Progress toward Proteome-Wide Photo-Cross-Linking to Enable Residue-Level Visualization of Protein Structures and Networks In Vivo.

Cross-linking mass spectrometry (XL-MS) is emerging as a method at the crossroads of structural and cellular biology, uniquely capable of identifying protein-protein interactions with residue-level resolution and on the proteome-wide scale. With the development of cross-linkers that can form linkages inside cells and easily cleave during fragmentation on the mass spectrometer (MS-cleavable cross-links), it has become increasingly facile to identify contacts between any two proteins in complex samples, including in live cells or tissues. Photo-cross-linkers possess the advantages of high temporal resolution and high reactivity, thereby engaging all residue-types (rather than just lysine); nevertheless, photo-cross-linkers have not enjoyed widespread use and are yet to be employed for proteome-wide studies because their products are challenging to identify. Here, we demonstrate the synthesis and application of two heterobifunctional photo-cross-linkers that feature diazirines and N-hydroxy-succinimidyl carbamate groups, the latter of which unveil doubly fissile MS-cleavable linkages upon acyl transfer to protein targets. Moreover, these cross-linkers demonstrate high water-solubility and cell-permeability. Using these compounds, we demonstrate the feasibility of proteome-wide photo-cross-linking in cellulo. These studies elucidate a small portion of Escherichia coli's interaction network, albeit with residue-level resolution. With further optimization, these methods will enable the detection of protein quinary interaction networks in their native environment at residue-level resolution, and we expect that they will prove useful toward the effort to explore the molecular sociology of the cell.

Morphological outcome and indication for laser following intravitreal bevacizumab monotherapy for posterior retinopathy of prematurity.

The purpose of this study is to determine the natural course of retinal vascular development and recurrence requiring laser in eyes receiving intravitreal bevacizumab (IVB) for posterior retinopathy of prematurity (ROP). Data of babies receiving IVB for posterior ROP was retrospectively analyzed. Birth weight, gestational age (GA) and post-menstrual age (PMA) at injection, need for laser, retinal maturation, and their timing were recorded. The study included 63 eyes of 32 babies, born at a median GA of 31 (IQR 29-32) weeks, and birth weight 1410 (1280-1697.5) g. Aggressive posterior ROP was seen in 36 (57%) eyes and staged ROP in 27 (43%). IVB was injected at a median PMA of 36 (34.5-37) weeks. Complete retinal vascularization was seen in 33 (52.4%) at a median PMA of 52 (47-60) weeks, prophylactic laser was needed in 17 (27%) at 61 (55.5-63) weeks, and only 13 (20.6%) eyes had recurrence needing treatment laser, at 42 (39-57) weeks respectively. Babies requiring laser had a significantly lower birth weight (p = 0.033) and received injection earlier (p = 0.08). Retinal vascular development progresses with IVB monotherapy with 21% of eyes developing recurrence that requires laser in this subset of Indian babies. Following IVB, monotherapy laser can be selectively performed only in cases with recurrence or failure to mature.

Proportion of diabetic retinopathy among diabetics presenting for the first time to a tertiary eye institute in South India.

PURPOSE: To detect the proportion of diabetic retinopathy (DR) among diabetics visiting a tertiary eye care institute and correlate presenting symptoms to clinical diagnosis. METHODS: The study recruited 1000 eyes of 1000 diabetics visiting a tertiary eye care institute in South India for the first time. Along with basic demographic data and systemic history, details of presenting complaints and clinical diagnosis were noted. RESULTS: Data from 956 cases were analyzed. There were 29 (3%) newly diagnosed diabetics and 927 (97%) known diabetics. The commonest reason for the hospital visit was diminution of vision (66%) followed by "visiting for a routine checkup" (22.3%). Diabetic retinopathy was seen in 492 (51.5%), cataract in 161(17%) and refractive error in 240 patients (79.2%). Vision-threatening DR was present in 216 cases (22.59%) and clinically significant macular edema in 73 cases (7.63%) at first presentation itself. CONCLUSION: The cohort from a tertiary eye care institute has higher proportion of diabetic retinopathy, with vision-threatening DR at presentation. These data emphasize the need for more robust screening for DR, along with population awareness programs.

Evaluation of [68Ga]Ga-DATA-TOC for imaging of neuroendocrine tumours: comparison with [68Ga]Ga-DOTA-NOC PET/CT.

PURPOSE: Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and radiolabelling of DATA-based octreotide derivative (TOC) at room temperature in contrast to tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) that needs 95 °C for effective labelling. However, the diagnostic potential of DATA-TOC has not been studied with other chelators in humans. The aim of this study was to compare the diagnostic efficacy of [68Ga]Ga-DATA-TOC with [68Ga]Ga-DOTA-NOC (which is the current standard for imaging neuroendocrine tumours (NET)) in patients of gastroenteropancreatic neuroendocrine tumours (GEP-NETs). METHODS: Fifty patients (thirty-one males and nineteen females) with biopsy-proven GEP-NETs were included in the study. Patients age ranged from 14 to 75 years (mean 46.11 years). All patients underwent two PET studies with [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC. Images were evaluated visually and semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour, mediastinum and liver. Tumour-to-liver (T/L) and tumour-to-mediastinum (T/M) SUVmax ratios were computed. For the purpose of comparison, patient-wise as well as lesion-wise analysis was carried out. The nonparametric-related samples Wilcoxon signed-rank test was used for comparison of the SUVmax values and ratios. RESULTS: On visual evaluation, the biodistribution and image quality of [68Ga]Ga-DATA-TOC was similar to [68Ga]Ga-DOTA-NOC. Physiological liver uptake was lower in [68Ga]Ga-DATA-TOC as compared with [68Ga]Ga-DOTA-NOC, 7.65 ± 5.37 vs 8.94 ± 5.95 (p = 0.009), respectively. On a patient-wise analysis, both [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were lesion-positive in the 44 patients (88%) and were negative in the 6 patients (12%). On a lesion-based analysis, [68Ga]Ga-DATA-TOC had 98.6% concordance with [68Ga]Ga-DOTA-NOC (232 out of 235 lesions detected). The target tumour SUVmax on [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were 36.63 ± 32.24 and 40.82 ± 36.89, respectively (p = 0.097). The T/L SUVmax ratios were not significantly different (5.99 ± 5.52 vs 5.67 ± 4.96, p = 0.77). CONCLUSION: [68Ga]Ga-DATA-TOC PET/CT imaging produced results that were comparable with [68Ga]Ga-DOTA-NOC. It, thus, has potential utility as an effective and safe alternative to 68Ga-DOTA-NOC with the added benefit of ease, cost-effective and improved yield of instant kit-type synthesis.

The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts.

BACKGROUND: Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. METHODS: A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. RESULTS: 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). CONCLUSION: Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).

Regulation of RyeA/SraC expression in Escherichia coli.

Small RNAs (sRNAs) play a central role in regulating almost all physiological processes in bacteria. Majority of those sRNAs base pair with their targets and modulate their expressions. RyeA, previously known as SraC in Escherichia coli, is transcribed from a DNA strand complementary to the one from which another stationary phase induced sRNA RyeB/SdsR is synthesised. RyeA and RyeB in the stationary phase constitute a toxin-antitoxin system where RyeA normalizes accumulation of RyeB toxin by acting as RNA sponge. Aside from that, no more information is known about the regulation of RyeA expression. In the current study, we have systematically investigated the regulation of RyeA expression in different growth phases, and identified that RyeA expression is regulated neither by stationary phase-specific σ-factor nor by RNA chaperon Hfq. A dual function ribonuclease RNase BN mitigate its expression in the exponential phase. Thus, deletion of rbn gene promoted the stability of RyeA in the exponential phase. Conversely, RyeB in the stationary phase act as RNA decoy leading to RyeA degradation, and consequently, the preclusion of RyeB in the E. coli genome elevated RyeA. These regulatory mechanisms will help identify the primary role of RyeA in E. coli.

Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity.

Prompted by the role of PDE5 and its closely associated cAMP and cGMP in hypertension, we have attempted to discover novel PDE5 inhibitors through ligand based virtual screening. Rigorously validated model comprising of one HBA, one HY and one RA was used as a query to search the NCI database leading to retrieval of many compounds which were screened on the basis of estimated activity, fit value and Lipinski's violation. Selected compounds were subjected to docking studies which resulted into visualization of potential interaction capabilities of NCI compounds in line to pharmacophoric features. Finally three compounds were subjected to in vitro evaluation using the isolated rat aortic model. The results showed that all three compounds are potent and novel PDE5 inhibitors with vasodilatory activity range from 10(-2) to 10(-5) M.

Low molecular weight chitosan from Pleurotus ostreatus waste and its prebiotic potential.

The booming mushroom industry envisages economic merits, and massive unutilized waste production (∼ 20 %) creates an opportunity for valorization. Chitosan, a bioactive polysaccharide, has drawn immense attention for its invaluable therapeutic potential. Thus, the present study was conducted to extract chitosan from mushroom waste (MCH) for its prebiotic potential. The structural characterization of MCH was carried out using NMR, FTIR, and XRD. The CP/MAS-13CNMR spectrum of MCH appeared at δ 57.67 (C2), 61.19 (C6), 75.39 (C3/C5), 83.53 (C4), 105.13 (C1), 23.69 (CH3), and 174.19 (C = O) ppm. The FTIR showed characteristic peaks at 3361 cm-1, 1582 cm-1, and 1262 cm-1 attributed to -NH stretching, amide II, and amide III bands of MCH. XRD interpretation of MCH exhibited a single strong reflection at 2θ =20.19, which may correspond to the "form-II" polymorph. The extracted MCH (∼ 47 kDa) exhibited varying degrees of deacetylation from 79 to 84 %. The prebiotic activity score of 0.73 to 0.82 was observed for MCH (1 %) when supplemented with probiotic strains (Lactobacillus casei, L. helveticus, L. plantarum, and L. rhamnosus). MCH enhanced the growth of Lactobacillus strains and SCFA's levels, particularly in L. rhamnosus. The MCH also inhibited the growth of pathogenic strains (MIC of 0.125 and 0.25 mg/mL against E. coli and S. aureus, respectively) and enhanced the adhesion efficiency of probiotics (3 to 8 % at 1 % MCH supplementation). L. rhamnosus efficiency was higher against pathogens in the presence of MCH, as indicated by anti-adhesion assays. These findings suggested that extracted polysaccharides from mushroom waste can be used as a prebiotic for ameliorating intestinal dysbiosis.

Additive Value of MR Simulation Prior to Chemoradiation in Evaluating Treatment Response and Pseudoprogression in High-Grade Gliomas.

BACKGROUND: A dedicated MRI Simulation(MRsim) for radiation treatment(RT) planning in high-grade glioma(HGG) patients can detect early radiological changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the impact of using post-op MRI vs. MRsim as the baseline for response assessment and reporting pseudo-progression on follow-up imaging at one month(FU1) after chemoradiation. METHODS: Histologically confirmed HGG patients were planned for six weeks of RT in a prospective study for adaptive RT planning. All patients underwent post-op MRI, MRsim, and follow-up MRI scans every 2-3 months. Tumor response was assessed by three independent blinded reviewers using Response Assessment in Neuro-Oncology(RANO) criteria when baseline was either post-op MRI or MRsim. Interobserver agreement was calculated using light's kappa. RESULTS: 30 patients (median age 60.5 years; IQR 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was post-op MRI vs. MRsim, including true progression vs. partial response(PR) or stable disease(SD) in 11 (37%) and SD vs. PR in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was post-op MRI vs 8 patients (26.7%) when the baseline was MRsim (p=.004). Pseudo-progression was observed at FU1 in 12 (40%) vs. 4 (13%) patients, when the baseline was post-op MRI vs. MRsim (p=.019). Interobserver agreement between observers was moderate (κ = 0.579; p<0.001). CONCLUSIONS: Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudo-progression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrolment to improve patient outcomes.

Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota-gut-brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota-gut-brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut-microbiota-brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder.

A Comparison Between the Effectiveness of Isoamyl 2-Cyanoacrylate Tissue Adhesive and Silk Sutures in Wound Closure Following Minor Oral Surgical Procedures: A Prospective Clinical Study.

Background In order to maintain the surgery site's shape, functionality, and aesthetics, closure of the wound is essential for intra-oral and general surgical procedures. Wound closure speeds up healing by reducing the buildup of inflammatory cells. For a wound to heal well, the incision must be precise, the tissue must be handled delicately, the wound must be precisely repositioned, and the closure material must have optimum functional properties and be sterile. Aim This study aims to conduct a clinical comparison of the effectiveness of silk suture versus isoamyl 2-cyanoacrylate (IAC) for intra-oral mucosal incisions. Methodology Fifty patients who needed a minor oral surgical operation under local anesthesia from the Department of Oral and Maxillofacial Surgery were recruited for this prospective clinical trial. Ethical clearance and informed consent were obtained for this study. Two groups were created from the sample of 50 patients in this investigation. An intra-oral mucosal incision was closed in one group using a 3-0 silk suture and in the second using two drops of IAC. An accurate approximation of the incised edges was used to avoid leaving any gaps between them. Parameters such as the time taken for closure, pain, bleeding, swelling, mouth opening, wound dehiscence, wound infection, and local ulceration were evaluated in this study. A visual analog scale (0-10) was used to assess the pain score. Facial swelling was evaluated by the tape method given by Gabka and Matsumura. The measurement was done from tragus to pogonion, tragus to oral commissure, and outer canthus to gonion. The sum of these measurements was calculated. By measuring the distance between the incisal edges of the upper and lower central incisors, the trismus was evaluated using a graduated metal scale. Assessment of bleeding (0-4) was done by asking the patient. Assessment of wound dehiscence and local ulceration was done based on visual inspection and palpation on the first, second, and seventh days postoperatively. All the recorded parameters were tabulated. The statistical analysis was done using SPSS version 25.0 (IBM Corp., Armonk, NY). The Chi-square test was used to compare the categorical variables between the study groups. The independent t-test was used to compare the means between the study groups. The statistical significance was kept at a p-value less than 0.05. Results The results showed that there was no statistically significant difference between suture and IAC in terms of incidence of pain and wound dehiscence. But the time taken for wound closure was less with IAC, and the pain score on the seventh day was higher with IAC and statistically significant. Conclusion We observed that IAC was as effective as the gold standard silk suture. The advantages of IAC are its hemostatic and bacteriostatic qualities, and IAC also took less time to complete the procedure.

Histopathological Changes in Placenta of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Infection and Maternal and Perinatal Outcome in COVID-19.

Background: Whether vertical transmission or placental pathology occurs after maternal infection during pregnancy remains unknown. There is a clear need for studies on the impact of COVID-19 on pregnancy outcome. A systemic inflammatory or hypercoagulable state may be the contributing factor for placental pathology. Methods: The pregnant women with COVID-19 who delivered between May 2020 and May 2021 were followed and data were collected about pregnancy course and placentas were examined for macro- and microscopical changes and were compared to controls with non-infected women. Results: Placenta of COVID-19-infected females had increased prevalence of decidual arteriopathy and placental injury reflecting hypoxia and uteroplacental insufficiency within the intervillous space. Features of maternal vascular malperfusion such as increased syncytial knots were present in 100% cases. Fibrinoid necrosis was seen in 100% cases and increased focal perivillous fibrin depositions were presented in 37.7% cases. About one fourth infected placentas had evidence of villitis. Even after matching for comorbidities like preeclampsia, these changes were present. Conclusion: The most common pathological findings of the placenta of COVID-19 infections are signs of maternal and fetal malperfusion. Future studies should target infections in different stage of gestation, including first and second trimesters.

Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors.

Inhibition of acetylcholinesterase (AChE) has been widely explored to develop novel molecules for management of Alzheimer's disease. In past research finding reported molecule 3-(4-(4-fluorobenzoyl)piperidin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one displayed a spectrum of anti-Alzheimer's properties herein, we report a library of 18 novel molecules that were rationally designed and synthesized employing known literature to mimic and explore the novel chemical space around the lead compound 6e and donepezil. All the compounds were docked in extra-precision mode with AChE (PDB ID 4EY7) using the Glide module. Molecular dynamics (MD) simulation studies were carried out for 100 ns along with MM-PBSA studies of the trajectory frames generated post-MD simulations. Docking and MD simulation studies suggested that the synthesized compounds showed a good binding affinity with AChE. and might form stable complexes. 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a; docking score: -18.59) and 1-(3,4-dimethoxybenzyl)-3-(4-(methyl(thiazol-2-ylmethyl)amino)piperidin-1-yl)pyrrolidin-2-one (14d; docking score: -18.057) showed higher docking score than donepezil (docking score: -17.257) while most of the compounds had docking score >-10.0. ADMET study predicted these compounds to be CNS active and most of the compounds were drug-like molecules with no HERG blockade and good to excellent oral absorption. We developed an atom-based 3 D-QSAR model with R^2 and Q^2 values of 0.9639 and 0.8779 to predict the activity of the synthesized compounds. The model predicted these compounds to be potent AChE inhibitors with IC50 values in the lower micromolar range. Based on the in silico findings, we report these newly synthesized compounds 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a) and 7-(2,6-difluorobenzyl)-2-(4-methoxybenzyl)-2,7-diazaspiro[4.5]decan-1-one (20 b) as potential AChE inhibitors.Communicated by Ramaswamy H. Sarma.

Artificial Intelligence in Neuroradiology: A Review of Current Topics and Competition Challenges.

There is an expanding body of literature that describes the application of deep learning and other machine learning and artificial intelligence methods with potential relevance to neuroradiology practice. In this article, we performed a literature review to identify recent developments on the topics of artificial intelligence in neuroradiology, with particular emphasis on large datasets and large-scale algorithm assessments, such as those used in imaging AI competition challenges. Numerous applications relevant to ischemic stroke, intracranial hemorrhage, brain tumors, demyelinating disease, and neurodegenerative/neurocognitive disorders were discussed. The potential applications of these methods to spinal fractures, scoliosis grading, head and neck oncology, and vascular imaging were also reviewed. The AI applications examined perform a variety of tasks, including localization, segmentation, longitudinal monitoring, diagnostic classification, and prognostication. While research on this topic is ongoing, several applications have been cleared for clinical use and have the potential to augment the accuracy or efficiency of neuroradiologists.

Integrative Imaging Informatics for Cancer Research: Workflow Automation for Neuro-Oncology (I3CR-WANO).

PURPOSE: Efforts to use growing volumes of clinical imaging data to generate tumor evaluations continue to require significant manual data wrangling, owing to data heterogeneity. Here, we propose an artificial intelligence-based solution for the aggregation and processing of multisequence neuro-oncology MRI data to extract quantitative tumor measurements. MATERIALS AND METHODS: Our end-to-end framework (1) classifies MRI sequences using an ensemble classifier, (2) preprocesses the data in a reproducible manner, (3) delineates tumor tissue subtypes using convolutional neural networks, and (4) extracts diverse radiomic features. Moreover, it is robust to missing sequences and adopts an expert-in-the-loop approach in which the segmentation results may be manually refined by radiologists. After the implementation of the framework in Docker containers, it was applied to two retrospective glioma data sets collected from the Washington University School of Medicine (WUSM; n = 384) and The University of Texas MD Anderson Cancer Center (MDA; n = 30), comprising preoperative MRI scans from patients with pathologically confirmed gliomas. RESULTS: The scan-type classifier yielded an accuracy of >99%, correctly identifying sequences from 380 of 384 and 30 of 30 sessions from the WUSM and MDA data sets, respectively. Segmentation performance was quantified using the Dice Similarity Coefficient between the predicted and expert-refined tumor masks. The mean Dice scores were 0.882 (±0.244) and 0.977 (±0.04) for whole-tumor segmentation for WUSM and MDA, respectively. CONCLUSION: This streamlined framework automatically curated, processed, and segmented raw MRI data of patients with varying grades of gliomas, enabling the curation of large-scale neuro-oncology data sets and demonstrating high potential for integration as an assistive tool in clinical practice.

Restoration and targeting of aberrant neurotransmitters in Parkinson's disease therapeutics.

Neurotransmitters are considered as a fundamental regulator in the process of neuronal growth, differentiation and survival. Parkinson's Disease (PD) occurs due to extensive damage of dopamine-producing neurons; this causes dopamine deficits in the midbrain, followed by the alternation of various other neurotransmitters (glutamate, GABA, serotonin, etc.). It has been observed that fluctuation of neurotransmission in the basal ganglia exhibits a great impact on the pathophysiology of PD. Dopamine replacement therapy, such as the use of L-DOPA, can increase the dopamine level, but it majorly ameliorates the motor symptoms and is also associated with long-term complications (for e.g., LID). While the non-dopaminergic system can efficiently target non-motor symptoms, for instance, the noradrenergic system regulates the synthesis of BDNF via the MAPK pathway, which is important in learning and memory. Herein, we briefly discuss the role of different neurotransmitters, implementation of neurotransmitter receptors in PD. We also illustrate the recent advances of neurotransmitter-based drugs, which are currently under in vivo and clinical studies. Reinstating normal neurotransmitter levels has been believed to be advantageous in the treatment of PD. Thus, there is an increasing demand for drugs that can specifically target the neurotransmission system and reinstate the normal levels of neurotransmitters, which might prevent or delay neurodegeneration in PD.

Power of compounding intravitreal Bevacizumab - Experience from a tertiary eye care hospital.

Background: Bevacizumab vials that are commercially available are fractionated into smaller quantities into the form of pre-filled syringes in a sterile and aseptic laboratory setting. Purpose: To share the long term experience of aliquoting of bevacizumab injections in a tertiary eye care center in India. Synopsis: Compounding of bevacizumab was found to be a cost-effective and sustainable practice that has benefited more patients with an affordable cost, while maintaining high levels of quality. Highlights: Compounding of bevacizumab, when done with aseptic precautions can be a safe and cost-effective practice, the benefits of which can be passed on to needful patients. Video Link: https://youtu.be/C5XOpKHFkew.

Molecular Imaging Assessment of Hormonally Sensitive Breast Cancer: An Appraisal of 2-[18F]-Fluoro-2-Deoxy-Glucose and Newer Non-2-[18F]-Fluoro-2-Deoxy-Glucose PET Tracers.

Hormone-sensitive breast cancer, which demonstrates hormone receptor positivity, accounts for approximately 75% of newly diagnosed breast cancer. 2-[18F]-Fluoro-2-deoxy-glucose is the nonspecific radiotracer of glucose metabolism as opposed to specific receptor based tracers like 16α-[18F]-fluoro-17ß-estradiol and [18F]-fluoro-furanyl-norprogesterone, which provide essential information about receptor status in the management of hormonally active malignancies. The complementary information provided by (a) 2-[18F]-fluoro-2-deoxy-glucose imaging for staging and prognostication along with (b) analyzing the hormonal receptor status with receptor-based PET imaging in breast cancer can optimize tumor characterization and influence patient management.

Central retinal vein occlusion post-COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) is known to cause thromboembolic episodes apart from acute respiratory distress syndrome (ARDS). With large vaccine drives all across the world, there are a few case reports on post-vaccine thrombotic events seen with the AZD1222, ChAdO × 1 vaccine. Here, we present two cases of central retinal vein occlusion presenting immediately after receiving the second dose of the Covishield vaccine. Although the causal relationship cannot be drawn, the ophthalmologist should be aware of this adverse reaction.

18F-Fluciclovine versus PSMA PET Imaging in Primary Tumor Detection during Initial Staging of High-Risk Prostate Cancer: A Systematic Review and Meta-Analysis.

Purpose Fluorine 18 (18F)-fluciclovine and prostate-specific membrane antigen (PSMA) tracers are commonly used for localizing biochemical recurrence of prostate cancer, but their accuracy in primary tumor detection in the initial staging of high-risk prostate cancer has not been established. Materials and Methods A systematic review was performed of the electronic databases for original studies published between 2012 and 2020. Included studies were those in which 18F-fluciclovine or PSMA PET was used for initial staging of patients with high-risk prostate cancer. The diagnostic performance data were collected for primary tumor with histopathologic results as reference standard. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for quality appraisal. A random-effects model was used to summarize the effect sizes and to evaluate the difference between two groups. Results Overall, 28 studies met the eligibility criteria, and 17 were included in the meta-analysis (18F-fluciclovine = 4, PSMA = 13). Of these 17 studies, 12 (70%) were judged to have high risk of bias in one of the evaluated domains, and nine studies were deemed to have applicability concerns. The pooled sensitivity, specificity, and diagnostic odds ratio for 18F-fluciclovine versus PSMA were 85% (95% CI: 73%, 92%) versus 84% (95% CI: 77%, 89%) (P = .78), 77% (95% CI: 60%, 88%) versus 83% (95% CI: 76%, 89%) (P = .40), and 18.88 (95% CI: 5.01, 71.20) versus 29.37 (95% CI: 13.35, 64.60) (P = .57), respectively, with no significant difference in diagnostic test accuracy. Conclusion 18F-fluciclovine and PSMA PET demonstrated no statistically significant difference in diagnostic accuracy in primary tumor detection during initial staging of high-risk prostate cancer. Keywords: PET, Prostate, Molecular Imaging-Cancer, Staging Supplemental material is available for this article. © RSNA, 2022.