Impact of radiation therapy on healthy and cancerous cell dynamics: a Mathematical analysis.

This study proposes a novel therapeutic model for cancer treatment with radiation therapy by analyzing the interactions among cancer, immune and healthy cells through a system of three ordinary differential equations. In this model, the natural influx rate of mature immune cells is assumed constant and is denoted by, a. The overall effect of radiation therapy on cancer cells is represented by a parameter, s; which is the surviving fraction of cells as determined by the Linear Quadratic (LQ) model. Conditions for the stability of equilibria in the interaction model modified to include the surviving fraction, are systematically established in terms of the dose and model parameters. Numerical simulations are performed in Wolfram MATHEMATICA software, investigating a spectrum of initial cell population values irradiated with 60Co γ-ray Low-LET radiation and High-LET 165 keV/µm Ni-ion radiation to facilitate improved visualization and in-depth analysis. By analyzing the model, this study identifies threshold values for the absorbed dose D for particular values of the model and radiation parameters for both High Linear Energy Transfer (high-LET) and Low Linear Energy Transfer (low-LET) radiations that ensure either eradication or minimization of cancer cells from a patient's body, providing valuable insights for designing effective cancer treatments.

Improving maternal update rates within the first hour of NICU admission.

BACKGROUND: Timely communication is essential in attaining maternal satisfaction, developing an excellent physician-patient rapport, and increasing trust. This study reports a significant improvement in maternal communication rates through the quality improvement method. METHODS: An educational module was developed, and NICU staff was presented with the slides, followed by a performance questionnaire to demonstrate understanding. The first phase was completed by obtaining feedback from mothers through a questionnaire. The first plan-do-study-act (PDSA) cycle, carried out for eight weeks looking at the rates of the maternal update provided within an hour of admission of their neonates to the NICU, was followed by the second PDSA cycle, carried out for ten weeks. The improvement was calculated using conventional statistics and a statistical process control chart. RESULTS: During the first phase of the study, thirty-six percent of the mothers were updated within an hour of admission of their neonates to the NICU. During the first PDSA cycle, we did not notice a special cause variation or process change. A significant shift, eight consecutive points above the mean, was noted on the control chart during PDSA cycle 2. The mean±SD of the weekly update rate increased significantly during PDSA cycle 2 (76.8±11) compared to PDSA cycle 1 (47.5±14), p-value = 0.0002. CONCLUSION: We improved the maternal update rates through the educational module following the QI improvement model using the PDSA cycles.

Papillary Carcinoma of Thyroglossal Duct Cyst- A Diagnostic and Therapeutic Conundrum.

Thyroglossal duct cysts (TGDC) are the most common congenital midline neck mass. It accounts for 70% of congenital neck masses in children and 7% in the general population. Untreated, Thyroglossal duct cyst may transform into a thyroid carcinoma in less than 1% of cases. A 47 year old female patient presented with complaints of swelling on the anterior aspect of neck for 1 year which was progressively increasing in size. Smears from needle aspiration revealed features suspicious of Papillary carcinoma of thyroid which was confirmed as on histopathology. Thyroid gland and the adjacent lymph nodes were free of the tumour on Computed Tomography (CT). Thyroglossal duct cysts undergoing neoplastic change is more common among women. Though sistrunk's procedure is widely accepted as a primary management, the role of total thyroidectomy with radioiodine therapy still remains a controversy due to contrasting opinions available in the literature.

A two-galectin network establishes mesenchymal condensation phenotype in limb development.

Previous work showed that Gal-1A and Gal-8, two proteins belonging to the galactoside-binding galectin family, are the earliest determinants of the patterning of the skeletal elements of embryonic chicken limbs, and further, that their experimentally determined interactions in the embryonic limb bud can be interpreted via a reaction-diffusion-adhesion (2GL: two galectin plus ligands) model. Here, we use an ordinary differential equation-based approach to analyze the intrinsic switching modality of the 2GL network and characterize the network behavior independent of the diffusive and adhesive arms of the patterning mechanism. We identify two states: where the concentrations of both the galectins are respectively, negligible, and very high. This bistable switch-like system arises via a saddle-node bifurcation from a monostable state. For the case of mass-action production terms, we provide an explicit Lyapunov function for the system, which shows that it has no periodic solutions. Our model therefore predicts that the galectin network may exist in low expression and high expression states separated in space or time, without any intermediate states. We test these predictions in experiments performed with high density cultures of chick limb mesenchymal cells and observe that cells inside precartilage protocondensations express Gal-1A at a much higher rate than those outside, for which it was negligible. The Gal-1A and -8-based patterning network is therefore sufficient to partition the mesenchymal cell population into two discrete cell states with different developmental (chondrogenic vs. non-chondrogenic) fates. When incorporated into an adhesion and diffusion-enabled framework this system can generate a spatially patterned limb skeleton.

ONCOLYTIC ACTIVITY OF HUMAN ORTHOPNEUMOVIRUS IN CANCER CELL LINES.

Oncolytic virotherapy is an emerging biotherapeutic platform for selectively infecting cancer cells and triggering apoptosis in a number of malignant cells due to robust viral replication. Studies related to the oncolytic activity of human orthopneumovirus (hOPV) are conflicting. AIM: This study was designed to elucidate the possible role of hOPV in the modulation of cell growth and apoptosis in cancer cell lines including human epidermoid carcinoma (HEp-2), lung epithelial cell line (A549), and breast cancer cell line (MCF-7). MATERIALS AND METHODS: The oncolytic activity of hOPV on cancer cells was studied in vitro. The virus titers were determined by tissue culture infectious dose (TCID50/mL) in A549 cell. The cytotoxic effect of the virus on HEp-2, A549, and MCF-7 was determined using MTT and trypan blue dye exclusion test assays. hOPV in the infected cells was detected using real-time reverse transcription polymerase chain reaction (rRT-PCR) and indirect immunofluorescence (IIF) assays. The relative expression of apoptosis-related genes (CASP-3, -8, -9, Bax, Bcl-2, Bcl-XL, TP53, P21) during virus infection was estimated using rRT-PCR assay in comparison with the house-keeping gene (GAPDH). RESULTS: hOPV infection inhibited the growth of HEp-2, A549, and MCF-7 cells in a dose-and time-dependent manner. At a multiplicity of infection (MOI) of 5, hOPV reduced the viability of A549 cells to about 16%, HEp-2 to 22%, and MCF-7 to 28% (p = 0.001), while no significant inhibitory effect was observed when cells were infected at MOI of 1 and 2. hOPV mRNA and antigens were detected in infected HEp-2, A549, and MCF-7 cells by RT-PCR and IIF. Upon hOPV infection, expression of CASP-3, -8, -9, as well as Bax, TP53, and p21 mRNA increased while expression of Bcl-2, Bcl-xL anti-apoptotic genes decreased. In hOPV-infected A549 cells, the fold increase of CASP-8 and CASP-9, Bax, TP53, and P21 expression exceeded significantly compared to that in HEp-2 or MCF-7 cells. CONCLUSIONS: Our results provide evidence that hOPV could be a potential candidate for oncolytic virotherapy.

TB disease patterns by HIV and diabetes status.

BACKGROUND: TB is commonly categorised as pulmonary (PTB) or extrapulmonary TB (EPTB). Knowledge of TB disease patterns (PTB and/or EPTB) and determining risk factors remains limited.METHODS: This was a prospective cohort study using point-of-care ultrasound (POCUS) in Indian patients with presumed TB. Clinical and imaging data were used to develop refined case definitions for PTB, concurrent PTB and EPTB (PTB + EPTB) and EPTB without PTB (EPTB). These groups were analysed by HIV (HIV+/-) and diabetes mellitus (DM+/-) status.RESULTS: Of 172 HIV-/DM- patients with TB, 48% had PTB, 23% PTB + EPTB and 29% had EPTB, totalling 52% with any EPTB (PTB + EPTB or EPTB). In HIV+/DM- patients with TB (n = 35), 6% had PTB, 40% had PTB + EPTB and 54% had EPTB, accounting for 94% with EPTB. In HIV-/DM+ patients with TB (n = 61), 61% had PTB, 28% had PTB + EPTB and 11% had EPTB, representing 39% with EPTB.CONCLUSION: Refined case definitions revealed high proportions of EPTB even without HIV or DM. HIV further altered the TB disease pattern towards EPTB and DM towards PTB. Therefore, the dichotomy between PTB or EPTB does not represent the actual spectrum of TB disease. EPTB should receive higher priority in research and clinical practice.

Online KidClot education for patients and families initiating warfarin therapy: The eKITE study.

Anticoagulation with Vitamin K antagonists (VKA) has always posed challenges in terms of monitoring requirements. These challenges were further exacerbated in the setting of the COVID-19 pandemic, with limited access to and/or avoidance of laboratory testing. The importance of utilizing point of care (POC) health technology for individualized patient management is salient. The foundation of effective home INR monitoring is establishing patient knowledge about their therapy and INR testing proficiency. The eKITE series was developed to support patients in establishing foundational knowledge required for VKA (warfarin) management and INR monitoring. The primary objectives were to evaluate eKITE, a patient-oriented innovative online education program for warfarin therapy, participant learning stress, and patient preference for online learning. This multi-center prospective study provided patients access to warfarin online education. Participants were required to complete written quizzes assessing warfarin knowledge of key concepts proficiency and identifying knowledge deficits. Patient preference, evaluating calm (lack of anxiety) while learning, and an INR on a home meter was completed. Participants performed INR tests at home and reported INRs by telephone. The analysis included 144 children and caregivers enrolled at five US and CDN sites. Most indications for anticoagulation were cardiac (congenital or acquired heart disease) with varied INR target ranges. Mean knowledge scores for warfarin and INR self-testing modules were 97%, with low anxiety with TTR of 84%. Patient preferred online learning. eKITE is an effective teaching modality for warfarin/home INR monitoring with safe INR testing and warfarin management that is appropriate for pediatrics and adults alike. PROLOGUE: The whir in the hallways is deafening. Lights bright, alarms are ringing in a chorus of unsynchronized beeps and screeches. It has been more than a week since I have slept. Snuggled beside me is my precious child, whining and equally irritated with the asynchronous symphony, further compounded by anxiety, procedures, and pain. The sun has broken. The staff smiles are welcoming and incessant, as one after one, they approach hurried, urgent, assiduous, their need to coach me for our upcoming departure to the warmth of home. Each provides essential information that I will require to keep my child, my treasure, safe and healthy. Yet, my eyes are heavy, blurred, and my brain foggy, trapped in a dark heavy cloud. How am I to follow? Comprehend? and retain anything? As they instruct, my precious child yearns for loving arms, compassion and love, whining, crying in disquiet. Overwhelmed does not adequately describe my ineffable exhaustion. Amidst this, how am I to learn about warfarin? Such a challenging medication, with so much to know. Concentrate, I tell myself, focus; now is my only opportunity to learn. I must be alert. It seems to be nonsensical.

Mid-term follow-up of percutaneous access for standard and complex EVAR using the ProGlide device.

OBJECTIVES: Endovascular Aneurysm Repair is an established treatment for abdominal aortic aneurysm which requires arterial access via the groin. Most centres perform percutaneous ultrasound-guided access into the common femoral artery for delivery of the stent graft. The profile of endovascular devices necessitates large sheath sizes, therefore formal closure of the arterial puncture site is required. Various percutaneous devices are available, with data lacking on efficacy and mid-term safety profile. We present outcomes from a single centre with the Perclose ProGlide™ (Abbott Vascular Devices, CA, USA) suture-mediated system, using the well described "pre-close" technique. MATERIALS & METHODS: Data were collected from operative records and electronic medical records. Patients undergoing standard (EVAR) or complex (F/B-EVAR) aneurysm repair between March 2015 and September 2019 were included. Complications were recorded per-patient and per-groin procedure. RESULTS: 266 patients were included; 182 (68.4%) standard infrarenal EVAR, 84 (31.6%) F/B-EVAR. There were a total of 484 groin procedures performed. Intraoperative Perclose ProGlide™ success was 98.1% (per patient) or 99.0% (per groin procedure). 30-day groin complication rate was 6.1% (per patient) or 3.1% (per groin procedure). There were no pre- or peri-operative factors which predicted the occurrence of groin complications. The rate of groin complications was not related to sheath size. CONCLUSIONS: Our data support the use of percutaneous access with a pre-close technique for a variety of endovascular aneurysm repair procedures with both large- and small-bore access. The Perclose ProGlide™ system provides excellent mid-term complication-free and reintervention-free outcomes for groin procedures.

Steroids use in non-oxygen requiring COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Corticosteroids have become the mainstay treatment in severe COVID-19. However, its role is mild disease is controversial due to lack of robust scientific evidence. This systematic review and meta-analysis were conducted to assess effect of steroids in mild COVID-19 patients. METHODS: PubMed, EMBASE, Web of Science and medRxiv were searched from 31 December 2019 to 14 May 2021 for studies that reported effectiveness of steroids in non-oxygen requiring COVID-19 patients in terms of progressing to severe disease, mortality, duration of fever, duration of viral clearance and length of hospital stay (LOHS). Studies on inhalational steroids, case reports and reviews were excluded. Risk of bias (ROB) was assessed by the Cochrane's ROB tool and ROBANS tool. Quantitative data synthesis was done using the generic inverse variance method. RESULTS: A total of 6411 studies were identified, 2990 articles were screened after exclusion. Seven studies which fit the criteria (involving 2214 non-oxygen requiring COVID-19 patients) were included and analysed. Overall odds of progression to severe disease among the non-oxygen requiring COVID-19 patients receiving steroids was 5.97 [95% confidence interval (CI): 1.27-27.99, I2 = 0%] and odds of death (OR: 1.35, 95% CI: 1.01-1.79; I2 = 0%) as compared to the patients not receiving steroids. Mean duration of fever (7.4 days), duration to viral clearance (18.9 days) and LOHS (20.8 days) were significantly higher in the steroid arm, as compared to that in no-steroid arm (6.7, 16.5 and 15.2 days, respectively). CONCLUSION: Steroids in non-oxygen requiring COVID-19 patients can be more detrimental than beneficial. PROTOCOL REGISTRATION: The study was prospectively registered in PROSPERO (CRD 42021254951).

COVID-19-associated mucormycosis presenting to the Emergency Department-an observational study of 70 patients.

BACKGROUND: Mucormycosis (MM) is a deadly opportunistic fungal infection and a large surge in COVID-19-associated mucormycosis (CAM) is occurring in India. AIM: Our aim was to delineate the clinico-epidemiological profile and identify risk factors of CAM patients presenting to the Emergency Department (ED). DESIGN: This was a retrospective, single-centre, observational study. METHODS: We included patients who presented with clinical features or diagnosed MM and who were previously treated for COVID-19 in last 3 months of presentation (recent COVID-19) or currently being treated for COVID-19 (active COVID-19). Information regarding clinical features of CAM, possible risk factors, examination findings, diagnostic workup including imaging and treatment details were collected. RESULTS: Seventy CAM patients (median age: 44.5 years, 60% males) with active (75.7%) or recent COVID-19 (24.3%) who presented to the ED in between 6 May 2021 and 1 June 2021, were included. A median duration of 20 days (interquartile range: 13.5-25) was present between the onset of COVID-19 symptoms and the onset of CAM symptoms. Ninety-three percent patients had at least one risk factor. Most common risk factors were diabetes mellitus (70%) and steroid use for COVID-19 disease (70%). After clinical, microbiological and radiological workup, final diagnosis of rhino-orbital CAM was made in most patients (68.6%). Systemic antifungals were started in the ED and urgent surgical debridement was planned. CONCLUSION: COVID-19 infection along with its medical management have increased patient susceptibility to MM.

Matrix adhesion and remodeling diversifies modes of cancer invasion across spatial scales.

The metastasis of malignant epithelial tumors begins with the egress of transformed cells from the confines of their basement membrane (BM) to their surrounding collagen-rich stroma. Invasion can be morphologically diverse: when breast cancer cells are separately cultured within BM-like matrix, collagen I (Coll I), or a combination of both, they exhibit collective-, dispersed mesenchymal-, and a mixed collective-dispersed (multimodal)- invasion, respectively. In this paper, we asked how distinct these invasive modes are with respect to the cellular and microenvironmental cues that drive them. A rigorous computational exploration of invasion was performed within an experimentally motivated Cellular Potts-based modeling environment. The model comprised of adhesive interactions between cancer cells, BM- and Coll I-like extracellular matrix (ECM), and reaction-diffusion-based remodeling of ECM. The model outputs were parameters cognate to dispersed- and collective- invasion. A clustering analysis of the output distribution curated through a careful examination of subsumed phenotypes suggested at least four distinct invasive states: dispersed, papillary-collective, bulk-collective, and multimodal, in addition to an indolent/non-invasive state. Mapping input values to specific output clusters suggested that each of these invasive states are specified by distinct input signatures of proliferation, adhesion and ECM remodeling. In addition, specific input perturbations allowed transitions between the clusters and revealed the variation in the robustness between the invasive states. Our systems-level approach proffers quantitative insights into how the diversity in ECM microenvironments may steer invasion into diverse phenotypic modes during early dissemination of breast cancer and contributes to tumor heterogeneity.

Peri-operative management of percutaneous fetoscopic spina-bifida repair: a descriptive review of five cases from the United Kingdom, with focus on anaesthetic implications.

We present a case-based review of the first five percutaneous fetoscopic in-utero spina bifida repair procedures undertaken in the UK. Our focus is on implications of anaesthesia and analgesia for the mother and fetus, provision of uterine relaxation and fetal immobilisation while providing conditions conducive to surgical access. Minimising risks for fetal acidosis, placental and fetal hypoperfusion, maternal and fetal sepsis and maternal fluid overload were the foremost priorities. We discuss optimisation strategies undertaken to ensure fetal and maternal well-being under anaesthesia, shortcomings in the current approach, and possible directions for improvement.

Developing Transposable Element Marker System for Molecular Breeding.

Transposable element (TE) marker system was developed considering the useful properties of the transposable elements such as their large number in the animal and plant genomes, high rate of insertion polymorphism, and ease of detection. Various methods have been employed for developing a large number of TE markers in several crop plants for genomics studies. Here we describe some of these methods including the recent whole genome search. We also review the application of TE markers in molecular breeding.

DNA methylation and expression analyses reveal epialleles for the foliar disease resistance genes in peanut (Arachis hypogaea L.).

OBJECTIVE: Low DNA sequence polymorphism despite enormous phenotypic variations in peanut indicates the possible role of epigenetic variations. An attempt was made to analyze genome-wide DNA methylation pattern and its influence on gene expression across 11 diverse genotypes of peanut. RESULTS: The genotypes were subjected to bisulfite sequencing after 21 days of sowing (DAS). CHG regions showed the highest (30,537,376) DNA methylation followed by CpG (30,356,066) and CHH (15,993,361) across 11 genotypes. The B sub-genome exhibited higher DNA methylation sites (46,294,063) than the A sub-genome (30,415,166). Overall, the DNA methylation was more frequent in inter-genic regions than in the genic regions. The genes showing altered methylation and expression between the parent (TMV 2) and its EMS-derived mutant (TMV 2-NLM) were identified. Foliar disease resistant genotypes showed significant differential DNA methylation at 766 sites corresponding to 25 genes. Of them, two genes (Arahy.1XYC2X on chromosome 01 and Arahy.00Z2SH on chromosome 17) coding for senescence-associated protein showed differential expression with resistant genotypes recording higher fragments per kilobase of transcript per million mapped reads (FPKM) at their epialleles. Overall, the study indicated the variation in the DNA methylation pattern among the diverse genotypes of peanut and its influence of gene expression.

IMRiS phase II study of IMRT in limb sarcomas: Results of the pre-trial QA facility questionnaire and workshop.

INTRODUCTION: Soft tissue sarcomas of the extremities (STSE) are rare malignancies. We report current UK practice for immobilisation of soft tissue sarcoma of STSE, as part of the initial study set-up within the IMRiS trial, a phase II study of intensity modulated radiotherapy (IMRT) in primary bone and soft tissue sarcoma. METHODS: A facility questionnaire (FQ) was circulated to 29 IMRiS centres investigating the variation in immobilisation devices, planning techniques, and imaging protocols. A workshop was held to address concerns raised by centres. It focused on STSE immobilisation and patient set-up. Robustness of patient set-up at each centre was evaluated based on the following criteria: evidence of local set-up audit, calculation of margins based on set-up audit results, imaging frequency, and number of patients treated per centre per annum. RESULTS: Twenty-seven (93%) questionnaires were returned. 30% (8/27) of responders routinely treated STSE with IMRT. The remaining 70% (19/27) had little or no experience with IMRT for STSE. Vacuum bags were the most frequent immobilisation device (9/27), followed by thermoplastic shells (7/27). Nine centres had audited their local set-up; however, only 4 had calculated margins in response to the results. Ten centres were classified as having high level of robustness. CONCLUSIONS: Immobilisation devices and planning techniques for STSE are inconsistent across centres. Robustness of set-up is an important tool to ensure quality of results in a multicentre trial setting with such different levels of experience. The IMRiS trial Quality Assurance programme encourages centres to assess robustness of set-up through local audit and subsequent calculation of treatment margins. IMPLICATIONS FOR PRACTICE: This is the first study that used robustness criteria to tailor QA support to individual centres.

A combined approach of 16S rRNA and a functional marker gene, soxB to reveal the diversity of sulphur-oxidising bacteria in thermal springs.

With the advent of new molecular tools, new taxa of sulphur-oxidising bacteria (SOB) in diverse environments are being discovered. However, there is a significant gap of knowledge about the ecology and diversity of SOB in thermal springs. Here, the species diversity and phylogenetic affiliations of SOB were investigated using 16S rRNA and functional gene marker, soxB in thermal springs of Thane district of Maharashtra, India. Most SOB detected by 16S rDNA sequences belong to different operational taxonomic units (OTU's): Firmicutes, α-, ß-, γ-Proteobacteria and Actinobacteria with the dominance of first class. However, the soxB gene clone library sequences had shown affiliation with the ß-, γ- and α-Proteobacteria. ß-Proteobacteria-related sequences were dominant, with 53.3% clones belonging to genus Hydrogenophaga. The thiosulphate oxidation assay carried out for different isolates having distinct identity showed the mean sulphate-sulphur production from 117.86 ± 0.50 to 218.82 ± 2.56 mg SO4-S l-1 after 9 days of incubation. Also, sulphur oxidation by the genus Nitratireductor, Caldimonas, Geobacillus, Paenibacillus, Brevibacillus, Tristrella and Chelatococcus has been reported for the first time that reveals ecological widening over which thiotrophs are distributed.

Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors / 药物分析学报

1, 3, 4-Oxadiazole derivatives (4a–5f) were previously synthesized to investigate their anticancer properties. However, studies relating to their antioxidant potential and signal transducer and activator of transcription (STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole de-rivatives (4a–5f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical (DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among al the derivatives, compound 5e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy re-leased in direct binding with the SH2 domain of STAT3 was the highest for compound 5e (-9.91kcal/mol). Through virtual screening, compound 5e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5e decreased the activation of STAT3 as observed with Western blot. In brief, compound 5e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

Comparison of Postoperative Analgesic Efficacy of Wound Site Infiltration and Ultrasound-guided Transversus Abdominis Plane Block with 0.5% Ropivacaine in Lower Abdominal Surgeries under Spinal Anesthesia.

CONTEXT: Optimization and providing excellent quality of postoperative analgesia after total abdominal hysterectomy is a determinant factor of better clinical outcome, increases patient satisfaction, and allows early mobilization of the patient. AIMS: The aim of this study is to compare the postoperative analgesic efficacy of wound site infiltration (WSI) and ultrasound-guided transversus abdominis plane block (TAPB) with 0.5% ropivacaine in lower abdominal surgeries under spinal anesthesia. SETTINGS AND DESIGN: This was a randomized controlled study. SUBJECTS AND METHODS: One hundred and ten patients undergoing lower abdominal surgeries were randomly allocated to two groups (WSI and TAP) of 55 patients in each. At the end of the surgical procedure, 2.5 mg/kg of the drug ropivacaine 0.5% was administered by an anesthesiologist through either of the routes of study. Visual analog score (VAS) assessment was done at every 30 min, for 1½ h, every 2 for 24 h postoperatively. Injection diclofenac sodium 75 mg intramuscularly was given whenever VAS was >3 as rescue analgesic. STATISTICAL ANALYSIS USED: Epi Info 7.0 version software for Windows was used. All analyses were performed using Kolmogorov-Smirnov test. Mann-Whitney test was applied to detect the difference between the two groups. P < 0.05 was considered statistically significant. RESULTS: Postoperative VAS scores in Group TAP were significantly reduced at 30 min, 1st h, 1 h 30 min, 2, 4, 6, 8, 10, 12, 18, and 24 h (P < 0.001). The total doses of rescue analgesics administered were also low in the Group TAP (1.41 ± 0.538) with P < 0.0001 in comparison to Group WSI (2.24 ± 0.637) with P < 0.001. CONCLUSIONS: The quality of analgesia along with lesser rescue analgesic requirement and their side effects makes the TAPB, a good and safer option for lower abdominal gynecological surgeries. Both WSI and USG TAPB are effective in providing postoperative analgesia as a part of multimodal analgesia in lower abdominal surgeries. However, in our study the quality of analgesia along with lesser rescue analgesic requirement and their side effects makes the TAPB, a good and safer option for lower abdominal gynecological surgeries.

Development of AhMITE1 markers through genome-wide analysis in peanut (Arachis hypogaea L.).

OBJECTIVE: In peanut, the DNA polymorphism is very low despite enormous phenotypic variations. This limits the use of genomics-assisted breeding to enhance peanut productivity. This study aimed to develop and validate new AhMITE1 and cleaved amplified polymorphic sequences (CAPS) markers. RESULTS: In total, 2957 new AhMITE1 markers were developed in addition to identifying 465 already reported markers from the whole genome re-sequencing data (WGRS) of 33 diverse genotypes of peanut. The B sub-genome (1620) showed more number of markers than the A sub-genome (1337). Distribution also varied among the chromosomes of both the sub-genomes. Further, 52.6% of the markers were from genic regions; where 31.0% were from intronic regions and 5.2% were from exonic regions. Of the 343 randomly selected markers, 82.2% showed amplification validation, with up to 35.5% polymorphism. From the SNPs on the A03, B01, B02 and B03 chromosomes, 11,730 snip-SNPs (potential CAPS sites) were identified, and 500 CAPS markers were developed from chromosome A03. Of these markers, 30.0% showed validation and high polymorphism. This study demonstrated the potential of the WGRS data to develop AhMITE1 and CAPS markers, which showed high level of validation and polymorphism. These marker resources will be useful for various genetic studies and mapping in peanut.

Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.

We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml-1; P<0.05). The PM status did not influence clinical outcomes in majority of the studies. However, only one study followed the Gaedigk activity scoring for phenotypic assignments, which predicted recurrence-free survival in CYP2D6 poor metabolizers. In two independent studies with 1676 patients, low endoxifen concentrations predicted poor BC-free survival. From our review of published data we found that standardization of CYP2D6 genotype-phenotype classification is needed in order to ensure effective evaluation of associations between CYP2D6 polymorphisms and endoxifen concentrations and BC outcomes. Universal implementation of this standardization classification system should be a priority among researchers and laboratories. Furthermore, additional clinical research is warranted to determine whether patients with CYP2D6 PM phenotypes or low endoxifen levels will have better clinical outcomes with increased tamoxifen dosing compared to standard dosing.