Multiplication of Annatto (Bixa orellana L.) using cotyledons and leaf explants

Annatto (Bixa orellana L.) is an important natural dye yielding plant. To improve theregeneration capacity of annatto, the effects of explants size, plant growth regulators, lightregime and leaf position were evaluated using cotyledons and leaf explants derived fromseedlings. Explants having entire lamina with petiole showed maximum response. Thecotyledonary explants produced highest regeneration frequency (78.1%) and maximumnumber of shoots (12.4) on Murashige and Skoog medium supplemented with 20 μM benzyladenine (BA). Leaf explants on MS medium containing 20 μM BA gave 67% regenerationfrequency and 11.3 new shoots per explant. A photoperiod of 16/8 h (light/dark) was foundto be superior to continuous dark or light. Position of leaf on the seedling had significantrole in organogenic response and is found decreasing from the base to shoot apex. Theregenerated shoots were rooted on MS medium supplemented with 10 μM IBA. The rootedplantlets were transferred initially in the growth chamber and then moved to a green house.The present protocol can be utilized for the mass multiplication and also for effective genetictransformation aimed at the improvement of annatto

Delivery System Design in Topically Applied Formulations

The skin provides a natural physical barrier against particle penetration. Delivery systems design can be used to overcome these barrier properties of the skin. One long-standing approach for improving topical drug delivery uses penetration enhancers which, penetrate into skin to reversibly decrease the barrier resistance. This review focuses on skin penetration pathways, different types of penetration enhancer and the technology for topical drug delivery as well as the probable mechanisms of action. Keywords: Topical drug delivery, penetration enhancer

Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.

IntroductionCurrently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid.MethodsIn this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations.ResultsMDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma.ConclusionMDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas

Seasonal Pattern of Acute Myocardial Infarction in the National Registry of Myocardial Infarction

ObjectivesThe purpose of this study was to determine whether the rate of hospital admission for acute myocardial infarction (AMI) varies seasonally in a large, prospective U.S. registry.BackgroundIdentification of specific patterns in the timing of the onset of AMI is of importance because it implies that there are triggers external to the atherosclerotic plaque. Using death certificate data, most investigators have noted a seasonal pattern to the death rate from AMI. However, it is unclear whether this observation is due to variation in the prevalence of AMI or to other factors that may alter the likelihood of a fatal outcome.MethodsWe examined the seasonal mean number of cases of AMI (adjusted for the length of days in each season) that were submitted to the National Registry of Myocardial Infarction (NRMI) by 138 high volume core hospitals over a 3-year period (December 21,1990 through December 20,1993) during which the number of hospitals participating in the Registry was stable. Data were analyzed using general linear modeling and analysis of variance.ResultsHigh volume core hospitals reported 83,541 cases of AMI to the Registry during the study period. Approximately 10% more such cases were entered into the Registry in winter or spring than in summer (p < 0.05). The same trends were seen in both northern and southern states, men and women, patients <70 versus ≥70 years of age and those with Q wave versus non-Q wave AMI.ConclusionsWe conclude that there is a seasonal pattern to the reporting rate of cases of AMI in the NRMI. This observation further supports the hypothesis that acute cardiovascular events may be triggered by events that are external to the atherosclerotic plaque

(E)-2-(4-Benz­yloxy-2-hy­droxy­benzyl­idene)-N-phenyl­hydrazinecarbothio­amide

The title compound, C21H19N3O2S, exists in the thione form. The configuration about the C=N bond is E. The hydrazinecarbothio­amide unit adopts an almost planar arrangement, with maximum deviations of 0.016 (3) and −0.016 (2) Å for the two thio­urea N atoms. An intra­molecular O—H⋯N hydrogen bond occurs. Weak inter­molecular N—H⋯S, C—H⋯O and C—H⋯π inter­actions are observed in the crystal structure

Moderate incidence of lost follow-up and risk factors among adult HIV patients on second-line ART regimens in Amhara region hospitals, Ethiopia

Background and Objectives: Loss to follow-up is a common problem of most patients on antiretroviral therapy in Ethiopia. Second-line antiretroviral therapy is the drug that would be used when the first-line therapy fails.&nbsp; Thus this study intends to determine the incidence and risk factors of time to losses to follow up among&nbsp; Human&nbsp; Immunodeficiency&nbsp; Virus (HIV) patients on second line regimens of&nbsp; Antiretroviral Therapy(ART) in Amhara region Hospitals, Ethiopia. Methods: Institutional based retrospective cohort study was conducted in the Amhara region hospitals from February to March 2016. A total of 1246 patient from eight hospitals in Amhara region were selected using simple random sampling method and data were extracted from patient charts.&nbsp; The log rank test was used to assess presence of significant difference in time to losses to follow among levels of categorical variables. Both bi-variiable and multivariable Cox proportional hazards models were used to identify factors that affect the time to losses to follow up.&nbsp;&nbsp;&nbsp; Results: The cumulative incidence of loss to follow up was 5.41% over the entire (eight) years of follow-up. The cumulative incidence rates of death and transfer out were 10.99%,10.02 %, respectively. In multivariable Cox regression analysis, ambulatory functional status (AHR=0.1967, 95% CI: 0.049- 0 .794), male gender (AHR=2.135, 95% CI: 1.053- 4.330),&nbsp; adherence to ART (AHR=0.442, 95% CI: 0.198- 0.989) were significant predictors of time to losses to follow up. The use of 2a, 2e and 2g types of second line regimen reduced the risk of&nbsp; loss to follow up. Interpretations and Conclusions: The incidence of loss to follow up in Amhara region hospitals was low. Loss to folow up was negatively&nbsp; associated with female gender, ambulatory&nbsp; baseline functional status, adherence, &amp; types of second line regimen types. Further research on the effect of&nbsp; types of drug is recommended by acertaining whether the reduction in loss to follow up&nbsp; for patients who took drug types of 2a, 2e, and 2g is associaed with improved or worsened health outcomes by trafcking lost patients closely.&nbsp;&nbsp

IMPROVING SOLUBILITY OF BCS CLASS II DRUGS USING SOLID DISPERSION: A REVIEW

Biopharmaceutics Classification System is important for determining the bioavailability of the drugs. Drug development tool that allows estimation of the 3 major factors that affect oral drug absorption from immediate release solid oral dosage form is Dissolution, Solubility and Intestinal permeability. The bioavailability issue can be due to insufficient solubility of permeability. Most compounds face the solubility problems. The dissolution rate of drug from its dosage form is considered as an important parameter in the absorption. Dissolution is the rate-limiting step in the absorption of drugs from 1 solid dosage form especially when the drug is poorly water soluble. Poor wettability of drugs leads to the decrease in their bioavailability. Presently only 8% of new drug candidates have both high solubility and permeability and more than 60% of the products have poor water solubility. As a result the potentially important drugs do not reach the market and are not achieving their full potential. Hence, with the advancement of chemical science, the need of development of pharmaceutical technologies is also increasing. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of many drugs belonging to BCS class II. Solid dispersion has been used over last 20 to 30 years and has been known to give fruitful result in improving the release rate and oral bioavailability of poorly water soluble drugs. Solid dispersion with different polymers and at different ratios is carried out and is known to show good release when compared to the drug alone and the physical mixture. Improvement in dissolution of drug was observed in all the solid dispersions as compared to pure drug. Keywords: Solid dispersion,eutectic mixtures,isothermal titration calorimetry,kneading metho

Unbiased Metagenomic Sequencing for Pediatric Meningitis in Bangladesh Reveals Neuroinvasive Chikungunya Virus Outbreak and Other Unrealized Pathogens.

The burden of meningitis in low-and-middle-income countries remains significant, but the infectious causes remain largely unknown, impeding institution of evidence-based treatment and prevention decisions. We conducted a validation and application study of unbiased metagenomic next-generation sequencing (mNGS) to elucidate etiologies of meningitis in Bangladesh. This RNA mNGS study was performed on cerebrospinal fluid (CSF) specimens from patients admitted in the largest pediatric hospital, a World Health Organization sentinel site, with known neurologic infections (n = 36), with idiopathic meningitis (n = 25), and with no infection (n = 30), and six environmental samples, collected between 2012 and 2018. We used the IDseq bioinformatics pipeline and machine learning to identify potentially pathogenic microbes, which we then confirmed orthogonally and followed up through phone/home visits. In samples with known etiology and without infections, there was 83% concordance between mNGS and conventional testing. In idiopathic cases, mNGS identified a potential bacterial or viral etiology in 40%. There were three instances of neuroinvasive Chikungunya virus (CHIKV), whose genomes were &gt;99% identical to each other and to a Bangladeshi strain only previously recognized to cause febrile illness in 2017. CHIKV-specific qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 (n = 472) revealed 17 additional CHIKV meningitis cases, exposing an unrecognized meningitis outbreak. Orthogonal molecular confirmation, case-based clinical data, and patient follow-up substantiated the findings. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis, conduct surveillance, and predict outbreaks. The improved patient- and population-level data can inform evidence-based policy decisions.IMPORTANCE Globally, there are an estimated 10.6 million cases of meningitis and 288,000 deaths every year, with the vast majority occurring in low- and middle-income countries. In addition, many survivors suffer from long-term neurological sequelae. Most laboratories assay only for common bacterial etiologies using culture and directed PCR, and the majority of meningitis cases lack microbiological diagnoses, impeding institution of evidence-based treatment and prevention strategies. We report here the results of a validation and application study of using unbiased metagenomic sequencing to determine etiologies of idiopathic (of unknown cause) cases. This included CSF from patients with known neurologic infections, with idiopathic meningitis, and without infection admitted in the largest children's hospital of Bangladesh and environmental samples. Using mNGS and machine learning, we identified and confirmed an etiology (viral or bacterial) in 40% of idiopathic cases. We detected three instances of Chikungunya virus (CHIKV) that were &gt;99% identical to each other and to a strain previously recognized to cause systemic illness only in 2017. CHIKV qPCR of all remaining stored 472 CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital uncovered an unrecognized CHIKV meningitis outbreak. CSF mNGS can complement conventional diagnostic methods to identify etiologies of meningitis, and the improved patient- and population-level data can inform better policy decisions

Clinical Characteristics and Cause of Death Among Hospitalized Decedents With Cancer and COVID-19

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among nonsurvivors, 31 (51%) patients had hematologic cancers, and 29 (48%) had undergone cancer-directed chemotherapy within 3 months before admission. The median time to death was 15 days (95% confidence interval [CI], 11.8 to 18.2). There were no differences in time to death by cancer category or cancer treatment intent. The majority of decedents (84%) had full code status at admission; however, 53 (87%) had do-not-resuscitate orders at the time of death. Most deaths were deemed to be COVID-19 related (88.5%). The concordance between the reviewers for the cause of death was 78.7%. In contrast to the belief that COVID-19 decedents die because of their comorbidities, in our study only 1 of every 10 patients died of cancer-related causes. Full-scale interventions were offered to all patients irrespective of oncologic treatment intent. However, most decedents in this population preferred care with nonresuscitative measures rather than full support at the end of life