Synchrotron X-ray Electron Density Analysis of Chemical Bonding in the Graphitic Carbon Nitride Precursor Melamine.

Melamine is a precursor and building block for graphitic carbon nitride (g-CN) materials, a group of layered materials showing great promise for catalytic applications. The synthetic pathway to g-CN includes a polycondensation reaction of melamine by evaporation of ammonia. Melamine molecules in the crystal organize into wave-like planes with an interlayer distance of 3.3 Šsimilar to that of g-CN. Here we present an extensive investigation of the experimental electron density of melamine obtained from modelling of synchrotron radiation X-ray single-crystal diffraction data measured at 25 K with special focus on the molecular geometry and intermolecular interactions. Both intra- and interlayer structures are dominated by hydrogen bonding and π-interactions. Theoretical gas-phase optimizations of the experimental molecular geometry show that bond lengths and angles for atoms in the same chemical environment (C-N bonds in the ring, amine groups) differ significantly more for the experimental geometry than for the gas-phase-optimized geometries, indicating that intermolecular interactions in the crystal affects the molecular geometry. In the experimental crystal geometry, one amine group has significantly more sp3 -like character than the others, hinting at a possible formation mechanism of g-CN. Topological analysis and energy frameworks show that the nitrogen atom in this amine group participates in weak intralayer hydrogen bonding. We hypothesize that melamine condenses to g-CN within the layers and that the unique amine group plays a key role in the condensation process.

Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional study.

BACKGROUND: Malnutrition in human immunodeficiency virus (HIV)-infected individuals is associated with faster disease progression, higher mortality rates, and suboptimal response to antiretroviral therapy (ART). METHODS: We conducted a prospective interventional study to evaluate the effects of an oral macronutrient supplement among HIV-infected adults in South India. Patients attending Tuberculosis Research Centre clinics from June 2005 through December 2007 had baseline nutritional assessment and laboratory investigations performed. Patients at 1 center received nutritional counseling and standard care, whereas patients at 2 centers additionally received a macronutrient providing 400 cal and 15 g of protein daily. Study outcomes were changes in anthropometry, body composition, blood chemistry, and immune status at 6 months. RESULTS: In total, 636 ART-naive patients were enrolled in the study; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). Mean age +/- standard deviation (SD) was 31 +/- 7 years, mean weight +/- SD was 50 +/- 10 kg, and 42% were male. Significant increases in body weight, body mass index, midarm circumference, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts <200 cells/microL. No changes were observed in lipid levels, whereas the CD4 cell count decreased in the control group. However, after adjusting for baseline differences, these changes were not statistically significantly different between the groups. CONCLUSIONS: Macronutrient supplementation did not result in significantly increased weight gain compared with standard care (including nutritional counseling) among patients with moderately advanced HIV disease. The effect of supplementation on specific subsets of patients and on preserving immune function needs further research.

Gender differences in sexual behaviour among people living with HIV in Chennai, India.

BACKGROUND & OBJECTIVE: Risky sexual behaviour is usually the focus of HIV prevention programmes and little attention has been given to sexual behaviour patterns among HIV positive individuals. In order to ensure that people with HIV receive high quality sexual and mental health services, providers must have a comprehensive understanding of the issues and challenges faced by men and women with HIV. This study was conducted to gain insight into the gender differences in sexual behaviour patterns among HIV seropositive men and women in south India. METHODS: This descriptive cross-sectional study on a cohort of 203 seropositive patients (102 women and 101 men) attending outpatient clinics in the Tuberculosis Research Centre and the STD clinic of the Government General Hospital, Chennai, India. A semi-structured interview schedule was administered to collect information from the respondents. RESULTS: Fifty three per cent of the women were discontented with the sexual relationship with their spouse as compared to 23 per cent of the men (P<0.001). Thirty two of the 54 women who refused sex said that their spouses reacted violently to their refusal. More men than women reported to having extramarital relationships most often with a commercial sex worker or a friend, without condoms and usually under the influence of alcohol. INTERPRETATION & CONCLUSION: There are gender differences in sexual behaviour patterns among men and women. Understanding these differences is important to plan gender based intervention strategies in order to ensure that people living with HIV have a better quality of life, addressing their sexual concerns both within and outside of marriage. The findings will also help in advocacy and prevention programmes aimed at HIV/AIDS control.

Gender and socio-cultural determinants of TB-related stigma in Bangladesh, India, Malawi and Colombia.

SETTING: Tuberculosis (TB) control programmes in Bangladesh, India, Malawi and Colombia. OBJECTIVE: Assess indicators of TB-related stigma and socio-cultural and gender-related features of illness associated with stigma. DESIGN: Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Indicators of self-perceived stigma were analysed individually and in a validated index, which was compared across sites and between men and women at each site. Cultural epidemiological explanatory variables for stigma and interactions with female sex were analysed at each site. Qualitative illness narratives were examined to explain the role and context of explanatory variables. RESULTS: The overall stigma index was highest in India, lowest in Malawi and greater for women in Bangladesh. In India and Malawi, women were more likely to be concerned about impact on marital prospects. Associations with HIV/AIDS were linked to TB stigma in Malawi, where sexual contact as a perceived cause was more associated with stigma for men and less for women. CONCLUSION: Stigma both influences and indicates the effectiveness of TB control. Cultural epidemiological methods clarify cross-cutting and local features of stigma and gender for TB control.

Feasibility of routine HIV testing among TB patients through a voluntary counselling and testing centre.

BACKGROUND: Despite the synergy between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics, the public health responses have largely been separate. Detection of HIV among TB patients is crucial to the holistic management of HIV-TB co-infected patients. OBJECTIVE: To assess the feasibility of screening all TB patients for HIV through referral to a voluntary counselling and testing centre. DESIGN: This cross-sectional study of 4802 newly diagnosed TB patients between July 2005 and June 2006 was performed in Tamilnadu, India, at six sites. RESULTS: Of 4802 patients invited, 69% were willing to participate in the test. The most significant variables that influenced willingness were sex, age and place of residence (P < 0.01). The other significant variables that influenced willingness to participate were higher education, being employed and being married (P < 0.05). The main reasons for refusal of HIV screening among the patients were 'no risk behaviour' (30%), followed by 'too old' (23%) and for reasons of privacy (12%). CONCLUSIONS: The present study suggests that it is feasible to routinely test TB patients for HIV. However it is crucial for health providers to focus on an effective referral process keeping patient concerns in mind. Motivation strategies need to be sex-, age-, education- and residence-specific.

How stigmatizing is stigma in the life of people living with HIV: a study on HIV positive individuals from Chennai, South India.

The nature and intensity of AIDS stigma are shaped by the social construction of the epidemic in different locales. Stigma therefore needs to be discussed in its cultural context. This clinic-based study aims at understanding stigma among 203 HIV positive individuals from Chennai, South India. The study throws light on the impact of stigma on the quality of life among these individuals. It also discusses the gender implications of stigma. This study brings out the findings that actual stigma experienced among those infected with HIV is much less (26%) as compared to the fear of being stigmatized or perceived stigma (97%). Internalizing of stigma was found to have a highly significant negative correlation with quality of life in the psychological domain and a significant negative correlation in the environmental domain. However individuals who did experience actual stigma seemed more determined to live and experience an above moderate quality of life. The implication of this study encourages HIV infected individuals to rise above stigma, avoid internalizing their stigmatized feelings and work toward a better quality of life. Health providers need to address these issues in their care for HIV infected individuals.

Torquoselectivity induced by lone-pair conjugation in the electrocyclic reactions of 1-azapolyenes.

Torquoselectivity in the electrocyclic interconversions of 1-azapolyenes and their heterocyclic isomers was investigated theoretically. The ring openings of 1,2-dihydroazete, 1,2-dihydropyridine, and 1,2-dihydroazocine were examined using HF, MP2, and B3LYP calculations. A large preference for inward rotation of the nitrogen lone pair and outward rotation of the N-H group was found for the four- and six-electron systems. No strong preference was observed for the eight-electron system.

Inducing a cell-mediated immune response against peptides of the Plasmodium vivax circumsporozoite protein.

An attempt was made to generate an unrestricted cellular immune response against peptide antigens of the circumsporozoite protein (CSP) of Plasmodium vivax. The peptides used represent the repeat-region sequences of the type-I variant (AA and DA) or type-II variant (ANG) and the conserved region (region II) containing the hepatocyte-binding region extended to include a T-cell epitope (HBP). The study was conducted in outbred mice and two genetically unrelated inbred strains of mice. Spleen cells, recovered from mice that had been primed either with one peptide or a conjugate formed of HBP linked to one of the repeat-region peptides, were pulsed in vitro with varying amounts of individual peptides/conjugates, both in soluble and particulate form (with and without a human beta-casein bio-active fragment analogue as adjuvant). In the tests using the cells from the mice primed with an individual peptide(s), HBP showed a high proliferation index, and the repeat-region peptides, especially AA, showed T-cell activity in at least one of the mouse strains studied. In vitro, higher concentrations of the free peptides than of liposomal preparations of the peptides had to be used to elicit the optimal proliferation of the cells from each strain of mice. Interestingly, the cells from the conjugate-primed mice showed enhanced proliferation (compared with that observed in the cells from mice primed with individual peptides) when stimulated with each component, and especially the repeat-region sequence, of the relevant conjugate. In such cases there was no evidence of restriction of the immune response by the major histocompatibility complex. The major secreted cytokines were found to be from CD4(+) Th1 (interferon-gamma and interleukin-2), with relatively low levels of the Th-2 cytokines interleukin-4 and interleukin-6. The delivery of cohered 'B-T' peptide(s) sequences from the same protein, ideally with an immunostimulatory adjuvant or as a liposomal preparation, should greatly enhance the cell-mediated immune response and should improve clearance of mosquito-inoculated P. vivax sporozoites.

Modulation of the humoral response to repeat and non-repeat sequences of the circumsporozoite protein of Plasmodium vivax using novel adjuvant and delivery systems.

In the use of sub-unit vaccines, it is important to identify the protective epitopes and to generate the optimal immune response by using appropriate immuno-modulatory adjuvants and/or delivery systems. The main aim of the present study was to generate an MHC-non-restricted immune response against one promising vaccine candidate, the circumsporozoite protein (CSP) of Plasmodium vivax. Four synthetic peptides were chosen: three repeat-region sequences (AA, DA and ANG) and a putative T-cell epitope extended from a conserved region (region II) containing a hepatocyte-binding region (HBP). The humoral response against each peptide was studied in outbred mice and three strains of inbred mice (with different genetic backgrounds). Delivery of each peptide in microspheres or inclusion of a bio-active casein-fragment analogue as adjuvant with alum/liposome delivery considerably enhanced the humoral response against the peptide (when compared with the response to the peptide delivered in alum alone). The maximal immune response was observed when the peptide was delivered in microspheres, with no booster doses required; the antibodies raised against peptide delivered with adjuvant or in modulatory delivery vehicles had two-to five-fold lower binding affinities. The predominant IgG isotypes elicited using microspheres or adjuvant with alum/liposome delivery were IgG(2a)/IgG(2b) and/or IgG(1). Importantly, conjugation of HBP to the B-cell repeat peptides increased the titres of peptide-specific antibodies, especially of antibodies against the supposedly cryptic HBP. Delivery of a mix of all four peptides in microspheres elicited an intense immune response in outbred mice, indicating that such a delivery system efficiently presents the peptides to the immune effector cells. That antibodies in the anti-peptide sera bound strongly to air-dried sporozoites of P. vivax was confirmed by immunofluorescence. The present results, based on the use of individual peptides or a conjugate or cocktail of the peptides, highlight the utility of the casein-fragment analogue as an adjuvant, when used with alum/liposome delivery, and also demonstrate the potential of microspheres as a single-shot delivery system for sub-unit peptides.

Design and synthesis of sialyl Lewis x mimics as E-selectin inhibitors.

The design and synthesis of novel beta-C-mannosides that inhibit the binding of sialyl Lewis x to E-selectin are described. Compounds that contained a phenyl substituent at the C-6 position were found to have increased potency.

Excision and radiotherapy for heterotopic ossification of the elbow.

Radiotherapy has a well-defined role in prophylaxis of recurrent heterotopic ossification of the hip, but has been described infrequently in other situations. This article reports the use of excision and low-dose external beam radiotherapy in three patients with heterotopic ossification of the elbow treated between February 1995 and September 1996. Radiotherapy was delivered in a single fraction of 7-8 Gy within 48 hours postoperatively using opposed anteroposterior portals. After a median follow-up of 10.5 months, all three patients demonstrated a significant increase in range of motion without any evidence of recurrence. These results indicate adjuvant postexcision radiotherapy may be used for prophylaxis of recurrent heterotopic ossification of the elbow.

Cervical spine injuries in football players.

Cervical spine injuries have been estimated to occur in 10% to 15% of football players, most commonly in linemen, defensive ends, and linebackers. The overwhelming majority of such injuries are self-limited, and full recovery can be expected. However, the presenting symptoms of serious cervical spine injuries may closely resemble those of minor injuries. The orthopaedic surgeon frequently must make a judgment, on the field or later in the office, about the advisability of returning the athlete to the game. These decisions can have an enormous impact on the player and his family. Most severe cervical spine injuries share the common mechanism of application of an axial load to the straightened spine. Avoiding techniques that employ head-down "spear" tackling and wearing properly fitted equipment markedly reduce the risk of serious injury.

Glycoprotein IIb/IIIa receptor antagonists inhibit the development of platelet procoagulant activity.

We examined the effects of glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists c7E3 Fab and DMP728 on the development of platelet prothrombinase (PT) activity. c7E3 Fab dose-dependently inhibited the rate of thrombin-stimulated thrombin generation over a 1-minute reaction time. The IC50 was 11 nM with an IC90 of 1000 nM. DMP728 inhibited PT activity maximally by 60% at 100 nM. A similar profile was observed for the inhibition of platelet tenase activity. Inhibition was platelet specific up to approximately 200 nM c7E3 Fab. Above 200 nM, inhibition was platelet independent, as shown by the inhibition of activity assembled on PS/PC vesicles. c7E3 Fab and DMP728 did not inhibit calcium ionophore-induced activity. DMP728 potency diminished with reaction time (over 6 minutes) whereas c7E3 Fab potency did not. Inhibition by 2 microM DMP728 was not further increased by 20 nM c7E3 Fab. Heparin inhibition of platelet PT activity was additive to that of c7E3 Fab. Studies with added von Willebrand factor (vWf) indicate that in the context of thrombin activation vWf activates platelets through mechanisms independent of GPIIb/IIIa to promote PT activity. Thrombin activation induced binding of FITC-Annexin V to a subpopulation of platelets which was reduced by approximately 50% by pretreatment with either c7E3 Fab or DMP728. Together, these data indicate that c7E3 Fab and DMP728 inhibit the development of GPIIb/IIIa-mediated platelet PT activity at events during platelet activation. The inhibitory activities are not additive, suggesting these agents compete for the same site or inhibit via the same mechanism. Inhibition accompanies a reduction in the number of phosphatidylserine binding sites, implying that GPIIb/IIIa receptor antagonists reduce platelet membrane scrambling induced by thrombin. The additivity of inhibition with heparin by c7E3 Fab suggests a combination of these agents might have a greater bleeding liability than the use of either agent alone.

Transition structures of the ene reactions of cyclopropene.

The transition structures for the ene reactions of cyclopropene with ethylene, propene, and cyclopropene have been located with ab initio molecular orbital calculations and the 6-31G* basis set and by DFT calculations with the Becke3LYP functional and the 6-31G* basis set. Several of the transition structures have also been located with CASSCF calculations. Energies of all stationary points were also evaluated with second-order Møller-Plesset theory using the RHF/6-31G* optimized geometry. The geometries of each transition structure and the energetics of each reaction are discussed and compared to the ene reaction of propene with ethylene. Calculations show that the cyclopropene ene reactions have much lower activation barriers than the propene-ethylene ene reaction, in agreement with experimental results. The transition structures have varying degrees of asynchronicity. The stabilities of the possible radical intermediates for each reaction are reflected in the geometries of the transition structures. The relief of strain in a cyclopropene, when acting as the enophile, accounts for the energetic differences in these reactions. The endo transition structure for the dimerization is lower in energy than the exo transition structure by 2.7 kcal/mol at the Becke3LYP/6-31G* + ZPE level of theory. Secondary orbital overlap of a CH bond of the enophile with the π-system at the central carbon of the ene is proposed to account for the preference for the endo transition structure. Barely stable diradical intermediates have been found for both endo and exo cyclopropene dimerization reactions, but it is likely that they are artifacts of the current level of theory.

Interaction between undulated and Patch leads to an extreme form of spina bifida in double-mutant mice.

The aetiology of spina bifida involves genetic and environmental factors, which may be why major genes contributing to pathogenesis have not been identified. Here we report that undulated-Patch double-mutant mice have a phenotype reminiscent of an extreme form of spina bifida occulta in humans. This unexpected phenotype in double-mutant but not single-mutant mice shows that novel congenital anomalies such as spina bifida can result from interaction between products of independently segregating loci. This example of digenic inheritance may explain the often sporadic nature of spina bifida in humans.

No association or linkage with HLA-DR or -DQ genes in south Indians with pulmonary tuberculosis.

Studies of the HLA class II genes were performed in patients and multiple families with pulmonary tuberculosis from South India to seek any association of disease susceptibility with an individual allele or haplotype. TaqI RFLP analysis of HLA-DRB, -DQA and -DQB genes was done in 38 patients and 36 healthy control subjects. No significant association with any particular allele or haplotype was obtained. Linkage analysis performed in 12 families and haplotype sharing analysis in 9 families showed that the genetic susceptibility to pulmonary tuberculosis was not linked to the HLA region. The results suggest that the RFLP patterns of HLA class II genes DRB, DQA and DQB are not associated with susceptibility to pulmonary tuberculosis and that the genes controlling susceptibility or resistance may be located outside the HLA region.

The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats.

Treatment with the beta-adrenergic agonist isoproterenol suppresses clinical and histological experimental allergic encephalomyelitis in Lewis rats. The effect of isoproterenol treatment is greater when the drug is given from the time of immunization through the acute phase of the illness or from 8 to 14 days post-immunization than when given for the first 7 days after immunization.