Genomics-assisted breeding in four major pulse crops of developing countries: present status and prospects

The global population is continuously increasing and is expected to reach nine billion by 2050. This huge population pressure will lead to severe shortage of food, natural resources and arable land. Such an alarming situation is most likely to arise in developing countries due to increase in the proportion of people suffering from protein and micronutrient malnutrition. Pulses being a primary and affordable source of proteins and minerals play a key role in alleviating the protein calorie malnutrition, micronutrient deficiencies and other undernourishment-related issues. Additionally, pulses are a vital source of livelihood generation for millions of resource-poor farmers practising agriculture in the semi-arid and sub-tropical regions. Limited success achieved through conventional breeding so far in most of the pulse crops will not be enough to feed the ever increasing population. In this context, genomics-assisted breeding (GAB) holds promise in enhancing the genetic gains. Though pulses have long been considered as orphan crops, recent advances in the area of pulse genomics are noteworthy, e.g. discovery of genome-wide genetic markers, high-throughput genotyping and sequencing platforms, high-density genetic linkage/QTL maps and, more importantly, the availability of whole-genome sequence. With genome sequence in hand, there is a great scope to apply genome-wide methods for trait mapping using association studies and to choose desirable genotypes via genomic selection. It is anticipated that GAB will speed up the progress of genetic improvement of pulses, leading to the rapid development of cultivars with higher yield, enhanced stress tolerance and wider adaptability

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Review Article - Limb salvage for malignant primary bone tumours: current status with a review of the literature

Though primary malignant bone tumours form only about 1% of all cancers, their aggressive natural history makes disease control very difficult. Effective chemotherapy has improved survival and advances in imaging, engineering and surgical techniques have made limb salvage feasible and the world has moved from amputation to limb salvage in the majority of cases with non-metastatic disease at presentation. Indigenously developed technology and chemotherapy protocols have allowed our own results to be comparable to those reported in the Western literature. Newer biomaterials and fabrication methods have allowed us to develop indigenously a high-quality yet affordable customized megaprosthesis which forms the backbone of limb salvage surgery. This paper broadly reviews the literature and presents our own experience with the current limb salvage methods as carried out at the Tata Memorial Hospital

Reconstructive Challenges of Proximal Ulnar Bone Tumors: Our Experience with Biological Osteoarticular Reconstruction Using Extracorporeal Irradiation and Reimplantation

Introduction. Limb salvage surgery following proximal ulna resection poses a challenge in reconstruction of the complex elbow anatomy. Various reconstruction methods described offer inadequate restoration of function and stability. Following resection of proximal ulna tumors, we aimed to restore the joint using the resected osteochondral segment of proximal ulna treated with extracorporeal irradiation and reimplantation. Questions/Purposes. (1) Does irradiated osteoarticular autograft reconstruction for proximal ulna allow anatomical joint restoration and what are the oncological and functional outcomes? (2) Is there evidence of graft-related complications or osteoarthritis at a minimum of 2 years follow-up with irradiated osteoarticular autografts for the proximal ulna? (3) How does our method of reconstruction fare as compared to reported reconstruction options in the literature? Materials and Methods. 3 patients with primary bone tumors involving the proximal ulna underwent limb salvage surgery with en bloc resection and reconstruction using the resected bone after treating it with extracorporeal irradiation of 50 Gy. Minimum follow-up of 2 years was considered for assessment of final outcomes. Radiographs were assessed for bony recurrence, union across osteotomy junction, and signs of joint arthritis. Functional outcome measures included range of movement, muscle power testing, and functional and disability scores. Results. 2 complete and 1 partial olecranon involving proximal ulnar resections were performed for three cases of Ewing’s sarcoma in 2 males and 1 female. Follow-up ranged from 28 to 42 months, and all patients continue to remain disease free. All 3 patients have achieved full range of flexion-extension and pronosupination movement in comparison to the contralateral side. Muscle power for flexion and extension was 5/5. MSTS score: 100% (30/30); MEPS score: 100; and DASH score: zero were achieved for all patients. Union across osteotomy junctions at median follow-up of 8 months without need for intervention/bone grafting was achieved. No complications related to joint laxity/subluxation, infection, graft fracture, or implant failure was noted. None of the patients have clinical or radiological signs of joint arthritis across the irradiated articulation. Conclusion. Biological restoration of elbow anatomy using osteoarticular irradiated graft for proximal ulna reconstruction offers great joint stability and functional outcomes. Although the potential risks of infection and graft failure need to be considered, reconstruction with the size-matched radiated autograft eliminates donor site morbidity, offers a low-cost alternative to endoprosthesis, and provides outcomes superior to any other methods of reconstruction as analyzed from the literature

Reconstructive Challenges of Distal Tibia Bone Tumors: Extracorporeally Irradiated Autograft Combined with a Nonvascularized Autograft Fibula for Superior Reconstruction and Functional Outcomes When Compared to Ipsilateral Pedicled Fibula Transfer Alone

Introduction. Traditionally, centralization of the fibula with fusion across the tibiotalar joint has been used to reconstruct distal tibial defects. Although effective, it requires long periods of protected weight-bearing. The fibula or the fixation often fails before fibular hypertrophy necessitating multiple additional surgeries. A method of using ECRT with the available ipsilateral fibula (nonvascularized) to reconstruct the distal tibia defect with the aim of early return to weight-bearing was evolved. This paper documents our early experience. Patients and Methods. Four patients; with the diagnosis of osteosarcoma in 3 patients and recurrent giant cell tumor of the bone in 1 patient, underwent resection of the distal tibia for tumors between 2017 and 2019. Extracorporeally irradiated (50 Gy) distal tibia along with ipsilateral nonvascularized fibula was used to bridge the defect and fuse the tibiotalar joint. A plate was used to rigidly hold the construct. The final outcome was compared to the historical control group that underwent only pedicled ipsilateral fibula transposition and ankle arthrodesis without recycled autograft or allograft between 2009 and 2017. Oncological reconstruction and functional outcomes were compared for each group. Patient reported outcomes on the acceptability of ankle fusion; cosmesis and function were analyzed and compared between the two groups. Results. The mean resection length in the study group (4 patients) was 7.75 cm (7 to 8.5 cm). As compared to the historical cohort of 7 patients, the study population showed statistically superior results in all reconstruction, functional, and patient-reported outcomes except time to proximal junction union (p=0.068). There were no reconstruction failures, infection, or nonunions in the study group, whereas the control comparative group had 2 proximal junction nonunions and a mean time to fibular hypertrophy of 143 weeks (82 to 430 weeks) with fibula centralization. Earlier weight-bearing was allowed (mean 26.75 weeks; median 27 weeks) compared to (mean 80.75 weeks; median 80 weeks) in the control group. Conclusion. We think that ECRT with ipsilateral vascularized fibula is a promising method of reconstructing the distal tibia. The recycled autograft tibia added strength to the distal tibia construct in our study and aided the anatomical reconstruction of the distal tibia. The patient-reported outcomes for cosmesis and acceptability add to the benefits of performing this procedure. Consistent early union across the proximal junction and earlier weight-bearing were clear advantages of this method