Solubility enhancement of fexofenadine using self-nano emulsifying drug delivery system for improved biomimetic attributes.

BACKGROUND: Fexofenadine is a poorly water-soluble drug, which limit its bioavailability and ultimately therapeutic efficacy. Liquid self-nano emulsifying drug delivery system (L-SNEDDs) is an approach that can enhance the solubility of fexofenadine by increasing its surface area and reducing the particle size, which increases the rate and extent of drug dissolution. METHOD: In this investigation, L-SNEDDs of fexofenadine was made up using surfactants and co-surfactant. The SNEDDS formulation was optimized using a pseudo-ternary phase diagram and characterized. RESULTS: The optimized L-SNEDDS incorporated fexofenadine were thermodynamically stable and showed mean droplet size and zeta potential of 155nm and -18mV, respectively unaffected by the media pH. In addition, the viscosity, and refractive index were observed 18.4 and 1.49 cps, respectively for optimized L-SNEDDS fortified fexofenadine. The results of Fourier transform infrared spectroscopy revealed an insignificant interaction between the fexofenadine and excipients. A drug loading efficiency of 94.20% resulted with a complete in vitro drug release in 2h, compared with the pure drug, which demonstrate significant improvement in the efficacy. Moreover, these results signify that on further in vivo assessment L-SNEDDS fortified fexofenadine can indicate improvement in pharmacokinetic and clinical outcome. CONCLUSION: Thus, the investigation revealed that, the L-SNEDDs incorporated fexofenadine was most effective with a mixture of surfactant and co-surfactant with improved solubility intend to relieve pain associated with inflammation with single-dose oral administration.

Evaluating the efficacy of bacterial consortium for decolorization of diazo dye mixture.

Textile wastewater contains dyes mixed with other contaminants in various concentrations. Bacteria-mediated decolorization and degradation of azo dyes have achieved momentum as a method of treatment attributed to their inexpensive, eco-friendly, and application to a wide range of azo dyes. However, a single species of bacteria is inefficient in decolorizing diverse groups of dyes which is one of the most significant challenges for environmental technologists working in bioremediation. In the present study, an aerobic bacterial consortium AUJ consisting of six different bacterial strains (Pseudomonas stutzeri AK1, Pseudomonas stutzeri AK2, Pseudomonas stutzeri AK3, Bacillus spp. AK4, Pseudomonas stutzeri AK5, and Pseudomonas stutzeri AK6) removed the individual azo dyes in the 24-94% range when used in more than 200 ppm concentration within 72-96 h. In addition, the consortium was able to decolorize 52.19% mixed dyes (100 ppm) and 44.55% Acid blue 113 when used at a concentration as high as 1100 ppm within 96 h. Optimization of various nutritional and environmental parameters revealed that glucose and yeast extract were the preferred carbon and nitrogen source, respectively, and analysis of treated dye products using high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography-mass spectrometry (GC-MS) confirmed the breakdown of dye. In all, we present a bacterial consortium with a good ability of dye decolorization that can be used for degrading a wide variety of azo dyes.

Enhancement of Zika virus infection by antibodies from West Nile virus seropositive individuals with no history of clinical infection.

BACKGROUND: Recent outbreaks of Zika Virus (ZIKV) infection and associated microcephaly has raised multiple scientific questions. The close antigenic relatedness between flaviviruses makes diagnosis of specific infection difficult. This relatedness also raises the potential of Antibody Dependent Enhancement (ADE) via cross reactive antibodies to flaviviruses like West Nile Virus (WNV) and Dengue Virus (DENV). Asymptomatic WNV infections are endemic throughout the US creating a large proportion of the population that is seropositive for WNV antibodies. Whether these sero-positive individuals potentially carry ZIKV enhancing antibodies remains unknown. RESULTS: Serum samples obtained from human subjects with symptomatic or asymptomatic WNV infection from a WNV endemic region in Texas were tested for their ability to enhance or neutralize ZIKV infection. Sero-surveillance data demonstrated a ~ 7% prevalence for WNV antibodies in the population. Sera from both symptomatic and asymptomatic WNV seropositive donors effectively neutralized WNV and to some extent DENV infection. Interestingly, WNV+ sera failed to inhibit ZIKV while significantly enhancing infection. Conversely, ZIKV specific sera effectively neutralized ZIKV, with ADE only evident at lower concentrations. The enhancement of ZIKV via WNV antibody positive sera was likely due to non-neutralizing Envelope (E) antibodies as seen with monoclonal ZIKV E antibodies. CONCLUSIONS: Overall, our findings suggest that WNV antibodies in the sera significantly enhance ZIKV infection in Fc receptor positive cells with limited neutralization activity. Further studies in more relevant models of ADE will be needed to confirm the relevance of these findings in vivo.

Combination gene therapy for HIV using a conditional suicidal gene with CCR5 knockout.

BACKGROUND: Gene therapy approaches using hematopoietic stem cells to generate an HIV resistant immune system have been shown to be successful. The deletion of HIV co-receptor CCR5 remains a viable strategy although co-receptor switching to CXCR4 remains a major pitfall. To overcome this, we designed a dual gene therapy strategy that incorporates a conditional suicide gene and CCR5 knockout (KO) to overcome the limitations of CCR5 KO alone. METHODS: A two-vector system was designed that included an integrating lentiviral vector that expresses a HIV Tat dependent Thymidine Kinase mutant SR39 (TK-SR39) and GFP reporter gene. The second non-integrating lentiviral (NIL) vector expresses a CCR5gRNA-CRISPR/Cas9 cassette and HIV Tat protein. RESULTS: Transduction of cells sequentially with the integrating followed by the NIL vector allows for insertion of the conditional suicide gene, KO of CCR5 and transient expression of GFP to enrich the modified cells. We used this strategy to modify TZM cells and generate a cell line that was resistant to CCR5 tropic viruses while permitting infection of CXCR4 tropic viruses which could be controlled via treatment with Ganciclovir. CONCLUSIONS: Our study demonstrates proof of principle that a combination gene therapy for HIV is a viable strategy and can overcome the limitation of editing CCR5 gene alone.

Effect of Mindfulness-Based Art Therapy (MBAT) on Psychological Distress and Spiritual Wellbeing in Breast Cancer Patients Undergoing Chemotherapy.

OBJECTIVES: Psychological distress and spiritual well-being (SWB) are directly related to the quality of life in cancer patients. Mindfulness-Based Art Therapy (MBAT) integrates mindfulness practices with art therapy and has shown to decrease distress levels and improve SWB in women with breast cancer. The objective of the study was to identify the effects of a 1-week MBAT intervention on psychological distress and SWB in breast cancer patients undergoing chemotherapy. MATERIALS AND METHODS: This was a single group, pre-test post-test study carried out in a clinical setting. The psycho-oncology assessment questionnaire, Distress Thermometer (DT) and Functional Assessment of Chronic Illness Therapy-SWB Scale 12 (FACIT-SP12) Version 4 were administered before, post1st supervised MBAT session and post 1 week of home practice to breast cancer patients undergoing chemotherapy (n = 30). The MBAT intervention included mindfulness meditation for 15 min and mindful coloring for 30 min daily for 1 week. Data analysis was done using R i386 4.0.3. RESULTS: The median DT score significantly decreased from pre-session to immediate post-session and pre-session to post 1-week session. The median of meaning, peace, and faith subscales of FACIT SP12 scores along with total FACIT SP12 score significantly increased from pre-session to immediate post-session as well as from pre-session to post 1 week. CONCLUSION: One-week MBAT intervention for breast cancer patients undergoing chemotherapy significantly decreased the psychological distress and significantly improved the SWB in terms of meaning, peace, and faith.

A case series of patients with left ventricular assist devices and concomitant mechanical heart valves.

Mechanical heart valves left in situ at the time of left ventricular assist device (LVAD) implantation are thought to potentially increase the risk of thromboembolism. Recommendations exist to replace dysfunctional mechanical mitral valves and any mechanical aortic valves at the time of LVAD implantation. Due to potential increases in cardiopulmonary bypass time and associated comorbidities with valve replacement, leaving a functional mechanical valve in place at LVAD implantation has been suggested to be a safe option. We retrospectively reviewed all patients with prior mechanical mitral or aortic valves undergoing LVAD implantation at our center between 2012 and 2017. Echocardiograms were read by a single cardiologist to assess for mechanical valve dysfunction. We identified 15 patients. Five patients had major bleeding requiring transfusion. On follow-up, 2 patients had hemorrhagic stroke and 2 had transient ischemic attach/ischemic stroke. In addition, 2 patients had LVAD thrombosis and 2 patients had LVAD driveline malfunction. Mild mechanical valve regurgitation was identified on follow-up echocardiograms of 2 patients. Rate of complications in patients with mechanical valves undergoing LVAD implantation was comparable to that reported for the general LVAD population. Leaving a functional mechanical valve in place at the time of LVAD implantation could be a reasonable alternative to valve replacement. More data are required to further guide patient care in these individuals.

Elevated Heart Rate Following Heart Transplantation Is Associated With Increased Graft Vasculopathy and Mortality.

BACKGROUND: The effect of elevated heart rate (HR) on outcomes after heart transplantation (HT) has not been well established. The aim of this study was to assess predictors of elevated HR following HT and its impact on outcomes. METHODS AND RESULTS: We retrospectively evaluated 394 patients who underwent HT at 2 academic medical centers from 2005 to 2016. Patients were divided into 2 groups based on HR 1 year after HT: HR ≥95 beats/min (n = 162; 41%) and HR <95 beats/min (n = 232; 59%). Median follow-up time was 6.6 (interquartile range [IQR] 2.2-7.5) years. HR ≥95 beats/min 1 year after HT was associated with younger donor age, whereas HR <95 beats/min was associated with heavy donor alcohol use and African-American recipient race. Left ventricular (LV) end-diastolic dimension, mass, and ejection fraction were lower and E/E' higher in the HR ≥95 group at the time of the last follow up. HR ≥95 beats/min at 1 year after HT was independently associated with the development of cardiac allograft vasculopathy and increased mortality. CONCLUSIONS: HR ≥95 beats/min 1 year after HT is associated with a reduction in LV size and function, increased incidence of cardiac allograft vasculopathy, and reduced survival. Studies investigating the effect of medical HR reduction on post-HT outcomes are warranted.

TLR9 polymorphism correlates with immune activation, CD4 decline and plasma IP10 levels in HIV patients.

BACKGROUND: The mechanism behind HIV mediated immune activation remains debated, although the role of virus replication in this process is increasingly evident. Toll like Receptor 9 (TLR9) has been implicated in HIV mediated immune activation via sensing of viral CpG DNA. Polymorphisms in the TLR9 gene and promoter region including TLR9 1635A/G and 1486C/T have been found to be associated with multiple infectious diseases and cancers. METHODS: In the current study, we looked at the correlation of TLR9 polymorphisms 1635A/G and 1486C/T with key hallmarks of HIV disease in a cohort of 50 HIV infected patients. We analyzed CD4 counts, T cell immune activation characterized by upregulation of CD38 and HLA-DR and upregulation of plasma biomarkers of inflammation like LPS, sCD14, IL-6 and IP10 in the HIV patient cohort and compared it to healthy controls. RESULTS: We found that TLR9 1635AA genotype was associated with lower CD4 counts and significantly higher immune activation in both CD4+ and CD8+ T cells. Analysis of HIV associated plasma biomarkers including LPS, sCD14, IL-6 and IP10 revealed a strong correlation between IP10 and immune activation. Interestingly, IP10 levels were also found to be higher in HIV patients with the 1635AA genotype. Furthermore, the TLR9 1486C/T polymorphism that is in linkage disequilibrium with 1635A/G was weakly associated with lower CD4 counts, higher CD8 immune activation and higher IP10 levels. CONCLUSIONS: As TLR9 stimulation is known to induce IP10 production by dendritic cells, our findings provide new insights into HIV mediated immune activation and CD4 loss. TLR9 stimulation by viral CpG DNA may be important to HIV immunopathogenesis and the TLR9 polymorphisms 1635A/G and 1486C/T may be associated with disease progression.

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus.

Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (C-prM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.

HIV-1 Env Glycoprotein Phenotype along with Immune Activation Determines CD4 T Cell Loss in HIV Patients.

The mechanism behind the selective depletion of CD4(+) cells in HIV infections remains undetermined. Although HIV selectively infects CD4(+) cells, the relatively few infected cells in vivo cannot account for the extent of CD4(+) T cell depletion, suggesting indirect or bystander mechanisms. The role of virus replication, Env glycoprotein phenotype, and immune activation (IA) in this bystander phenomenon remains controversial. Using samples derived from HIV-infected patients, we demonstrate that, although IA in both CD4(+) and CD8(+) subsets correlates with CD4 decline, apoptosis in CD4(+) and not CD8(+) cells is associated with disease progression. Because HIV-1 Env glycoprotein has been implicated in bystander apoptosis, we cloned full-length Envs from plasma of viremic patients and tested their apoptosis-inducing potential (AIP). Interestingly, AIP of HIV-1 Env glycoproteins were found to correlate inversely with CD4:CD8 ratios, suggesting a role of Env phenotype in disease progression. In vitro mitogenic stimulation of PBMCs resulted in upregulation of IA markers but failed to alter the CD4:CD8 ratio. However, coculture of normal PBMCs with Env-expressing cells resulted in selective CD4 loss that was significantly enhanced by IA. Our study demonstrates that AIP of HIV-1 Env and IA collectively determine CD4 loss in HIV infection.

Availability and use of magnesium sulphate at health care facilities in two selected districts of North Karnataka, India.

BACKGROUND: Pre-eclampsia and eclampsia are major causes of maternal morbidity and mortality. Magnesium sulphate is accepted as the anticonvulsant of choice in these conditions and is present on the WHO essential medicines list and the Indian National List of Essential Medicines, 2015. Despite this, magnesium sulphate is not widely used in India for pre-eclampsia and eclampsia. In addition to other factors, lack of availability may be a reason for sub-optimal usage. This study was undertaken to assess the availability and use of magnesium sulphate at public and private health care facilities in two districts of North Karnataka, India. METHODS: A facility assessment survey was undertaken as part of the Community Level Interventions for Pre-eclampsia (CLIP) Feasibility Study which was undertaken prior to the CLIP Trials (NCT01911494). This study was undertaken in 12 areas of Belagavi and Bagalkote districts of North Karnataka, India and included a survey of 88 facilities. Data were collected in all facilities by interviewing the health care providers and analysed using Excel. RESULTS: Of the 88 facilities, 28 were public, and 60 were private. In the public facilities, magnesium sulphate was available in six out of 10 Primary Health Centres (60%), in all eight taluka (sub-district) hospitals (100%), five of eight community health centres (63%) and both district hospitals (100%). Fifty-five of 60 private facilities (92%) reported availability of magnesium sulphate. Stock outs were reported in six facilities in the preceding six months - five public and one private. Twenty-five percent weight/volume and 50% weight/volume concentration formulations were available variably across the public and private facilities. Sixty-eight facilities (77%) used the drug for severe pre-eclampsia and 12 facilities (13.6%) did not use the drug even for eclampsia. Varied dosing schedules were reported from facility to facility. CONCLUSIONS: Poor availability of magnesium sulphate was identified in many facilities, and stock outs in some. Individual differences in usage were identified. Ensuring a reliable supply of magnesium sulphate, standard formulations and recommendations of dosage schedules and training may help improve use; and decrease morbidity and mortality due to pre-eclampsia/ eclampsia. TRIAL REGISTRATION: The CLIP trial was registered with ClinicalTrials.gov ( NCT01911494 ).

The feasibility of task-sharing the identification, emergency treatment, and referral for women with pre-eclampsia by community health workers in India.

BACKGROUND: Hypertensive disorders are the second highest direct obstetric cause of maternal death after haemorrhage, accounting for 14% of maternal deaths globally. Pregnancy hypertension contributes to maternal deaths, particularly in low- and middle-income countries, due to a scarcity of doctors providing evidence-based emergency obstetric care. Task-sharing some obstetric responsibilities may help to reduce the mortality rates. This study was conducted to assess acceptability by the community and other healthcare providers, for task-sharing by community health workers (CHW) in the identification and initial care in hypertensive disorders in pregnancy. METHODS: This study was conducted in two districts of Karnataka state in south India. A total of 14 focus group discussions were convened with various community representatives: women of reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N = 3), and community leaders (N = 3). One-to-one interviews were held with medical officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health administrators (N = 2), Taluka (county) health officers (N = 2), and obstetricians (N = 4). All data collection was facilitated by local researchers familiar with the setting and language. Data were subsequently transcribed, translated and analysed thematically using NVivo 10 software. RESULTS: There was strong community support for home visits by CHW to measure the blood pressure of pregnant women; however, respondents were concerned about their knowledge, training and effectiveness. The treatment with oral antihypertensive agents and magnesium sulphate in emergencies was accepted by community representatives but medical practitioners and health administrators had reservations, and insisted on emergency transport to a higher facility. The most important barriers for task-sharing were concerns regarding insufficient training, limited availability of medications, the questionable validity of blood pressure devices, and the ability of CHW to correctly diagnose and intervene in cases of hypertensive disorders of pregnancy. CONCLUSION: Task-sharing to community-based health workers has potential to facilitate early diagnosis of the hypertensive disorders of pregnancy and assist in the provision of emergency care. We identified some facilitators and barriers for successful task-sharing of emergency obstetric care aimed at reducing mortality and morbidity due to hypertensive disorders of pregnancy.

Multi-walled carbon nanotubes applied through seed-priming influence early germination, root hair, growth and yield of bread wheat (Triticum aestivum L.).

BACKGROUND: Reports of multi-walled carbon nanotubes (MWCNTs) incorporated into plants have indicated better yield and productivity, yet the phenomena need in-depth understanding especially when agricultural crops are tested. We primed wheat seeds with MWCNTs to understand the effects on germination, growth, anatomy, physiology and yield. RESULT: This study, carried out in field conditions, is a step forward over the previous reports. Early germination, excessive root hair, denser stomata and larger root length result in faster growth and higher yield of wheat plants. Denser root hair facilitated the uptake of both water and essential minerals such as phosphorus (P) and potassium (K), which boosted the crop yield by significantly improving grain yield per plant from 1.53 to 2.5 g, a 63% increase. Increase in cell elongation by 80% was recorded, while xylem and phloem sizes dilated to almost 83% and 85% of control, thus enhancing their capacity to conduct water and nutrients. CONCLUSION: Augmented growth of MWCNT-primed wheat, enhancement in grain number, biomass, stomatal density, xylem-phloem size, epidermal cells, and water uptake is observed while finding no DNA damage. This opens up an entirely new aspect to using cost-effective nanomaterials (the MWCNTs were produced in-house) for enhancing the performance of crop plants. © 2017 Society of Chemical Industry.

Eligibility criteria for therapeutic hypothermia: From trials to clinical practice.

AIM: Whole body therapeutic hypothermia (TH) for hypoxic ischaemic encephalopathy was introduced into clinical practice in New South Wales (NSW) and Australian Capital Territory in 2007. State-wide policy adopting the eligibility criteria and practice based on trial-designs was published in 2009. METHODS: The study was conducted by retrospectively reviewing medical records of all TH infants born between 2007 and 2011 in NSW and Australian Capital Territory to examine if eligibility criteria (assessed against evidence-based policy directives) were met. RESULTS: A total of 207 infants received TH, 104 (50%) did not meet the eligibility criteria defined in NSW policy directive. Over the 5-year period, the proportion of infants meeting the eligibility criteria did not change. Seventy percent of infants (73 out of 104) not meeting eligibility criteria did not fulfil the criteria for 'evidence of asphyxia', although half of them met 'moderate or severe encephalopathy criterion'. Adverse events (hypotension, coagulopathy and arrhythmia), were more common in the 'criteria met' group than the 'criteria not met' group (89 vs. 71%, P = 0.001). Similar proportions of infants had TH discontinued before 72 h (criteria met: 32 (31%) vs. criteria not met: 27(26%)). Most frequent reason for early cessation was 'palliation' (19/32, 59%) in criteria met and 'clinical improvement' (16/27, 59%) in criteria not met group. CONCLUSIONS: Many TH infants were treated based on clinician judgement, though not meeting the trial-design policy criteria. Early TH cessation (<72 h) was common. Future studies are warranted on long-term neurodevelopmental outcomes for all infants receiving TH particularly those with early cessation of therapy.

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial.

BACKGROUND: Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS: In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS: The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

GGA and Arf proteins modulate retrovirus assembly and release.

The Gag protein is the major structural determinant of retrovirus assembly. Although a number of cellular factors have been reported to facilitate retrovirus release, little is known about the cellular machinery that directs Gag to the site of virus assembly. Here, we report roles for the Golgi-localized gamma-ear containing Arf-binding (GGA) and ADP ribosylation factor (Arf) proteins in retrovirus particle assembly and release. Whereas siRNA-mediated depletion of GGA2 and GGA3 led to a significant increase in particle release in a late domain-dependent manner, GGA overexpression severely reduced retrovirus particle production by impairing Gag trafficking to the membrane. GGA overexpression inhibited retroviral assembly and release by disrupting Arf protein activity. Furthermore, disruption of endogenous Arf activity inhibited particle production by decreasing Gag-membrane binding. These findings identify the GGA proteins as modulators of HIV-1 release and the Arf proteins as critical cellular cofactors in retroviral Gag trafficking to the plasma membrane.

Utilization of maternal health care services and their determinants in Karnataka State, India.

BACKGROUND: Karnataka State continues to have the highest rates of maternal mortality in south India at 144/100,000 live births, but lower than the national estimates of 190-220/100,000 live births. Various barriers exist to timely and appropriate utilization of services during pregnancy, childbirth and postpartum. This study aimed to describe the patterns and determinants of routine and emergency maternal health care utilization in rural Karnataka State, India. METHODS: This study was conducted in Karnataka in 2012-2013. Purposive sampling was used to convene twenty three focus groups and twelve individual interviews with community and health system representatives: Auxiliary Nurse Midwives and Staff Nurses, Accredited Social Health Activists, community leaders, male decision-makers, female decision-makers, women of reproductive age, medical officers, private health care providers, senior health administrators, District health officers, and obstetricians. Local researchers familiar with the setting and language conducted all focus groups and interviews, these researchers were not known to community participants. All discussions were audio recorded, transcribed, and translated to English for analysis. A thematic analysis approach was taken utilizing an a priori thematic framework as well as inductive identification of themes. RESULTS: Most women in the focus groups reported regular antenatal care attendance, for an average of four visits, and more often for high-risk pregnancies. Antenatal care was typically delivered at the periphery by non-specialised providers. Participants reported that sought was care women experienced danger signs of complications. Postpartum care was reportedly rare, and mainly sought for the purpose of neonatal care. Factors that influenced women's care-seeking included their limited autonomy, poor access to and funding for transport for non-emergent conditions, perceived poor quality of health care facilities, and the costs of care. CONCLUSIONS: Rural south Indian communities reported regular use of health care services during pregnancy and for delivery. Uptake of maternity care services was attributed to new government programmes and increased availability of maternity services; nevertheless, some women delayed disclosure of pregnancy and first antenatal visit. Community-based initiatives should be enhanced to encourage early disclosure of pregnancies and to provide the community information regarding the importance of facility-based care. Health facility infrastructure in rural Karnataka should also be enhanced to ensure a consistent power supply and improved cleanliness on the wards. TRIAL REGISTRATION: NCT01911494.

Genetic signatures of HIV-1 envelope-mediated bystander apoptosis.

The envelope (Env) glycoprotein of HIV is an important determinant of viral pathogenesis. Several lines of evidence support the role of HIV-1 Env in inducing bystander apoptosis that may be a contributing factor in CD4(+) T cell loss. However, most of the studies testing this phenomenon have been conducted with laboratory-adapted HIV-1 isolates. This raises the question of whether primary Envs derived from HIV-infected patients are capable of inducing bystander apoptosis and whether specific Env signatures are associated with this phenomenon. We developed a high throughput assay to determine the bystander apoptosis inducing activity of a panel of primary Envs. We tested 38 different Envs for bystander apoptosis, virion infectivity, neutralizing antibody sensitivity, and putative N-linked glycosylation sites along with a comprehensive sequence analysis to determine if specific sequence signatures within the viral Env are associated with bystander apoptosis. Our studies show that primary Envs vary considerably in their bystander apoptosis-inducing potential, a phenomenon that correlates inversely with putative N-linked glycosylation sites and positively with virion infectivity. By use of a novel phylogenetic analysis that avoids subtype bias coupled with structural considerations, we found specific residues like Arg-476 and Asn-425 that were associated with differences in bystander apoptosis induction. A specific role of these residues was also confirmed experimentally. These data demonstrate for the first time the potential of primary R5 Envs to mediate bystander apoptosis in CD4(+) T cells. Furthermore, we identify specific genetic signatures within the Env that may be associated with the bystander apoptosis-inducing phenotype.

Therapeutic role of yoga in hypertension.

Systemic hypertension is an established risk factor for coronary artery disease and cerebrovascular accident and control of blood pressure reduces the risk of a major cardiovascular event. Both non-pharmacological and pharmacological treatment options are available to treat hypertension. Yoga, recently received more attention as a treatment modality for various lifestyle disorders, even though practiced in India since ancient times. In this review, we are analyzing the role of yoga in the treatment of systemic hypertension.

Effect of a Single-Session Mindfulness-Based Swinging Technique (MBST) Intervention on Emotional Distress in Cancer Patients Undergoing PET-CT Scan: A Randomized Controlled Trial.

Introduction: Undergoing complex diagnostic investigation of positron emission tomography-computed tomography (PET-CT) scans is associated with high levels of distress, fear, and anxiety in oncological patients. This study evaluated the effects of a single 20-min session of an innovative mindfulness-based swinging technique (MBST) intervention on emotional distress in cancer patients scheduled for PET-CT scans. Material and Methods: Adult cancer patients undergoing PET-CT scans (n = 57) were assigned to the intervention group (n = 27) or the control group (n = 30). The emotion thermometer (ET) was used to measure distress, anxiety, depression, anger, and need for help at baseline and after the PET-CT scan. Participants in the intervention group received a 5-min psycho-education followed by listening to an audio recording of the MBST intervention just before their PET-CT scan. The session included mindfulness-based visualization, imaginary swinging activity, and synchronized breathing. The control group participants received brief 5-min counseling. Results: There was a statistically significant reduction in distress (p < 0.001), anxiety (p < 0.001), depression (p < 0.001), anger (p = 0.002), and need for help (p < 0.001) in the intervention group compared with the control group. Safety: None of the participants reported adverse events caused by the MBST intervention. The intervention was well accepted by the participants. However, n = 3 participants could not complete the intervention due to mind wandering, inability to focus, difficulty complying with the guided instructions, falling asleep, and physical discomfort unrelated to the intervention. Conclusion: The findings suggest the potential role of MBST intervention in mitigating emotional distress in patients undergoing complex diagnostic imaging procedures. Integrating this with conventional care in nuclear medicine settings can provide patient-centered care that addresses their unmet requirements. There is a need for further validation with a larger sample size. Clinical Trial Registration Number: CTRI/2023/04/051243 (Registered prospectively on 03/04/2023).