Drought stress in Lens culinaris: effects, tolerance mechanism, and its smart reprogramming by using modern biotechnological approaches.

Among legumes, lentil serves as an imperative source of dietary proteins and are considered an important pillar of global food and nutritional security. The crop is majorly cultivated in arid and semi-arid regions and exposed to different abiotic stresses. Drought stress is a polygenic stress that poses a major threat to the crop productivity of lentils. It negatively influenced the seed emergence, water relations traits, photosynthetic machinery, metabolites, seed development, quality, and yield in lentil. Plants develop several complex physiological and molecular protective mechanisms for tolerance against drought stress. These complicated networks are enabled to enhance the cellular potential to survive under extreme water-scarce conditions. As a result, proper drought stress-mitigating novel and modern approaches are required to improve lentil productivity. The currently existing biotechnological techniques such as transcriptomics, genomics, proteomics, metabolomics, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/cas9), and detection of QTLs (quantitative trait loci), proteins, and genes responsible for drought tolerance have gained appreciation among plant breeders for developing climate-resilient lentil varieties. In this review, we critically elaborate the impact of drought on lentil, mechanisms employed by plants to tolerate drought, and the contribution of omics approaches in lentils for dealing with drought, providing deep insights to enhance lentil productivity and improve resistance against abiotic stresses. We hope this updated review will directly help the lentil breeders to develop resistance against drought stress.

Emerging Role of Gallium-68 DOTANOC PET/CT Guided Radiofrequency Ablation in the Treatment of Tumor-induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare acquired form of hypophosphatemia that can be cured when the tumor responsible is completely removed. These tumors can be small and located in anatomically challenging areas, rendering surgery both risky and extensive. Radiofrequency ablation (RFA) has been explored as an effective treatment option for such tumors. We present a case of a 35-year-old man exhibiting clinical and biochemical features consistent with TIO. The culprit lesion was not detectable on the whole-body computed tomography (CT) scan. Gallium (Ga-68) DOTANOC positron emission tomography (PET)/CT showed increased uptake in the left acetabulum and magnetic resonance imaging (MRI) confirmed the location of the tumor. Given the risky anatomical location, we opted for less-invasive RFA. Following an unsuccessful attempt at CT-guided RFA of the lesion, we used real-time Ga-68 DOTANOC PET/CT guidance for precise imaging during the ablation procedure. Our patient achieved complete remission both clinically and biochemically after RFA. This response was also evident by the absence of tracer uptake in follow-up imaging. In conclusion, DOTANOC PET/CT-guided RFA can serve as a safe and effective treatment for patients with tumors causing TIO. This modality proves valuable when surgical resection is not a viable option.

Management of Extraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced stage presentation of RB is common in low middle-income countries (LMICs) due to lack of awareness, social taboos associated with enucleation, seeking alternative conservative treatment options, and poor accessibility to health care. Over the last few decades, there have been significant advancements in the management of extraocular RB (EORB) which have improved outcomes and helped in minimizing treatment-related toxicities. The incorporation of multimodality approaches including chemotherapy, surgery, and radiotherapy (RT) has shown promising results; however, prognosis remains poor especially in LMICs. In this article, authors have discussed the ICMR consensus guidelines on the management of EORB, including metastatic RB.

Quest for a Desolvated Structure Unveils Breathing Phenomena in a MOF Leading to Greener Catalysis in a Solventless Setup: Insights from Combined Experimental and Computational Studies.

The crystal structure of the metal-organic framework (MOF), {Mn2(1,4-bdc)2(DMF)2}n (1) (1,4-bdcH2, 1,4-benzenedicarboxylic acid; DMF, N,N-dimethylformamide), is known for a long time; however, its desolvated structure, {Mn2(1,4-bdc)2}n (1'), is not yet known. The first-principles-based computational simulation was used to unveil the structure of 1' that shows the expansion in the framework, leading to pore opening after the removal of coordinated DMF molecules. We have used 1' that contains open metal sites (OMSs) in the structure in cyanosilylation and CO2 cycloaddition reactions and recorded complete conversions in a solventless setup. The pore opening in 1' allows the facile diffusion of small aldehyde molecules into the channels, leading to complete conversion. The reactions with larger aldehydes, 2-naphthaldehyde and 9-anthracenecarboxaldehyde, also show 99.9% conversions, which are the highest reported until date in solventless conditions. The in silico simulations illustrate that larger aldehydes interact with Mn(II) OMSs on the surfaces, enabling a closer interaction and facilitating complete conversions. The catalyst shows high recyclability, exhibiting 99.9% conversions in the successive reaction cycles with negligible change in the structure. Our investigations illustrate that the catalyst 1' is economical, efficient, and robust and allows reactions in a solventless greener setup, and therefore the catalysis with 1' can be regarded as "green catalysis".

ECEL1 related distal arthrogryposis 5D in an Indian cohort-Report of recognizable musculoskeletal phenotype and a possible founder variant.

Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D. We also report a possible founder variant in ECEL1 along with four novel variants and further expand the genotypic spectrum of DA5D.

Evaluation of the three different doses of cisatracurium during general anaesthesia: A prospective randomized study.

Background and Aims: The present study was conducted to determine the optimal dose of cisatracurium for intubating conditions and onset and offset of neuromuscular blockade. Data in Indian population are scarce, and hence, the present study was planned to evaluate different doses of cisatracurium. Material and Methods: The prospective randomized double-blind study was conducted on 180 patients of either sex in the age group of 20-60 yrs., having physical status class I to III, scheduled for surgery under general anesthesia. After exclusion 154 patients were randomly divided into three groups comprising 52, 51, and 51, respectively, in Group A, Group B, and group C. They received 0.1 mgkg-1, 0.2 mgkg-1, and 0.3 mgkg-1 of cisatracurium, respectively, to facilitate endotracheal intubation. Time of onset, intubating conditions, hemodynamic parameters, signs of histamine release, and recovery time were noted. Results: Mean time to onset was maximum in group A (4.37 ± 0.48 minutes) and minimum in group C (2.33 ± 0.43 minutes). Intubating conditions were found excellent in 88% patients in group. Change in HR was found to be non-significant at all time periods, but decrease in MAP was found between 2 and 10 minutes in group C. Duration of action was longest in group C. Conclusion: We conclude that cisatracurium in dose of 0.2 mgkg-1 and 0.3 mgkg-1 provides good-to-excellent intubating conditions within less than 3 minutes.

Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities.

OBJECTIVES: Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. METHODS: A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. RESULTS: IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. CONCLUSIONS: We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

In vitro comparison to study the antimicrobial effect of silver nanoparticles gel and its various combinants as an intracanal medicament against Enterococcus faecalis.

Background: Endodontic infections have been clearly described as biofilm-mediated infections. Bacteria and their by-products have been known to cause these infections. With the introduction of new drugs and the use of nanoparticles in recent times, there has been a significant reduction in the bacterial load in endodontic infections. Aims and Objectives: The in vitro study focuses on checking the antibacterial efficacy of silver nanoparticles and its combination with other medicaments against the root canal pathogen - Enterococcus faecalis (E. faecalis). Methodology: In the present study, 140 extracted human teeth were used. The teeth were sectioned, and biomechanical preparation was done. The root canals of the extracted teeth were inoculated with the culture of E. faecalis. The teeth were divided into six groups based on the intracanal medicament used: Group 1 - Silver nanocure gelGroup 2 - Silver nanocure gel + Cavisept gel (1:1)Group 3 - Silver nanocure gel + Aveu-Cal gel (1:1)Group 4 - Silver nanocure gel + Cavisept gel + Aveu-Cal gel (1:1:1)Group 5 - Positive control (specimens were inoculated with Enterococcus faecalis and left untreated to confirm the presence of infection)Group 6 - Negative control (no bacterial contamination of specimens). The colony-forming units were recorded after 48 h of incubation. Results: The statistical analysis of the colony-forming units was done using the Kruskal-Wallis tests. Silver nanocure gel + Cavisept gel + Aveu-Cal gel (1:1:1) showed the least colony-forming units. Conclusion: The present study is an in vitro study, in which we concluded that the combination of all the intracanal medicaments is the best for the elimination of E. faecalis biofilm from the root canal. The above findings need to be tested in vivo also.

Platelet-to-albumin ratio and radiation-induced lymphopenia-prognostic biomarker for carcinoma esophagus.

BACKGROUND: Esophageal cancer has a poor survival outcome with 5-year OS at 16.7% despite treatment. Some inflammation-based prognostic indicators like the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously studied as potential biomarker for predicting outcome in esophageal cancer. Recently, platelet-to-albumin ratio (PAR) has been reported as a promising prognostic factor in gastrointestinal malignancies. METHODS: We performed a retrospective analysis of prospectively treated patients of carcinoma esophagus to evaluate the prognostic significance of inflammation-based prognostic indicators-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and a composite inflammation-nutrition index: platelet-to-albumin ratio (PAR) in esophageal cancer. Based on previous studies, the optimal cut-off value of PAR was kept at 5.7 × 10^9, and 2.62 for NLR. RESULTS: A total of 71 patients of locally advanced esophageal cancer treated between 2019 and 2022, with either neoadjuvant or definitive chemoradiotherapy, were included. Median follow-up time was 19 months [range: 7-44 months]. Median OS and PFS in our study cohort were 11.3 months [range: 7-23 months] and 7.8 months [range: 3-17 months], respectively. In univariate analysis, lower PAR was found to be significantly correlated with shorter survival time (HR = 2.41; 1.3-4.76; p = 0.047). There was no association found between the OS and the NLR [HR = 1.09; 0.95-1.26; p = 0.222]. Univariate and multivariate linear and logistic regressions found no association between V15, V10, V5, or V2 of spleen and nadir lymphocyte count or between Dmax or Dmean and nadir lymphocyte counts. CONCLUSION: Present analysis found a trend toward an inverse association between PAR and OS. PAR, in the not-so-distant future, may evolve as a novel, convenient, and inexpensive prognostic indicator in esophageal cancer.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

Comparison of different rainfall products with gauge-based measurements over Narmada River Basin, India.

The present study evaluates and compares the performance of different rainfall products, namely, Climate Hazards Group InfraRed Precipitation with Station (CHIRPS), India Meteorological Department (IMD) gridded, Prediction of Worldwide Energy Resource (POWER), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Network-Climate Data Record (PERSIANN-CDR) with gauge-based measurements over Narmada River basin, India. The ground-based daily rainfall data (1981-2020) of 11 gauging stations have been collected from the Water Resources Department, Madhya Pradesh and the evaluation of rainfall product has been accomplished on a point-to-grid basis (nearest neighbor method) at annual and seasonal scales with the help of continuous and categorical statistical metrics. The results reveal a strong positive correlation (> 0.75) between rainfall estimates of different products and gauge-based measurements at annual scale demonstrating higher similarity in rainfall estimates and observed data, whereas seasonal estimates have exhibited comparatively weaker relationship. Likewise, percent bias (PBIAS) demonstrates least bias in annual and monsoon rainfall estimates and high in other seasons. These findings reveal that rainfall estimates tend to improve with increasing time scale (season to annual). However, majority of the rainfall products have overestimated the low rainfall (western region) and underestimated the high rainfall (eastern and southeastern regions). Further, the values of critical success index (CSI) indicate IMD gridded product outperforms in detecting rainfall events accurately followed by POWER, PERSIANN-CDR, and CHIRPS. These results suggest that IMD gridded estimates provide the best alternate to ground-based rain measurements. However, rainfall estimates from POWER, PERSIANN-CDR and CHIRPS can also be used in various hydrometeorological investigations over Narmada River basin.

Profiling Kinase Activities for Precision Oncology in Diffuse Gastric Cancer.

Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. This is due to the fact that majority of the cases of GC are diagnosed at an advanced stage when the treatment options are limited and prognosis is poor. The diffuse subtype of gastric cancer (DGC) under Lauren's classification is more aggressive and usually occurs in younger patients than the intestinal subtype. The concept of personalized medicine is leading to the identification of multiple biomarkers in a large variety of cancers using different combinations of omics technologies. Proteomic changes including post-translational modifications are crucial in oncogenesis. We analyzed the phosphoproteome of DGC by using paired fresh frozen tumor and adjacent normal tissue from five patients diagnosed with DGC. We found proteins involved in the epithelial-to-mesenchymal transition (EMT), c-MYC pathway, and semaphorin pathways to be differentially phosphorylated in DGC tissues. We identified three kinases, namely, bromodomain adjacent to the zinc finger domain 1B (BAZ1B), WNK lysine-deficient protein kinase 1 (WNK1), and myosin light-chain kinase (MLCK) to be hyperphosphorylated, and one kinase, AP2-associated protein kinase 1 (AAK1), to be hypophosphorylated. LMNA hyperphosphorylation at serine 392 (S392) was demonstrated in DGC using immunohistochemistry. Importantly, we have detected heparin-binding growth factor (HDGF), heat shock protein 90 (HSP90), and FTH1 as potential therapeutic targets in DGC, as drugs targeting these proteins are currently under investigation in clinical trials. Although these new findings need to be replicated in larger study samples, they advance our understanding of signaling alterations in DGC, which could lead to potentially novel actionable targets in GC.

Identification of Sr67, a new gene for stem rust resistance in KU168-2 located close to the Sr13 locus in wheat.

KEY MESSAGE: Sr67 is a new stem rust resistance gene that represents a new resource for breeding stem rust resistant wheat cultivars Re-appearance of stem rust disease, caused by the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), in different parts of Europe emphasized the need to develop wheat varieties with effective resistance to local Pgt populations and exotic threats. A Kyoto University wheat (Triticum aestivum L.) accession KU168-2 was reported to carry good resistance to leaf and stem rust. To identify the genomic region associated with the KU168-2 stem rust resistance, a genetic study was conducted using a doubled haploid (DH) population from the cross RL6071 × KU168-2. The DH population was phenotyped with three Pgt races (TTKSK, TPMKC, and QTHSF) and genotyped using the Illumina 90 K wheat SNP array. Linkage mapping showed the resistance to all three Pgt races was conferred by a single stem rust resistance (Sr) gene on chromosome arm 6AL, associated with Sr13. Presently, four Sr13 resistance alleles have been reported. Sr13 allele-specific KASP and STARP markers, and sequencing markers all showed null alleles in KU168-2. KU168-2 showed a unique combination of seedling infection types for five Pgt races (TTKSK, QTHSF, RCRSF, TMRTF, and TPMKC) compared to Sr13 alleles. The phenotypic uniqueness of the stem rust resistance gene in KU168-2 and null alleles for Sr13 allele-specific markers showed the resistance was conferred by a new gene, designated Sr67. Since Sr13 is less effective in hexaploid background, Sr67 will be a good source of stem rust resistance in bread wheat breeding programs.

Emerging role of osmoprotectant glycine betaine to mitigate heavy metals toxicity in plants: a systematic review.

Heavy metals (HMs) toxicity has become one of the major global issues and poses a serious threat to the environment in recent years. HM pollution in agricultural soil is caused by metal mining, smelting, volcanic activity, industrial discharges, and excessive use of phosphate fertilizers. HMs above a threshold level adversely affect the cellular metabolism of plants by producing reactive oxygen species (ROS), which attack cellular proteins. There are different mechanisms (physiological and morphological) adopted by plants to survive in the era of abiotic stress. Various osmoprotectants or compatible solutes, including amino acids, sugar, and betaines, enable the plants to counteract the HM stress. Glycine betaine (GB) is an effective osmolyte against HM stress among compatible solutes. GB has been shown to improve plant growth, photosynthesis, uptake of nutrients, and minimize oxidative stress in plants under HM stress. Additionally, GB increases the activity of antioxidant enzymes such as CAT (catalase), SOD (superoxide dismutase), and POD (peroxidase), which are effective in scavenging unwarranted ROS. Since not all species of plants can naturally produce or accumulate GB in response to stress, various approaches have been explored for introducing them. Plant hormones like salicylic acid, ABA (abscisic acid), and JA (jasmonic acid) co-ordinately stimulate the accumulation of GB inside the cell under HM stress. Apart from the exogenous application, the introduction of GB pathway genes in GB deficient species via genetic engineering also seems to be efficient in mediating HM stress. This review complied the beneficial effects of GB in mitigating HM stress and its role as a plant growth regulator. Additionally, the review explores the potential for engineering GB biosynthesis in plants as a strategy to bolster their resilience to HMs.

New insights from the genetic work-up in early onset nephrotic syndrome: report from a registry in western India.

BACKGROUND: Eighty-five percent of infants with congenital nephrotic syndrome (CNS) and 66% with infantile NS (INS) are likely to have a monogenic etiology. There exists a significant genetic variability between different regions and ethnic groups. This study aimed to determine the genetic defects in children with CNS and INS by establishing a registry in western India. METHODS: In this cross-sectional study, pediatric nephrologists from 13 private and government institutions shared relevant clinical data and details of the genetic evaluation of children presenting with NS within the first year of life. RESULTS: The median age at presentation was 9 months (range 1-23, IQR 3-13 months), history of consanguinity between parents existed in 14 patients (34%), family history of similar illness in 6 (15%), and extra-renal manifestations in 17 (41%). Twenty-five (61%) were confirmed to have a monogenic etiology. NPHS1 gene was the most implicated (9/25) followed by PLCE1 (5/25). There were 12 variants of uncertain significance (VUS) involving 10 genes (10/25, 40%), and no definite genetic abnormality was found in 4 (25%). A re-analysis of these VUS attempted 2-3 years later facilitated reclassification of 7/12 (58%); increasing the diagnostic yield from 61 to 68.2%. CONCLUSIONS: Consistent with worldwide data, variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort. NUP93 and COL4A3 were reported in early onset NS for the first time. Reclassification of VUS should be attempted, if feasible, since it may lead to a useful revision of diagnosis.

Syntheses and characterization of novel antimony (III) and bismuth (III) derivatives containing ß-enamino ester along with antimicrobial evaluation, DFT calculation, and cytotoxic study.

Four novel antimony (III) and bismuth(III) complexes of the kind Cl-Sb-O-C(OR)-CH(CH3 )C-NH-(CH2 )2 -NH-C(CH3 )CH:C(OR)-O [where R = -CH3 , M = Sb (1a); R = -C2 H5 , M = Sb (1b); R = -CH3, M = Bi (1c); R = -C2 H5 , M = Bi (1d)] were successfully prepared by reacting antimony(III)chloride and bismuth(III)chloride with sodium salt of ß-enamino esters in 1:1 stoichiometry, which were further structurally characterized by physicochemical and IR, 1 H, 13 C NMR spectral and mass spectrometry. Structural analysis revealed that all four derivatives of both antimony and bismuth display octahedarl geometry which has been optimized through computational studies. These derivatives along with their parent ligands were subsequently assayed in vitro for antibacterial (Bacillus subtilis, Pseudomonas aeruginosa) and antifungal (Aspergillus niger and Candida albicans) activities. Synthesized complexes were more efficacious in terms of biological activities as compared to parent ligands Further synthesized compounds were evaluated for their in vitro cytotoxic activity against lung cancer cell line A549 using MTT method. IC50 value for all four complexes was determined and all of them are found active. Computational studies of the representative complexes have been done using B3LYP/631-G* basis sets to provide optimized geometry.

Post-tonsillectomy bleeding rate decreases with limitation in maximum post-operative ibuprofen dosage: A quality improvement study.

OBJECTIVE: The objective of this study is to investigate the effect of a reduction in the prescribed post-operative ibuprofen dosage on frequency of post-tonsillectomy bleeding. METHODS: A quality improvement study was conducted at a single tertiary care pediatric hospital with patients weighing >40 kg undergoing tonsillectomy. The intervention was limiting the post-operative ibuprofen dosage to a maximum of 400 mg per dose. Data was collected on all patients returning to the hospital with bleeding after tonsillectomy. The primary outcome was the rate of post-tonsillectomy bleeding. Statistical analysis was conducted using nonparametric comparisons and a run chart. RESULTS: A total of 199 tonsillectomy patients >40 kg were included in the study. There were 119 (59.8 %) females and 80 (40.2 %) males total. The pre-intervention group had a total of 56 patients while the post-intervention group had a total of 143 patients. There was no statistical difference in age, weight, or sex between the pre- and post-intervention groups (p > .05). The post-tonsillectomy hemorrhage rate was 11/56 (19.6 %) before the intervention, and 11/143 (7.7 %) after the intervention (p = .016). Children who experienced a bleeding event were significantly older (mean 15.9 years, 95 % CI 14.5-17.3) than those who did not (13.5 years, 95 % CI 12.9-14.1; p = .011). The run chart revealed that the intervention resulted in a nonrandom decrease in rate of post-tonsillectomy bleeding. CONCLUSIONS: Post-tonsillectomy bleeding rate decreased with a ceiling post-operative ibuprofen dose of 400 mg/dose in this quality improvement study. Further research is warranted.