Facing the conundrum: which first-line therapy should be used for patients with metastatic triple-negative breast cancer carrying germline BRCA mutation?

Pembrolizumab combined with chemotherapy has been established as the preferred first-line therapy for treating metastatic triple-negative breast cancer (mTNBC) with programmed cell death ligand-1 (PD-L1)-positive disease since its approval for that indication. However, the optimal sequencing of therapy remains an unanswered question for a subset of mTNBC patients who harbor germline breast cancer gene 1/2 (BRCA1/2; gBRCA1/2) mutation. This article aims to offer insights into the optimal therapy sequencing for mTNBC patients with gBRCA1/2 mutations and its impact on clinical decision-making. The perspective offered is based on the best currently available data and propose a practical algorithm to guide the management of this subgroup in the frontline setting

RNAi-Mediated Control of Lepidopteran Pests of Important Crop Plants

Insects as pests destroy annually an estimated 18–20% of the crop production worldwide. Caterpillars, the larval stage of moths, are the major pests of agricultural products owing to their voracious feeding habits. In the past few decades, the potent methods of insect control, such as insecticides and Bt toxins, have been constrained as a result of health hazards, environmental issues, and development of resistance, after their prolonged application. Thus, there is need to find alternative options to improve plant protection strategies. Recently, RNA interference (RNAi), the post-transcriptional gene-silencing mechanism, has emerged as one of such a novel, sustainable, and environment friendly approaches for insect management and crop protection. RNAi technology relies on selection of a vital insect pest target gene and its expression as a double stranded RNA or stem-loop RNA molecule, which is recognized by the host RNAi machinery and processed into small interfering RNAs (siRNAs) or microRNAs (miRNAs). The siRNA/miRNA along with the RNA-induced silencing complex (RISC) binds to the complimentary mRNA and induce gene silencing at post-transcriptional level. With effective target-gene selection and transgenic plants expressing these precursor RNA molecules, insect pests of various crops have been efficiently managed. In this chapter, we discuss the basic mechanism of RNAi and its application in controlling lepidopteran pests of important crop plants

Association of a Frailty Screening Initiative With Postoperative Survival at 30, 180, and 365 Days

IMPORTANCE As the US population ages, the number of operations performed on elderly patients will likely increase. Frailty predicts postoperative mortality and morbidity more than age alone, thus presenting opportunities to identify the highest-risk surgical patients and improve their outcomes. OBJECTIVE To examine the effect of the Frailty Screening Initiative (FSI) on mortality and complications by comparing the surgical outcomes of a cohort of surgical patients treated before and after implementation of the FSI. DESIGN, SETTING, AND PARTICIPANTS This single-site, facility-wide, prospective cohort quality improvement project studied all 9153 patients from a level 1b Veterans Affairs medical center who presented for major, elective, noncardiac surgery from October 1, 2007, to July 1, 2014. INTERVENTIONS Assessment of preoperative frailty in all patients scheduled for elective surgery began in July 2011. Frailty was assessed with the Risk Analysis Index (RAI), and the records of all frail patients (RAI score,≥ 21) were flagged for administrative review by the chief of surgery (or designee) before the scheduled operation. On the basis of this review, clinicians from surgery, anesthesia, critical care, and palliative care were notified of the patient’s frailty and associated surgical risks; if indicated, perioperative plans were modified based on team input. MAIN OUTCOMES AND MEASURES Postoperative mortality at 30, 180, and 365 days. RESULTS From October 1, 2007, to July 1, 2014, a total of 9153 patients underwent surgery (mean [SD] age, 60.3 [13.5] years; female, 653 [7.1%]; and white, 7096 [79.8%]). Overall 30-day mortality decreased from 1.6%(84 of 5275 patients) to 0.7%(26 of 3878 patients, P \u3c .001) after FSI implementation. Improvement was greatest among frail patients (12.2% [24 of 197 patients] to 3.8% [16 of 424 patients], P \u3c .001), although mortality rates also decreased among the robust patients (1.2% [60 of 5078 patients] to 0.3% [10 of 3454 patients], P \u3c .001). The magnitude of improvement among frail patients increased at 180 (23.9% [47 of 197 patients] to 7.7% [30 of 389 patients], P \u3c .001) and 365 days (34.5% [68 of 197 patients] to 11.7% [36 of 309 patients], P \u3c .001). Multivariable models revealed improved survival after FSI implementation, controlling for age, frailty, and predicted mortality (adjusted odds ratio for 180-day survival, 2.87; 95% CI, 1.98-4.16). CONCLUSIONS AND RELEVANCE Implementation of the FSI was associated with reduced mortality, suggesting the feasibility of widespread screening of patients preoperatively to identify frailty and the efficacy of system-level initiatives aimed at improving their surgical outcomes. Additional investigation is required to establish a causal connection

A micropropagation protocol for mass multiplication of Terminalia arjuna - a valuable medicinal tree

A reliable and efficient micropropagation protocol was developed through axillary shoot proliferation from nodal explants of mature Terminalia arjuna. Season of explants collection and maturity of explants showed direct influence on bud-break. Nodal stem segments collected during the months of April and May gave best response. Nodal segments of fresh sprouts originated from lopped tree of T. arjuna were used as explants for establishment of in vitro culture. Surface sterilized explants produced optimum number of shoots through activation of axillary buds - on modified Murashige and Skoog’s (M-MS) medium. Maximum (100%) in vitro shoot proliferation was obtained on M-MS medium supplemented with 8.86 µM BAP + additives (100 mg L-1 of ascorbic acid, 50 mg L-1 of citric acid, 50 mg L-1 of adenine sulphate and 25 mg L-1 PVP). Modified M-MS medium supplemented with 4.44 µM BAP + 0.54 µM NAA + additives was found to be best for 11.38±0.26 shoot multiplication. After four week of culturing the in vitro regenerated shoots were rooted when pulse treated with 984 µM IBA for 10 min and transferred on hormone free half strength MS medium containing 100 mg L-1 activated charcoal. In vitro regenerated plants were transferred to field after gradual hardening and acclimatization procedure. Present method can be used for large scale commercial production of this medicinally important tree