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The mechanism of formation of catalytic sites in the important Mizoroki–Heck reaction used in modern fine organic synthesis has been studied. It was found that the catalysts based on palladium complexes with N-heterocyclic carbene ligands transform into a "ligand-free" form under the conditions of the Mizoroki–Heck reaction. Molecular modeling performed using quantum-chemical methods showed that these processes compete with the target reaction at three of the six stages of the catalytic cycle. The presence of catalyst transformation products in the reaction system was confirmed by nuclear magnetic resonance and mass spectrometry. Important mechanistic data were obtained for rational design of catalyst systems for cross-coupling reactions. [ABSTRACT FROM AUTHOR]

The little millet variety ‘GV-4’ (Ambika) is a pure line selection from the local germplasm collected from the Dang District. A little millet variety ‘GV-4’ was tested as a genotype name ‘WV-126’. ‘WV 126’ was tested under the various state trials found to be superior for grain yield (2933 kg/ha) by 21.20, 13.78, 44.39 and 31.44 per cent over the existing checks i.e. GV-2 (LC), GNV-3 (LC), CO-2 (NC) and OLM-203 (NC), respectively over thirteen trials and seven years (2014-15 to 2020-21) of study. The genotype matures in 120-125 days includes under medium duration variety. The genotype WV-126 has 9-10 branches per panicle and 35.5 cm average panicle length. It has special attributes of synchronized maturity and non-lodging growth habit. WV-126 is rich in calcium (17.1 mg/100g), protein (12.91 g/100g), fat (3.3 %), crude fiber (7.5 %), carbohydrates (70.40 g/100g) and minerals (2.7 g/100g). It is resistant to blast (leaf, neck and panicle) and moderately resistant to grain smut and sheath blight when compared to local check GV-2 and GV-3 and national check CO-2, OLM-203 and JK-8. A little millet variety ‘GV-4’ (Gujarat Vari-4) was released as a new variety for cultivation during kharif under rainfed conditions of Gujarat state. [ABSTRACT FROM AUTHOR]

BACKGROUND Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy--only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy--only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.) [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) may simulate Pulmonary Tuberculosis (PTB) in its clinical and radiological expression posing a diagnostic dilemma and challenge to the treating physician, especially in high TB prevalent countries. Though recent emerging data indicates inter-human transmission, infection with non-tuberculous mycobacteria (NTM) is commonly acquired from the environmental sources [1]. NTM can produce disease not only in immunocompromised populations but also in healthy individuals leading to significant morbidity and mortality [2]. Unlike PTB, NTM-PD is usually difficult to confirm and speciate in resource limited clinical settings and high TB endemic countries due to non-availability, poor accessibility and affordability to a specific culture facility. Apart from diagnostic challenges, adverse drug effects with treatment leading to non-adherence are another vexing problem. We present here case descriptions of four patients of NTM-PD, confirmed by culture isolates, one was a rapid grower and the other three were slow growers. All four patients were treated with available guideline-based treatment protocols and followed up., Competing Interests: The authors: No reported conflicts of interest. All authors have submitted the ICMJE form for Disclosure of Potential Conflicts of Interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Superparamagnetic iron oxide nanoparticles (SPIO) are non-inferior to radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) detection. Previously, 2 mL SPIO (Sienna+ ® ) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace ® ) (1.5 vs. 1.0 mL) were tested in different timeframes (0-24 h perioperative vs. 1-7 days preoperative) and injections sites (subareolar vs. peritumoral). Two consecutive breast cancer cohorts ( n = 328) scheduled for SLN-biopsy were included from 2017 to 2019. All patients received isotope ± blue dye as back-up. SLNs were identified primarily with the SentiMag ® probe and thereafter a gamma-probe. The primary endpoint was SLN detection rate with SPIO. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from the previously published Nordic Trial ( n = 206) as a third, reference cohort. In 534 patients, the SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 and the 2.0 mL cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Lower SPIO volumes injected up to 7 days before the operation have comparable efficacy to standard SPIO dose and RI + BD for SLN detection.

Background: The rapid outbreak of coronavirus disease 2019 (COVID-19), a public health emergency of grave concern, warranted hospital admissions with almost 90,000 cases in June 2020 in city of Mumbai. 3-10% of the patients with moderate to severe involvement required intensive care unit (ICU) admission with respiratory support. Patients admitted in ICU with an acute COVID event present with respiratory dysfunction and are more likely to have critical illness myopathy and neuropathy (CIMN). Physiotherapy services being integral part of non-pharmacological management of any ICU was implemented for patients with COVID 19; a novel viral disease., Objective: This retrospective study was undertaken to explore the physiotherapy practices that could be implemented in patients admitted with COVID 19 in the ICU and its effect on mobility and oxygen requirement as an outcome., Methodology: Following ethical permission of institute, the data was extracted from electronic data record sheet in which daily parameters for physiotherapy intervention were recorded. Data from a single ICU and step down unit (SDU) from 5th June to 5th July 2020 was analysed. Records of patients diagnosed with COVID 19 and admitted in ICU or SDU were studied. Those in the age group of 18 to 90 years, of either gender were included. Demographic characteristics, disease severity, oxygen requirement, mobility status, physiotherapy intervention were studied., Results: 278 record sheets (110 ICU and 168 SDU) were retrospectively analysed for demographics. 44.55% of patients improved with side lying position, 37.27% with prone position and 10.91% with quarter prone position. 4.55% of patient maintained oxygenation in propped up sitting. 2.73% could not be positioned. Chest physiotherapy techniques applied were deep breathing, ACBT, paced breathing and diaphragmatic breathing. Deep intercostal pressure on NIV along with vibrations was given to 12.72% of patients in the ICU. Group therapy sessions were conducted in SDU where 50.59% patients participated. ICU mobility score showed significant improvement on Wilcoxon Signed Ranks test status on day 7 in the ICU (z=-5.99, p=0.00) and SDU (z= 7.676, p=0.00) compared to day 1. Descriptive analysis showed a definitive reduction in oxygen support requirement., Conclusion: Most common form of physiotherapy interventions in patients with Covid 19 were therapeutic positioning, early mobilization and breathing exercises. Physiotherapy intervention appears promising in facilitating early patient ambulation and discharge. This study shows that it is safe and feasible to provide early physiotherapy treatment techniques in patients with COVID-19 using appropriate measures of infection prevention and cross contamination., (© Journal of the Association of Physicians of India 2011.)

Background: Although small, node-negative breast cancer (ie, T1abN0) constitutes 20% of all newly diagnosed breast cancers, data on prognosis and prognostic factors are limited., Methods: We conducted a population-based cohort study including 20 114 Swedish women treated for T1abN0 breast cancer from 1977 onward. Patient and tumor data were collected from Swedish breast cancer registries. Cohort subjects were followed through linkage to the Cause of Death Register. We calculated the cumulative incidence of breast cancer-specific and overall death and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: During a median follow-up of 9.1 years (range = 0-38), 915 women died of breast cancer and 5416 of any cause. The 10-, 20-, and 30-year cumulative incidences of breast cancer death were 3.4% (95% CI = 3.1% to 3.7%), 7.6% (95% CI = 7.1% to 8.2%), and 10.5% (95% CI = 9.6% to 11.4%), respectively. The multivariable hazard ratios and 95% confidence intervals of breast cancer death were 0.92 (95% CI = 0.88 to 0.97) for each additional calendar year of diagnosis, 4.38 (95% CI = 2.79 to 6.87) for grade 3 vs grade 1 tumors, 0.43 (95% CI = 0.31 to 0.62) for progesterone receptor-positive vs progesterone receptor-negative disease, and 2.01 (95% CI = 0.99 to 4.07) for HER2-positive vs HER2-negative disease. Women with grade 3 vs grade 1 tumors had a 56% increased risk of death from any cause (HR = 1.56, 95% CI = 1.30 to 1.88)., Conclusions: The risk of breast cancer death in T1abN0 disease continues to increase steadily beyond 10 years after diagnosis, has improved over time, and varies substantially by tumor characteristics., (© The Author(s) 2020. Published by Oxford University Press.)

Objectives: To determine if women with tubal patency experience more fluid loss compared to those with bilateral tubal occlusion following intrauterine instillation of fluid via a balloon catheter., Study Design: In this prospective cohort pilot study, we enrolled women with prior Essure® procedures and healthy controls from September 2016 to July 2017. We excluded women using an implant or intrauterine device, or with a prior cesarean delivery or permanent contraception procedures other than Essure®. An infusion pump delivered saline via balloon catheter under continuous pressure monitoring. After one minute, we withdrew the fluid and recorded volumes in and out. Subjects then underwent hysterosalpingogram for evaluation of tubal patency. We conducted crude analyses with t-tests and sensitivity analyses., Results: We recruited 23 participants; ten provided analyzable data in each group. Hysterosalpingogram confirmed patency in all control and occlusion in all post-Essure® subjects in the analysis group. We found the median volume of saline lost among control subjects [7.8 mL (7.4, 8.4)] larger than post-Essure® participants [2.2 mL (2.0, 3.8), p < 0.01]. While 50% of control subjects tolerated the full 10 mL of fluid instillation, none of the post-Essure® subjects tolerated this volume (p = 0.03). A combination of saline loss ≤4 mL and participant intolerance of the full 10 mL volume yielded sensitivity of 0.80 (95% CI: 0.57, 1.00) and specificity of 1.00 for bilateral tubal occlusion., Conclusion: Instillation of a fixed volume into the uterus may discriminate between women with tubal patency and occlusion following permanent contraception procedures with high specificity and adequate sensitivity. These findings should be validated in larger, more diverse study populations., Implications: Confirmation of tubal occlusion following permanent contraception with an office-based approach could improve acceptability of transcervical approaches. The recent removal of Essure® from the U.S. market increases the need for novel transcervical procedures and occlusion verification methods., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Breast cancer (BC) intrinsic subtype classification is based on the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation marker Ki-67. The expression of these markers depends on both the genetic background of the cancer cells and the surrounding tumor microenvironment. In this study, we explore macrophage traits in cancer cells and intra-tumoral M2-macrophage infiltration (MI) in relation to intrinsic subtypes in non-metastatic invasive BC treated with breast conserving surgery, with and without postoperative radiotherapy (RT). Immunostaining of M2-macrophage-specific antigen CD163 in cancer cells and MI were evaluated, together with ER, PR, HER2, and Ki-67-expression in cancer cells. The tumors were classified into intrinsic subtypes according to the ESMO guidelines. The immunostaining of these markers, MI, and clinical data were analyzed in relation to ipsilateral local recurrence (ILR) as well as recurrence-free (RFS) and disease-free specific (DFS) survival. BC intrinsic subtypes are associated with T-stage, Nottingham Histologic Grade (NHG), and MI. Macrophage phenotype in cancer cells is significantly associated with NHG3-tumors. Significant differences in macrophage infiltration were observed among the intrinsic subtypes of pT1-T2 stage BC. Shorter RFS was observed in luminal B HER2neg tumors after RT, suggesting that this phenotype may be more resistant to irradiation. Ki-67-expression was significantly higher in NHG3 and CD163-positive tumors, as well as those with moderate and high MI. Cancer cell ER expression is inversely related to MI and thus might affect the clinical staging and assessment of BC.

Setting: A prospective observational study conducted in Medical college hospital, in a high-TB- prevalence region of northern Telangana, India., Objective: To know the diagnostic role of Xpert MTB/RIF assay in bronchoalveolar lavage fluid (BALF) in sputum-scarce, suspected pulmonary tuberculosis (PTB) patients., Design: Study period was between October 2014 and March 2017. Suspected pulmonary tuberculosis patients aged 15 years or more, who were sputum-scarce and conforming to the inclusion criteria were submitted to bronchoscopy. BALF thus obtained was submitted to smear for acid fast bacilli (AFB) and Xpert MTB/RIF assay as index tests along with culture for Mycobacterium tuberculosis complex (MTBC). Culture for M. tuberculosis complex was considered as gold standard for the diagnosis of PTB. The sensitivity, specificity and predictive values were calculated for smear AFB and Xpert MTB/RIF assay., Results: 56 of the 81 patients were included and evaluated in the final analysis. In 10 of these 56 patients PTB was confirmed by culture positivity. The sensitivity and specificity of Xpert MTB/RIF assay was 90% (9/10,95%CI 59.6- 98.2) and 52.2% (24/46, 95%CI 38. 1-65.9) respectively and that of the smear AFB was 60% (6/10, 95%CI 31.2-83.1) and 67.4% (31/46, 95%CI 53.0-79.1). All the patients considered 'probable' PTB (pending culture results), were administered antituberculous treatment and showed complete clinicoradiological improvement on follow up. Three of the 31 Xpert MTB/RIF positive patients were detected as resistance to rifampicin (RR)., Conclusions: Xpert MTB/RIF assay of BALF in the study cohort provides rapid diagnosis of Mycobacterium tuberculosis , and detection of rifampicin resistance at the very outset, aiding in selection of appropriate ATT regimen. In this context, it can be recommended as the first line investigation. Xpert MTB/RIF assay aided by HRCT Chest and suggestive clinical presentation may be helpful in early institution of ATT especially in smear negative, culture negative cases., (© 2018 The Authors.)

Objective: The objective was to determine if intrauterine pressure can distinguish bilateral tubal occlusion (BTO) from unilateral or bilateral tubal patency (TP) in women following a permanent contraception procedure., Study Design: We used a small inline pressure sensor to continuously monitor intrauterine pressure during hysterosalpingogram (HSG) in a cross-sectional study that enrolled women having HSGs for any indication. The primary outcome was the peak intrauterine pressure compared between women with BTO and TP as verified by HSG., Results: We enrolled 150 subjects, of which 111 (74.0%) provided usable pressure readings. Of these, 98/111 (88.3%) had TP, and 13 (11.7%) had BTO. There was no difference in peak intrauterine pressure for subjects with TP (mean 293.8±58.7 mmHg) compared to those with BTO (292.7±71.3 mmHg, p=.95). Among parous women, peak intrauterine pressure in subjects with BTO (311.9±78.0 mmHg) was higher but not significantly different from subjects with TP (282.7±49.2 mmHg, p=.20). In linear regression analysis, peak intrauterine pressure was not associated with age, body mass index, gravidity or having at least one prior live birth., Conclusions: Measurement of peak intrauterine pressure does not distinguish between women with patent and blocked fallopian tubes. This approach would not be clinically useful to verify occlusion following permanent contraception., Implications: Peak intrauterine pressure does not differ between women with patent and occluded fallopian tubes and cannot be used to confirm tubal occlusion after nonsurgical permanent contraception., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background Hysterosalpingram (HSG) evaluation of tubal patency is typically performed in the follicular phase, but data to support this timing are lacking. Purpose To determine whether menstrual cycle phase or hormonal treatments affect observation of tubal patency during HSG. Material and Methods Ten participants underwent repeated HSG examinations: during the follicular and luteal phase of a natural menstrual cycle; 30 days following continuous administration of a combined oral contraceptive (COC); and 30 days after an intramuscular injection of depo medroxyprogesterone (DMPA) acetate. Participants with tubal blockade following DMPA had a fifth HSG 30 days following a second course of COCs. The primary outcome was tubal patency. Results All 10 participants demonstrated bilateral tubal patency (BTP) on at least one HSG examination during the study. One participant showed bilateral functional occlusion (FO) during the follicular phase examination, but BTP with the luteal phase, COC cycle, and DMPA exams. One participant with BTP discontinued participation and nine completed the COC HSG exam with BTP in seven, and one each with bilateral or unilateral FO. Seven participants completed the DMPA HSG with BTP in six and unilateral FO in one; BTP was seen in the final HSG after restarting the COC. Conclusion This pilot study supports the luteal phase of natural cycles as the optimum time for evaluation of tubal patency. The occurrence of functional occlusion of the fallopian tube on HSG examination performed during the follicular phase and following contraceptive steroid treatment supports a role of hormonal action on the utero-tubal junction.

Permanent contraception is a highly desired and commonly used contraceptive option for women around the world who desire never to become pregnant. Current methods of female permanent contraception require surgery. Postpartum tubal ligation and interval surgical tubal ligation are safe and effective, do not interfere with menstrual cycles, and require no ongoing cost or medical checkups. Hysteroscopic tubal occlusion offers a less invasive surgical approach, but requires an imaging study for verification of correct placement. However, not all women have access to a surgeon trained to provide permanent contraception, or they may face other prohibitive logistic or financial burdens. The development of novel permanent contraception methods that are immediately effective and/or nonsurgical could help improve access to and acceptability of permanent contraception. The expansion of permanent contraception options could help women achieve their family planning goals and reduce unintended pregnancies., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Immediate postabortion intrauterine device (IUD) insertion is a safe, effective strategy to prevent subsequent unplanned pregnancy. Oregon is one of 5 US states where advanced practice clinicians perform aspiration abortions. This study compares outcomes of first-trimester aspiration abortion with immediate IUD insertion between advanced practice clinicians and physicians., Methods: We conducted a historical cohort study of first-trimester aspiration abortions with immediate IUD insertion performed at our center from 2009 to 2011. We extracted demographic and clinical data from patient charts. Immediate complications including excessive blood loss, perforation, and reaspirations were recorded at the time of procedure. We used descriptive statistics and multivariable logistic regression to test for differences in outcomes by clinician type., Results: Data were available on 669 of the 1134 combined procedures. Advanced practice clinicians performed 224 of these. There were no significant differences in immediate outcomes. The only immediate complications were reaspirations; 1.8% (4/224) in the advanced practice clinician group, and 2.0% (9/445) in the physician group (P = .83)., Discussion: We found no differences in outcomes between provider type for immediate IUD insertion after first-trimester aspiration abortion. This study helps reinforce that advanced practice clinicians can provide immediate postaspiration abortion IUD insertions with similar outcomes to those of physicians. Many countries do not allow advanced practice clinicians to perform this service, but a change in policy could help address family planning provider shortages., (© 2016 by the American College of Nurse-Midwives.)

Placement of an intrauterine device (IUD) immediately after a first or second trimester surgical abortion is safe and convenient and decreases the risk of repeat unintended pregnancy. Immediate postabortion IUD placement is not recommended in the setting of postprocedure hemorrhage, uterine perforation, infection, or hematometra. Otherwise, there are few contraindications to IUD placement following surgical abortion. Sexually transmitted infection screening should follow US Centers for Disease Control and Prevention guidelines. No additional antibiotics are needed beyond those used for the abortion. Placing immediate postabortion IUDs makes highly-effective long-acting reversible contraception more accessible to women., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose of Review: Permanent methods are the most commonly used contraceptive options worldwide. Even with the increase in popularity and accessibility of long-acting reversible methods, there remains high demand for permanent options, especially among women in developing countries., Recent Findings: Traditional methods of permanent contraception, such as postpartum tubal ligation and interval surgical tubal occlusion or electrocautery by mini-laparotomy or laparoscopy are well tolerated and highly effective. Bilateral total salpingectomy for ovarian cancer risk reduction is currently being investigated. Hysteroscopic tubal occlusion reduces or eliminates the need for anesthesia, but requires surgical training and specialized equipment. Alternative permanent contraception methods are being explored including immediately effective hysteroscopic methods, and nonsurgical permanent contraception methods that have the potential to improve access and reduce cost., Summary: Permanent contraception methods are an important part of the contraceptive methods mix designed to meet the needs of women who have completed desired family size or wish never to become pregnant. Current surgical approaches to permanent contraception are well tolerated and highly effective. The development of a highly effective nonsurgical approach could simplify the provision of permanent contraception.

Permanent contraception with hysteroscopic tubal ligation is an increasingly popular choice for women around the world. However, inconveniences associated with the required confirmation test for tubal occlusion can be prohibitive. As new methods of permanent contraception are being investigated, ways of making all aspects of the procedure more accessible and comfortable for women should be considered. Means of examining tubal patency in the infertility population, such as tubal perfusion pressures measured at the time of hysterosalpingogram (HSG), provide inspiration for alternative methods of tubal occlusion confirmation after contraception. Evaluation of intrauterine pressures measured by a manometer attached to an intrauterine balloon catheter could serve as a preliminary tool for verification of tubal occlusion; higher pressures would indicate tubal occlusion and lower pressures would indicate the need for confirmatory HSG. The development and validation of this technique is ongoing and could reduce overall costs and patient burdens associated with the current tubal occlusion confirmation procedure., (Copyright © 2015 Elsevier Inc. All rights reserved.)