Cost-Effective Isolation of a Process Impurity of Pregabalin

Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin.     

Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer

We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log₂ratio ≥1) 9p24 amplicon was found in TNBC (12/41), glioblastomas (2/44), and colon carcinomas (2/68). The shortest region of overlap for the amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15) breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon in TNBCs was correlated with clinical outcomes in group comparisons by two-sample t-tests for continuous variables and chi-squared tests for categorical variables. TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC is associated with elevated expression of JAK2 and of the PD-1 ligands. These initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets signaling pathways that activate the PD-1 mediated immune checkpoint, and identifies patients with a poor prognosis.     

Spinal cord pharmacology of adrenergic agonist-mediated antinociception

Intrathecal administration of norepinephrine (NE) and alpha adrenergic agonists in rats with chronic spinal catheters produced a significant elevation of the nociceptive threshold as measured by hot plate and tail flick. The intrathecal NE effect was dose-dependent and antagonized in a competitive fashion by pretreatment with phentolamine (alpha antagonist) but not by propranolol (beta antagonist). Intrathecal administration of isoproterenol (beta agonist) did not alter the nociceptive threshold. Effective doses of intrathecal NE did not produce demonstrable motor effects. Doses 20 times greater than the maximum analgesic dose produced marked weakness of the hindlimbs and tails. The intrathecal NE effect was not antagonized by intrathecal papaverine of bradykinin (vasodilators) or mimicked by angiotensin-II (vasoconstrictor). The intrathecal NE effect was not altered by intrathecal administration of subconvulsant doses of either picrotoxin (gamma-aminobutyric acid antagonist) or strychnine (glycine antagonist) or by i.p. administration of either naloxone (opiate antagonist) or methysergide (serotinin antagonist). The nociceptive threshold was significantly decreased 1 week after intrathecal administration of 6-hydroxydopamine, which depleted spinal cord NE by 85%. Intrathecal administration of tyramine (indirectly acting sympathomimetic amine) produced an elevation of the nociceptive threshold in a control group of animals but was less effective in animals pretreated with intrathecal 6-hydroxydopamine. The tyramine effect was antagonized by intrathecal phentolamine. Intravenous administration of aminophylline (phosphodiesterase inhibitor) did not potentiate the intrathecal NE effect. The relative antinociceptive potencies of alpha adrenergic agonists after intrathecal administration were: l-norepinephrine = dl-epinephrine greater than dl-alpha-methyl norepinephrine greater than clonidine greater than or equal to l-phenylephrine greater than or equal to 3,4-dihydroxytolazoline greater than or equal to oxymetazoline. The relative potencies of intrathecally administered alpha antagonists in antagonizing the intrathecal NE effect were: phentolamine greater than phenoxybenzamine greater than tolazoline greater than or equal to yohimbine.     

Knowledge of multidrug-resistant tuberculosis amongst Durban University of Technology students in KwaZulu-Natal,South Africa: the need for integrating public health education

BackgroundKwazulu-Natal is the epicenter of South Africa''s Multidrug-resistant Tuberculosis (MDR-TB) burden which represents a growing threat to public health. Knowledge and awareness of MDR-TB are crucial for effective management and University students are an important vehicle for knowledge transfer of public health education.ObjectiveThis study aimed to evaluate the knowledge of MDR TB and risk factors for transmission, prevention, treatment and control of MDR-TB among Durban University of Technology (DUT) students.MethodsThis quantitative cross-sectional study was conducted among 150 randomly sampled undergraduate students from 3 faculties and data was collected using a validated questionnaire.ResultsWhile a majority of participants (70.67%) had previous knowledge on TB, only 30.67% knew of MDR-TB. Only 23.49% of students reported knowledge of preventative measures associated with MDR TB. Women had a lower probability of having knowledge of MDR-TB compared to men (OR=0.45; CI:0.22,0.95; p<0.05) and students from the Accounting and Informatics faculty were less likely to believe that MDR-TB was a life-threatening illness (OR=0.24; CI:0.05,1.44; p<0.05) and showed limited knowledge of MDR-TB transmission.ConclusionThis study showed that students lacked knowledge of MDR-TB with respect to risk factors, treatment and prevention, which necessitates intervention strategies at a tertiary level to educate and inform students about MDR-TB.     

Impact of teleconsultation on visual and refractive outcomes in patients undergoing laser refractive surgery during COVID-19

Purpose:To assess the role of remote teleconsultation (TC) follow-up care following a successful and uneventful laser vision correction.Methods:The study is a retrospective, comparative analysis of patients undergoing laser vision correction at tertiary care eye hospital in Southern India. The patients were divided into two groups. The first group included patients operated on before the coronavirus disease (COVID-19) pandemic and were followed up with physical consultations during their follow-up visit (Group 1). The second group comprised patients operated on during the pandemic and had at least one remote TC during their post-operative follow-up (Group 2).Results:A total of 1088 eyes of 564 patients and 717 eyes of 372 patients were included in Group 1 and 2, respectively. The mean number of visits for the patients from Group 2 during the COVID period (2.56 +/- 0.74 days) was significantly lesser (P < 0.0001) than that of Group 1 in the pre-COVID period (3.53 +/- 1.07 days). Close to 90% of the eyes achieved an uncorrected distance visual acuity (UDVA) of 20/20 in both groups (P = 0.925). 96.50% of the eyes in Group 1 and 98.18% of the eyes in Group 2 achieved UCVA 20/25 or better (P = 0.049). Eight eyes (0.73%) in Group 1 and one eye (0.14%) in Group 2 reported a loss of 2 or more lines. However, the results were not statistically significant (P = 0.156). None of the groups had any patients who had a sight-threatening complication.Conclusion:Remote TC following refractive surgery is safe and can be effectively integrated into routine refractive practice to reduce travel to the hospital for a physical consult.     

Supercritical CO2-Induced Evolution of Alkali-Activated Slag Cements

The phase changes in alkali-activated slag samples when exposed to supercritical carbonation were evaluated. Ground granulated blast furnace slag was activated with five different activators. The NaOH, Na₂SiO₃, CaO, Na₂SO₄, and MgO were used as activators. C-S-H is identified as the main reaction product in all samples along with other minor reaction products. The X-ray diffractograms showed the complete decalcification of C-S-H and the formation of CaCO₃ polymorphs such as calcite, aragonite, and vaterite. The thermal decomposition of carbonated samples indicates a broader range of CO₂ decomposition. Formation of highly cross-linked aluminosilicate gel and a reduction in unreacted slag content upon carbonation is observed through ²⁹Si and ²⁷Al NMR spectroscopy. The observations indicate complete decalcification of C-S-H with formation of highly cross-linked aluminosilicates upon sCO₂ carbonation. A 20–30% CO₂ consumption per reacted slag under supercritical conditions is observed.     

Comparison of different endophthalmitis prophylactic measures in cataract surgery - An analysis of 2.4 lakh cases

Purpose:To compare different endophthalmitis prophylaxis methods adopted in cataract surgery (manual small-incision cataract surgery and phacoemulsification) between the years 2013 and 2021 in the community eye care section of a tertiary eye care hospital in South India and report their outcomes.Methods:All cataract surgeries performed from January 2013 to December 2021 (2,46,874 surgeries) at a single center were included in this retrospective study. The different endophthalmitis rates with each regimen were analyzed and evaluated.Results:70,081 surgeries were performed from January 2013 to February 2015, where Tobramycin was added to Balanced Salt Solution (BSS) (Group A). From March 2015 to January 2017, 63,245 surgeries were performed when intracameral Moxifloxacin was given (Group B). From February 2017 to December 2021, 1,13,548 surgeries were performed were Amikacin was added to BSS (Group C). In total, 42 cases of postoperative endophthalmitis were reported during the study period (0.02%). There was no significant difference in the endophthalmitis rates between groups A and B (P = 0.4152); however, there was a significant decrease in endophthalmitis rates in group C when compared with group A (P = 0.04) and group B (P = 0.006).Conclusion:There was a significant reduction in the rates of endophthalmitis following the addition of amikacin in irrigating BSS. Nocardia was one of the predominant organisms isolated from these endophthalmitis patients. This is the first single-center study to report a comparative analysis of different endophthalmitis prophylactic measures in a community eye care set up with a high incidence of Nocardia endophthalmitis prevented with amikacin in BSS irrigating solution.     

Clinical presentation and treatment outcomes of an algorithmic approach to uveal effusion syndrome

Purpose:To describe the clinical features and treatment outcomes in spontaneous uveal effusion syndrome (UES).Methods:A 10-year retrospective chart review of UES patients from a tertiary eye center was carried out. Optical coherence tomography (OCT), fundus fluorescein angiography, and ultrasound biomicroscopy (UBM) scans were performed. UES was managed based on presenting best-corrected visual acuity (BCVA), symptoms, and fundus findings. Patients with secondary causes of uveal effusion were excluded.Results:Twenty-five eyes of 16 patients were included. Of the 16 patients, 14 (88%) were male and 9 (56%) had bilateral disease. Fifteen of 25 affected eyes had nanophthalmos (axial length (AL) <20.5 mm) and 6 had hyperopia with AL >20.5 mm. The presenting mean distance BCVA was 0.74 ± 0.64 logMAR (mean Snellen: 20/100). Eleven eyes had exudative retinal detachment, and 4 also had exudative choroidal detachment (CD). Choroidal thickness (CT) was increased in 11 eyes on B-scan ultrasonography, and the mean CT was 1.74 ± 0.38 mm. Sub-retinal fluid (SRF) and retinal folds were the most common OCT findings. UBM findings included shallow angles, peripheral CD, and supra-ciliary effusion. A combination of local and systemic corticosteroids was used to successfully treat 12 eyes, 6 needed surgery, and 7 were observed. Partial sclerectomy with anterior chamber maintainer-assisted SRF drainage was the favored surgery. The median period of follow-up was 6.5 months (0.1–76 months), and the mean distance BCVA at the last follow-up was 0.58 ± 0.42 logMAR (mean Snellen: 20/80).Conclusion:UES can be suitably managed both medically and surgically based on clinical presentation.     

dsDentinal translucency and width of cementum: predicting the age over 55 years in South Indian adults using extracted sectioned teeth

The main intention of this article was to evaluate the reliability of root dentine translucency (RDT) and the width of cementum (CW) in indicating the age over 55 years in forensic and criminal investigations. 600 non-restored, single rooted teeth (300 males and 300 females) which were extracted for periodontal or orthodontic reasons were collected. Each tooth was sectioned longitudinally until the desired thickness (250 µm) was obtained. Both the length of the RDT and CW were measured from these unstained ground sections of teeth using ImageJ computer software. Pearson’s correlation coefficient indicated a very strong and positive correlation for RDW and CW with age in both sexes. Cut-off values of RDT= 7.07 and CW= 52.06 were obtained using the maximum Youden’s index. The value for the area under the curve (AUC) was 0.987 for RDT and 0.910 for CW was seen as indicating a very high discrimination. The performance of these cut-off values was tested in a separate sample of sectioned teeth (n= 300) and was analyzed using contingency tables in both sexes. The sensitivity was 88.2% and 92.3%, while specificity was 98.9% for RDT in males and females. For CW, the sensitivity was 96.1% and 90.3%, and specificity was 76.7% and 74.4% in males and females, respectively. Bayes post-test probability was 98.9% for RDT in both sexes, while 80.5% in males and 78% in females, for CW. Based on our study findings, it can be concluded that both variables have performed well in predicting the age over 55 years. Further research concerning the radiographic study of secondary dentine deposition to predict legal age thresholds would be a great benefit for living adults who require age estimation in civil proceedings.