SPECTROPHOTOMETRIC METHOD FOR THE ESTIMATION OF TOTAL ALKALOIDS IN THE TINOSPORA CORDIFOLIA M. AND ITS HERBAL FORMULATIONS

Objective: A simple spectrophotometric method was developed for the estimation of total alkaloids in Tinospora cordifolia M. and its formulations.Methods: The method based on the formation of yellow colored complex by reaction between bromocresol green (BCG) and alkaloids in medicinal plants. A yellow colored complex forms is easily extractable by chloroform at pH 4.7.Results: The method was linear in concentration range of 2-10 μg/ml with λmax at 415 nm. The LOD and LOQ were found to be 0.215 and 0.652 respectively. The intra-day and inter-day precision and accuracy were within the acceptable criteria (relative standard deviation<2.0% and accuracy within 100±2%). Conclusion: The developed method is simple, precise and accurate and can be adopted for the routine quality control and standardization of plant materials containing alkaloids and its pharmaceutical products.Â

Formulation, evaluation and optimization of stomach specific in situ gel of clarithromycin and metronidazole benzoate

The present investigation deals with the formulation, optimization and evaluation of sodium alginate based In situ gel of Clarithromycin and Metronidazole Benzoate. Sodium alginate used as a polymer and CaCO3 was used as a cross-linking agent. The In situ formulation exhibited well, viscosity, drug content and sustained drug release; this study reports that oral administration of aqueous solutions containing sodium alginate results in formation of In situ gel, such formulations are homogenous liquid when administered orally and become gel at the contact site. The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of CaCO3 significantly affected the dependent variables Q1, Q12 and T80. These In situ gels are, thus, suitable for oral sustained release of Clarithromycin and Metronidazole Benzoate.Keywords: In situ gel; Stomach specific; Gastric residence time

Formulation, evaluation and optimization of stomach specific in situ gel of clarithromycin and metronidazole benzoate

The present investigation deals with the formulation, optimization and evaluation of sodium alginate based In situ gel of Clarithromycin and Metronidazole Benzoate. Sodium alginate used as a polymer and CaCO3 was used as a cross-linking agent. The In situ formulation exhibited well, viscosity, drug content and sustained drug release; this study reports that oral administration of aqueous solutions containing sodium alginate results in formation of In situ gel, such formulations are homogenous liquid when administered orally and become gel at the contact site. The results of a 32 full factorial design revealed that the concentration of sodium alginate and concentration of CaCO3 significantly affected the dependent variables Q1, Q12 and T80. These In situ gels are, thus, suitable for oral sustained release of Clarithromycin and Metronidazole Benzoate.Keywords: In situ gel; Stomach specific; Gastric residence time

Results of Posterior Dislocation of Elbow Associated with Bony and Soft Tissue Injury

Elbow trauma is challenging to manage by virtue of its complex articular structure and capsuloligamentous and musculotendinous arrangements. We included 17 patients with elbow dislocation and associated injuries in this study. The study protocol included early elbow reduction and planned fixation of the medial or lateral condyle, coronoid and radial head. The sample was 73% male and 27% female with mean duration follow-up of 8 months, and mean age of 37 years. The mean Mayo Elbow Performance Score was 96 points at conclusion of follow-up, indicating an excellent result in 14 patients. Whenever the radial head was excised, we performed a strong transosseous ligamentous repair of the medial and lateral collateral ligaments. Fixation of the coronoid is essential for elbow stability. A small avulsed fragment can be fixed using an ACL jig. We found this technique very useful. Early planned intervention, stable fixation, and repair provide sufficient stability and enhance functional outcomes

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant. </p

Comprehensive Evaluation of Healthy Volunteers Using Multi-Modality Brain Injury Assessments: An Exploratory, Observational Study

Introduction: Even though mild traumatic brain injury is common and can result in persistent symptoms, traditional measurement tools can be insensitive in detecting functional deficits after injury. Some newer assessments do not have well-established norms, and little is known about how these measures perform over time or how cross-domain assessments correlate with one another. We conducted an exploratory study to measure the distribution, stability, and correlation of results from assessments used in mild traumatic brain injury in healthy, community-dwelling adults.Materials and Methods: In this prospective cohort study, healthy adult men and women without a history of brain injury underwent a comprehensive brain injury evaluation that included self-report questionnaires and neurological, electroencephalography, sleep, audiology/vestibular, autonomic, visual, neuroimaging, and laboratory testing. Most testing was performed at 3 intervals over 6 months.Results: The study enrolled 83 participants, and 75 were included in the primary analysis. Mean age was 38 years, 58 were male, and 53 were civilians. Participants did not endorse symptoms of post-concussive syndrome, PTSD, or depression. Abnormal neurological examination findings were rare, and 6 had generalized slowing on electroencephalography. Actigraphy and sleep diary showed good sleep maintenance efficiency, but 21 reported poor sleep quality. Heart rate variability was most stable over time in the sleep segment. Dynavision performance was normal, but 41 participants had abnormal ocular torsion. On eye tracking, circular, horizontal ramp, and reading tasks were more likely to be abnormal than other tasks. Most participants had normal hearing, videonystagmography, and rotational chair testing, but computerized dynamic posturography was abnormal in up to 21% of participants. Twenty-two participants had greater than expected white matter changes for age by MRI. Most abnormal findings were dispersed across the population, though a few participants had clusters of abnormalities.Conclusions: Despite our efforts to enroll normal, healthy volunteers, abnormalities on some measures were surprisingly common.Trial Registration: This study was registered at www.clinicaltrials.gov, trial identifier NCT01925963

Genome-Wide Compensatory Changes Accompany Drug- Selected Mutations in the Plasmodium falciparum crt Gene

Mutations in PfCRT (Plasmodium falciparum chloroquine-resistant transporter), particularly the substitution at amino acid position 76, confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. Moreover, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR). Reemergence of CQ sensitive parasites after cessation of CQ use indicates that changes in PfCRT are deleterious to the parasite. Some CQR parasites, however, persist in the field and grow well in culture, which may reflect adaptive changes in the parasite genome to compensate for the mutations in PfCRT. Using three isogenic clones that have different drug resistance profiles corresponding to unique mutations in the pfcrt gene (106/1K76, 106/176I, and 106/76I-352K), we investigated changes in gene expression in these parasites grown with and without CQ. We also conducted hybridizations of genomic DNA to identify copy number (CN) changes in parasite genes. RNA transcript levels from 45 genes were significantly altered in one or both mutants relative to the parent line, 106/1K76. Most of the up-regulated genes are involved in invasion, cell growth and development, signal transduction, and transport activities. Of particular interest are genes encoding proteins involved in transport and/or regulation of cytoplasmic or compartmental pH such as the V-type H+ pumping pyrophosphatase 2 (PfVP2), Ca2+/H+ antiporter VCX1, a putative drug transporter and CN changes in pfmdr1. These changes may represent adaptations to altered functionality of PfCRT, a predicted member of drug/metabolite transporter superfamily found on the parasite food vacuole (FV) membrane. Further investigation of these genes may shed light on how the parasite compensates for functional changes accompanying drug resistance mutations in a gene coding for a membrane/drug transporter

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

International audienceIn 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Design analysis of rotary turret of poucher machine

SummaryThis paper present design analysis of rotary turret plate of 5kg capacity for food product packaging machine. The turret plate has been designed considering two different criteria, first one is inertia force approach with only self-weight of turret plate and second is with mass of pouches. A 3-dimenssional CAD model of rotary turret assembly has been prepared in using solid modelling packages CRE-O. The finite element analysis (FEA) of turret plate has been carried out using analysis software ANSYS 15.0. Consideration of inertia force is one of the criteria to analyze the performance and behaviour of component in working condition. The rotational velocity is applied at the central axis of turret and friction less support is applied on inner surface, where shaft is being attached. Also, pressure is applied on the same surface to incorporate the shrink fit condition of the assembly of turret plate with shaft. The boundary conditions as fixed support have been considered at the different sixteen faces, where bolts have been attached. The obtained simulation results for induced stress, deformation and strain depict that the modified design of rotary turret plate is well within the allowable stress limits of considered material. And, further optimization can be performed for topological and strength based more efficient design of turret plate