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1.
Sci Rep ; 11(1): 12197, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108516

RESUMO

Forty-five African or Asian origin pearl millet populations bred either in Africa or Asia were investigated to generate information on heterotic pools. They were clustered into seven groups (G1 to G7) when genotyped, using 29 highly polymorphic SSRs. Fourteen parental populations representing these seven marker-based groups were crossed in diallel mating design to generate 91 population hybrids. The hybrids evaluated at three locations in India showed mean panmictic mid-parent heterosis (PMPH) and better-parent heterosis (PBPH) for grain yield ranging from - 21.7 to 62.08% and - 32.51 to 42.99%, respectively. Higher grain yield and heterosis were observed in G2 × G6 (2462 kg ha-1, 43.2%) and G2 × G5 (2455 kg ha-1, 42.8%) marker group crosses compared to the most popular Indian open-pollinated variety (OPV) ICTP 8203. Two heterotic groups, Pearl millet Population Heterotic Pool-1 (PMPHP-1) comprising G2 populations and Pearl millet Population Heterotic Pool-2 (PMPHP-2) comprising G5 and G6 populations, were identified based on hybrid performance, heterosis and combining ability among marker group crosses. Population hybrids from two heterotic groups, PMPHP-1 × PMPHP-2 demonstrated PMPH of 14.75% and PBPH of 6.8%. Populations of PMPHP-1 had linkages with either African or Asian origin populations, whereas PMPHP-2 composed of populations originating in Africa and later bred for Asian environments. Results indicated that parental populations from the two opposite heterotic groups can be used as base populations to derive superior inbred lines to develop high yielding hybrids/cultivars.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34120918

RESUMO

OBJECTIVE: To determine the predictors of mortality following early rescue surfactant therapy in preterm babies with respiratory distress syndrome. STUDY DESIGN: Prospective cohort study enrolling babies between 28 weeks to 34 weeks with respiratory distress syndrome requiring early rescue surfactant therapy. For statistical analysis babies were further divided into two subgroups: survivors and non-survivors. Maternal and neonatal variables were compared between the two groups to find out the predictors of mortality. RESULTS: Out of total 110 babies, 72 (65.45%) survived. The mean birth weight and mean gestational age of the study population was 1614.36 (±487.86) g and 31.40 (±2.0)1 weeks, respectively. Birth weight <  1500 g, gestational age <  32 weeks, primiparity, vaginal delivery, prolonged rupture of membranes, lack of antenatal steroid cover, bag and mask ventilation at birth, sepsis, apneic episodes and mechanical ventilation were significantly associated with death on univariate analysis. On multivariate analysis, very low birth weight, vaginal delivery, lack of antenatal steroid cover, bag and mask ventilation at birth and mechanical ventilation were found to be independent predictors of mortality. CONCLUSIONS: Some of the identified predictors of mortality are modifiable and can be used to draw up a screening tool to predict the clinical severity and mortality among these babies.

3.
Eur Cell Mater ; 41: 546-557, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34008855

RESUMO

Marrow stimulation, including subchondral drilling and microfracture, is the most commonly performed cartilage repair strategy, whereby the subchondral bone plate is perforated to release marrow-derived cells into a cartilage defect to initiate repair. Novel scaffolds and therapeutics are being designed to enhance and extend the positive short-term outcomes of this marrow stimulation. However, the translation of these newer treatments is hindered by bony abnormalities, including bone resorption, intralesional osteophytes, and bone cysts, that can arise after marrow stimulation. In this study, three different marrow stimulation approaches - microfracture, subchondral drilling and needle-puncture - were evaluated in a translationally relevant large-animal model, the Yucatan minipig. The objective of the study was to determine which method of marrow access (malleted awl, drilled Kirschner wire or spring-loaded needle) best preserved the underlying subchondral bone. Fluorochrome labels were injected at the time of surgery and 2 weeks post-surgery to capture bone remodelling over the first 4 weeks. Comprehensive outcome measures included cartilage indentation testing, histological grading, microcomputed tomography and fluorochrome imaging. Findings indicated that needle-puncture devices best preserved the underlying subchondral bone relative to other marrow access approaches. This may relate to the degree of bony compaction occurring with marrow access, as the Kirschner wire approach, which consolidated bone the most, induced the most significant bone damage with marrow stimulation. This study provided basic scientific evidence in support of updated marrow stimulation techniques for preclinical and clinical practice.

4.
BMC Cancer ; 21(1): 593, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030643

RESUMO

BACKGROUND: ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). METHODS: Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. RESULTS: Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. CONCLUSIONS: Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).

5.
Artigo em Inglês | MEDLINE | ID: mdl-33663899

RESUMO

The objective of this study was to describe the authors' long-term experience with the management of odontogenic keratocysts (OKCs). All OKC cases treated at the study centre between 1999 and 2015, with a minimum of 5 years of follow-up by December 2019, were reviewed retrospectively. Operative procedures including decompression/marsupialization, enucleation (E), E+Carnoy's solution (CS), E+CS+peripheral ostectomy (PO), and resection were assessed for complete resolution, partial resolution, and recurrence rates. In the parakeratinized non-syndromic group, E+CS+PO resulted in the lowest recurrence rate among the minimally invasive procedures (4.3%), while enucleation resulted in the highest rate (60%). Regarding the other modalities, recurrence was 12.5% for decompression, 11.5% for marsupialization, 16.7% for E+CS, 26.7% for E+PO, and 0% for resection. In the syndromic group, marsupialization resulted in a significantly higher recurrence (23.1%), while E+CS+PO cases showed no recurrence. No recurrence was observed in the orthokeratinized group patients treated with marsupialization or with E+CS. Based on clinico-radiographic features and observed results, it is concluded that OKC, although having a high recurrence rate, is a benign lesion and responds well to conservative procedures in most cases. Radical procedures should be reserved for unresponsive lesions and those with extensive tissue destruction.

6.
Biomaterials ; 271: 120735, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33721571

RESUMO

The central vision-threatening event in glaucoma is dysfunction and loss of retinal ganglion cells (RGCs), thought to be promoted by local tissue deformations. Here, we sought to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, i.e. the scleral region immediately adjacent to the optic nerve head. Previous scleral stiffening studies to treat glaucoma or myopia have used either pan-scleral stiffening (not regionally selective) or regionally selective stiffening with limited access to the posterior globe. We present a method for selectively stiffening the peripapillary sclera using a transpupillary annular light beam to activate methylene blue administered by retrobulbar injection. Unlike prior approaches to photocrosslinking in the eye, this approach avoids the damaging effects of ultraviolet light by employing red light. This targeted photocrosslinking approach successfully stiffened the peripapillary sclera at 6 weeks post-treatment, as measured by whole globe inflation testing. Specifically, strain was reduced by 47% when comparing treated vs. untreated sclera within the same eye (n = 7, p=0.0064) and by 54% when comparing the peripapillary sclera of treated vs. untreated eyes (n = 7, p<0.0001). Post-treatment characterization of RGCs (optic nerve axon counts/density, and grading), retinal function (electroretinography), and retinal histology revealed that photocrosslinking was associated with some ocular toxicity. We conclude that a transpupillary photocrosslinking approach enables selective scleral stiffening targeted to the peripapillary region that may be useful in future treatments of glaucoma.


Assuntos
Glaucoma , Disco Óptico , Fenômenos Biomecânicos , Colágeno , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Esclera
7.
Br J Surg ; 108(5): 511-520, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33724296

RESUMO

BACKGROUND: The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. METHODS: In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. RESULTS: Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III-IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). CONCLUSION: Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.

8.
Pancreatology ; 21(4): 746-754, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33632664

RESUMO

PURPOSE: The aim of this study was to evaluate the diagnostic performance of dual-time-point-PET/CT, CECT and EUS + FNA in diagnosing pancreatic-ductal-adenocarcinomas (PDAC), in context of concomitant Chronic Pancreatitis (CP). METHODS: 18F-FDG-PET/CTs were prospectively acquired in 22 confirmed CP and 23 confirmed PDAC patients (calculated for 90% power); and cut-offs of 2.2 for early-SUV(∼1hr), 2.4 for delayed-SUV(∼3hr) and 1.36 for Retention-index (RI), were derived. These cut-offs were validated in PET/CTs of 75 patients (51.9 ± 13.3years; 54 men) with pancreatic masses of unknown nature. Comparisons were made with triple-phase-CECT (73 patients) and EUS + FNA (54 patients). Histopathology was obtained in 68 patients (including all PDACs) and 7 were followed up for minimum of 2 years. RESULTS: In patients without concomitant CP, sensitivity, specificity and accuracy for diagnosing malignancy in standard-acquisition-PET/CT, dual-time-point-PET/CT, CECT and EUS + FNA were 97.4%, 83.3%, 94.0%; 97.4%, 75.0%, 92%; 94.6%, 66.7%, 87.8% and 92.6%, 88.9%, 91.7% respectively. Corresponding values in patients with concomitant CP were 88.9%, 57.1%, 80.0%; 100%, 57.1%, 88%; 82.4%, 57.1%, 75% and 100%, 100%, 100% respectively. In lesions ≤2 cm (AJCC-T1), dual-time-point-PET/CT was the most sensitive (95.8%). ROC-analysis revealed significantly higher area-under-the-curve for RI over early-SUV (p = 0.002) in cases with concomitant CP only. In patients with confirmed liver-metastases, PET/CT and CECT identified 15/16 and 13/16 lesions. PET/CT identified additional lung-metastases in 3 and bone-metastasis in one patient. CONCLUSION: In patients without concomitant CP and with larger lesions, PET/CT and CECT are equivocal as screening modalities, with no benefit of dual-time-point-PET/CT acquisitions. However, in patients with concomitant CP and smaller lesions, dual-time-point PET/CT is better; with sensitivity comparable to EUS + FNA.

9.
Cancer Rep (Hoboken) ; : e1359, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33624448

RESUMO

BACKGROUND: Abandonment of treatment, a major cause of treatment failure in low- and middle-income countries like India, is particularly high during the diagnostic and initial phase of treatment. Tracking of patients during this risk period may reduce treatment abandonment rates and increase quality of care. AIM: The primary aim was to pilot the use and check the acceptability of a tool for tracking children with cancer in New Delhi during the initial part of their treatment. Secondary aim was to estimate abandonment rates among these patients. METHODS: This prospective study was carried out in two centers of North India in New Delhi and enrolled children less than 18 years diagnosed with cancer at these centers and who had registered with Cankids for social support. Parent support group (PSG) workers maintained contact with the child's family at least once a week for the first 12 weeks. Details of each contact and subsequent action were recorded in a customized book (called "You are not alone" or YANA Book). Descriptive analysis of these contacts was done in Microsoft Excel and presented in frequencies and percentages. The five-point Likert scale was used to check the acceptability of the tool among the PSG workers. RESULTS: Seven PSG workers enrolled and tracked 81 patients (73% male with a median age of 6 years). During the 12-week study period, 986 contacts were attempted and three (3.7%) patients had abandoned their treatment. All PSG workers strongly agreed that the YANA book was simple to understand and use, decreased their workload, and helped provide better assistance to patients. CONCLUSION: The tool for patient tracking was well accepted by the PSG workers and considered easy to use. We now plan to implement our model as a routine service at all the partnering hospitals in India.

10.
Microbiol Res ; 247: 126720, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33592359

RESUMO

Microbial co-inoculation strategy utilizes a combination of microbes to stimulate plant growth concomitant with an increased phytopathogen tolerance. In the present study, 15 endophytic bacterial isolates from rhizosphere and roots of wild chickpea accessions (Cicer pinnatifidum, C. judiacum, C. bijugum and C. reticulatum) were characterized for morphological, biochemical and physiological traits. Two promising isolates were identified as Pseudomonas fluorescens strain LRE-2 (KR303708.1) and Pseudomonas argentinensis LPGPR-1 (JX239745.1) based on 16S rRNA gene sequencing. Biocompatibility of selected endophytes with Mesorhizobium sp. CH1233, a standard isolate used as a national check in All India Coordinated Research Project (AICRP) was assessed to develop functional combinations capable of producing Indole acetic acid, gibberellins, siderophores and improving seed vigour (in vitro). In vivo synergistic effect of promising combinations was further evaluated under national AICRP, (Chickpea) at two different agro-climatic zones [North-West plain (Ludhiana and Hisar) and Central zones (Sehore)] for three consecutive Rabi seasons (2015-18) to elucidate their effect on symbiotic, soil quality and yield parameters. On the pooled mean basis across locations over the years, combination of Mrh+LRE-2 significantly enhanced symbiotic, soil quality traits and grain yield over Mrh alone and highly positive correlation was obtained between the nodulation traits and grain yield. Superior B: C ratio (1.12) and additional income of Rs 6,505.18 ha-1 was obtained by application of Mrh+LRE-2 over Mrh alone and un-inoculated control. The results demonstrate that dual combination of Mrh and Pseudomonas sp. from wild Cicer relatives can be exploited as a potential bio-fertilizer for increasing soil fertility and improving chickpea productivity under sustainable agriculture.

12.
J Endocrinol Invest ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502721

RESUMO

BACKGROUND: Post thyroidectomy hypocalcemia is a major sequel of thyroidectomy and continues to trouble the endocrinologists and the endocrine surgeons as there is no ideal predictive marker of hypocalcemia which has the potential to develop into a life-threatening complication. The role of early serum intact parathormone (iPTH) to predict post thyroidectomy hypocalcemia is becoming useful but the literature is still unclear regarding the optimal time of testing and the optimal cut-off value of serum iPTH. PATIENTS AND METHODS: This is a prospective cohort study of 111 patients who underwent total thyroidectomy in a tertiary care endocrine surgery referral unit. Serum iPTH was measured after 20 min and 4 h of surgery. Receiver-Operator characteristic Curve (ROC) was used to find out of the best cut-off value of S. iPTH 20 min and 4 h after surgery in predicting hypocalcemia. RESULTS: Hypocalcemia was noted in 60 (54%) out of 111 subjects who underwent total thyroidectomy. The best cut-off values of Serum iPTH to predict hypocalcemia was found to be 4.28 pmol/l at 20 min post total thyroidectomy with a sensitivity and specificity of 81.7% and 51%, respectively. In addition, patients with malignancy or central lymph nodal dissection were significantly over-represented in the hypocalcemia group with serum iPTH above the threshold level of 4.28 pmol/l. Below the cut off level, parenteral calcium supplementation was required in 23% (17/74) subjects while the rate was only 5.4% (2/37) patients when serum iPTH was above the cut-off level. CONCLUSIONS: The decline of serum iPTH below a specific level after surgery has predictive value together with other factors strictly related to patient, the thyroid disease itself and surgery. The risk of development of hypocalcemia and consequent need for calcium supplementation should be evaluated by clinical assessment along with serum PTH measurement.

13.
Opt Lett ; 46(2): 182-185, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448983

RESUMO

All-dielectric metamaterials conforming to an optical reflectionless potential (ORP) offer broadband, omni-directional suppression of reflection. Though they are predicted to possess broadband negative group velocity dispersion (GVD), ultrashort pulse propagation through such materials has not been studied so far, to the best of our knowledge. In this work, we demonstrate negative GVD and group delay dispersion over broadband covering visible to near-infrared wavelengths. We investigate the role of ORP in supercontinuum generation (SC), which is observed to be polarization independent. The negative GVD in ORPs is interesting for pulse compression, phase compensation, dispersion engineering, and controlled SC generation.

14.
Int Endod J ; 54(5): 793-801, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33368371

RESUMO

AIM: To determine and compare the accuracy and efficiency of a dynamic navigation system (DNS) with a freehand (FH) technique when conducting root-end resection in a human cadaver model. METHODOLOGY: Forty roots in cadaver heads were included and divided into two groups: DNS (n = 20) and FH (n = 20). Cone beam computed tomography (CBCT) scans of all teeth were taken. The drilling path and depth were planned virtually to using the X-guide software (X-Nav Technologies, Lansdale, PA, USA). Osteotomy and root-end resection were done under navigation in the DNS group, and freehand under the dental operating microscope in the FH group. Post-operative CBCTs were taken. Linear deviations, angular deflection, time of operation and number of mishaps were compared with determine the accuracy and efficiency. Shapiro-Wilk, one-way ANOVA and Fisher exact tests were used (P < 0.05). RESULTS: Linear deviations, angular deflection and operation time were significantly less in the DNS group (P < 0.05). The number of mishaps was not different between the two groups (P > 0.05). Subgroup analyses revealed that the distance of >5 mm from buccal cortical plate was significantly associated with lower accuracy, increased operation time and greater incidence of mishaps in the FH group (P < 0.05), but not in the DNS group. CONCLUSIONS: The dynamic navigation system was more accurate and more efficient in root-end resection in a cadaver model than the freehand technique. The distance of the roots from the buccal cortical plate had a significant negative impact on the accuracy and efficacy of the root-end resection procedure when using the freehand technique. The dynamic navigation system has the potential to be a safe and reliable technological addition to endodontic microsurgery.


Assuntos
Cirurgia Assistida por Computador , Dente , Cadáver , Tomografia Computadorizada de Feixe Cônico , Humanos , Microcirurgia
16.
Clin Radiol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33268083

RESUMO

AIM: To report on the multidisciplinary approach, focusing specifically on the role of the interventional radiologist (IR), used to support the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) and BATTLE-2 trials. MATERIALS AND METHODS: Patients who underwent percutaneous image-guided biopsy for the BATTLE and BATTLE-2 trials were reviewed. A radiology-based, three-point, lesion-scoring system was developed and used by two IRs. Lesions were given a score of 3 (most likely to yield sufficient material for biomarker analysis) if they met the following criteria: size >2 cm, solid mass, demonstrated imaging evidence of viability, and were technically easy to sample. Lesions not meeting all four criteria were scored 2 with the missing criteria noted as negative factors. Lesions considered to have risks that outweighed potential benefits receive a score of 1 and were not biopsied. Univariate and multivariate analyses were performed to evaluate the score's ability to predict successful yield for biomarker adequacy. RESULTS: A total of 555 biopsies were performed. The overall yield for analysis of the required biomarkers was 86.1% (478/555), and 84% (268/319) and 88.9% (210/236) for BATTLE and BATTLE-2, respectively (p=0.09). Lesions receiving a score of 3 were adequate for biomarker analysis in 89% of cases. Lesions receiving a score of 2 with more than two negative factors were adequate for molecular analysis in 69.2% (IR1, p=0.03) and 74% (IR2, p=0.04) of cases. The two IRs scored 78.4% of the lesions the same indicating moderate agreement (kappa=0.55; 95% confidence interval [CI]: 0.48, 0.61). CONCLUSIONS: IRs add value to clinical trial teams by optimising lesions selected for biopsy and biomarker analysis.

17.
Biochim Biophys Acta Proteins Proteom ; 1869(2): 140562, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221341

RESUMO

Affinity maturation of U33, a recombinant Fab inhibitor of uPA, was used to improve the affinity and the inhibitory effect compared to the parental Fab. Arginine scanning of the six CDR loops of U33 was done to identify initial binding determinants since uPA prefers arginine in its primary substrate binding pocket. Two CDR loops were selected to create an engineered affinity maturation library of U33 that was diversified around ArgL91 (CDR L3) and ArgH52 (CDR H2). Biopanning of the randomized U33 library under stringent conditions resulted in eight Fabs with improved binding properties. One of the most potent inhibitors, AB2, exhibited a 13-fold decrease in IC50 when compared to U33 largely due to a decrease in its off rate. To identify contributions of interfacial residues that might undergo structural rearrangement upon interface formation we used X-ray footprinting and mass spectrometry (XFMS). Four residues showed a pronounced decrease in solvent accessibility, and their clustering suggests that AB2 targets the active site and also engages residues in an adjacent pocket unique to human uPA. The 2.9 Å resolution crystal structure of AB2-bound to uPA shows a binding mode in which the CDR L1 loop inserts into the active site cleft and acts as a determinant of inhibition. The selectivity determinant of this binding mode is unlike previously identified inhibitory Fabs against uPA related serine proteases, MTSP-1, HGFA and FXIa. CDRs H2 and L3 loops aid in interface formation and provide critical salt-bridges to remodel loops surrounding the active site of uPA providing specificity and further evidence that antibodies can be potent and selective inhibitors of proteolytic enzymes.

18.
Eur J Pharm Sci ; : 105635, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33160045

RESUMO

BACKGROUND: Organochlorine pesticides such as DDT as well as postprandial hypertriglyceridemia have been linked with insulin resistance and diabetes mellitus. The cardiometabolic risk of PPhTg could also be due to its potential to increase the serum levels of this highly lipophilic pesticide. We studied the effect of postprandial triglyceride responses to a standard oral fat challenge on the levels of DDT and its metabolites in subjects with varying degree of glucose intolerance METHODS: A standard fat challenge was performed in 60 subjects who were categorized as NGT, prediabetes, and NDDM based on an earlier OGTT. Fasting and postprandial levels of serum triglycerides, plasma DDT and its metabolites were estimated and compared in the 3 groups and their association with each other, and measures of glycemia and insulin resistance were also determined. RESULTS: Peak Tg and TgAUC levels were significantly higher in NDDM group as compared to NGT and PD groups. TgAUC showed positive correlation with fasting plasma glucose (r=0.33, p=0.01), postprandial plasma glucose (r=0.39, p=0.002) and HOMA IR(r=0.63, p=0.001). ppDDE levels were found to be significantly higher in NDDM subjects compared with NGT group. ppDDE-AUC was significantly higher in the NDDM group compared with the other two study groups. Mean ppDDE levels also showed strong positive correlation with peak Tg (r=0.295 p=0.022), TgAUC (r=0.303 p=0.018), iPPTgAUC(r=0.57 p≤0.001) and iPPpeakTg(r=0.51 p≤0.001) as well as with FPG (r=0.269 p=0.038) PPPG (r=0.424 p=0.001) and HbA1c (r=0.321 p=0.012). CONCLUSION: The findings of this study support the concept that the cardiometabolic risk associated with PPhTg may at least in part be related to the associated increase in serum levels of lipophilic OCPs like DDT.

19.
J Dent Res ; : 22034520970536, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138663

RESUMO

Understanding the pathophysiology of the coronavirus disease 2019 (COVID-19) infection remains a significant challenge of our times. The gingival crevicular fluid being representative of systemic status and having a proven track record of detecting viruses and biomarkers forms a logical basis for evaluating the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study aimed to assess gingival crevicular fluid (GCF) for evidence of SARS-CoV-2 in 33 patients who were deemed to be COVID-19 positive upon nasopharyngeal sampling. An attempt was also made to comparatively evaluate it with saliva in terms of its sensitivity, as a diagnostic fluid for SARS-CoV-2. GCF and saliva samples were collected from 33 COVID-19-confirmed patients. Total RNA was extracted using NucliSENS easyMAG (bioMérieux) and eluted in the elution buffer. Envelope gene (E gene) of SARS-CoV-2 and human RNase P gene as internal control were detected in GCF samples by using the TRUPCR SARS-CoV-2 RT qPCR kit V-2.0 (I) in an Applied Biosystems 7500 real-time machine. A significant majority of both asymptomatic and mildly symptomatic patients exhibited the presence of the novel coronavirus in their GCF samples. Considering the presence of SARS-CoV-2 RNA in the nasopharyngeal swab sampling as gold standard, the sensitivity of GCF and saliva, respectively, was 63.64% (confidence interval [CI], 45.1% to 79.60%) and 64.52% (CI, 45.37% to 80.77%). GCF was found to be comparable to saliva in terms of its sensitivity to detect SARS-CoV-2. Saliva samples tested positive in 3 of the 12 patients whose GCF tested negative, and likewise GCF tested positive for 2 of the 11 patients whose saliva tested negative on real-time reverse transcription polymerase chain reaction. The results establish GCF as a possible mode of transmission of SARS-CoV-2, which is the first such report in the literature, and also provide the first quantifiable evidence pointing toward a link between the COVID-19 infection and oral health.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33131029

RESUMO

In the present study, bacterial isolates were screened for arsenic resistance efficiency. Environmental isolates were isolated from arsenic-rich soil samples (i.e., from Rajnandgaon district of Chhattisgarh state, India). Amplification and sequencing of 16S rRNA gene revealed that the isolates were of Bacillus firmus RSN1, Brevibacterium senegalense RSN2, Enterobacter cloacae RSN3, Stenotrophomonas pavanii RSN6, Achromobacter mucicolens RSN7, and Ochrobactrum intermedium RSN10. Arsenite efflux gene (arsB) was successfully amplified in E. cloacae RSN3. Atomic absorption spectroscopy (AAS) analysis showed an absorption of 32.22% arsenic by the RSN3 strain. Furthermore, results of scanning electron microscopy (SEM) for morphological variations revealed an initial increase in the cell size at 1 mM sodium arsenate; however, it was decreased at 10 mM concentration in comparison to control. This change of the cell size in different metal concentrations was due to the uptake and expulsion of the metal from the cell, which also confirmed the arsenite efflux system.

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