Radiological presentation of transient perivascular inflammation of carotid artery syndrome in a patient with myelodysplasia.

Transient Perivascular Inflammation of Carotid artery syndrome (TIPIC syndrome) is a non-specific inflammatory thickening of the carotid artery. The exact etiology of this syndrome is poorly understood. We will describe the radiological findings of a rare case of TIPIC syndrome in a patient with myelodysplastic syndrome and discuss the potential pathophysiological mechanisms.

Network pharmacology on mechanistic role of Thymus linearis Benth. against gastrointestinal and neurological diseases.

BACKGROUND: Thymus linearis Benth. (TL) is native to the Himalayas and has been used traditionally to cure various diseases. Thymus is a well-known aromatic perennial herb commonly known as Van ajwain or Himalayan Thyme. The main components of the TL essential oil are thymol, terpinene, and p-cymene. There are many biological properties that TL has been reported to exhibit, including antioxidant, analgesic, anti-inflammatory, antipyretic, antibacterial, anticancerogenic, and neuroprotective effects. PURPOSE: In this study, the network pharmacology and molecular docking were used to explore the potential compounds of TL and their interaction mechanism toward gastrointestinal complications and neurological diseases. METHODS: Network pharmacology was used to analyze the active compounds and protein targets of TL on gastrointestinal and neurological related diseases. Protein-protein interaction and Kyoto Encyclopaedia of Genes and Genomes analysis were used to enrich and evaluate key pathways of target proteins. To ensure the reliability of the network pharmacology prediction estimates, molecular docking was used to confirm the relationships between the core components and targets of TL. RESULT: 77 physiologically active compounds and their 717 predicted protein targets with high association to the neuroactive ligand-receptor interaction pathway were derived from TL. Beta-citronellol, piperitol, p-cymen-8-ol, and alpha-humulene were found to have a role in gastrointestinal diseases associated with neurological diseases. These compounds showed significant levels of multitargeting cluster regulatory activity. The molecular docking results showed regulatory activity of highlighted multi-targeting compounds and the highest docking energy was reported in piperitol. CONCLUSION: The study shows that Thymus linearis Benth., a medicinal plant with traditional use, possesses valuable biologically active compounds. It emphasizes the potential of Thymus in treating gastrointestinal and neurological diseases by regulating oxidative stress pathways. This research opens up possibilities for discovering antioxidant molecules for future drug development. It is an interesting study with promising implications for further research.

Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective.

The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.

Quantitative assessment of antioxidant potential of selected homeopathic preparations in clinical practice.

OBJECTIVES: Antioxidant property like radical scavenging is a primary target to elucidate the efficacy mechanism of a drug against diseases linked to oxidative stress such as cancer, metabolic disorders, rheumatoid arthritis, etc. In alternative therapies, homeopathy is one of the preferred choices by patients and clinicians due to its potential to cure chronic and complex illnesses. However, the efficacy of homeopathic preparations at high diluted potencies attracts rational criticism due to insufficient scientific knowledge supporting the mechanism of action. Therefore, an attempt was made to estimate the total phenolic content (TPC) and radical scavenging activity of clinically prescribed homeopathic drugs. METHODS: With gallic acid as a reference control, mother tinctures (MTs) and different potencies of Eucalyptus globulus (EG), Syzygium jambolanum (SJ), Ruta graveolens (RG), and Thuja occidentalis (TO) were used to perform Folin-Ciocalteu test, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. RESULTS: The results showed TPC of MTs equivalent to µg/mL of gallic acid viz; EG (4,872.5 ± 133.2), SJ (8,840.5 ± 14.8), RG (985.6 ± 39.1), and TO (341.5 ± 19.5) with significant ABTS and DPPH radical scavenging potential. Whereas 30C and 200C potencies of each homeopathic drug showed undetectable phenolic content and insignificant radical scavenging potential compared to vehicle control, i.e., alcohol 90% (2.0 ± 1.5). CONCLUSIONS: The reported efficacy of 30C and 200C potencies of homeopathic medicines against oxidative stress-related illnesses might be due to mechanisms other than radical scavenging. Furthermore, the assays studied can be helpful in drug standardization and quality control of MTs that are used as starting material in homeopathic preparations.

Delayed collapse of flow diverter due to acute severe vasospasm: another concern for flow diversion in ruptured aneurysms.

In vivo morphological change of flow diverter stents (FDS) is a known phenomenon and can be seen secondary to various device- and vasculature-related factors such as improper sizing of the device, twisting of the device in tortuous anatomy, insufficient proximal landing zone, and insufficient chronic resistive force of the stent, etc. However, we have encountered a case where severe vasospasm due to aneurysmal subarachnoid hemorrhage led to the collapse of the proximal end of the FDS. Development of vasospasm and consequent possible failure of the device should be taken into consideration when planning flow diversion in ruptured aneurysms.

Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation.

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

Assessment of indicators on drinking water, sanitation, and hygiene (WASH) practices from rural schools of Kathua.

Introduction: Safe and adequate water supply and sanitation in schools are prerequisites for right to basic education for school children. The provision of water, sanitation, and hygiene (WASH) facilities has been linked to the achievement of Sustainable Development Goals. Objective: The objective of this study is to assess the indicators of WASH in schools falling under the Rural Health and Training Centre (RHTC), Budhi, GMC Kathua. Material and Methodology: A cross-sectional study was conducted during a period of two months in the month of September 2019 to October 2019. It was done in the rural area under CHC Nagri Parole Kathua. The total number of schools under CHC is 981. Interview of the head of the school was done using world health organization (WHO) and united nations international children's emergency fund (UNICEF) Standardized Questionnaire for WASH Practices. The Questionnaire includes core and expanded questions on drinking water, sanitation, and hygiene practices. Data were entered in Microsoft Excel and descriptive statistics was analyzed in the form of number and percentages. Results: Out of total 139 schools, 57.72% schools had basic drinking water facilities. Only 29.11% schools have basic hand-washing facilities with soap and water; 81.29% of the schools have improved toilets. Conclusion: Political will and financing and effective delivery of interventions will be required to ensure universal access to WASH in schools.

Unusual case of coexisting large intramyometrial anterior uterine wall leiomyoma with term pregnancy.

Leiomyomas are the most common benign smooth muscle tumors of the uterus. The incidence during pregnancy ranges between 1.6 to 10%. The management of fibroids encountered during caesarean section poses a therapeutic dilemma. We present a case of giant anterior wall leiomyoma complicating term pregnancy which posed a great surgical challenge. We didn't go for myomectomy in the same setting because the patient was primigravida and leiomyoma occupied complete anterior wall of the uterus, an attempt of myomectomy could result in profuse uncontrollable bleeding.

Multi-scale mechanism of antiviral drug-alike phytoligands from Ayurveda in managing COVID-19 and associated metabolic comorbidities: insights from network pharmacology.

The novel coronavirus disease (COVID-19), which emerged in Wuhan, China, is continuously spreading worldwide, creating a huge burden on public health and economy. Ayurveda, the oldest healing schema of Traditional Indian Medicinal (TIM) system, is considered as a promising CAM therapy to combat various diseases/ disorders. To explore the regulatory mechanisms of 3038 Ayurvedic herbs (AHs) against SARS-CoV-2, in this study, multi-targeting and synergistic actions of constituent 34,472 phytochemicals (APCs) are investigated using a comprehensive approach comprising of network pharmacology and molecular docking. Immunomodulatory prospects of antiviral drug-alike potentially effective phytochemicals (PEPs) are presented as a special case study, highlighting the importance of 6 AHs in eliciting the antiviral immunity. By evaluating binding affinity of 292 PEPs against 24 SARS-CoV-2 proteins, we develop and analyze a high-confidence "bi-regulatory network" of 115 PEPs having ability to regulate protein targets in both virus and its host human system. Furthermore, mechanistic actions of PEPs against cardiovascular complications, diabetes mellitus and hypertension are also investigated to address the regulatory potential of AHs in dealing with COVID-19-associated metabolic comorbidities. The study further reports 12 PEPs as promising source of COVID-19 comorbidity regulators.

High-resolution intracranial vessel wall imaging in cerebral viral infections evaluations.

PURPOSE: Vascular complications can be seen in various viral CNS infections. Variable neuro-imaging findings have been described in the literature elucidating the parenchymal changes with vascular involvement. Vessel wall imaging (VWI) can help to detect these vascular involvements. We aimed to describe the role and usefulness of VWI in the evaluation of various viral CNS infections. METHODS: In this prospective study, we included 15 cases of various diagnosed viral CNS infections (varicella, HIV encephalopathy, HSV encephalitis, Japanese encephalitis, dengue, COVID-19). VWI and time-of-flight MR angiography (TOF MRA) were included in imaging protocol. All cases were evaluated for the presence of cerebral parenchymal changes, vascular enhancement, and vascular stenosis. RESULTS: We found infarctions in all 5 cases of varicella, 1 case of HIV encephalopathy, and 1 case of COVID-19 encephalopathy. All these cases also showed vascular enhancement and stenosis on VWI. The rest of the cases, including 1 case of HIV encephalopathy, 3 cases of herpes encephalitis, 2 cases of dengue, and 2 cases of Japanese encephalitis did not have any vascular complication, and also did not show vascular enhancement or stenosis. CONCLUSION: VWI can be useful in the detection of vascular involvement in various viral infections of CNS which show a relatively higher cerebrovascular complication rate like varicella, HIV encephalopathy, and COVID-19. However, VWI may not be useful in the routine evaluation of other viral infections like herpes, dengue, and Japanese encephalitis, which have a very low rate of cerebrovascular complication rate.

MR vessel wall imaging in cerebral bacterial and fungal infections.

PURPOSE: Central nervous system (CNS) bacterial and fungal infections can cause secondary vasculitis which worsens the prognosis due to development of complications like infarctions or hemorrhages. In this prospective study, we aim to study intracranial vessel wall imaging findings in bacterial and fungal infections. METHODS: We included 12 cases of nontubercular bacterial and fungal CNS infections each, in whom definitive microbiological diagnosis could be made. High-resolution vessel wall imaging (VWI) and time of flight MR angiography (TOF MRA) were incorporated in the routine imaging protocol. All cases were evaluated for the presence of vascular enhancement, pattern of enhancement, and stenosis on VWI. Statistical analysis was done to evaluate association between findings of vessel wall imaging and infarctions. RESULTS: We found infarctions in 5 out of 12 cases (41.7%) of the bacterial group and 7 out of 12 cases (58.3%) of the fungal group. Vessel wall enhancement was seen in 5 cases (41.7%) of the bacterial group and 9 cases (75%) of the fungal group. There was a significant association between infarctions and vessel wall enhancement in the fungal group. However, pattern of enhancement or stenosis on VWI was not significantly associated with presence of infarction. VWI detected more cases of vascular involvement than TOF MRA. CONCLUSION: Secondary infectious vasculitis in bacterial and fungal infections can be detected by VWI, which can play an important role in better patient management as detection of vascular involvement can prompt early treatment to prevent complications like infarctions or hemorrhages.

Mechanical clot dissolution technique for surgical clip-related occlusions: An emergent triple-step approach.

Cerebral ischemia following clipping of cerebral aneurysms constitutes major cause of morbidity and mortality. Clip-related injury to vessel, postoperative clip rotation, prolonged temporary occlusion, intraoperative rupture, and vasospasm are some etiological factors compromising forward flow in parent or branch vessel. On suspicion of compromised forward flow, immediate intraoperative evaluation is done to detect the cause of vascular compromise and further management is done by microsurgical or endovascular means. We describe a case of ruptured distal anterior cerebral artery (ACA) aneurysm complicated by occlusion of ACA after surgical clipping. The patient was managed by endovascular means by combined technique of intra-arterial nimodipine, antiplatelet infusion, and mechanical clot disruption using J-tip microwire.

Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals.

Amide-based chelators DTPAm, EGTAm and ampam were synthesized to investigate which chelator most ideally coordinates [nat/203Pb]Pb2+ ions for potential radiopharmaceutical applications. 1H NMR spectroscopy was used to study each metal-ligand complex in the solution state. The 1H NMR spectrum of [Pb(DTPAm)]2+ revealed minimal isomerization and fluxional behaviour compared to [Pb(EGTAm)]2+ and [Pb(ampam)]2+, both of which showed fewer spectral changes indicative of less static behaviour. The solid-state coordination properties of each complex were also examined from single crystal structures that were studied by X-ray diffraction (XRD). In the solid-state, octadentate DTPAm coordinated Pb2+ to form an eight-coordinate hemidirected complex; octadentate EGTAm coordinated Pb2+ forming a ten-coordinate holodirected complex with a bidentate NO3- ion also coordinated to the metal centre; decadentate ampam completely encapsulated the Pb2+ ion to form a ten-coordinate holodirected complex with a C2 axis of symmetry. Potentiometric titrations were carried out to assess the thermodynamic stability of each metal-ligand complex. The pM values obtained for [Pb(DTPAm)]2+, [Pb(EGTAm)]2+ and [Pb(ampam)]2+ were 9.7, 7.2 and 10.2, respectively. The affinity of each chelator for Pb2+ ions was tested by [203Pb]Pb2+ radiolabeling studies to evaluate their prospects as chelators for [203/212Pb]Pb2+-based radiopharmaceuticals. DTPAm radiolabeled [203Pb]Pb2+ ions achieving molar activities as high as 3.5 MBq µmol-1 within 15 minutes, at 25 °C, whereas EGTAm and ampam produced lower molar activities of 0.25 MBq µmol-1 within 30 minutes, at 37 °C. EGTAm and ampam were therefore deemed unsuitable for [203/212Pb]Pb2+-based radiopharmaceutical applications, while DTPAm warrants further studies.

H4HBEDpa: Octadentate Chelate after A. E. Martell.

H4HBEDpa, a new octadentate chelator inspired by the 1960s ligand HBED of Arthur E. Martell, has been investigated for a selection of trivalent metal ions useful in diagnostic and therapeutic applications (Sc3+, Fe3+, Ga3+, In3+, and Lu3+). Complex formation equilibria were thoroughly investigated using combined potentiometric and UV-vis spectrophotometric titrations which revealed effective chelation and high metal-sequestering capacity, in particular for Fe3+, log KFeL = 36.62, [Fe(HBEDpa)]-. X-ray diffraction study of single crystals revealed that the ligand is preorganized and forms hexa-coordinated complexes with Fe3+ and Ga3+ at acidic pH. Density functional theory (DFT) calculations were applied to probe the geometries and energies of all the possible conformers of [M(HBEDpa)]- (M = Sc3+, Fe3+, Ga3+, In3+, and Lu3+). DFT calculations confirmed the experimental findings, indicating that [Fe(HBEDpa)]- is bound tightly in an asymmetric pattern as compared to the symmetrically bound and more open [Ga(HBEDpa)]-, prone to hydrolysis at higher pH. DFT calculations also showed that a large metal ion such as Lu3+ fully coordinates with HBEDpa4-, forming a binary octadentate complex in its lowest-energy form. Smaller metal ions form six or seven coordinate complexes with HBEDpa4-.

Molecular docking, DFT analysis, and dynamics simulation of natural bioactive compounds targeting ACE2 and TMPRSS2 dual binding sites of spike protein of SARS CoV-2.

The scientific community is continuously working to discover drug candidates against potential targets of SARS-CoV-2, but effective treatment has not been discovered yet. The virus enters the host cell through molecular interaction with its enzymatic receptors i.e., ACE2 and TMPRSS2, which, if, synergistically blocked can lead to the development of novel drug candidates. In this study, 1503 natural bioactive compounds were screened by HTVS, followed by SP and XP docking using Schrodinger Maestro software. Bio-0357 (protozide) and Bio-597 (chrysin) were selected for dynamics simulation based on synergistic binding affinity on S1 (docking score -9.642 and -8.78 kcal/mol) and S2 domains (-5.83 and -5.3 kcal/mol), and the RMSD, RMSF and Rg analyses showed stable interaction. The DFT analysis showed that the adsorption of protozide/chrysin, the band gap of protozide/chrysin-F/G reduced significantly. From SERS, results, it can be concluded that QDs nanocluster will act as a sensor for the detection of drugs. The docking study showed Bio-0357 and Bio-0597 bind to both S1 and S2 domains through stable molecular interactions, which can lead to the discovery of new drug candidates to prevent the entry of SARS-CoV-2. This in-silico study may be helpful to researchers for further in vitro experimental validation and development of new therapy for COVID-19.

Secretory carcinoma of the breast, commonly exhibits the features of low grade, triple negative breast carcinoma- A Case report with updated review of literature.

Secretory carcinoma of the breast (SBC) is a rare breast neoplasm. Most of the patients present at an early stage with a relatively indolent clinical course. Lymph node and distant metastasis are also very infrequent. The histomorphological features of the secretory breast carcinoma are quite characteristic. Predominantly three histological patterns, solid, microcystic, and tubular, have been noted with copious amounts of intra and extracellular secretory material. Most commonly, no positivity for estrogen receptor (ER), progesterone receptor (PR) and ERBB2(HER2/neu) is observed in SBCs. As SBC can occasionally be hormone receptor-positive, they should not be categorized in the triple-negative breast carcinoma (TNBC) group in general. A very characteristic genetic translocation t (12;15) has been noted in this rare tumor, resulting in a fusion between ETV6 and NTRK3 proteins. We present a case of a 60-year-old lady who presented with right breast lump of 1-month duration and was managed by lumpectomy and sentinel lymph node dissection. Axillary dissection was not performed because the sentinel lymph node biopsy was negative. Postoperative radiotherapy was given to the right breast with a boost to the tumor bed. No adjuvant chemotherapy was given No recurrence has been noted even after a year of the completion of treatment.

H2pyhox - Octadentate Bis(pyridyloxine).

A new versatile chelating ligand for intermediate size and softness radiometals [64Cu]Cu2+ and [111In]In3+, H2pyhox, was synthesized by introducing pyridine as a new donor moiety to complement 8-hydroxyquinoline on an ethylenediamine backbone. The combination of pyridine and oxine as donor sets was explored through structural analysis, and crystals of the three metal complexes with Cu2+, La3+, and In3+ demonstrate how the ligand adapts to accommodate metal ions of different sizes and charge. Exhaustive in-batch UV solution studies characterized the protonation constants of the free ligand as well as the formation constants of the metal complexes with Cu2+, In3+, and La3+. Preliminary concentration-dependent radiolabeling studies with [111In]In3+ and [64Cu]Cu2+ show the robustness of H2pyhox to successfully coordinate both radiometals under mild conditions (<15 min, room temperature, pH 6). H2pyhox is the first oxinate ligand to successfully radiolabel [225Ac]Ac3+, albeit only at high concentrations (0.1-1 mM) with gentle heating to 37 °C. Whole serum, protein, and ligand challenge assays further demonstrate the kinetic inertness of the [111In]In3+ and [64Cu]Cu2+ radiometal-ligand complexes, confirming H2pyhox to be a promising versatile radiopharmaceutical chelator.

Pattern of Tobacco consumption among urban slum population in Jammu region: A cross-sectional study.

INTRODUCTION: Consumption of tobacco leads to a myriad of ill effects among the smokers as well as those in their proximity. The study related to tobacco consumption was conducted among individuals over 15 years of age, residing in urban slums. OBJECTIVE: To assess the pattern of tobacco consumption in urban slum population, using WHO standardized questionnaire which is Global Tobacco Surveillance System (GTSS); questions related to tobacco from the surveys, which are the subset of GATS 2nd Edition key questions. MATERIALS AND METHODS: The present study was observational cross-sectional in nature which was conducted over a period of 6 months i.e., from September 2019 to February 2020 in urban slums of Trikuta Nagar, urban health training centre which is a field practice area of Postgraduate Department of Community Medicine, GMC Jammu. The information about the tobacco consumption was gathered by interview sessions after taking consent from all the participants. Totally, 718 individuals were met, out of which, 539 were over 15 years of age and 510 agreed to participate in the study. RESULTS: 36% (maximum) belonged to 36-45 year age group and lowest (3%) among individuals >66 years. 48% prevalence of active smoking; maximum indulgence (53%) observed in 36-55 year group. Highest exposure to passive smoking seen in 56-65 year group (75%). 45% prevalence of smokeless tobacco consumption, highest in 56-65 year group (72%), lowest in 15-25 year age group (17%). CONCLUSION: Regular conducting of IEC activities for generating awareness with the strict implementation of tobacco control measures by the government needs to be carried out as urban slum population is a vulnerable group and most susceptible to the vicious cycle of disease and poverty.