low in chronic cases. Counts of CD8 cells were also low in bone marrow of acute and chronic cases, as well as in splenic aspirates of chronic cases only. All these differences were significant (P < 0.05). After treatment, the CD4 cell count in the peripheral blood increased, but decreased in bone marrow and splenic aspirates. The CD8 cell count remained unaltered in the peripheral blood but increased significantly (P < 0.05) in bone marrow and spleen. The results suggest that in VL the peripheral blood picture may not reveal the actual T cell subset profile in the reticuloendothelial system. The changes in CD8 cell counts in the bone marrow and spleen seem to be independent, and are probably influenced by antileishmanial therapy.

The overlap between depression and anxiety on different levels of psychopathology.

Symptoms, syndromes, and diagnoses (DSM-III-R) for depression and anxiety were assessed and evaluated in 150 psychiatric outpatients. It was hypothesized that the coexistence of depression and anxiety within subjects strongly depends on the psychopathological level determined. The results confirmed this assumption. Overlap proportions for symptoms were almost twice as high as for diagnoses (52% vs. 29%). Intermediary rates were obtained for syndromes. Implications of these results for research on anxious depression, often considered to be qualitatively distinct from pure depression or anxiety disorders, are discussed.

Reliability of checklist-guided diagnoses for DSM-IIIR affective and anxiety disorders.

The test-retest reliability of DSM-IIIR diagnoses for affective and anxiety disorders was determined under clinical routine conditions in a psychiatric outpatient department. The sample consisted of 60 patients, and the Munich Diagnostic Checklists (MDCL) were administered for diagnostic evaluation and classification. Each subject was independently examined by two of four participating diagnosticians (two psychiatrists, two psychologists). Acceptably high levels of agreement were indicated by several statistics (including kappa) for most disorders. Reliability was analyzed for diagnoses, subclassifications, and symptoms. Reduced agreement was found only for dysthymia, agoraphobia, and social phobia. Major causes were information variance and weaknesses of operationalization. Overall results were satisfactory when compared with other reliability studies.

Acetoxy-4-methylcoumarins confer differential protection from aflatoxin B(1)-induced micronuclei and apoptosis in lung and bone marrow cells.

The ability of various acetoxy derivatives of 4-methylcoumarins to inhibit the genotoxic changes due to aflatoxin B(1) (AFB(1)) is reported here. Several 4-methylcoumarins (test compounds), such as 7,8-diacetoxy-4-methylcoumarin (DAMC), monoacetoxy-4-methylcoumarin (MAC), 5-N-acetyl-6-acetoxy-4-methylcoumarin (NAMC) and 7,8-dihydroxy-4-methylcoumarin (DHMC) were separately administered intraperitoneally (i.p.) to male wistar rats followed by AFB(1) administration i.p. or intratracheally (i.t.) (2-8 mg/kg b.wt.) and another dose of the test compound. The animals were sacrificed 26h after AFB(1) administration. From animals receiving AFB(1) i.p., bone marrow (BM) cells were isolated and stained with Mayer's haematoxylin and eosin. Micronuclei (MN) in BM were scored by light microscopy. From animals receiving AFB(1) i.t., bronchoalveolar lavage (BAL) was obtained, lung cells (LG) were isolated and stained with fluorochrome 6-diamidino-2-phenylindole (DAPI) for the analysis of MN, apoptotic bodies (AP) and cell cycle variations. Rats were separately treated with the vehicle DMSO to serve as the proper control. AFB(1) caused significant dose-dependent induction of MN in BM as well as LG. AP were observed in LG of rats receiving AFB(1) and was found to correlate with MN induction. DAMC injection caused significant decrease in AP due to AFB(1) in LG and MN in both BM and LG. The effectiveness of MAC was approximately half that of DAMC, thereby indicating that number of acetoxy groups on the coumarin molecule determine the efficacy. The fact that NAMC had no effect either on MN or AP indicate that neither acetoxy group at C-6 nor the N-acetyl group at C-5 facilitate the transfer of acetyl group to P-450 required for inhibition of AFB(1)-epoxidation. DHMC, the deacetylated product of DAMC had no normalizing effect on the induction of MN and AP. These findings confirm our earlier hypothesis that DAMC-mediated acetylation of microsomal P-450 (catalysing epoxidation of AFB(1)) through the action of microsomal transacetylase is responsible for the protective action of DAMC. The relative number and position of acetoxy groups on the coumarin nucleus determine the specificity to the transacetylase necessary for the chemopreventive action.

Velocity distribution for a two-dimensional sheared granular flow.

The velocity distribution for a two-dimensional collection of disks of number density n per unit area and radius a in a channel of width L is studied. The particle-particle collisions are considered to be inelastic with a coefficient of restitution e, while the particle-wall coefficients of restitution are inelastic with a tangential and normal coefficients of restitution, e(t) and e(n), respectively. The Knudsen number, which is the ratio of the channel width and the mean free path of the particles, is varied from Kn<<1 to Kn>>1. In the limit of high Knudsen number, the distribution function for the streamwise velocity is bimodal, as predicted by theory [J. Fluid Mech. 340, 3l9 (1997)]], and the scalings of the moments of the velocity distribution with the Knudsen number are in agreement with the theory. In the low Knudsen number limit, the distribution function for the streamwise velocity is a Gaussian if the coefficient of restitution is close to 1, but assumes the form of a "composite Gaussian" if the coefficient of restitution is not close to 1. The distribution function has a complex structure in the intermediate regime, where there are three maxima in the distribution function near the wall, while the distribution function is bimodal at the center. The granular temperature is accurately predicted by kinetic theory at the center of the channel, but there is dissipation at the wall due to inelastic particle-wall collisions, which results in a significant decrease in the temperature even when the coefficient of restitution is 0.9; this finding is in agreement with previous results with bumpy wall boundary conditions and with specular reflection conditions. The slip velocity at the wall has a power law dependence on the Knudsen number, and the exponent in this power law depends on the coefficients of restitution.

Spatiotemporal dynamics near a supercritical Turing-Hopf bifurcation in a two-dimensional reaction-diffusion system.

Pattern formation in semiconductor heterostructures is studied on the basis of a spatially two-dimensional model of reaction-diffusion type. In particular, we investigate the neighborhood of a codimension-two Turing-Hopf instability by analytical methods. Amplitude equations are derived which predict the absence of mixed modes but extended ranges of bistability between homogeneous oscillatory states and hexagonal Turing patterns. Our results are confirmed by numerical simulations. The features are not confined to a neighborhood of the bifurcation point so that the conclusions of the weakly nonlinear analysis explain the observations in large portions of the parameter space at least qualitatively

Seroepidemiological investigations on human immunodeficiency virus infections in some parts of India.

PIP: 2597 serum samples from individuals belonging to various groups were screened for antibodies to human immunodeficiency virus (HIV). The majority of the sera screened were from residents of India; 16 were from foreigners. Screening was done using ELISA kits from 4 different commercial sources. Samples which were reactive initially were retested using the same kit. 4 samples were reactive repeatedly in all the kits used. 2 of these were from patients with Acquired Immune Deficiency Syndrome (AIDS), 1 from a patient with AIDS-related complex, and 1 from an apparently healthy female prostitute living in Bombay. These 4 samples were confirmed to be positive by Western Blot, immunofluorescence, and the Karpas AIDS test. Among the sexually promiscuous persons screened for antibodies to HIV in India, female prostitutes appear to be the only risk group in whom antibodies to HIV virus have been detected. This also has been reported from Tamil Nadu. Positive reactors among blood donors screened even in areas of high incidence of AIDS has been very low. There were no positive reactors among the tribals, naval personnel, and individuals from jails. Overall, the data and an earlier report from Delhi suggest that the activity of AIDS retrovirus remains low in India, but the possible threat of spread of this disease should be considered. As prostitutes have been the only risk group with positive serological evidence of HIV infection, surveillance of this group is indicated.^ieng