Studies of nephrotoxicity due to mixed exposure to styrene and toluene

Adult male Sprague-Dawley rats were treated simultaneously with 4 mmol styrene per kg i.p., twice a day at an interval of 4 h, and 10 mmol toluene per kg once a day, 5 days a week for 4 consecutive weeks. After the last day of treatment, the rats were placed in metabolism cages for collection of urines for 24 h and then were sacrificed. Such mixed exposure produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, glucose and proteins as compared to those with either solvent alone. An increase, but not significant, in the urinary excretion of N-acetyl-beta-D-glucosaminidase was also noticed due to such exposure. Electron microscopic examination of renal cortex 24 h after the mixed exposure showed the appearance of many vacuoles of various sizes surrounded by a single membrane, which were not seen in rats treated with either styrene or toluene alone. Metabolism studies showed only a significant increase in the urinary excretion of hippuric acid due to mixed exposure. These data indicate that under certain conditions, mixed subchronic exposure to styrene and toluene may have the potential to increase further the nephrotoxic response as compared to that of either solvent alone.     

Composition of treatment alliance in bipolar disorder: A cross-sectional study of patients’ perspectives

BACKGROUNDTreatment alliance has an impact on several key patient outcomes in all psychiatric disorders, including bipolar disorder (BD). It has been suggested that the construct of treatment alliance is different among patients from routine psychiatric settings compared to psychotherapeutic settings. However, research on the composition of treatment alliance in psychiatric disorders, such as BD, is relatively limited.AIMTo determine whether a broader construct of treatment alliance was prevalent among outpatients with BD.METHODSThis is a cross-sectional study, conducted in the psychiatric unit of a multi-specialty hospital in north India over 12 mo (September 2018 to September 2019). A consecutive sample of 160 remitted adult outpatients with BD on mood stabilizers for at least a year were selected. The principal instrument to assess treatment alliance was the Working Alliance Inventory-client version (WAI-Client). Other potential constituents of the alliance explored were perceived trust in clinicians assessed by the Trust in Physicians (TRIP) scale, perceived support from clinicians assessed by the Psychosocial Care by Physicians (PCP) scale, and perceived treatment satisfaction assessed by the Patient Satisfaction Questionnaire (PSQ). Associations between scores on all scales were determined by correlational and multiple regression analyses. Exploratory factor analysis of combined items of all scales was conducted using a principal components analysis.RESULTSScores on all the three WAI-Client subscales were significantly correlated with each other (r = 0.66-0.81; P < 0.0001). The total TRIP scores were associated with the total WAI-Client scores (r = 0.28; P < 0.01). The total TRIP scores and the total PCP scores were also significantly associated with the WAI-Client scores on the Task subscale (r = 0.28-0.29; P < 0.01). The total TRIP scores were significantly associated with the total PSQ scores (r = 0.45; P < 0.0001). Factor analysis yielded two independent and coherent factors, which explained 69% of the variance in data. Factor-1 (“alliance and support”), which explained about 41% of the variance, was comprised of a combined WAI-Client goal-task-bond component as well as the PCP support items. Factor-2 (“trust and satisfaction”), which explained about 28% of the variance, consisted of all the TRIP trust and the PSQ treatment satisfaction items.CONCLUSIONA broader construct of treatment alliance in BD was found. Apart from collaborative components, this construct included patients’ perceptions regarding trust in clinicians, support from clinicians, and treatment satisfaction.     

Effects of visible-light irradiation on vitreous structure in the presence of a photosensitizer

Sensitized photo-induced changes of vitreous structure were investigated using both in vivo and in vitro model systems. In the former, rabbit eyes were injected with the photosensitizer riboflavin, and in the latter, calf vitreous samples were treated with riboflavin or Methylene Blue prior to irradiation with white light. The active species of oxygen, i.e. singlet oxygen, superoxide anion, hydroxyl radical and hydrogen peroxide, generated by the photodynamic action of the sensitizer, caused significant liquefaction of the calf vitreous in vitro. There was little liquefaction of the rabbit vitreous in vivo, suggesting the presence of a protective mechanism in vivo. hyaluronidase induced significantly greater liquefaction in vitro than either Methylene Blue or riboflavin. This study suggests that loss of gel vitreous structure can result from extensive depolymerization of hyaluronidase by hyaluronidase and less drastic conformation and molecular weight changes in the photosensitized reactions. Although light-induced liquefaction was less marked than enzyme-induced liquefaction, the mechanism of the former is more pertinent to age-related vitreous synchysis.     

Evidence-Based Nutrition Interventions Improved Adolescents’ Knowledge and Behaviors in Indonesia

Adolescence is a nutritionally vulnerable and critical life stage. However, few programs and policies focus on improving adolescent nutrition in Indonesia. To address this gap, we implemented a gender-responsive package of interventions: (1) breakfast and weekly iron-folic acid supplementation (WIFS), (2) a school-based nutrition education program, and (3) a social behavior change communication strategy. We surveyed 514 adolescents at baseline (2019) and endline (2020) in Klaten and Lombok Barat districts in Indonesia. The survey included a knowledge assessment on nutrition, as well as indicators of attitudes and behaviors on diet, physical activity, and WIFS. We employed multivariable linear and logistic regression to test for pre–post intervention differences. Overall knowledge was significantly higher post-intervention (β: 3.3; 95% confidence interval [CI]: 2.6, 3.9). Diet diversity was high at both timepoints, however, at post-intervention there was significantly higher odds of consuming vitamin A-rich fruits and vegetables (Odds Ratio [OR]: 1.5; 95% CI: 1.1, 2.0) and lower odds of consuming sugar-sweetened beverages (OR: 0.4; 95% CI: 0.3, 0.5). Post-intervention, there was higher odds of reporting 60 min of daily physical activity (OR: 2.3; 95% CI: 1.7, 3.2) and WIFS among girls (OR: 6.7; 95% CI: 1.5, 30.9). The package of interventions may be a promising first step to improving adolescent nutrition in Indonesia.     

Outer membrane protein A (OmpA) from Shigella flexneri 2a: A promising subunit vaccine candidate

Shigellosis is the leading cause of childhood mortality and morbidity. Despite many years of extensive research a practical vaccine is not yet available against the disease. Recent studies illustrate that bacterial outer membrane proteins are budding target as vaccine antigen. Outer membrane proteins A (OmpA) are among the most immunodominant antigens in the outer membrane of gram negative bacteria and possess many characteristics desired of a vaccine candidate. We observe that OmpA of Shigella flexneri 2a is crossreactive and common antigen among Shigella spp. and the epitope is widely exposed on the cell surface as well as capable of evoking protective immunity in mice. The protective immunity involves participation of both the humoral and cellular immune responses, since OmpA boosts rapid induction of IgG and IgA in both the systemic and mucosal compartments and also activates Th1 cells. The immunopotentiating activity of OmpA is mediated by its ability to bind and stimulate macrophages and up-regulate the surface expression of MHCII, CD80 and CD40, leading to activation of CD4⁺ T cells to secrete cytokines and express chemokine receptor and IL-12Rβ2, thereby orchestrating the bridge between innate and adaptive immune responses. This ability is dependent on Toll-like receptor 2 (TLR2), as demonstrated by lack of response by TLR2 knockdown macrophages to OmpA. Hence this property of OmpA to link innate and adaptive immunity via TLR2 offers a novel vista to develop vaccine against shigellosis.     

From the Cover: Rational design of helical architectures

Nature has mastered the art of creating complex structures through self-assembly of simpler building blocks. Adapting such a bottom-up view provides a potential route to the fabrication of novel materials. However, this approach suffers from the lack of a sufficiently detailed understanding of the noncovalent forces that hold the self-assembled structures together. Here we demonstrate that nature can indeed guide us, as we explore routes to helicity with achiral building blocks driven by the interplay between two competing length scales for the interactions, as in DNA. By characterizing global minima for clusters, we illustrate several realizations of helical architecture, the simplest one involving ellipsoids of revolution as building blocks. In particular, we show that axially symmetric soft discoids can self-assemble into helical columnar arrangements. Understanding the molecular origin of such spatial organisation has important implications for the rational design of materials with useful optoelectronic applications.     

Enterovirus infections following T-cell depleted allogeneic transplants in adults

Anecdotally, enteroviruses have been reported to cause serious complications post BMT, but the exact impact of these viruses in the post transplant period has not been reported. We prospectively evaluated stool, urine and throat samples for enteroviruses by viral culture together with relevant body fluids by RT-PCR in 64 allograft recipients receiving grafts T-cell depleted by Campath-1H, following both conventional and reduced-intensity conditioning. Seven patients (10.4%) developed nine episodes of enterovirus infections at a median of 146 days post transplant. Four episodes were associated with symptomatic illnesses, which could be attributable to enteroviruses. There was no mortality directly related to enteroviruses. There was no correlation between dose and mode of Campath-1H use, lymphocyte recovery, IgG and IgA levels and enterovirus isolation. Although enteroviruses tended to be more frequent in TBI-based conventional conditioning recipients, the only significant risk factor for enterovirus infection was unrelated donor graft. The low incidence of the severe enterovirus infections could have been related to a low lymphocyte count in this cohort in the absence of GVHD, particularly CD4+ count, which has been implicated in tissue damage in experimental animals. Further studies are needed to define its impact in different allograft settings.     

Roles of a 67-kDa polypeptide in reversal of protein synthesis inhibition in heme-deficient reticulocyte lysate.

During heme deficiency in reticulocyte lysates, the heme-regulated protein synthesis inhibitor, HRI, phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF-2) and thus inhibits protein synthesis. Two factors, eIF-2 and a reticulocyte-lysate supernatant factor that we term RF, reverse this inhibition. We now report the following. (i) An active eIF-2 preparation contained, in addition to the three subunits (alpha, beta, and gamma), a 67-kDa polypeptide. Pretreatment of eIF-2 with polyclonal antibodies against either isolated alpha subunit or 67-kDa polypeptide almost completely inhibited the reversal activity. Upon further fractionation, three-subunit eIF-2 and the 67-kDa polypeptide were resolved. Neither the three-subunit eIF-2 nor the 67-kDa polypeptide alone was active in protein synthesis inhibition reversal. The activity was, however, restored by combining both the three-subunit eIF-2 and the 67-kDa polypeptide. (ii) Active RF preparations contained eIF-2 alpha (unphosphorylated) and beta subunits and the 67-kDa polypeptide. As with eIF-2, prior treatment of the RF preparation with antibodies to either the alpha subunit or the 67-kDa polypeptide almost completely inhibited the reversal activity. The RF preparation devoid of eIF-2 gamma subunit did not form ternary complex (Met-tRNA(fMet).eIF-2.GTP). The eIF-2 gamma subunit in the free form was isolated, and addition of this isolated gamma subunit to RF promoted significant ternary-complex formation. (iii) Purified HRI efficiently phosphorylated the alpha subunit in the three subunit eIF-2. However, the extent of such phosphorylation was significantly reduced when eIF-2 containing the 67-kDa polypeptide was used. The 67-kDa polypeptide apparently protected eIF-2 alpha subunit from HRI-catalyzed phosphorylation but did not inhibit HRI activity. Based on these results, we suggest that the protein synthesis inhibition reversal activity in both eIF-2 and RF is due to the same components--namely, eIF-2 alpha subunit and the 67-kDa polypeptide. The 67-kDa polypeptide protects eIF-2 alpha subunit from HRI-catalyzed phosphorylation and may also be a necessary component of the functioning eIF-2 molecule.     

Detection and characterization of HIV type 2 in Calcutta, India

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.