Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Novel biogenic silver nanoconjugates of Abrus precatorius seed extracts and their antiproliferative and antiangiogenic efficacies.

Biogenic silver nanoconjugates (AgNCs), derived from medicinal plants, have been widely explored in the field of biomedicines. AgNCs for the first-time were synthesized using ethyl acetate seed extracts of Abrus precatorius and their antiproliferative and antiangiogenic efficacies were evaluated against cervical and oral carcinoma. Ultraviolet-Visible spectrophotometry, dynamic light Scattering (DLS), and scanning electron microscopy (SEM) were used for characterization of AgNCs. Antiproliferative activity was investigated using MTT, DNA fragmentation and in-vitro antioxidant enzyme activity assays. In-vivo chick chorioallantoic membrane (CAM) model was used to evaluate antiangiogenic activity. A total of 11 compounds were identified in both the extracts in GCMS analysis. The synthesized AgNCs were spherical shaped with an average size of 97.4 nm for AgAPE (Sox) and 64.3 nm for AgAPE (Mac). AgNCs possessed effective inhibition against Hep2C and KB cells. In Hep2C cells, AgAPE (Mac) revealed the highest SOD, catalase, GST activity and lower MDA content, whereas AgAPE (Sox) showed the highest GSH content. On the other hand, in KB cells, AgAPE (Sox) exhibited the higher SOD, GST activity, GSH content, and least MDA content, while AgAPE (Mac) displayed the highest levels of catalase activity. Docking analysis revealed maximum binding affinity of safrole and linoleic acid with selected targets. AgAPE (Sox), AgAPE (Mac) treatment profoundly reduced the thickness, branching, and sprouting of blood vessels in the chick embryos. This study indicates that A. precatorius-derived AgNCs have enhanced efficacies against cervical and oral carcinoma as well as against angiogenesis, potentially limiting tumour growth.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Patterns of Whole Exome Sequencing in Resected Cholangiocarcinoma.

BACKGROUND: With minimally effective chemotherapy options, cholangiocarcinoma patients have 5 year survival rate of 10%. Tumor genetic profiling (TGP) can identify mutations susceptible to targeted therapies. We sought to describe the use of TGP and frequency of actionable results in resected cholangiocarcinoma. METHODS: A retrospective review of patients undergoing curative intent resection at a comprehensive cancer center (2010-2020). Clinicopathologic and partial or whole exome sequencing data were reviewed. RESULTS: 114 patients (mean age 65 ± 11 years, 45% female) underwent resection of cholangiocarcinoma (46% poorly differentiated, 54% intrahepatic, 36% node positive, 75% margin negative). Additionally, 32% of patients underwent TGP, yielding a mean of 3.1 actionable mutations per patient (range 0-14). Mutations aligned with a median of one drug per patient (range 0-11). Common mutations included TP53 (33%), KRAS (31%), IDH1/2 (14%), FGFR (14%), and BRAF (8%). Targeted therapies were administered in only 4% of patients (23% of eligible sequenced patients). After a median 22 months, 23% had recurrence and 29% were deceased. DISCUSSION: TGP for cholangiocarcinoma has increased over the last decade with targeted therapies identified in most sequenced tumors, impacting treatment in a quarter of eligible patients. Precision medicine will play a central role in the future care of cholangiocarcinoma.

Chemotherapy-induced early transient increase and surge of CA 19-9 level in patients with pancreatic Adenocarcinoma✰.

This study aimed to characterize chemotherapy-induced transient increase and surge of CA 19-9 level to treatment response in patients with advanced pancreatic ductal adenocarcinoma (PDAC). A retrospective case series was performed of advanced PDAC patients treated with first-line chemotherapy at City of Hope Comprehensive Cancer Center from Jan 2017 to May 2020. CA 19-9 surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CA 19-9 levels compared to baseline. Out of 106 advanced PDAC patients, 38 were evaluable for CA 19-9 surge. Fourteen (51.9%) patients treated with FOLFIRINOX and 3 (27.3%) patients treated with nab-P + Gem chemotherapy demonstrated an early transient rise in CA 19-9 level. A CA 19-9 surge was documented in 9 (23.7%) patients, all with duration of surge lasting < 16 weeks. Five out of 9 (55.6%) patients (4: FOLFIRINOX, 1: nab-P + Gem) with CA 19-9 surge demonstrated partial objective response rate on surveillance cross-sectional imaging. One patient (FOLFIRINOX) had stable disease, and 2 patients (1: FOLFIRINOX, 1: nab-P + Gem) were found to have disease progression after treatment interruption. The initial early rise of CA 19-9 levels during chemotherapy in patients with advanced PDAC may not indicate tumor progression. Rather, it may represent a chemotherapy-induced transient increase or surge phenomenon of the tumor marker in patients responding to treatment.

Genome-wide interologous interactome map (TeaGPIN) of Camellia sinensis.

Tea, prepared from the young leaves of Camellia sinensis, is a non-alcoholic beverage globally consumed due to its antioxidant properties, strong taste and aroma. Although, the genomic data of this medicinally and commercially important plant is available, studies related to its sub-cellular interactomic maps are less explored. In this work, we propose a genome-wide interologous protein-protein interaction (PPI) network of tea, termed as TeaGPIN, consisting of 12,033 nodes and 216,107 interactions, developed using draft genome of tea and known PPIs exhaustively collected from 49 template plants. TeaGPIN interactions are prioritized using domain-domain interactions along with the interolog information. A high-confidence TeaGPIN consisting of 5983 nodes and 58,867 edges is reported and its interactions are further evaluated using protein co-localization similarities. Based on three network centralities (degree, betweenness and eigenvector), 1302 key proteins are reported in tea to have p-value <0.01 by comparing the TeaGPIN with 10,000 realizations of Erdos-Rényi and Barabási-Albert based corresponding random network models. Functional content of TeaGPIN is assessed using KEGG and GO annotations and its modular architecture is explored. Network based characterization is carried-out on the transcription factors, and proteins involved flavonoid biosynthesis and photosynthesis pathways to find novel candidates involved in various regulatory processes. We believe the proposed TeaGPIN will impart useful insights in understanding various mechanisms related to growth and development as well as defence against biotic and abiotic perturbations.

Readmission and complications after robotic surgery: experience of 10,000 operations at a comprehensive cancer center.

Evaluation of safety is of paramount importance with adoption of novel surgical technology. Although robotic surgery has become widely used in oncologic surgery, analysis of safety is lacking in comparison to traditional techniques. Standardized assessment of robotic surgical outcomes and adverse events following oncologic surgery is necessary for quality improvement with innovative technology. Between 2003 and 2016, 10,013 unique robotic operations were performed in 9,858 patients. Our prospectively maintained database was retrospectively reviewed for hospital readmissions and Clavien-Dindo grade ≥ 2 complications within 30 days. Multivariable logistic regression was used to identify predictors of surgical complications and hospital readmissions. Cases were stratified by discipline: genitourinary (n = 8240), gynecologic (n = 857), thoracic (n = 457), gastrointestinal (n = 322), hepatobiliary (n = 60), ear/nose/throat (n = 44) and general (n = 33). Intraoperative complications occurred in 42 surgeries (0.4%). Postoperative complications occurred in 946 patients [9.4%, highest grade 2 (n = 574), 3 (n = 288), 4 (n = 72), 5 (n = 10)]. Most frequent complications were ileus (154, 16.3%), anemia (91, 9.6%), cardiac arrhythmia (62, 6.6%), deep vein thrombosis/pulmonary embolus (47, 5.0%), wound infection (45, 4.8%) and urinary leak (43, 4.5%). 405 patients (4.0%) required readmission. Most common causes for hospital readmission were ileus (44, 10.9%), urinary leak (23, 5.7%), urinary tract infection (23, 5.7%), intra-abdominal abscess/fluid collection (23, 5.7%), and small bowel obstruction (19, 4.7%). On multivariable analysis, longer operative time and older age predicted complications and readmissions (p ≤ 0.02). Robotic-assisted surgery appears a safe for oncologic surgery with acceptable hospital readmission and complication rates. Older age and longer operative time were associated with complications and readmission.

A cross-sectional study of errors in physicians orders' of antiseizure medications among people with epilepsy from rural India.

AIMS: To enumerate and classify errors in physicians' orders of antiseizure medications (ASMs) to people with epilepsy presenting to neurology clinic. METHODS: This cross-sectional study was conducted in the neurology clinic of a teaching hospital catering to a predominantly rural population. People in whom a diagnosis of epilepsy was confirmed and who presented for the first time with a prior prescription for antiseizure medication/s were included. Their immediate previous prescriptions were assessed for errors, enumerated and classified according to WHO guidelines for prescription writing. RESULTS: Hundred prescriptions of 334 patients screened were analyzed. The number of ASMs prescribed to a participant was 2 ±â€¯0.6 (mean ±â€¯SD). We identified a mean of 5 ±â€¯4 (median: 3; range: 1-7) errors in each order. These included superscription errors, e.g., missing information on seizure control and frequency (n = 90, 90%), generic name (n = 62, 62%), patient identifiers (n = 57, 57%), prescribers' identifiers (n = 29, 29%) and diagnosis or indication for prescribing the medication/s (n = 55, 55%). The most common inscription and subscription errors were dosing errors (22%) and pharmaceutical form errors (20%) followed by omission (13%), duplication (13%), substitution (12%), commission (9%) and frequency errors (8%). Errors were more common among prescriptions provided by primary-care and Ayurvedic, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) physicians compared to specialists (P < 0.05). CONCLUSIONS: Errors are common among medication orders provided by non-specialist and specialist physicians. Primary care and AYUSH are more liable to make errors underscoring the need to educate them in basic epilepsy treatment.

Persistence and dissipation kinetics of tebuconazole in apple, tomato, chilli and onion crops of Himachal Pradesh, India.

Tebuconazole is a broad-spectrum fungicide extensively used worldwide for the control of many diseases such as powdery mildew and scab in apple, early blight of tomato, anthracnose of chilli, white rot and purple blotch of onion etc. Maximum residue level of this compound has not been worked out on these crops in India; the persistence and dissipation kinetics of tebuconazole on apple, tomato, chilli and onion were studied following three foliar applications of the formulation Folicur 430 SC at a standard dose (X) 322, 268.75, 215 and 215 g a.i./ha and at double dose (2X) 645, 537.5, 430 and 430 g a.i./ha, respectively, to work out the safe waiting periods and half-life period of tebuconazole. Extraction was done using QuEChERS method and cleanup by using dispersive solid-phase method. Tebuconazole residues were estimated on gas chromatograph-mass spectrometry (GC-MS). The recovery of tebuconazole in fortified matrix was above 90% with a limit of quantification (LOQ) at 0.05 mg kg-1. The initial deposits of tebuconazole on apple at two locations under study ranged from 1.986-2.011 mg kg-1at X dose to 3.698-3.843 mg kg-1 at 2X dose. The initial deposits in tomato, chilli and onion were 1.129, 1.760 and 1.169 mg kg-1 at X dose and 2.213, 2.784 and 2.340 mg kg-1, respectively at the 2X dose. Dissipation of the fungicide followed first-order of kinetics and the half life of degradation ranged from 1.30-2.25 days at X dose to 1.40-2.62 days at 2X days on different crops under study. Residues declined below the determination limit (LOQ) of 15 and 20 days after spraying, respectively, at X and 2X dose in apple; 7 and 10 days in tomato; 10 and 15 days in chilli and onion. Waiting periods of 5, 2, 7 and 12 days, respectively, are suggested for apple, tomato, chilli and onion at 2X dose.

Construction and analysis of an interologous protein-protein interaction network of Camellia sinensis leaf (TeaLIPIN) from RNA-Seq data sets.

KEY MESSAGE: An interologous PPI network of tea leaf is designed by developing reference transcriptome assembly and using experimentally validated PPIs in plants. Key regulatory proteins are proposed and potential TFs are predicted. Worldwide, tea (Camellia sinensis) is the most consumed beverage primarily due to the taste, flavour, and aroma of its newly formed leaves; and has been used as an important ingredient in several traditional medicinal systems because of its antioxidant properties. For this medicinally and commercially important plant, design principles of gene-regulatory and protein-protein interaction (PPI) networks at sub-cellular level are largely un-characterized. In this work, we report a tea leaf interologous PPI network (TeaLIPIN) consisting of 11,208 nodes and 197,820 interactions. A reference transcriptome assembly was first developed from all the 44 samples of 6 publicly available leaf transcriptomes (1,567,288,290 raw reads). By inferring the high-confidence interactions among potential proteins coded by these transcripts using known experimental information about PPIs in 14 plants, an interologous PPI network was constructed and its modular architecture was explored. Comparing this network with 10,000 realizations of two types of corresponding random networks (Erdos-Rényi and Barabási-Albert models) and examining over three network centrality metrics, we predict 2750 bottleneck proteins (having p values < 0.01). 247 of these are deduced to have transcription factor domains by in-house developed HMM models of known plant TFs and these were also mapped to the draft tea genome for searching their probable loci of origin. Co-expression analysis of the TeaLIPIN proteins was also performed and top ranking modules are elaborated. We believe that the proposed novel methodology can easily be adopted to develop and explore the PPI interactomes in other plant species by making use of the available transcriptomic data.

Base Excess as a Predictor of Complications in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Base excess is important in assessing metabolic status. Postoperative management in patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies can be a challenge, and we therefore sought to investigate perioperative predictors of overall morbidity in CRS/HIPEC patients at our institution. METHODS: Patients who underwent CRS/HIPEC from 2012 to 2016 were identified retrospectively from a prospectively collected institutional database. Patient demographics and perioperative variables were obtained and the comprehensive complication index (CCI) was calculated for each patient in order to assess perioperative morbidity. Stepwise linear regression analyses were performed, with CCI as the outcome variable. RESULTS: A total of 72 CRS/HIPEC patients had recorded base excesses in the first 48 h postoperatively. Mean immediate postoperative base excess was -6.0 mmol/L (interquartile range [IQR] -8 to -4.1), mean delta base excess at 48 h was +4.3 mmol/L (IQR +2.1 to +6.2), and mean CCI was 25.2 (IQR 8.7-36.7). On multivariate analysis, delta base excess was the only significant predictor of CCI, demonstrating a protective effect (p = 0.001). In patients who experienced less than the mean delta base excess of +4.3 mmol/L, lower delta base excess was an independent predictor of complications (p < 0.001). CONCLUSIONS: Delta base excess is an independent predictor of morbidity in patients undergoing CRS/HIPEC. A delta base excess of greater than +4.3 mmol/L at 48 h may be an appropriate goal for resuscitation of CRS/HIPEC patients in the immediate postoperative period. Standardized protocols to correct the base deficit in CRS/HIPEC patients during the early postoperative period can potentially help mitigate perioperative morbidity.

Wireless Monitoring Program of Patient-Centered Outcomes and Recovery Before and After Major Abdominal Cancer Surgery.

IMPORTANCE: A combined subjective and objective wireless monitoring program of patient-centered outcomes can be carried out in patients before and after major abdominal cancer surgery. OBJECTIVE: To conduct a proof-of-concept pilot study of a wireless, patient-centered outcomes monitoring program before and after major abdominal cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: In this proof-of-concept pilot study, patients wore wristband pedometers and completed online patient-reported outcome surveys (symptoms and quality of life) 3 to 7 days before surgery, during hospitalization, and up to 2 weeks after discharge. Reminders via email were generated for all moderate to severe scores for symptoms and quality of life. Surgery-related data were collected via electronic medical records, and complications were calculated using the Clavien-Dindo classification. The study was carried out in the inpatient and outpatient surgical oncology unit of one National Cancer Institute-designated comprehensive cancer center. Eligible patients were scheduled to undergo curative resection for hepatobiliary and gastrointestinal cancers, were English speaking, and were 18 years or older. Twenty participants were enrolled over 4 months. The study dates were April 1, 2015, to July 31, 2016. MAIN OUTCOMES AND MEASURES: Outcomes included adherence to wearing the pedometer, adherence to completing the surveys (MD Anderson Symptom Inventory and EuroQol 5-dimensional descriptive system), and satisfaction with the monitoring program. RESULTS: This study included a final sample of 20 patients (median age, 55.5 years [range, 22-74 years]; 15 [75%] female) with evaluable data. Pedometer adherence (88% [17 of 20] before surgery vs 83% [16 of 20] after discharge) was higher than survey adherence (65% to 75% [13 of 20 and 15 of 20] completed). The median number of daily steps at day 7 was 1689 (19% of daily steps at baseline), which correlated with the Comprehensive Complication Index, for which the median was 15 of 100 (r = -0.64, P < .05). Postdischarge overall symptom severity (2.3 of 10) and symptom interference with activities (3.5 of 10) were mild. Pain (4.4 of 10), fatigue (4.7 of 10), and appetite loss (4.0 of 10) were moderate after surgery. Quality-of-life scores were lowest at discharge (66.6 of 100) but improved at week 2 (73.9 of 100). While patient-reported outcomes returned to baseline at 2 weeks, the number of daily steps was only one-third of preoperative baseline. CONCLUSIONS AND RELEVANCE: Wireless monitoring of combined subjective and objective patient-centered outcomes can be carried out in the surgical oncology setting. Preoperative and postoperative patient-centered outcomes have the potential of identifying high-risk populations who may need additional interventions to support postoperative functional and symptom recovery.

Spatial transcriptome analysis provides insights of key gene(s) involved in steroidal saponin biosynthesis in medicinally important herb Trillium govanianum.

Trillium govanianum, an endangered medicinal herb native to the Himalaya, is less studied at the molecular level due to the non-availability of genomic resources. To facilitate the basic understanding of the key genes and regulatory mechanism of pharmaceutically important biosynthesis pathways, first spatial transcriptome sequencing of T. govanianum was performed. 151,622,376 (~11.5 Gb) high quality reads obtained using paired-end Illumina sequencing were de novo assembled into 69,174 transcripts. Functional annotation with multiple public databases identified array of genes involved in steroidal saponin biosynthesis and other secondary metabolite pathways including brassinosteroid, carotenoid, diterpenoid, flavonoid, phenylpropanoid, steroid and terpenoid backbone biosynthesis, and important TF families (bHLH, MYB related, NAC, FAR1, bZIP, B3 and WRKY). Differentially expressed large number of transcripts, together with CYPs and UGTs suggests involvement of these candidates in tissue specific expression. Combined transcriptome and expression analysis revealed that leaf and fruit tissues are the main site of steroidal saponin biosynthesis. In conclusion, comprehensive genomic dataset created in the current study will serve as a resource for identification of potential candidates for genetic manipulation of targeted bioactive metabolites and also contribute for development of functionally relevant molecular marker resource to expedite molecular breeding and conservation efforts in T. govanianum.

Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze).

To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.

Substance-abusing schizophrenics: do they self-medicate?

In spite of having been formulated nearly two decades back, there is as yet no consensus on the validity of the clinically popular self-medication hypothesis (SMH) of substance use disorders in patients with dual diagnosis. SMH broadly proposes that patients use substances in a non-random fashion so that the psychopharmacologic characteristics of particular substances are used to alleviate a variety of psychiatric symptoms and emotional distress. In order to test the SMH empirically, it was broken down to five sub-hypotheses, which were tested in a group of dual-diagnosis schizophrenia (DDS) patients vis-à-vis a group of only-schizophrenia (S) patients (n = 22 each). The DDS group scored lower than the S group regarding general and some specific psychopathology. The DDS patients ascribed reasons for substance use more often for hedonistic pursuit but also for reduction in symptoms and distress. There was a trend for alcohol to be used more for self-medication purposes compared to opioids and cannabis. The perceived effects of these three substances were significantly different on several symptom/distress dimensions. Finally, there was some degree of "match" between symptom-oriented reasons for use of substances and the effect that was perceived. All of this evidence provides a consistent but modest support for the SMH for "some patients, some substances, and some symptoms." The implications are discussed.