Marker-assisted enhancement of bacterial blight (Xanthomonas oryzae pv. oryzae) resistance in a salt-tolerant rice variety for sustaining rice production of tropical islands.

Introduction: Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae is a major disease of rice, specially in the tropical regions of the world. Developing rice varieties with host resistance against the disease is the most effective and economical solution for managing the disease. Methods: Pyramiding resistance genes (Xa4, xa5, xa13,and Xa21) in popular rice varieties using marker-assisted backcross breeding (MABB) has been demonstrated as a cost-effective and sustainable approach for establishing durable BB resistance. Here, we report our successful efforts in introgressing four resistance genes (Xa4, xa5, xa13, and Xa21) from IRBB60 to CARI Dhan 5, a popular salt-tolerant variety developed from a somaclonal variant of Pokkali rice, through functional MABB. Results and discussion: Both BB and coastal salinity are among the major challenges for rice production in tropical island and coastal ecosystems. Plants with four, three, and two gene pyramids were generated, which displayed high levels of resistance to the BB pathogen at the BC3F2 stage. Under controlled salinity microplot environments, the line 131-2-175-1223 identified with the presence of three gene pyramid (Xa21+xa13+xa5) displayed notable resistance across locations and years as well as exhibited a salinity tolerance comparable to the recurrent parent, CARI Dhan 5. Among two BB gene combinations (Xa21+xa13), two lines, 17-1-69-334 and 46-3-95-659, demonstrated resistance across locations and years, as well as salt tolerance and grain production comparable to CARI Dhan 5. Besides salinity tolerance, five lines, 17-1-69-179, 46-3-95-655, 131-2-190-1197, 131-2-175-1209, and 131-2-175-1239, exhibited complete resistance to BB disease. Following multilocation testing, potential lines have been identified that can serve as a prospective candidate for producing varieties for the tropical Andaman and Nicobar Islands and other coastal locations, which are prone to BB and coastal salinity stresses.

Discrete optimal quadratic AGC based cost functional minimization for interconnected power systems.

The increasing complexity and difficulty of the Automatic generation control (AGC) problem has resulted from the increasing scale of interconnected power networks and changing daily demands. The primary goals of AGC are to control frequency variations at nominal levels and tie-line power variances at planned levels. To effectively deal with AGC control difficulties, this study introduces Discrete Optimal Quadratic Automatic Generation Control (OQAGC). One advantages of this method is the differentiation of quadratic cost function results into linear terms while minimizing control actions and minimizing state deviations. This developed control method leads to a simple and easy discrete control law that can be implemented for both linear and nonlinear systems. For optimizing the controller, this research work utilized an optimum control theorem using Lagrangian multipliers, while the functional minimization technique is used for systematically selecting the state and control weighting matrices in discrete form for N control regions (where N is the number of interconnected power systems). The discrete cost function needs are derived using this technique in terms of area control errors, integral area control errors, and control energy expenditure. Four interconnected power systems were analyzed with/without disturbances and area control errors, each with one thermal, hydro, and gas-generating unit. A two-area multi-source power system with renewable energy in control area 2 is analyzed for the performance of the proposed controller with generation rate constraints (GRCs). The functional minimization technique simplifies and eases the choosing of weighting matrices. Furthermore, the simulation findings suggest that the developed discrete optimum quadratic AGC control-based cost functional minimization approach enhances power system dynamics in terms of stability, steady-state performance, and the closed-loop control system's robustness to input load disturbances. As a result, the newly developed OQAGC approach demonstrates the significance of the discrete LQR controller for N multi-area power systems.

Energy utilization during ovarian development of the cichlid fish Oreochromis mossambicus (Peters) inhabiting a perennial lentic water body in Bangalore, India.

Mozambique tilapia Oreochromis mossambicus (Peters) is an invasive fish and a continuous breeder in inland waters of India. Present investigation highlights the distinct developmental stages of developing ovary and associated changes in the energy content. This investigation helps to understand the allocation of energy for development of eggs, prespawn and also oral brooding by the female. Although it is a continuous breeder, based on size of the ovary, number of eggs, their size and energy content, immature, early maturing, developing, prespawning and spawning stages are clearly noticed. Egg diameter during development of ovary varied between 0.31 mm (immature) and 2.21 mm (spawning). Energy content of ovary from immature to spawning stage ranged from 20.7515 kJ g-1 dry ovary to 31.1560 kJ g-1 dry ovary. Nearly 28.73% of energy content of ovary is expended for spawning. Similarly, yolk-sac fry utilized nearly 25.85% of energy of the fertilized egg for its development. Energy content of ovary of mouth-brooding female averaged 22.9528 kJ g-1 dry ovary, which is comparable to energy content of early maturing stage of ovary (24.5558 kJ g-1 dry ovary). A strong correlation between body weight and energy content of the developing ovary (P < 0.01), and between ovary weight and energy content of ovary (P < 0.01), was evident. During mouth-brooding, the fish continues to allocate energy to its developing ovary. Energy investment by the fish is the result of simultaneous processes associated with gonadal and somatic energy. As body size growth and gonadal development are interconnected, information on energy utilization by an iteroparous mouth-brooding fish could provide the pattern of energy allocation during ovarian developmental phase. Further details of energy utilization, as explained in this paper, could be used as one of the factors to predict the efficiency of fish production.

Genome wide association study of MAGIC population reveals a novel QTL for salinity and sodicity tolerance in rice.

The present study was conducted to identify the novel QTLs controlling salinity and sodicity tolerance using indica MAGIC rice population. Phenotyping was carried out in salinity (EC ~ 10 dS/m) and sodicity (pH ~ 9.8) at the seedling stage. Among 391 lines, 43 and 98 lines were found tolerant and moderately tolerant to salinity. For sodicity condition, 2 and 45 lines were showed tolerance and moderately tolerance at seedling stage. MAGIC population was genotyped with the help of genotyping by sequencing (GBS) and filtered 27041SNPs were used for genome wide marker trait association studies. With respect to salinity tolerance, 25 SNPs were distributed on chromosomes 1, 5, 11 and 12, whereas 18 SNPs were mapped on chromosomes 6, 4 and 11 with LOD value of > 3.25 to sodicity tolerance in rice. The candidate gene analysis detected twelve causal genes including SKC1 gene at Saltol region for salinity and six associated genes for sodic stress tolerance. The significant haplotypes responsible for core histone protein coding gene (LOC_Os12g25120) and three uncharacterized protein coding genes (LOC_Os01g20710, LOC_Os01g20870 and LOC_Os12g22020) were identified under saline stress. Likewise, five significant haplotypes coding for ribose 5-phosphate isomerise (LOC_Os04g24140), aspartyl protease (LOC_Os06g15760), aluminum-activated malate transporter (LOC_Os06g15779), OsFBX421-Fbox domain containing protein (LOC_Os11g32940) and one uncharacterized protein (LOC_Os11g32930) were detected for sodic stress tolerance. The identified novel SNPs could be the potential candidates for functional characterization. These candidate genes aid to further understanding of genetic mechanism on salinity and sodicity stress tolerance in rice. The tolerant line could be used in future breeding programme to enhance the salinity and sodicity tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01174-8.

Photon emission enhancement studies from the interaction of ultraintense laser pulses with shaped targets.

We study the photon emission by bremsstrahlung and nonlinear Compton scattering from interaction of ultra-intense laser pulses with cone target and flat foil using particle-in-cell simulations. The simulations are performed for laser pulses interacting with Al and Au targets. The strength of the two mechanisms of photon emission from bremsstrahlung and nonlinear Compton scattering are compared. When an ultra-intense (I>10^{22}W/cm^{2}) laser interacts with a cone and a foil target, photon emission by bremsstrahlung is found to be comparable to that from nonlinear Compton scattering. The obtained electron energy as well as the energy and number of photons emitted were found to be higher in case of cone shaped target compared with that of a foil target. The enhanced photon emission from cone shaped target is attributed to the guiding or collimation of hot electrons towards the cone tip from the self-generated magnetic field and electrostatic field along the cone surface which pushes the hot electrons towards the tip.

Effect of Preoperative Biliary Stenting on Outcomes of Pancreaticoduodenectomy.

Biliary drainage before pancreaticoduodenectomy was introduced to decrease morbidity from obstructive jaundice. Recent retrospective and randomised data show that preoperative biliary drainage (PBD) increases perioperative infectious complications. Most patients presenting to our tertiary care centre have undergone drainage procedures prior to surgical consultation. We analysed the impact of PBD, specifically endoscopic stent placement, on the postoperative outcome of pancreaticoduodenectomy at our centre. A cohort of 87 patients undergoing pancreaticoduodenectomy from 2012 to 2016 was identified. Data was collected retrospectively and a comparative analysis of stented and nonstented patients was done. Comparison of the 23 stented patients was done with 23 nonstented patients after matching them for age, sex and bilirubin levels. Median total bilirubin level in stented patients was 10.2 mg/dl versus 7.7 mg/dl in nonstented patients. The infectious complication rate in the stented group was 39.1% versus 12.7% in the nonstented group (P value < 0.05). There was no difference in the anastomotic leak rate between the two groups. Time to curative surgery in the stented group was significantly more than in the nonstented group. Stented patients are at a higher risk for postoperative infectious complications. Patients with obstructive jaundice awaiting surgery should undergo selective biliary drainage after careful planning and discussion between the operating surgeon and the endoscopist.

Marker aided introgression of 'Saltol', a major QTL for seedling stage salinity tolerance into an elite Basmati rice variety 'Pusa Basmati 1509'.

Marker assisted backcross breeding was used to transfer Saltol, a major QTL for seedling stage salinity tolerance from the donor FL478 to Pusa Basmati 1509 (PB 1509), a high yielding and early maturing Basmati rice variety. Foreground selection was carried out using three markers namely, AP3206f, RM3412b and RM10793, linked to Saltol. In addition, 105 genome-wide SSR markers polymorphic between FL478 and PB 1509 were used in background selection. Among the BC3F4 near isogenic lines (NILs) developed, recurrent parent genome recovery ranged from 96.67 to 98.57%. Multi-season evaluation identified some of the NILs showing significantly higher yield with grain and cooking quality comparable to PB 1509. All the NILs exhibited tolerance to salinity with significantly higher relative water content, membrane stability index and proline content as compared to PB 1509. The root and shoot concentration of Na+, K+ and Na+/K+ in NILs was at par with FL478 under stress conditions. The gene OsHKT1;5 located in the Saltol region showed higher expression levels under stress indicating its role in conferring salinity tolerance. Salt tolerant NILs of PB 1509 will be useful in stabilizing production in salt affected areas.

Introgressed Saltol QTL Lines Improves the Salinity Tolerance in Rice at Seedling Stage.

Rice is a staple food crop in Asia and plays a crucial role in the economy of this region. However, production of rice and its cultivating areas are under constant threat of soil salinity. A major QTL, Saltol, responsible for salinity tolerance at seedling stage has been mapped on chromosome 1 using Pokkali/IR29 Recombinant Inbred Lines (RIL) population. The present study was aimed to incorporate Saltol Quantitative Trait Loci (QTL) in two high yielding mega rice varieties i.e. Pusa44 and Sarjoo52 through Marker Assisted Backcross Breeding (MABB). To improve the seedling stage salinity tolerance in these cultivars, we introgressed the Saltol QTL from donor parent FL478 a derivative of Pokkali. A total of three backcrosses (BC3) followed by selfing have led to successful introgression of Saltol QTL. Foreground selection at each breeding cycle was done using micro-satellite markers RM3412 and AP3206 to confirm Saltol QTL. The precise transfer of Saltol region was established using recombinant selection through flanking markers RM493 and G11a. Finally, 10 Saltol near isogenic lines (NILs) of Pusa44 and eight NILs of Sarjoo52 were successfully developed. These NILs (BC3F4) were evaluated for seedling stage salinity under hydroponic system. The NILs PU99, PU176, PU200, PU215, PU229, PU240, PU241, PU244, PU252, PU263 of Pusa44 and SAR17, SAR23, SAR35, SAR39, SAR77, SAR87, SAR123, SAR136 NILs of Sarjoo52 confirmed tolerance to salinity with low salt injury score of 3 or 5. Ratio of Na+/K+ content of Saltol NILs ranged from 1.26 to 1.85 in Pusa44 and 1.08 to 1.69 in Sarjoo52. The successfully developed NILs were further phenotyped stringently for morphological traits to estimate Phenotypic Recovery. Background selection of NILs along with parents was carried out with 50K SNP chip and recovered 94.83-98.38% in Pusa44 NILs and 94.51 to 98.31% in Sarjoo52 NILs of recurrent genome. The present study of MAB has accelerated the development of salt tolerant lines in the genetic background of Pusa44 and Sarjoo52. These NILs could be used for commercial cultivation in saline affected area.

Enhancing trehalose biosynthesis improves yield potential in marker-free transgenic rice under drought, saline, and sodic conditions.

Edaphic factors such as salinity, sodicity, and drought adversely affect crop productivity, either alone or in combination. Despite soil sodicity being reported as an increasing problem worldwide, limited efforts have been made to address this issue. In the present study, we aimed to generate rice with tolerance to sodicity in conjunction with tolerance to salinity and drought. Using a fusion gene from E. coli coding for trehalose-6-phosphate synthase/phosphatase (TPSP) under the control of an ABA-inducible promoter, we generated marker-free, high-yielding transgenic rice (in the IR64 background) that can tolerate high pH (~9.9), high EC (~10.0 dS m-1), and severe drought (30-35% soil moisture content). The transgenic plants retained higher relative water content (RWC), chlorophyll content, K+/Na+ ratio, stomatal conductance, and photosynthetic efficiency compared to the wild-type under these stresses. Positive correlations between trehalose overproduction and high-yield parameters were observed under drought, saline, and sodic conditions. Metabolic profiling using GC-MS indicated that overproduction of trehalose in leaves differently modulated other metabolic switches, leading to significant changes in the levels of sugars, amino acids, and organic acids in transgenic plants under control and stress conditions. Our findings reveal a novel potential technological solution to tackle multiple stresses under changing climatic conditions.

Harmonizing technological advances in phenomics and genomics for enhanced salt tolerance in rice from a practical perspective.

Half of the global human population is dependent on rice as a staple food crop and more than 25% increase in rice productivity is required to feed the global population by 2030. With increase in irrigation, global warming and rising sea level, rising salinity has become one of the major challenges to enhance the rice productivity. Since the loss on this account is to the tune of US$12 billion per annum, it necessitates the global attention. In the era of technological advancement, substantial progress has been made on phenomics and genomics data generation but reaping benefit of this in rice salinity variety development in terms of cost, time and precision requires their harmonization. There is hardly any comprehensive holistic review for such combined approach. Present review describes classical salinity phenotyping approaches having morphological, physiological and biochemical components. It also gives a detailed account of invasive and non-invasive approaches of phenomic data generation and utilization. Classical work of rice salinity QLTs mapping in the form of chromosomal atlas has been updated. This review describes how QTLs can be further dissected into QTN by GWAS and transcriptomic approaches. Opportunities and progress made by transgenic, genome editing, metagenomics approaches in combating rice salinity problems are discussed. Major aim of this review is to provide a comprehensive over-view of hitherto progress made in rice salinity tolerance research which is required to understand bridging of phenotype based breeding with molecular breeding. This review is expected to assist rice breeders in their endeavours by fetching greater harmonization of technological advances in phenomics and genomics for better pragmatic approach having practical perspective.

Amalgamation of Central Lymph Node Dissection in Papillary Thyroid Carcinoma: Study from South Indian Population.

The aim of this study was to evaluate the correlation between central lymph node (CLN) metastasis and Clinicopathological characteristics of papillary thyroid cancer (PTC). In addition, we investigated the incidence and risk factors for ipsilateral and contra lateral CLN metastasis in unilateral PTC and the appropriate surgical extent for CLN dissection. A prospective study of 143 patients with unilateral PTC who underwent total thyroidectomy and prophylactic bilateral CLN dissection was conducted. Of 143 patients, 58 had CLN metastases. The rate of CLN metastasis was considerably higher in cases of maximal tumor size > 1 cm (P < 0.0001; OR 5.81). Ipsilateral CLN metastasis was detected in 41% of cases of unilateral PTC, and contra lateral CLN metastases was found in 14% of cases where as bilateral CLN metastases in 8% of cases. The rate of contra lateral CLN metastasis was considerably higher in cases of PTC with a large tumor size (≥ 1 cm) (P = 0.0003; OR = 0.144) and with ipsilateral CLN metastasis (P = 0.0002; OR 0.12). Tumor size > 1 cm was independent risk factors for CLN metastasis. Maximal tumor size > 1 cm and presence of ipsilateral CLN macro metastasis were independent risk factors for contra lateral CLN metastasis. Therefore, both ipsilateral and contra lateral CLN dissections should be considered for unilateral PTC with a maximal tumor size > 1 cm or presence of ipsilateral CLN macro metastasis.

Heterologous Expression of Serine Hydroxymethyltransferase-3 From Rice Confers Tolerance to Salinity Stress in E. coli and Arabidopsis.

Among abiotic stresses, salt stress adversely affects growth and development in rice. Contrasting salt tolerant (CSR27), and salt sensitive (MI48) rice varieties provided information on an array of genes that may contribute for salt tolerance of rice. Earlier studies on transcriptome and proteome profiling led to the identification of salt stress-induced serine hydroxymethyltransferase-3 (SHMT3) gene. In the present study, the SHMT3 gene was isolated from salt-tolerant (CSR27) rice. OsSHMT3 exhibited salinity-stress induced accentuated and differential expression levels in different tissues of rice. OsSHMT3 was overexpressed in Escherichia coli and assayed for enzymatic activity and modeling protein structure. Further, Arabidopsis transgenic plants overexpressing OsSHMT3 exhibited tolerance toward salt stress. Comparative analyses of OsSHMT3 vis a vis wild type by ionomic, transcriptomic, and metabolic profiling, protein expression and analysis of various traits revealed a pivotal role of OsSHMT3 in conferring tolerance toward salt stress. The gene can further be used in developing gene-based markers for salt stress to be employed in marker assisted breeding programs. HIGHLIGHTS: - The study provides information on mechanistic details of serine hydroxymethyl transferase gene for its salt tolerance in rice.

Participatory evaluation guides the development and selection of farmers' preferred rice varieties for salt- and flood-affected coastal deltas of South and Southeast Asia.

Rice is the staple food and provides livelihood for smallholder farmers in the coastal delta regions of South and Southeast Asia. However, its productivity is often low because of several abiotic stresses including high soil salinity and waterlogging during the wet (monsoon) season and high soil and water salinity during the dry season. Development and dissemination of suitable rice varieties tolerant of these multiple stresses encountered in coastal zones are of prime importance for increasing and stabilizing rice productivity, however adoption of new varieties has been slow in this region. Here we implemented participatory varietal selection (PVS) processes to identify and understand smallholder farmers' criteria for selection and adoption of new rice varieties in coastal zones. New breeding lines together with released rice varieties were evaluated in on-station and on-farm trials (researcher-managed) during the wet and dry seasons of 2008-2014 in the Indian Sundarbans region. Significant correlations between preferences of male and female farmers in most trials indicated that both groups have similar criteria for selection of rice varieties. However, farmers' preference criteria were different from researchers' criteria. Grain yield was important, but not the sole reason for variety selection by farmers. Several other factors also governed preferences and were strikingly different when compared across wet and dry seasons. For the wet season, farmers preferred tall (140-170 cm), long duration (160-170 d), lodging resistant and high yielding rice varieties because these traits are required in lowlands where water stagnates in the field for about four months (July to October). For the dry season, farmers' preferences were for high yielding, salt tolerant, early maturing (115-130 d) varieties with long slender grains and good quality for better market value. Pest and disease resistance was important in both seasons but did not rank high. When farmers ranked the two most preferred varieties, the ranking order was sometimes variable between locations and years, but when the top four varieties that consistently ranked high were considered, the variability was low. This indicates that at least 3-4 of the best-performing entries should be considered in succeeding multi-location and multi-year trials, thereby increasing the chances that the most stable varieties are selected. These findings will help improve breeding programs by providing information on critical traits. Selected varieties through PVS are also more likely to be adopted by farmers and will ensure higher and more stable productivity in the salt- and flood-affected coastal deltas of South and Southeast Asia.

Estrogen receptor, Progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India.

AIM: The aim of the study was to analyze the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7 years in South Indian women with breast cancer. Further analysis of a subgroup was done to study clinically defined subtypes and the role of preanalytical factors in needle core biopsies (NCBs) and excised specimens. MATERIALS AND METHODS: This was a retrospective study from January 2010 to December 2016. Patients diagnosed with invasive breast cancer and available immunohistochemistry (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year 2016 were analyzed further to observe the impact of preanalytical factors on the IHC staining patterns and surrogate status. RESULTS: A total of 5436 patients were included with a median age of 48 years. Among these, 65% were ≤ 55 years. The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2 positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in patients <56 years and over 55 years, respectively (P < 0.001). There was an increase in HR positivity and decrease in TNBCs over time. There was no significant difference in the staining patterns in NCBs and excised specimens. CONCLUSION: With time, there is an increase in hormone-positive tumors which may be attributed to better IHC techniques and tissue handling. There was no statistical difference in the patterns of ER, PR, and HER2 immunostaining in core biopsy and excised specimens.

Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane.

Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results: Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions: Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC. ClinicalTrials.gov: NCT01095003.

Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Impact of gene polymorphism of TNF-α rs 1800629 and TNF-ß rs 909253 on plasma levels of South Indian breast cancer patients.

AIM: Inflammation plays a lead role in the tumor microenvironment and promotes metastasis. Single-nucleotide polymorphism (SNP) in the tumor necrosis factor (TNF) gene locus may alter the expression of genes and proteins. The objective of the study is to find the distribution of genetic polymorphism in the sites of TNF-α -308G>A and TNF- ß +252A>G in breast cancer and evaluate polymorphism effects on plasma levels. MATERIALS AND METHODS: The study group consisted of 109 invasive ductal primary breast cancer patients and 75 age-matched healthy female controls. Plasma cytokine concentrations were measured by the MILLIPLEX® MAP Human Cytokine/Chemokine Panel magnetic bead kits. The genotyping procedure for SNP included allele-specific polymerase chain reaction for TNFα and restriction fragment length polymorphism for TNFß. RESULTS: Odds ratio with 95% confidence interval showed that these polymorphisms were not a causative risk factor, and both polymorphisms were consistent with Hardy-Weinberg equilibrium. Plasma TNFα and TNFß median concentrations were significantly higher in cases when compared to controls (P < 0.01). When plasma TNFα levels were grouped under polymorphic subtypes, patients with mutant TNF- α -308A allele showed significantly higher values (P < 0.001). In addition, plasma TNFα values were significantly elevated in mutant TNF-ß +252G allele (P < 0.01). CONCLUSION: This study demonstrated that there is no significant association between SNPs and breast cancer susceptibility in South Indian population. However, plasma TNFα level is significantly elevated with mutant-recessive TNF-α -308 A and TNF-ß +252 G alleles of patients.

Primary Hyperoxaluria Type 1 with Homozygosity for a Double-mutated AGXT Allele in a 2-year-old Child.

Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported.