Topical Chlorhexidine 0.2% versus Topical Natamycin 5% for the Treatment of Fungal Keratitis in Nepal: A Randomized Controlled Noninferiority Trial.

PURPOSE: To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis. DESIGN: Randomized controlled, single-masked, noninferiority clinical trial. PARTICIPANTS: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. METHODS: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621. MAIN OUTCOME MEASURES: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. RESULTS: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013). CONCLUSIONS: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.

A Randomized Controlled Trial to Evaluate the Role of Brief Delay in Cord Clamping in Preterm Neonates (34-36 weeks) on Short-term Neurobehavioural Outcome.

AIM: To study the effect of brief delay in cord clamping on short-term neurobehavioural outcome of preterm neonates. METHODS: All preterm neonates born between 34-36 weeks and 6 days were included and randomized into either a control or intervention group. In the control group, clamping was done within 20 s after delivery, and this was termed as immediate cord clamping (ICC). In the intervention group, delayed cord clamping (DCC) took place between 30 and 60 s. A total of 120 preterm neonates were enrolled. The primary outcome studied was short-term neurobehavioural outcome at 37 weeks after conceptional age using the Neurobehavioral Assessment of Preterm Infants (NAPI) score as the outcome measure. RESULTS: NAPI scores at 37 weeks of corrected gestational age revealed a mean (95% confidence interval) score of motor development and vigour of 64.21±27.31 (57.27 - 71.14) vs. 76.69±25.29 (70.04-83.34), p= 0.01; and alertness and orientation of 29.31±12.78 (26.06-32.55) vs. 42.77±15.75 (38.63-46.91), p= 0.00 across the ICC vs. DCC groups, respectively. CONCLUSION: A brief delay of 30-60 s in cord clamping is beneficial in improving neurobehavioural outcome of late preterm infants.

Development of SYBR Green and TaqMan quantitative real-time PCR assays for hepatopancreatic parvovirus (HPV) infecting Penaeus monodon in India.

Hepatopancreatic parvovirus (HPV) infects Penaeus monodon and causes mortality in the larval stages. Further, it has been implicated in the growth retardation in cultured P. monodon. Though different geographical isolates of HPV show large sequence variations, a sensitive PCR assay specific to Indian isolate has not yet been reported. Here, we developed a sensitive SYBR Green-based and TaqMan real-time PCR for the detection and quantification of the virus. A 441-bp PCR amplicon was cloned in pTZ57 R/T vector and the plasmid copy number was estimated. A 10-fold serial dilution of the plasmid DNA from 1 × 10(9) copies to 1 copy was prepared and used as the standard. The primers were tested initially using the standard on a conventional PCR format to determine the linearity of detection. The standards were further tested on real-time PCR format using SYBR Green and TaqMan chemistry and standard curves were generated based on the Ct values from three well replicates for each dilution. The assays were found to be sensitive, specific and reproducible with a wide dynamic range (1 × 10(9) to 10 copies) with coefficient of regression (R(2)) > 0.99, calculated average slope -3.196 for SYBR Green assay whereas, for TaqMan assay it was >0.99 and -3.367, respectively. The intra- and inter-assay variance of the Ct values ranged from 0.26% to 0.94% and 0.12% to 0.81%, respectively, for SYBR Green assay, and the inter-assay variance of the Ct values for TaqMan assay ranged from 0.07% to 1.93%. The specificity of the assays was proved by testing other DNA viruses of shrimp such as WSSV, IHHNV and MBV. Standardized assays were further tested to detect and quantify HPV in the post-larvae of P. monodon. The result was further compared with conventional PCR to test the reproducibility of the test. The assay was also used to screen Litopeneaus vannamei, Macrobrachium rosenbergii and Scylla serrata for HPV.

Prosthetic rehabilitation of a hemimandibulectomy patient.

This report presents a case in which a patient was treated with a segmental hemimandibulectomy to improve function and esthetics. Crowns were placed on the remaining teeth and the remaining space was rehabilitated with an acrylic partial denture in the maxillary arch and a cast partial denture in the mandibular arch. The treatment and rehabilitation of a patient with a resected mandible involves taking full advantage of all remaining structures.

Serum Zinc Levels in Women with Polycystic Ovarian Syndrome are Lower as Compared to Those without Polycystic Ovarian Syndrome: A Cohort Study.

Background: Zinc is an essential micronutrient, a vital stabiliser and a cofactor in many enzymes such as superoxide dismutase and phospholipase C and also acts as an antioxidant by protecting the sulfhydryl groups of different proteins and enzymes against free radicals. It is unclear if serum zinc levels are correlated with polycystic ovary syndrome (PCOS) and its pathophysiology, although relation between diabetes and insulin resistance has been established. Aims: This study aimed to investigate circulating serum zinc levels in PCOS subjects compared with non-PCOS subjects. Settings and Design: In this cohort study, PCOS subjects were compared with normal subjects aged between 18 and 35. Materials and Methods: All the included subjects underwent measurement of anthropometric parameters, fasting insulin, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, progesterone, oestrogen and serum zinc levels. These values were taken on days 2-5 of the menstrual cycle. Statistical Analysis Used: Univariate analysis and linear regression were performed for serum zinc levels and fasting insulin levels in PCOS subjects and non-PCOS subjects using SPSS (version 21) and Microsoft Excel (2019). Results: Serum zinc levels in the PCOS group were lower than in the control group (P = 0.012). Fasting insulin levels in the PCOS group were higher than in non-PCOS subjects (P = 0.001). We found a negative correlation between zinc and fasting insulin (r = -0.580, P < 0.0001) in the normal group and (r = -0.332, P = 0.019) in the PCOS group. A positive correlation was found between body mass index (BMI) and fasting insulin levels in both the PCOS group (r = 0.227, P = 0.112) and normals (r = 0.612, P < 0.0001). A negative statistically significant correlation between BMI and zinc in both the PCOS group (r = -0.378, P = 0.007) and the non-PCOS group (r = -0.7452, P < 0.0001) was seen. Conclusion: The data suggest that serum zinc levels were found to be lower in PCOS subjects as compared to normal controls and evaluation of these levels may indicate that zinc has a vital role in PCOS pathophysiology.

An image analysis approach to characterize micronuclei differences in different subtypes of breast cancer.

BACKGROUND: Micronuclei (MN) have been used as screening, diagnostic and prognostic markers in multiple cancer types, including breast cancer (BC). However, the question that the MN present in all subtypes of BC are similar or different remains unanswered. We thus hypothesized that MN present in different subtypes of BC may differ in their contents which may be visible as differences in their morphologic and morphometric features. This study was thus carried out with the aim to identify the differences between MN morphometry, complexity, and texture in different subtypes of BC, such as estrogen and progesterone receptor-positive (ER+/PR+; MCF-7, T-47D), human epidermal growth factor receptor-positive (Her2 +;SKBR3) and triple-negative BC (TNBC; MDA-MB-231, MDA-MB-468) cell lines (CLs) by ImageJ software. METHODS: For analysis of MN dimensions, MN irregularity, and texture, we used morphometry and two mathematical computer-assisted algorithms, i.e., fractal dimension (FD) and grey level co-occurrence matrix (GLCM) of ImageJ software. RESULTS: MN area and perimeter values showed differences in the size of MN in different subtypes of BC, with the largest MN in TNBC CLs. GLCM parameters (entropy, angular second moment, inverse difference moment, contrast, and correlation) showed highly heterogenous texture in case of TNBC MN as compared to the others. FD analysis also revealed more complexity and irregularity in MN found in TNBC cells. CONCLUSION: The study for the first time showed morphometric, architectural and texture related differences amongst MN present in different subtypes of BC. The above may reflect differences in their composition and contents. Further, these differences may point towards the distinct mechanisms involved in the formation of MN in different subtypes of BC that need to be explored further.

Aspirin as a potential drug repurposing candidate targeting estrogen receptor alpha in breast cancer: a molecular dynamics and in-vitro study.

Estrogen receptor alpha (ERα) is expressed by 70% of breast cancers (BCs). Any deregulation in ERα signaling is crucial for the initiation and progression of BC. Because of development of resistance to anti-estrogenic compounds, repurposing existing drugs is an apt strategy to avoid a long drug-discovery process. Substantial epidemiologic evidence suggests that Aspirin use reduces the risk of different cancers including BC, while its role as an adjuvant or a possible antineoplastic agent in cancer treatment is being investigated. In this study, we attempted to explore possibilities of ERα inhibition by Aspirin which may act through competitive binding to the ligand binding domain (LBD) of ERα. A list of 48 ERα-LBD crystal structures bound with agonists, antagonists, and selective ER modulators (SERMs) was thoroughly analysed to determine interaction patterns specific to each ligand category. Exhaustive docking and 500 ns molecular dynamics (MD) studies were performed on three ERα - Aspirin complexes generated using agonist, antagonist, and SERM-bound crystal structures. Besides, three ERα crystal structures bound to agonist, antagonist, and SERM respectively were also subjected to MD simulations. Aspirin showed good affinity to LBD of ERα. Comparative analyses of binding patterns, conformational changes and molecular interaction profiles from the docking results and MD trajectories suggests that Aspirin was most stable in complex generated using SERM bound crystal structure of ERα and showed interactions with Gly-521, Ala-350, Leu-525 and Thr-347 like SERMs. In addition, in-vitro assays, qPCR, and immunofluorescent assay demonstrated the decline in the expression of ERα in MCF-7 upon treatment with Aspirin. These preliminary bioinformatical and in-vitro findings may form the basis to consider Aspirin as a potential candidate for targeting ERα, especially in tamoxifen-resistant cancers.Communicated by Ramaswamy H. Sarma.

Maternal Mortality and COVID-19 Pandemic: Looking Beyond SARS CoV-2 Infection.

Objective: To study the impact of COVID-19 pandemic on maternal mortality ratio, aetiological and modifiable factors for maternal mortality and key interventions performed. Method: Retrospective exploratory study evaluating maternal mortality between April to November 2020 (study group) and 2019 (control group). Results: Demographic variations existed in the two groups. Increased maternal age and illiteracy were significantly more in the study group. Maternal mortality ratio (MMR) was significantly high in the study group (792 vs. 296 p value = 0.0). Hemorrhage accounted for 20% and COVID-19-related maternal deaths accounted for 15% deaths in the study group. Level 3 delay (delay in receiving care/inadequate care) was observed in 35% in the study group and 28% in control group (p value = 0.349). 17.5% of mothers in the study group as compared to 8% of control group were dead on arrival to hospital though not statistically significant (p value = 0.28). Significantly more women in study group died within 24 h of admission (45% vs. 20%, p value 0.04). Among the key interventions, the use of supplemental oxygen was significantly high in study group (p value = 0.02). Conclusion: Maternal mortality ratio was high in the pandemic year because of a significant decline in hospital delivery rate. The lesson learnt from this pandemic needs to be documented to guide better planning in the future to face similar situations.

Bottom-up approach to explore alpha-amylase assisted membrane remodelling.

Soluble alpha-amylases play an important role in the catabolism of polysaccharides. In this work, we show that the malt α -amylase can interact with the lipid membrane and further alter its mechanical properties. Vesicle fluctuation spectroscopy is used for quantitative measurement of the membrane bending rigidity of phosphatidylcholines lipid vesicles from the shape fluctuation based on the whole contour of Giant Unilamellar Vesicles (GUVs). The bending rigidity of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid vesicles in water increases significantly with the presence of 0.14 micromolar alpha-amylase (AA) in the exterior solution. It appears that the enzyme present in the external solution interacts with the outer layer of the bilayer membrane, leading to an asymmetry of the solution on either side of the bilayer membrane and altering its elasticity. At AA concentration of 1.5 micromolars and above, changes in the morphology of the GUV membrane are observed. The interaction between AA in the external solution and the external leaflet causes the bilayer membrane to curve spontaneously, leading to the formation of outbuds, giving a positive spontaneous curvature of C0 ≤ 0.05 µm-1 at ≈ 1 mg / ml of the AA concentration. We validate and characterize its concentration-dependent role in stabilizing the membrane curvature. Our findings indicate that the involvement of the enzyme, depending on the concentration, can have a considerable effect on the mechanical characteristics of the membrane.

Investigating active area dependent high performing photoresponse through thin films of Weyl Semimetal WTe2.

WTe2 is one of the wonder layered materials, displays interesting overlapping of electron-hole pairs, opening of the surface bandgap, anisotropy in its crystal structure and very much sought appealing material for room temperature broadband photodection applications. Here we report the photoresponse of WTe2 thin films and microchannel devices fabricated on silicon nitride substrates. A clear sharp rise in photocurrent observed under the illumination of visible (532 nm) and NIR wavelengths (1064 nm). The observed phoresponse is very convincing and repetitive for ON /OFF cycles of laser light illumination. The channel length dependence of photocurrent is noticed for few hundred nanometers to micrometers. The photocurrent, rise & decay times, responsivity and detectivity are studied using different channel lengths. Strikingly microchannel gives few orders of greater responsivity compared to larger active area investigated here. The responsivity and detectivity are observed as large as 29 A/W and 3.6 × 108 Jones respectively. The high performing photodetection properties indicate that WTe2 can be used as a broad band material for future optoelectronic applications.

Touch imprint smear: A prerequisite to obtain better quality and "true" tumor RNA in breast tissues.

BACKGROUND: RNA is the primary genetic material required for various molecular studies. RNA derived from breast tissue has low quality and quantity compared to that extracted from other tissues. Therefore, optimization of techniques for breast tissue RNA extraction is a challenging but essential requirement. METHODS: RNA was extracted from 60 samples of breast cancer after dividing them into 2 groups. Each tissue was divided into 2 halves for RNA extraction and histopathology respectively. In group 2 RNA was extracted after taking touch imprints whereas group1 was not subjected to any such procedure. Concentration and purity of RNA was assessed by using spectrophotometer and 1% agarose gel followed by RT-PCR for 18 S rRNA and CCND1 gene. RESULTS: Based on microscopic observations of imprints, group 2 samples were further subdivided into 2 subgroups. Group 2 A (n = 30) showing tumor in imprint smears were found to yield best concentration of pure RNA (1846.50 ng/µl and 1.92) as compared to group 2B (n = 15) with no malignancy in imprints (102.61 ng/µl and 1.53). The correlation of imprint smears with their corresponding H&E-stained slides further leads to grouping of each group in 2 groups. RT-PCR analyses showed better melting peaks and high relative expression of CCND1 in group 2 A. CONCLUSION: Touch imprints may provide valuable information regarding presence or absence of tumor in tissue samples being used for extraction of genetic material. This approach can be used as easy, cheap and fast strategy to resolve the doubts associated with RNA being truly representative of the tumor.

Primary fallopian tube endometroid carcinoma: A rare case report.

ABSTRACT: Primary fallopian tube carcinoma is an extremely rare tumor accounting for only 0.14-1.8% of genital tract cancers. A 47-year-old female presented with post-menopausal bleeding and heaviness in the lower abdomen. Imaging revealed the right adnexal mass, suggestive of neoplastic origin. She was prepared for surgery. Per-operatively, there was a solid irregular mass, firm to hard in consistency, around 8 × 5 cm involving the whole of the right fallopian tube, and the right ovary appeared normal. Histopathological examination of the specimen showed endometroid adenocarcinoma of the right fallopian tube. Endometroid carcinoma is important to recognize because it carries the best prognosis of all the fallopian tube cancers. The patient underwent surgery, followed by adjuvant chemotherapy, and was doing well in follow-up.

Ocular and Neuro-ophthalmic Manifestations Post COVID-19 Infection.

A 39-year-old male with a history of COVID-19 infection presented with ocular manifestations: dendritic ulcer in the left eye cornea followed by diplopia in the same eye. Extraocular motility was restricted in the levo-lateral gaze with maximum diplopia measuring 25∆ exotropia. Slit lamp biomicroscopy showed dendritic patterned lesion with diffused superficial punctate keratitis in the cornea. There are various reports associated with COVID-19 and the neuro-ophthalmic system. Although the clinicopathological aspect of COVID-19 and the neurological system is still to explicate. However, the patient showed gradual improvement with topical and systemic antiviral therapy and orthoptic exercise. This points to the need for detailed neurological and ophthalmic workup in symptomatic COVID-19 patients. Taking the risk of viral spread into serious consideration, a thorough evaluation is though mandatory. Keywords: COVID-19; dendritic ulcer; lateral rectus palsy; superficial punctate keratopathy.

Impact of Action Taken in Response to Stillbirth Audit: A Success Story.

Objectives: Study the impact of intra-facility interventions on the modifiable factors causing stillbirths (SB), using point-of-care quality improvement (POCQI) methodology. Material and Methods: Stillbirth data during the 9 months pre-intervention period were reviewed to identify the common preventable causes. Two interventions, namely, ultrasound at 34-36 weeks gestation and intrapartum monitoring on a common customized labor chart for all health-care providers, were done. Post-intervention data were collected to observe the impact of the interventions. Results: The stillbirth rate reduced from 212/5940 deliveries (35.7/1000) in the pre-intervention period to 165/5993 deliveries (27.7/1000) in the post-intervention period (p = 0.011). The intra-facility failure to identify FGR significantly reduced in the post-intervention group (p = 0.033), leading to 63% (RR 0.37) reduction in its risk. Using a common customized labor chart led to a significant decline in the inadequate monitoring as a provider-related cause of stillbirth (p < 0.001) leading to its 42% decline as contributor to modifiable cause of SB (RR 0.48). Conclusion: Reviewing the perinatal death surveillance response (PDSR) data, identifying gaps in care, and using improvement methodology for instituting corrective measures play an important role in reducing intramural stillbirths.

Perceiving placental ultrasound image texture evolution during pregnancy with normal and adverse outcome through machine learning prism.

INTRODUCTION: The objective was to perform placental ultrasound image texture (UPIA) in first (T1), second(T2) and third(T3) trimesters of pregnancy using machine learning( ML). METHODS: In this prospective observational study the 2D placental ultrasound (US) images from 11-14 weeks, 20-24 weeks, and 28-32 weeks were taken. The image data was divided into training, validating, and testing subsets in the ratio of 80%, 10%, and 10%. Three different ML techniques, deep learning, transfer learning, and vision transformer were used for UPIA. RESULTS: Out of 1008 cases included in the study, 59.5% (600/1008) had a normal outcome. The image texture classification was compared between T1&T2, T2 &T3 and T1&T3 pairs. Using Inception v3 model, to classify T1& T2 images, gave the accuracy, Cohen Kappa score of 83.3%, 0.662 respectively. The image classification between T1&T3 achieved best results using EfficientNetB0 model, having the accuracy, Cohen Kappa score, sensitivity and specificity of 87.5%, 0.749, 83.4%, and 88.9% respectively. Comparison of placental image texture among cases with materno-fetal adverse outcome and controls was done using Efficient Net B0. The F1 score, was found to be 0.824 , 0.820, and 0.892 in T1, T2 and T3 respectively. The sensitivity and specificity of the model was 77.4% at 80.2% at T1 but increased to 81.0% and 93.9% at T2 &T3 respectively. DISCUSSION: The study presents a novel technique to classify placental ultrasound image texture using ML models and could differentiate first and third-trimester normal placenta and normal and adverse pregnancy outcome images with good accuracy.

Highly Responsive Near-Infrared Si/Sb2Se3 Photodetector via Surface Engineering of Silicon.

The development of imaging technology and optical communication demands a photodetector with high responsiveness. As demonstrated by microfabrication and nanofabrication technology advancements, recent progress in plasmonic sensor technologies can address this need. However, these photodetectors have low optical absorption and ineffective charge carrier transport efficiency. Sb2Se3 is light-sensitive material with a high absorption coefficient, making it suitable for photodetector applications. We developed an efficient, scalable, low-cost near-infrared (NIR) photodetector based on a nanostructured Sb2Se3 film deposited on p-type micropyramidal Si (made via the wet chemical etching process), working on photoconductive phenomena. Our results proved that, at the optimized thickness of the Sb2Se3 layer, the proposed Si micropyramidal substrate enhanced the responsivity nearly two times, compared with that of the Sb2Se3 deposited on a flat Si reference sample and a glass/Sb2Se3 sample at 1064 nm (power density = 15 mW/cm2). More interestingly, the micropyramidal silicon-based device worked at 0 V bias, paving a path for self-bias devices. The highest specific detectivity of 2.25 × 1015 Jones was achieved at 15 mW/cm2 power density at a bias voltage of 0.5 V. It is demonstrated that the enhanced responsivity was closely linked with field enhancement due to the Kretschmann configuration of Si pyramids, which acts as hot spots for Si/Sb2Se3 junction. A high responsivity of 47.8 A W-1 proved it suitable for scalable and cost-effective plasmonic-based NIR photodetectors.

Virtual repurposing of ursodeoxycholate and chenodeoxycholate as lead candidates against SARS-Cov2-Envelope protein: A molecular dynamics investigation.

Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2in absence of any specific medication/vaccine. The present work employs state of art computational methods like homology modelling, molecular docking and molecular dynamics simulations to evaluate the potential of two widely used surfactant drugs namely chenodeoxycholate(CDC) and ursodeoxycholate (UDC), to bind to the envelope protein of SARS-Cov2(SARS-Cov2-E).The monomeric unit of SARS-Cov2-E was modelled from a close homologue (>90% sequence identity) and a pentameric assembly was modelled using symmetric docking, followed by energy minimization in a DPPC membrane environment. The minimized structure was used to generate best scoring SARS-Cov2-E-CDC/UDC complexes through blind docking. These complexes were subjected to 230 ns molecular dynamics simulations in triplicates in a DPPC membrane environment. Comparative analyses of structural properties and molecular interaction profiles from the MD trajectories revealed that, both CDC and UDC could stably bind to SARS-Cov2-E through H-bonds, water-bridges and hydrophobic contacts with the transmembrane-channelresidues.T30 was observed to be a key residue for CDC/UDC binding. CDC/UDC binding affected the H-bonding pattern between adjacent monomeric chains, slackening the compact transmembrane region of SARS-Cov2-E. Additionally, the polar functional groups of CDC/UDC facilitated entry of a large number of water molecules into the channel. These observations suggest CDC/UDC as potential candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitating the entry of solvents/polar inhibitors inside the viral cell.Communicated by Ramaswamy H. Sarma.

Evaluating the pesticidal impact of plant protease inhibitors: lethal weaponry in the co-evolutionary battle.

In the arsenal of plant defense, protease inhibitors (PIs) are well-designed defensive products to counter field pests. PIs are produced in plant tissues by means of 'stable defense metabolite' and triggered on demand as the perception of the signal and well established as a part of plant active defense. PIs have been utilized for approximately four decades, initially as a gene-alone approach that was later replaced by multiple gene pyramiding/gene stacking due to insect adaptability towards the PI alone. By considering the adaptive responses of the pest to the single insecticidal gene, the concept of gene pyramiding gained continuous appreciation for the development of transgenic crops to deal with co-evolving pests. Gene pyramiding approaches are executed to bypass the insect's adaptive responses against PIs. Stacking PIs with additional insecticidal proteins, plastid engineering, recombinant proteinase inhibitors, RNAi-based methods and CRISPR/Cas9-mediated genome editing are the advanced tools and methods for next-generation pest management. Undoubtedly, the domain associated with the mechanism of PIs in the course of plant-pest interactions will occupy a central role for the advancement of more efficient and sustainable pest control strategies. © 2021 Society of Chemical Industry.

Primary Pure Large-Cell Neuroendocrine Carcinoma of the Ovary: A Rare Case Report.

Primary pure large-cell neuroendocrine carcinoma is a rare entity with 17 cases reported till now. A 48-year-old, Para6 Live4, postmenopausal woman presented with complaints of pain abdomen, constipation for 6 months, and postmenopausal bleeding for 1 month. On per abdominal examination, an irregular, hard, fixed, and tender mass was felt in the pelvis corresponding to 32 weeks size gravid uterus. Her magnetic resonance imaging findings were suggestive of a large abdominopelvic mass of size 10.2 cm × 12.7 cm × 14.2 cm with inferior extension into the left adnexa and 3.1 cm × 2.2 cm × 2.1 cm right adnexal mass. Debulking surgery was done. The intraoperative findings were of a large abdominopelvic mass adhered to the sigmoid colon and retroperitoneal space. Histopathological and immunohistochemistry findings were suggestive of bilateral large-cell neuroendocrine carcinoma of ovaries with strong positive for Bcl2, CD56, NSE, PR, and P53. The patient was started on tablet etoposide as adjuvant treatment. After 5 months of primary surgery, contrast-enhanced computed tomography of the chest, abdomen, and pelvis revealed recurrence. She succumbed to her illness 6 months after primary surgery. Owing to its rarity and difficulty in diagnosis, it is suggested that all such cases should be registered at national level and critically analyzed to find the high risk and associated prognostic factors.