The effect of different decontamination processes on the residues of fipronil and its metabolites in chili fruits (Capsicum annuum L.).

Fipronil is a broad-spectrum phenyl pyrazole insecticide that has a high degree of environmental toxicity. Commonly available chilies in the market are treated with fipronil insecticides. Demand for insecticide-free chili has thus been increasing globally. This needs various sustainable and economical methods to remove insecticides from chilies. The present study examined the effectiveness of several cleaning methods to remove pesticide residues in chili fruits. A supervised field trial was conducted in randomized block design at Rajasthan Agricultural Research Institute, Durgapura, Jaipur, India. Chili samples were subjected to seven different household methods. The samples were extracted using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. The residues were analyzed using a gas chromatograph-electron capture detector and confirmed by GC-MS. Of the seven methods, the acetic acid treatment removes the maximum residue effect of fipronil and its metabolites (desulfinyl [MB046513]), sulfide (MB045950), and sulfone (MB046136) on chili fruits. By contrast, the tap water treatment was the least effective. The Food Safety and Standards Authority of India (FSSAI) have set the maximum residue limit value of 0.001 mg kg-1 for fipronil on green chili.

Mechanical, microstructural and fracture studies on inconel 825-SS316L functionally graded wall fabricated by wire arc additive manufacturing.

This paper presents a novel method that uses the cold metal transfer based wire arc additive manufacturing process to fabricate functionally graded Inconel 825-SS316L walls. The optical micrograph of Inconel 825 exhibits continuous and discontinuous dendritic structures. The SS316L region comprises 5% of δ-ferrite in primary austenitic (γ) dendrites which was confirmed by the Creq/Nieq ratio of 1.305. The functionally graded interface reveals a partially mixed zone with a transition from the elongated dendrites to fine equiaxed dendrites. The tensile properties of the fabricated wall were determined at room temperature using specimens extracted from Inconel 825, SS316L, and the interface regions. The morphology of the tensile tested specimens revealed significant plastic deformation, indicating ductile failure. The fracture toughness of the wall was experimentally investigated by employing the crack tip opening displacement (CTOD) test. The fracture morphology exhibited a ductile mode of fracture with striations perpendicular to the direction of crack development. Elemental mapping revealed that there was no evidence of elemental segregation on the fractured surfaces, and the elements were uniformly dispersed. The CTOD measures 0.853 mm, 0.873 mm on the Inconel 825 side and the SS316L side respectively. The test results confirm that both the Inconel 825 and SS316L sides have good fracture toughness.

Darbepoetin Alfa for Late-onset Anemia in Neonates with Rhesus Hemolytic Disease.

Neonates with Rhesus hemolytic disease can present with anemia beyond 1 wk of age due to bone marrow suppression and low erythropoietin secretion. Erythropoietin stimulating agents (ESA) were tried to manage anemia in these neonates. Darbepoetin alfa (DA) is a long-acting ESA used to treat anemia in premature neonates and in children with chronic kidney disease or on cancer chemotherapy. The authors present their experience of using DA to treat late-onset hyporegenerative anemia in 3 neonates with Rhesus isoimmunization. Darbepoetin alfa 4 mcg/kg was given subcutaneously at a 1-2-wk interval to target hemoglobin of 10-12 g/dL. No adverse effects were observed, and the treated infants had a reduced need for the packed red blood cell transfusions.

Genetic diversity among local mango (Mangifera indica L.) germplasm using morphological, biochemical and chloroplast DNA barcodes analyses.

BACKGROUND: In this study, the genetic diversity of local mango (Mangifera indica L.) germplasm including 14 genotypes were evaluated by using morphological, biochemical markers and DNA barcoding technique. Morphological characterization is the first step towards utilizing these germplasm in crop improvement studies. The advanced chloroplast based DNA barcode method can be utilized to assess the genetic diversity and phylogenetic structure in such populations. METHODS: The study was carried out during 2018-2019 years to evaluate local mango germplasm including 14 diverse genotypes based on a number of morphological and biochemical traits and chloroplast DNA barcoding as well. The experiment was laid out in one way ANOVA design with fourteen germplasm indicated with indigenous collection number. RESULTS: Among local mango germplasm, IC 589756 was found to be the most promising with respect to high magnitudes of fruit length, fruit width, fruit weight, pulp weight, soluble solid content (SSC)/Acidity ratio, pH and low acidity followed by IC 589746 exhibiting the highest pulp percentage and SSC accompanied with lowest stone weight and stone percent as compared to the other genotypes. Further, the dendrogram and cluster analyses based on sequencing of chloroplast marker i.e., trnH- psbA and trnCD depicted the relationship among mango genotypes and clearly clustered them into two main clusters at a similarity coefficient 0.035 and 0.150, respectively. The first cluster includes only one genotype and cluster-II contains 13 genotypes. CONCLUSIONS: Particularly results revealed that DNA barcoding of local mango germplasm can assist not only in molecular identification but also help in elucidation of their phylogenetic relationship and thus important in maintaining biodiversity inventories.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Preventing disease after exposure to COVID-19 using hydroxychloroquine: A summary of a protocol for exploratory re-analysis of age and time-nuanced effects.

BACKGROUNDA recently published randomized trial (Boulware et al., 2020, NCT04308668) of hydroxychloroquine (HCQ) for post-exposure prophylaxis found a reduction in Covid-19 of 17%. In the context of ambitious powering to detect a 50% reduction, this non-statistically significant finding could translate to a reduction of 22,000/130,828 cases (CDC 8/12/20) among US health care workers (HCW), impacting trajectory and resource utilization models that drive decisions on lockdowns and social distancing. Data found only in the appendix of Boulware et al. suggested greater differences in the effect HCQ among sub-groups. There were reductions (36%) in younger (<35 years) and increases (110%) in older (>50 years) subjects. Our preliminary analysis revealed a significant negative correlation (slope -0.211, CI -0.328-0.094, p=0.016) between treatment lag and disease reduction, reaching 49% when initiated within one day (RR 0.51, CI 0.176-1.46, p=0.249). There were also differences in disease reduction by HCQ by type of exposure (HCW - 8% vs. household contacts - 31%; RR 0.691, CI 0.398-1.2). The definitions of exposure severity did not discriminate between the numbers or duration (> 10 minutes) of exposures. Differences between exposure types may result from younger HCW and higher risks in less trained household contacts with little access to advanced PPE. The ex-protocol use of zinc and ascorbic acid were likely confounders, as was the possibly active folate placebo. Exploratory reanalysis of the raw dataset may inform an age- and stage- nuanced approach to COVID-19 using HCQ testable by prospective studies and may provide insight into the various proposed mechanisms of HCQ. OBJECTIVESTo conduct an exploratory re-analysis of the de-identified raw dataset from a randomized study of the use of HCQ for post-exposure prophylaxis of COVID-19 with view to further defining: a) The time dependent effect of HCQ, b) The age dependent effect of HCQ; c) The sub-stratification of time- and age-dependent effects by exposure type and risk level, as well as by the use of zinc and ascorbic acid. d) The design of future clinical trials to test the hypotheses generated by this study. METHODSShould granularity of data (by age, time-lag, level and type of exposure) be greater than that originally reported, Fisher Exact test will be used to compare the incidence of COVID-19 in HCQ- and control groups, for each sub-group stratification. Since the degree of loss of data granularity due to de-identification is yet unknown, exploratory analyses involving other demographic characteristics cannot be planned. Where sufficient data granularity exists, univariate regression analyses will be conducted to examine the effect of age- and time lag on any effect of HCQ. The possibility will be explored of conducting multivariate Cox regression analyses with propensity score matching to examine observational data relating to the use of zinc and ascorbic acid. This analysis will be expanded should a dataset from a similarly designed study (Mitja et al., 2020, NCT04304053), with directionally similar results, become available. This protocol was devised using the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) incorporating the WHO Trial Registration Data Set. Study StatusProtocol version 1.1 (August 19 2020) Protocol registered at: OSF Registries August 19 2020 Registration doi: https://doi.org/10.17605/OSF.IO/9RPYT

Sensor-Assisted Assessment of the Tribological Behavior Patterns of AA7075 Hybrid MMC Reinforced with Multi-Wall Carbon Nanotubes and Pulverized Fuel Ash.

In recent years, the deployment of sensors and other ancillary technologies has turned out to be vital in the investigation of tribological behavioral patterns of composites. The tribological behavioral patterns of AA7075 hybrid metal matrix composites (MMCs) reinforced with multi-wall carbon nanotubes (MWCNTs), and pulverized fuel ash (PFA) were investigated in this work. The stir casting technique was used to fabricate the composites. The mechanical properties such as tensile strength and hardness were determined for the fabricated material. Besides, microstructure analysis was performed for these AA7075 hybrid MMCs reinforced with MWCNTs and pulverized fuel ash. A pin-on-disc wear testing setup was used to evaluate the wear rate, in which the EN 31 steel disc was used as the counter-face. Taguchi's design of the experiments was used to optimize the input parameters that impact the characteristics of the hybrid composites, and ANOVA (analysis of variance) was used to determine the contribution of input parameters on the wear behavior. Electrical discharge machining (EDM) was conducted on the AA7075 hybrid metal matrix composites using a copper electrode for determining the material removal rate. These investigations and the results were utilized for determining the optimized output process parameter values of the AA7075 metal matrix composite.

A Systematic Review and Meta-analysis of Therapeutic options against SARS-CoV-2

ImportanceTreatment options for Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on the efficacy and safety profiles. ObjectiveTo assess if the effect estimate of any intervention improves the outcomes and safety profile. Data sourcesPubMed, Embase, Cochrane Central were searched from December 1, 2019 to May 11, 2020. Study selectionAny prospective/retrospective clinical study on SARS-CoV-2 patients [≥]18 years of age with report on therapeutic interventions. Data synthesis and extractionData was screened and extracted by two independent investigators. Main outcomes and measuresThe primary outcome was all-cause in-hospital mortality. The secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, progression to severe disease, median time for clinical recovery and anti-viral clearance. Pooled rates and odds ratios (OR) were calculated. ResultsA total of 29 studies with 5207 participants were included in the analysis. The pooled all-cause in-hospital mortality rate was 12.8% (95%CI: 8.1%-17.4%) in intervention arm. There was no significant difference in mortality between both arms overall (OR: 1.36, 95% CI: 0.97-1.89). The mortality was significantly higher in the Hydroxychloroquine (HCQ) group compared to control: (1.86, 95% CI: 1.38 - 2.50). The need for mechanical ventilation in patients with mild-moderate disease was 13.5% vs 9.8% in intervention and control groups, with no significant difference (OR: 1.58, 95% CI: 0.60 - 4.15).The median duration for viral clearance in the intervention arm was 6.1 (IQR: 4.3 - 8.8) days and control arm was 9 (IQR: 4.5 - 14) days, with no significant difference between the groups (p = 0.37). There was no significant difference between pooled adverse event rates in intervention and control groups: 34% vs 29.5% (OR: 1.44, 95% CI: 0.70 - 2.94), respectively. However, incidence of adverse events was significantly higher in HCQ sub-group (OR: 3.88, 95% CI: 1.60 - 9.45, I2 = 0%). There was no significant difference in other secondary outcomes. Conclusion and relevanceThe use of hydroxychloroquine was associated with increased mortality and adverse event rates. No other therapeutic intervention including Lopinavir/Ritonavir, Remdesivir or Tocilizumab seem to alter the natural course of the disease. There is a further need for well-designed randomized clinical trials. Article summary lineThe use of hydroxychloroquine was associated with increased mortality and adverse event rates in Severe acute respiratory syndrome-related coronavirus-2 infection and other therapeutic interventions did not show any difference in outcomes

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

BackgroundThere is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. MethodsWe conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of pre and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality was the primary outcome measure. All patients had at least 14 days of follow-up. ResultsWe analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in post-corticosteroid group compared to pre-corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.45; 95% CI [0.25 - 0.81]). ConclusionAn early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes. SummaryIn this multi-center quasi-experimental study of 213 patients, we demonstrate early short course of methylprednisolone in moderate to severe COVID-19 patients reduced the composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality.

Lower oesophageal peptic stricture after laparoscopic sleeve gastrectomy: World's first case report.

Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric surgery worldwide. De novo gastroesophageal reflux disease after LSG has been reported in the range of 0%-34.9%. Benign lower oesophageal peptic stricture is rare and has not been reported till date. We present the first case report of benign oesophageal peptic stricture post-sleeve gastrectomy and its management. The management modalities for peptic stricture post-LSG include proton pump inhibitors, endoscopic dilatation and surgical management. Revisional Roux-en-Y gastric bypass along with optimal usage of serial dilatation and medical treatment has been shown to be an effective treatment for the same.

Emerging Landscape of Antibiotic Resistance and Use of Endoscopic Injection in Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) in children is often treated with antimicrobials for prolonged durations, which often leads to antimicrobial resistance. In this context, this review article discusses the use of endoscopic injection in VUR as a safe and efficacious option for these children. The literature pertaining to VUR- its clinical manifestation and management, antibiotic resistance- with special reference to management of VUR, and endoscopic dextranomer/hyaluronic acid gel injection for management of VUR was reviewed by identifying key words in a PubMed search. Vesicoureteral reflux is managed using antibiotic prophylaxis, urotherapy, or surgical correction (open, endoscopic injection therapy, or laparoscopic). Continuous antibiotic prophylaxis for urinary tract infections in VUR can lead to antibiotic resistance. Urotherapy cures about 75% of cases with dysfunctional voiding and the rest have to be managed at specialized centers. While open surgery provides relief of VUR and related complications in majority, it requires hospitalization. Endoscopic injection of dextranomer/hyaluronic acid gel into the submucosa of bladder or ureter near ureteral orifice increases the tissue bulk and creates a valve function. Various studies show the efficacy and safety of endoscopic injection of dextranomer/hyaluronic acid gel in VUR. The use of endoscopic injection being a non-invasive modality, can be performed in children with VUR in the outpatient department, precluding hospitalization. In view of the threat of developing antimicrobial resistance and also realising the need for definitive treatment of VUR, endoscopic injection is an efficacious and safe option in primary VUR.

Cadaveric Study of Mode of Termination of Gonadal Veins: Implications for Procedures Utilizing Terminal Ends of Gonadal Veins as Entry Portals.

CONTEXT: The terminal ends of gonadal veins act as an entry portal in gonadal embolization procedures used for treating varicocele in males and pelvic congestion disease in females. Here, we studied the modes of termination of gonadal veins in adult cadavers. MATERIALS AND METHODS: Thirty-five adult formalin-fixed cadavers (seventy sides) were studied over a period of 4 years. The modes of termination of gonadal veins were observed under the following study variables: (a) number, (b) locale of termination, and (c) termination angle. RESULTS: Variations in study parameters were observed in eight sides of seven cadavers (seven unilateral and one bilateral). Double veins at termination were observed in six cadavers; anomalous termination was observed in three cadavers. Angle of termination differed from normal in 3 cadavers. In one of these cadavers, the left ovarian vein drained into the left suprarenal vein. CONCLUSION: Duplication of terminal ends, anomalous drainage site, and varied angles of termination call for caution to ensure the success of procedures, which use terminal ends of gonadal veins as entry portals.

Quick, painless, and atraumatic gingival retraction: An overview of advanced materials.

The success of any fixed prosthesis depends on the accuracy of impressions. Finish line exposure has to be adequate during impression making. The goal of gingival retraction is to atraumatically displace gingival tissues to allow access for impression material to record the finish line and provide sufficient thickness of gingival sulcus so that the impression does not tear off during removal. Numerous advanced materials are available for gingival retraction. This article describes the different advanced materials available.

Low Serum Concentrations of Rifampicin and Pyrazinamide Associated with Poor Treatment Outcomes in Children with Tuberculosis Related to HIV Status.

OBJECTIVES: To compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between HIV-infected and HIV-uninfected children with tuberculosis (TB) and correlate it with TB treatment outcome. METHODS: HIV-uninfected (n = 84) and HIV-infected (n = 77) children with TB receiving standard thrice weekly treatment were recruited from 6 hospitals in India. Semi-intensive pharmacokinetic sampling was performed during intensive phase of TB treatment after directly observed administration of drugs. Drug concentrations were measured by high performance liquid chromatography. INH acetylator status was determined, and nutritional assessment was done. Children were followed-up and treatment outcomes noted. RESULTS: Children with HIV and TB had significantly lower RMP peak concentration (Cmax) (2.6 vs. 5.1 µg/mL; P < 0.001) and exposure [area under the time-concentration curve (AUC0-8); 10.4 vs. 23.4 µg/mL h; P < 0.001] than those with TB. Among HIV-infected children, a significantly higher proportion had stunting (77% vs. 29%; P < 0.001) and underweight (73% vs. 38%; P < 0.001) compared with children with TB. Combining both groups, RMP Cmax (P = 0.001; adjusted odds ratio = 1.437; 95% confidence interval: 1.157-1.784) and PZA Cmax (P = 0.027; adjusted odds ratio = 1.041; 95% confidence interval: 1.005-1.079) significantly influenced treatment outcome. CONCLUSIONS: HIV infection was associated with lower Cmax of RMP and INH and AUC0-8 of RMP. Over 90% of children in both groups had subtherapeutic RMP Cmax. Cmax of RMP and PZA significantly influenced TB treatment outcome in children with TB. The findings have important clinical implications and suggest the need to increase anti-TB drug doses in children with HIV and TB.

Two Common Trunks Arising From Arch of Aorta: Case Report and Literature Review of A Very Rare Variation.

Arch of aorta normally gives off three branches, the brachiocephalic trunk, left common carotid artery and left subclavian artery. Due to its complex development, variations in the branching pattern are not infrequent and since many such variants remain asymptomatic, they are detected incidentally at diagnostic imaging, autopsy and surgery. The classical branching pattern is reported to be present in 63.5%-89.4% cases and the most common variant observed is the presence of common trunk of brachiocephalic and left common carotid arteries. Direct aortic arch origin of left vertebral artery is the second most common pattern observed. We report here an extremely rare branching pattern of two common trunks arising from the arch, the first common trunk of brachiocephalic and left common carotid arteries and the second designated as vertebro-subclavian trunk, the common trunk of origin of left subclavian and left vertebral arteries. To the best of our knowledge this is the second such case to be reported.

Hypothyroidism and non-cardiogenic pulmonary edema: are we missing something here?

UNLABELLED: We report the case of a 42-year-old female with a history of hypothyroidism and asthma presenting with progressive dyspnea and orthopnea after 2 days of an upper respiratory tract infection (URTI). Based on the clinical and radiological findings, the patient was admitted as a case of cardiogenic pulmonary edema secondary to possible viral myocarditis. However, a normal brain natriuretic peptide (BNP) level with a normal ejection fraction (EF) on echocardiogram changed our working diagnosis from cardiogenic to non-cardiogenic pulmonary edema. Further questioning revealed a history of nocturnal snoring, frequent awakening, and daytime fatigue, suggesting a possible sleep apnea syndrome (SAS). In conclusion, we believe that SAS was the missing link between our patient's hypothyroidism and non-cardiogenic pulmonary edema. LEARNING POINTS: Always keep an open mind and look for a pathology that would explain the whole clinical scenario.The involvement of the respiratory system in hypothyroidism can range from SAS, pulmonary hypertension, hypoventilation, and severe respiratory failure.Hypothyroidism and SAS should be considered in the differential diagnosis of non-cardiogenic pulmonary edema.Patients should be instructed to take levothyroxine on an empty stomach 30-60 min before food to avoid erratic absorption of the hormone.

Temperature controlled radiofrequency ablation at different sites for treatment of obstructive sleep apnea syndrome: a systematic review and meta-analysis.

BACKGROUND: This study seeks to determine the efficacy of temperature controlled radiofrequency tissue ablation (TCRFTA) to alleviate symptoms of obstructive sleep apnea (OSA) and reduce polysomnographic measures of OSA in the first year post-treatment. METHODS: Systematic review and meta-analysis. Two independent searches of MEDLINE, EMBASE bibliographic databases, and Evidence Based Medicine Reviews to identify publications relevant to OSA and TCRFTA. Effectiveness of TCRFTA was measured separately for application of TCRFTA at the base of tongue and soft palate, and for multilevel intervention using the respiratory disturbance index (RDI), lowest oxygen saturation (LSAT), Epworth sleepiness scale (ESS), and bed partner's rating of snoring using a visual analogue scale (VAS snoring). The most recent search was conducted in April 2013. Statistical analysis was performed using Review Manager Version 5.2 using a relative measure of effect, i.e., ratio of means (RoM). RESULTS: Our initial search resulted in 29 eligible studies, and subsequently, 20 studies were included in the meta-analysis. Substantial and consistent improvement in PSG and subjective outcomes were observed post-TCRFTA in the base of tongue (BOT) and multilevel surgery groups only. Application of TCRFTA at the BOT was associated with a significant reduction in RDI (RoM 0.60, CI 0.47-0.76), ESS (RoM 0.59, CI 0.51-0.67), and VAS snoring (RoM 0.48, CI 0.37-0.62) and increase in lowest oxygen saturation (RoM 1.05, CI 1.01-1.10). Similarly, a significant reduction in RDI (RoM 0.61, CI 0.47-0.80) and ESS (RoM 0.79, CI -0.71 to 0.88) was observed after multilevel TCRFTA, but substantial heterogeneity between these studies was observed. CONCLUSION: TCRFTA is clinically effective in reducing RDI levels and symptoms of sleepiness in patients with OSA syndrome when directed at the base of tongue or as a multilevel procedure.

Pharmacokinetics of first-line antituberculosis drugs in HIV-infected children with tuberculosis treated with intermittent regimens in India.

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0-8]) of INH (Cmax, 2.5 versus 5.1 µg/ml, respectively [P=0.016]; AUC0-8, 11.1 versus 22.0 µg/ml·h, respectively [P=0.047[) and PZA (Cmax, 34.1 versus 42.3 µg/ml, respectively [P=0.055]; AUC0-8, 177.9 versus 221.7 µg/ml·h, respectively [P=0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 µg/ml, respectively; P=0.002) and PZA (31.9 versus 44.4 µg/ml, respectively; P=0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P=0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.

Cadmium and copper toxicity in three marine macroalgae: evaluation of the biochemical responses and DNA damage.

Marine macroalgae have evolved a different mechanism to maintain physiological concentrations of essential metal ions and non-essential metals. The objective of the present work was to evaluate the antioxidant response and DNA damage of copper and cadmium ions in three halophytes, namely, Acanthophora spicifera, Chaetomorpha antennina, and Ulva reticulata. Accumulation of copper was significantly higher (P < 0.05) than that of cadmium. Biochemical responses showed that copper was considerably more toxic than cadmium (P < 0.05). Decreases in glutathione content and fluctuations of super oxide dismutase, catalase, and glutathione peroxidase activities were observed corresponding to time and concentration of exposure. Interestingly, it was also observed that antioxidant levels decreased as a result of metal accumulation, which may be due to free radicals generated by copper and cadmium in seaweeds. The present study also showed that copper and cadmium increased oxidative stress and induced antioxidant defense systems against reactive oxygen species. The order of toxicity for metals in the studied seaweeds was U. reticulata > A. spicifera > C. antennina. DNA damage index analysis supported that copper was significantly (P < 0.05) more toxic than cadmium. Bioaccumulation, biochemical responses, and DNA damage observed in the here analyzed marine macroalgae after exposure to selected metals indicate that these marine organisms represent useful bioindicators of marine pollution.