Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid.

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.

Opioid Receptor Modulators with a Cinnamyl Group.

To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist weaker than alvimopan (1). We replaced the arylpiperidine unit by an arylpiperazine to obtain the 1-(α-carboxycinnamyl)-4-arylpiperazines like 13h, which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of arylpiperazines 4 and 5 were reported to be pan opioid receptor antagonists, while 6 was a MOR agonist. Two compounds (13l and 11b) showed analgesic response in tail flick test which was blocked by pretreatment with norbinaltorphimine (norBNI). Among 10 1-(α-carboxycinnamyl)-4-arylpiperidines, compound 28g and five others were specific MOR antagonists. Interestingly, compound 26b of this series was found to be more potent than naloxone but weaker than 1. Docking studies have explained differential activities of the above piperazines and piperidines.

Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV.

BACKGROUND: Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE: To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION: Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION: It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

Nucleic acid testing: Is it the only answer for safe Blood in India?

BACKGROUND: With the implementation of NAT in countries around the world, there is a growing pressure on the transfusion services in India to adopt NAT testing. India has about 2545 licensed Blood Centres. The Transfusion Services in India are fragmented, poorly regulated and the quality standards are poorly implemented. Blood Centres are still dependent on replacement/family donors and in most places laboratory testing for Transfusion transmitted infections is not quality assured, laboratory equipment are not calibrated and maintained, and validation of results is not carried out. Against the current scenario introducing NAT for screening of blood donors in India would pose a challenge. AIM: To study the prudence of universal NAT testing in India. MATERIALS AND METHODS: A retrospective study of 5 years from 2008-2012 was undertaken to study the true reactivity of donors using WHO strategy II and III and therefore the true seroprevalence of TTI infections in the donor populations. RESULTS: The true reactivity of the donors was much less as compared to the initially reactive donors due to the use of a well designed testing algorithm. In addition having a total voluntary blood collection along with good pre-donation counseling program also reduces the transmission of infections. CONCLUSIONS: What India essentially needs to do is religiously implement the strategies outlined in the WHO Aide-memoire. The blood should be collected only from voluntary non remunerative and repeat donors, there should be stringent donor selection with pre-donation counseling instituted. Strict implementation of quality management system, development of well defined testing startegies and strong haemovigilance system could take us a step in the right direction.

Comparison of flexural strength in three types of denture base resins: An in vitro study.

AIM: The aim of this study was to evaluate whether the flexural strength of a commercially available, heat polymerized acrylic denture base material could be improved using reinforcements. MATERIALS AND METHODS: A total of 30 specimens (65 mm × 10 mm × 3 mm) were fabricated; the specimens were divided into three groups with 10 specimens each. They were Group 1 - conventional denture base resins, Group 2 - high impact denture base resins, and Group 3 - glass reinforced denture base resins. The specimens were loaded until failure on a three-point bending test machine. An one-way analysis of variance was used to determine statistical differences among the flexural strength of three groups. Data were analyzed by SPSS software version 21.0© (IBM Corporation, Armonk, NY, USA) and the results were obtained. RESULTS: The flexural strength values showed statistically significant differences among experimental groups (P < 0.005). CONCLUSION: Within the limitations of the study polymethyl methacrylate (PMMA) reinforced with glass fibers showed the highest flexural strength values this was followed by PMMA reinforced with butadiene styrene, and the least strength was observed in the conventional denture base resins.

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration.

BACKGROUND: The kallikrein-kinin system (KKS) is an endogenous pathway involved in angiogenesis and tumourigenesis, both vital for cancer growth and progression. OBJECTIVES: To investigate the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumour (DU145) and micro-vascular endothelial cells (dMVECs). METHODS: Increasing concentrations of selective B1R and B2R agonists were added to cultured cells. Cell proliferation and migration were assessed using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and modified Boyden Chamber assays, respectively. Where significant stimulation was found, the influence of an antagonist was also investigated. RESULTS: Neither growth nor motility of endothelial cells was affected by either agonist. In DU145 cells, while the B2R agonist was without any significant effect, the B1R agonist stimulated proliferation and migration at concentrations of 10nM and 50nM respectively. Further, this effect was abrogated when cells were pre-incubated with a B1R antagonist. CONCLUSIONS: Unlike the physiologically-active B2R, the pathologically-inducible B1R may be implicated in prostate tumourigenic events. The involvement of the KKS in malignant prostate pathology supports on-going exploration of bradykinin receptor antagonists as target candidates in the development of alternate approaches to cancer therapy.

Can everyone become highly intelligent? Cultural differences in and societal consequences of beliefs about the universal potential for intelligence.

We identify a novel dimension of people's beliefs about intelligence: beliefs about the potential to become highly intelligent. Studies 1-3 found that in U.S. American contexts, people tend to believe that only some people have the potential to become highly intelligent. In contrast, in South Asian Indian contexts, people tend to believe that most people have the potential to become highly intelligent. To examine the implications of these beliefs, Studies 4-6 measured and manipulated Americans' beliefs about the potential for intelligence and found that the belief that everyone can become highly intelligent predicted increased support for policies that distribute resources more equally across advantaged and disadvantaged social groups. These findings suggest that the belief that only some people have the potential to become highly intelligent is a culturally shaped belief, and one that can lead people to oppose policies aimed at redressing social inequality.

Coexisting iodine avid and iodine nonconcentrating lesions with multiple distant soft tissue metastasis in papillary thyroid cancer.

Distant soft tissue metastasis and the simultaneous presence of iodine concentrating and nonconcentrating lesions in papillary thyroid cancer are extremely rare. The concerned patient, a histopathologically proven case of papillary thyroid cancer with nodal metastases treated with total thyroidectomy, bilateral cervical nodal dissection, and radioablation, subsequently developed lung, muscle, and liver metastasis. Triggered by increased thyroglobulin, the iodine-131 whole body scan and 200 mci iodine-131 post-therapy scan showed a left gluteus maximus lesion and a liver lesion. Fludeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) scan intended to find additional lesions revealed iodine and FDG nonconcentrating bilateral pulmonary nodules and a single FDG avid hepatic and two muscle metastases. Although FDG concentration in metastatic pulmonary nodules is generally low, the CT characteristics were classical for metastatic lesion. A follow-up FDG PET-CT study six months after 200 mci iodine-131 radioablation showed treatment response in muscle and liver lesions but not lungs.

Deference in Indians' decision making: introjected goals or injunctive norms?

We examine the claim that Indians are more likely than Americans to act deferentially in the presence of authority figures and explore 2 possible psychological mechanisms for this cultural difference: introjected goals and injunctive norms. Studies 1 and 2 showed that after reflecting upon an authority's expectations, Indians were more likely than Americans to make clothing and course choices consistent with the authority's expectations, but there was no such cultural difference for peers' expectations. Study 3 showed that merely activating the concept of authority figures, without highlighting specific expectations, was sufficient to influence Indians' choices but not their evaluations. Examining a more basic distinction underlying introjected goals versus injunctive norms, Study 4 showed that authority primes influenced Indians' sense of what they should do but not what they want to do. Study 5 showed that, inconsistent with the internalized goal mechanism, the effect of explicit authority primes did not increase after brief delays. However, Indian participants who were less likely to accommodate to the salient authority experienced more guilt across delay conditions, which supported the injunctive norms mechanism. The findings suggest that manipulating injunctive norms can be an effective means for inducing or eliminating deferential behaviors in Indian settings.

Beliefs about emotional residue: the idea that emotions leave a trace in the physical environment.

Drawing upon the literatures on beliefs about magical contagion and property transmission, we examined people's belief in a novel mechanism of human-to-human contagion, emotional residue. This is the lay belief that people's emotions leave traces in the physical environment, which can later influence others or be sensed by others. Studies 1-4 demonstrated that Indians are more likely than Americans to endorse a lay theory of emotions as substances that move in and out of the body, and to claim that they can sense emotional residue. However, when the belief in emotional residue is measured implicitly, both Indians and American believe to a similar extent that emotional residue influences the moods and behaviors of those who come into contact with it (Studies 5-7). Both Indians and Americans also believe that closer relationships and a larger number of people yield more detectable residue (Study 8). Finally, Study 9 demonstrated that beliefs about emotional residue can influence people's behaviors. Together, these finding suggest that emotional residue is likely to be an intuitive concept, one that people in different cultures acquire even without explicit instruction.

The determination of cobalt(II) at DME using catalytic hydrogen current technique in various water samples, agricultural materials and pharmaceuticals.

Two novel and facile ligands ammonium piperidine dithiocarbamate (Amm Pip-DTC) and ammonium morpholine dithiocarbamate (Amm Mor-DTC) were synthesized for the development of rapid and cost effective catalytic hydrogen current technique to analyze cobalt(II) in the presence of NH(4)Cl-NH(4)OH at pH 7.8 and 8.4 with Amm Pip-DTC and Amm Mor-DTC. These ligands produce catalytic hydrogen currents with Co(II) at peak potentials -1.24 V and -1.44 V vs. SCE respectively. Quantitative experimental conditions are developed by studying effect of pH, supporting electrolyte (NH(4)Cl), ligand and metal ion concentrations and effect of adverse ions on peak height to improve the sensitivity, selectivity and detection limits of the catalytic hydrogen current technique and compared it in terms of Student's t test and variance ratio f test with differential pulse polarographic (DPP) method. The developed technique was applied for the analysis of cobalt(II) in various water samples, agricultural materials and pharmaceuticals and the results obtained are in good agreement with the DPP data.

Cultural conditioning: understanding interpersonal accommodation in India and the United States in terms of the modal characteristics of interpersonal influence situations.

We argue that differences between the landscapes of influence situations in Indian and American societies induce Indians to accommodate to others more often than Americans. To investigate cultural differences in situation-scapes, we sampled interpersonal influence situations occurring in India and the United States from both the influencee's (Study 1) and the influencer's (Study 2) perspectives. We found that Indian influence situations were dramatically more likely than U.S. situations to feature other-serving motives and to result in positive consequences for the relationship. Yet Study 3 found that targets of influence felt no less free to decide whether to accommodate in India than the United States, but felt more concerned about the influencer. To investigate the effects of situation-scapes on people's expectations and decisions, we exposed Indian and American participants to descriptions of situations from both societies (with their origins obscured). Study 4 found that both groups of participants expected more positive consequences from accommodation in Indian situations than in American situations. Finally, Study 5 found that both groups decided to accommodate more often in Indian situations than in American situations. At the same time, Indian participants were more likely than Americans to accommodate across all situations, but both groups converged over 100 trials as they were exposed to more and more situations drawn from each other's cultures. We interpret these effects in terms of the default decisions or biases conditioned by people's recently encountered situations.

What counts as a choice? U.S. Americans are more likely than Indians to construe actions as choices.

People everywhere select among multiple alternatives, but are they always making choices? In five studies, we found that people in U.S. American contexts, where the disjoint model of agency is prevalent, are more likely than those in Indian contexts to construe their own and other individuals' behaviors as choices, to construe ongoing behaviors and behaviors recalled from memory as choices, to construe naturally occurring and experimentally controlled behaviors as choices, to construe mundane and important actions as choices, and to construe personal and interpersonal actions as choices. Indians showed a greater tendency to construe actions as choices when these actions involved responding to other people than when they did not. These findings show that whether people construe actions as choices is significantly shaped by sociocultural systems of meanings and practices. Together, they suggest that the positive consequences associated with maximizing the availability of personal choice may not be universal and instead may be limited to North American contexts.

Tracking based baseline restoration for acquisition of impedance cardiogram and other biosignals.

Most of the biosignals have a baseline which may drift over a large range compared to the excursion of the signal of interest. To make effective use of the input dynamic range of the signal acquisition setup, this offset drift needs to be cancelled. The circuit reported here uses amplitude tracking technique for estimation and removal of the baseline drift. This circuit is independent of the processor to which the signal acquisition unit is interfaced.

Exposure assessment to synthetic food colours of a selected population in Hyderabad, India.

An exposure assessment of synthetic food colours was carried out among 1-5- and 6-18-year-old individuals by the food frequency method. Children had an intake of solid food consumption in the range 2-465 g day(-1) and liquid food consumption in the range 25-840 ml day(-1) with added colours. Among the eight permitted colours in India, six were consumed by the subjects of the study. The intakes of some subjects exceeded the acceptable daily intake for colours such as tartrazine, sunset yellow and erythrosine, which is 7.5, 2.5 and 0.1 mg kg(-1) body weight, respectively. Therefore, a uniform permissible limit of 100 mg kg(-1) prescribed under the Prevention of Food Adulteration Act in India for all foods is not justified. The limits need to be revised according to the Codex Alimentarius Commission, which permits different maximum levels of additives to various food categories based on both the extent of consumption and the technological justification for its use.

Electrochemical study of potassium isobutyl xanthate at a mercury electrode.

Polarographic studies of potassium isobutyl xanthate at a mercury electrode reveal that the product of an anodic reaction is strongly adsorbed at the mercury surface, as indicated by a prewave. The adsorbed film greatly affects the characteristics of the anodic wave of xanthate in an aqeous medium. The current of total wave is proportional to the concentration of xanthate from 0.32 to 1.6 mM.

Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems.

The objective of the work is physicochemical characterization of meloxicam (ME)-cyclodextrin (CD) binary systems both in solution and solid states and to improve the dissolution properties of meloxicam via complexation with alpha-, beta- and gamma-cyclodextrins. Detection of inclusion complexation was done in solution state by means of phase solubility analysis, mass spectrometry and 1H nuclear magnetic resonance (NMR) studies, and in solid state using differential scanning calorimetry (DSC), powder X-ray diffractometry, and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H NMR studies in solution state revealed 1:1M complexation of meloxicam with all CDs. A true inclusion of ME with gamma-CD at 1:1 and 1:2M in solid state was confirmed by DSC, powder XRD and scanning electron microscopy (SEM) studies. Dissolution properties of ME-CDs binary systems were superior when compared to pure ME.

Cystic disease of the liver following prenatal and perinatal exposure to aflatoxin B1 in rats.

Experiments were designed to elucidate the differences, if any, in the liver histology induced by aflatoxin B in newborn and adult animals. The transfer of toxic metabolites from pregnant rats to their litters was confirmed by thin layer chromatography of liver homogenates in the latter. Extensive cystic lesions of the biliary and hepatic type developed only in young animals. Multifocal hepatic necrosis, bile ductular proliferation, areas of altered hepatocytes, neoplastic nodules and hepatocellular carcinoma constituted the total spectrum in both adult and newborn animals. Increased susceptibility to the toxins early in life appears to be responsible for this intriguing phenomenon. These aspects may have a bearing on the genesis of childhood liver disease.