Using Coronary Guide Catheters with the Sheath-in-sheath Technique to Retrieve a Micra™ Leadless Pacemaker.

As the prevalence of leadless pacemaker systems increases, identifying various methodologies for retrieval of these devices in certain instances becomes even more paramount. We describe a case demonstrating the utility of a coronary guide catheter as part of an improvised sheath-in-sheath technique for the challenging retrieval of a Micra™ leadless pacing system (Medtronic, Minneapolis, MN, USA).

Design, synthesis and neuroprotective evaluation of nitrogen heterocyclic and triazole derivatives of sarracinic acid.

Novel sarracinic acid derivatives bearing triazole or N-heterocyclic moiety were prepared via two separate reaction schemes. The triazoles and the N-heterocyclic derivatives were synthesised using standard click chemistry approach and amination of 2-bromoethyl ester of sarracinic acid respectively. All the synthesised derivatives were screened for in vitro neuroprotective activity against corticosterone induced impairment in neuroblastoma cell line SH-SY5Y. Two analogs SA-2 and SA-12 exhibited strong neuroprotective activity. The cell viability, after high dose corticosterone induced cell death, increased remarkably with the pre treatment of SA-2 and SA-12. The in vitro biological activity of SA-2 and SA-12 was verified through docking studies. The docking studies were in good agreement with the biological results. SA-2 and SA-12 showed strong binding affinities with the target protein having ΔGb = -8.88 and -7.52; inhibition constant (ki) = 3.08 nM and 30.9 nM respectively.

Keeping Healthy in Your Skin-Plants and Fungi Used by Indigenous Himalayan Communities to Treat Dermatological Ailments.

Dermatological ailments are a major health problem, especially when related to human immune deficiency syndrome and acquired immune deficiency. The goal of this study was to identify the medicinal plants used by the indigenous peoples of the Northwestern Himalayas to treat dermatological diseases. Several field trips were conducted in the spring and summer seasons of 2020-2021 to collect the plants of dermatological value and information about their use through open-ended semi-structured interviews (n = 53) and group discussions (n = 33). The current investigation found 64 ethnomedicinal plants belonging to 34 families commonly used to treat a variety of dermatological ailments. The main growth form was herbs (80%), followed by trees (8%) and ferns (6%). It was found that leaves (51%) were the most commonly used plant part, followed by roots and the whole plant. Wound healing was the most dominant application, with 18 plant species used, followed by skin burns cured by 11 plant species and skin boils by eight plant species. Out of the total (18%) of medicinal plants with cosmetic uses, i.e., roots of Jurinea dolomiaea, Rheum webbianum, and Rheum spiciforme were crushed into powder and mixed with turmeric, and the paste is applied topically for glowing skin. Among the various preparation methods, paste (38%) was the most common way of preparation, followed by poultice (29%) and infusion (9%). Between ethnic groups, the maximum homogeneity was between Gujjar and Bakarwal ethnic groups (23 species, 36%), followed by Gujjars and Kashmiri (14 species, 22%). Bakarwals and Gujjar people live in the same geographical location, and they graze their animals in pastures, practice extensive transhumance pastoralism, and pass through different ecological landscapes, thus having sufficient experiences with certain plants and retaining more knowledge. The species identified with the highest utilization based on the number of citations and use value included Ficus carica, Cichorium intybus, Euphorbia wallichii, Pinus wallichiana, Plantago major, Jurinea dolomiaea, and Artemisia absinthium. The findings of this study demonstrate that people who reside in the Northwestern Himalayas region still rely on medicinal plants.

Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset.

Acute postoperative pain is common, distressing and associated with increased morbidity. Targeted interventions can prevent its development. We aimed to develop and internally validate a predictive tool to pre-emptively identify patients at risk of severe pain following major surgery. We analysed data from the UK Peri-operative Quality Improvement Programme to develop and validate a logistic regression model to predict severe pain on the first postoperative day using pre-operative variables. Secondary analyses included the use of peri-operative variables. Data from 17,079 patients undergoing major surgery were included. Severe pain was reported by 3140 (18.4%) patients; this was more prevalent in females, patients with cancer or insulin-dependent diabetes, current smokers and in those taking baseline opioids. Our final model included 25 pre-operative predictors with an optimism-corrected c-statistic of 0.66 and good calibration (mean absolute error 0.005, p = 0.35). Decision-curve analysis suggested an optimal cut-off value of 20-30% predicted risk to identify high-risk individuals. Potentially modifiable risk factors included smoking status and patient-reported measures of psychological well-being. Non-modifiable factors included demographic and surgical factors. Discrimination was improved by the addition of intra-operative variables (likelihood ratio χ2 496.5, p < 0.001) but not by the addition of baseline opioid data. On internal validation, our pre-operative prediction model was well calibrated but discrimination was moderate. Performance was improved with the inclusion of peri-operative covariates suggesting pre-operative variables alone are not sufficient to adequately predict postoperative pain.

Phenology and Diversity of Weeds in the Agriculture and Horticulture Cropping Systems of Indian Western Himalayas: Understanding Implications for Agro-Ecosystems.

Weeds are a major threat to agriculture and horticulture cropping systems that reduce yield. Weeds have a better ability to compete for resources compared to the main crops of various agro-ecosystems and act as a major impediment in reducing overall yield. They often act as energy drains in the managed agroecosystems. We studied weed infestation for five different agro-ecosystems in the part of Indian Western Himalayas represented by paddy, maize, mustard, apple and vegetable orchards. Systematic random sampling was done to record flowering phenology and diversity of weeds during the assessment period 2015-2020. We recorded 59 weed species, taxonomically distributed among 50 genera in 24 families. The Asteraceae family has the most species (15% species), followed by Poaceae (14% species), and Brassicaceae (12% species). The Therophytes were the dominant life form followed by Hemicryptophytes. The majority of the weeds were shown to be at their most blooming in the summer (predominantly from June to July). The Shannon index based diversity of weeds ranged from 2.307-3.325 for the different agro-ecosystems. The highest number of weeds was in the horticulture systems (apple > vegetable) followed by agriculture fields (maize > paddy > mustard). Agriculture and horticulture cropping systems were distinguished using indicator species analysis, which was supported by high and significant indicator values for a number of species. Persicaria hydropiper, Cynodon dactylon, Poa annua, Stellaria media, and Rorippa palustris had the highest indicator value in agriculture cropping systems, while Trifolium repens, Phleum pratense, and Trifolium pratense had the highest indicator value in horticulture cropping systems. We found that eleven weed species were unique to apple gardens followed by nine in maize, four in vegetables, two in mustard and one in paddy fields. Spatial turnover (ßsim) and nestedness-resultant components (ßsne) of species dissimilarity revealed dissimilarity lower than 50% among the five cropping systems. The study is expected to assist in formulating an appropriate management strategy for the control of weed infestation in the study region.

Isolation and characterisation of pharmaceutically versatile molecules from Rumex dentatus and evaluation of their cytotoxic activity against human cancer cell lines.

The disclosed study reveals isolation, characterization and anticancer evaluation of Rumex dentatus. The extracts and isolated compounds were used for cytotoxic activity against (lung (A549), pancreatic (MIAPaCa), colon (HCT-116), breast (MDA-MB-231) and breast (MDA-MB-468) cell lines. The extracts were screened for cytotoxicity using MTT colorimetric assay. Out of all extracts, methanolic (30) %: chloroform fraction (TAW6) with 75.01% inhibition at a concentration 100 µg/mL was observed. The selected extracts were further processed for column chromatography and led to isolation of seven compounds (A to G). The structural determination of isolated compounds was carried out using 1HNMR, 13CNMR, IR and HRMS. All the isolates were tested for cytotoxic activity and compound B was found most active with IC50 values 11.29 µg against HCT-116 (Colon). The compound B was then used for detailed study via transwell invasion assay and wound healing assay. Thus the significant anticancer activity particularly against colon cancerous cell lines recommends that the (Rumex dentatus) could act as a potential drug candidate for cancer, more particularly for colon cancer.

TFA-mediated stereoselective aza-Michael addition for the synthesis of 3ß-arylamine derivatives of withaferin A and evaluation of their anticancer potential.

A simple and efficient protocol for the aza-Michael addition of various aromatic anilines to ring A of withaferin A has been developed. Stereoselectivity, functional group tolerance, broad substrate scope, short reaction time and moderate to high yield are the merits of the protocol. One of the synthesized compounds 11 shows an IC 50 value of 3.8 µM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231.

CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion.

To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.

Attitudinal behaviour of agriculturalists towards pesticide use in Pir Panjal Range of Kashmir Himalayas.

BACKGROUND: Attainment of safety during pesticide spraying relies on the farmer's knowledge of pesticide use, attitude and sense of safety. However, such investigations are insufficient in the current study area. METHODS: The study is based on a primary survey of 384 orchardists about the myriad of aspects affecting the use of pesticides and their subsequent effects. RESULTS: The study revealed that knowledge, attitude, and perception had a weighted average index (WAI) and a standard deviation (SD) of 2.85 ± 1.17, 3.55 ± 1.34, and 3.81 ± 0.98 correspondingly. The findings reflect the farmers have a low to moderate level of knowledge, a moderate attitude toward pesticides, and a favourable perception on their utilization. Thus, for farmer personal protective equipment (PPE) use, it scored 2.77 ± 0.90 on the WAI scale, indicating that most farmers use PPEs 'rarely to occasionally' and that none use full protective gear. Furthermore, attitude and PPE usage exhibited a negative relationship with age, as younger people use PPE more than older ones. The findings were consistent for both farming experience and PPE usage. Moreover, there exists a positive association between age with perception and farming experience, knowledge with perception and PPE use, and attitude with perception. CONCLUSIONS: The coefficient of determination (R2) shows that 67.2% of the variability in farmers' PPE use was attributed to factors including knowledge, attitude, perception, and education. A favorable behavioral shift in pesticide usage may be achieved by enhancing farmers' knowledge, attitudes and perceptions, and adequate PPE usage.

High incidences of chromosomal aberrations and Y chromosome micro-deletions as prominent causes for recurrent pregnancy losses in highly ethnic and consanguineous population.

PURPOSE: Recurrent Miscarriages (RM) commonly complicates the reproductive outcome where prominently chromosomal aberrations and molecular factors lead to recurrent miscarriages. We investigated couples with RM for cytogenetic abnormalities and Y chromosome microdeletions in males along with detection of aneuploidies de novo in the product of conception from a highly ethnic consanguineous population (Kashmir, North India) . STUDY DESIGN: Chromosomal analysis was done by Karyotyping on peripheral blood lymphocyte cultures and analyzed by Cytovision software Version 3.9. Microdeletion in Y chromosome was performed by STS-PCR and QF-PCR was used to detect aneuploidy in the product of conception. RESULTS: Of the 380 samples (190 couples) screened for cytogenetic analysis, 50 (13.1%) chromosomal aberrations were detected in both couples. Numerical aberrations were detected in 16.0%, inversions 22%, duplications 16.0% and translocations were found in 26.0% with three unique reciprocal translocations in males. The couples bonded consanguineously had 32% chromosomal changes with a significant difference in chromosomal inversions (37.5% vs. 14.7%) and translocations (37.5% vs. 20.6%) for consanguineous and non-consanguineous group, respectively (p < 0.05). Further, translocations and inversions (44.5% and 33.3%) were significantly implicated in couples with a positive family history of RM (p < 0.05). Y chromosome deletions were found in 2.1% cases of males. CONCLUSION: We conclude 15.2% couples affected either by chromosomal or Y chromosome deletions contribute hugely in the diagnosis and management of repeated pregnancy losses. It is recommended that couples that belong to consanguineous and multigenerational group of RM should be considered for cytogenetic and molecular testing after two abortions for successful pregnancy outcomes and management of RM.

Safety of the transradial approach to carotid stenting.

BACKGROUND: The multicenter prospective CREST-2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS. OBJECTIVE: To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach. METHODS: Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access-related complications. Comparisons were made using propensity-score matched logistic regression. RESULTS: The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access-related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42). CONCLUSION: We found no significant differences in rates of major access-related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.

Proton Pump Inhibitor "Lansoprazole" Inhibits Locus Coeruleus's Neuronal Activity and Increases Rapid Eye Movement Sleep.

Alteration of the bodily CO2 concentration and proton pump activity affects the sleep architecture. The brainstem locus coeruleus (LC) area plays an essential role in rapid eye movement (REM) sleep generation and chemoregulation. Previously, we reported that lansoprazole injections (intraperitoneal) increased REM sleep in the rats. However, it is not known if proton pumps in the LC influence REM sleep. Here, we studied the effects of lansoprazole in the LC on the neuronal activity and REM sleep expression. Male Wistar rats (250-300 g) were surgically prepared for sleep recording and drug microinjections into the LC. We determined the localization of proton pumps and expression levels of cFOS in the LC neurons immunohistochemically. Sleep-wake was recorded before and after the microinjections of drugs/vehicles. Our results demonstrate (i) the presence of proton pumps in the LC neurons, (ii) that the microinjection of lansoprazole into the LC reduced the number of cFOS+ve-TH+ve double-labeled neurons in the LC by 52.6% (p < 0.001) compared to the vehicle and (iii) that low and high doses of lansoprazole significantly increased REM sleep by 32% (p < 0.001) and 60% (p < 0.001), respectively, compared to the vehicle. Our results suggest that the proton pumps modulate the LC's noradrenergic (NE-ergic) neuronal activity and REM sleep. The increased amount of REM sleep can be attributed to the inhibition of the LC NE-ergic activity. Further, the REM sleep amount increased after the lansoprazole microinjections into the LC with a significant increase in the REM sleep episode numbers. Overall, our results suggest that proton pumps in the LC may be involved in REM sleep generation.

Phylogeny and Optimization of Trichoderma harzianum for Chitinase Production: Evaluation of Their Antifungal Behaviour against the Prominent Soil Borne Phyto-Pathogens of Temperate India.

Trichoderma is the most commonly used fungal biocontrol agent throughout the world. In the present study, various Trichoderma isolates were isolated from different vegetable fields. In the isolated microflora, the colony edges varied from wavy to smooth. The mycelial forms were predominantly floccose with hyaline color and conidiophores among all the strains were highly branched. Based on morphological attributes, all the isolates were identified as Trichoderma harzianum. The molecular identification using multilocus sequencing ITS, rpb2 and tef1α, genes further confirmed the morphological identification. The average chitinase activity varied from 1.13 units/mL to 3.38 units/mL among the various isolates, which increased linearly with temperature from 15 to 30 °C. There was an amplified production in the chitinase production in the presence of Mg+ and Ca2+ and Na+ metal ions, but the presence of certain ions was found to cause the down-regulated chitinase activity, i.e., Zn2+, Hg2+, Fe2+, Ag+ and K+. All the chitinase producing Trichoderma isolates inhibited the growth of tested pathogens viz., Dematophora necatrix, Fusarium solani, Fusarium oxysporum and Pythium aphanidermatum at 25% culture-free filtrate concentration under in vitro conditions. Also, under in vivo conditions, the lowest wilt incidence and highest disease control on Fusarium oxysporum was observed in isolate BT4 with mean wilt incidence and disease control of 21% and 48%, respectively. The Trichoderma harzianum identified in this study will be further used in formulation development for the management of diseases under field conditions.

Neuroprotective activity of natural products isolated from Senecio graciliflorus DC against corticosterone-induced impairment in SH-SY5Y cells.

Senecio graciliflorus DC root extract was studied for secondary metabolite composition following the bioactivity-guided isolation technique. The ethyl acetate extract of Senecio graciliflorus root yielded nine chemical constituents: 3,4-di-tert-butyl toluene, stigmasterol, ß-sitosterol, 2ß-(angeloyloxy)furanoeremophilane, gallic acid, 2ß-{[(Z)-2-hydroxymethylbut-2-enoyl]oxy}furanoeremophilane, 1-hydroxypentan-2-yl-4-methylbenzoate, sarcinic acid, and sitosterol 3-O-ß-D-glucopyranoside. The structures of the chemical constituents were elucidated on the basis of spectral data analysis in the light of literature. All the compounds are being reported for the first time from this plant. The isolated constituents were screened for neuroprotective effects against corticosterone-induced impairment in neuroblastoma cell lines (SH-SY5S cells). The viability of SH-SY5S cells was determined using MTT assay. Among various isolated compounds, three natural products (sarcinic acid, gallic acid, and ß-sitosterol) displayed robust neurotropic activity. The compounds increased neuronal cell survival in differentiated neuroblastoma cells (SH-SY5Y) from high-dose corticosterone (400 µM)-induced cell death. All the three constituents showed maximum AKT/ERK pathway activation at 20 µM concentration. The studies are aimed to explore small molecules for treating neurodegeneration underlying various neurological disorders to restore neuronal cell plasticity.

The Incidence of Acute Pulmonary Embolism with COVID-19 Pneumonia in Saudi Arabia: A Retrospective Single-Center Study.

Acute pulmonary embolism (APE) is a common and prognostically significant complication of COVID-19 infection. We investigated the clinical characteristics and chest CT findings of COVID-19 positive patients complicated with APE. A retrospective, record-based, case-series study was performed examining 483 patients admitted to King Saud Medical City during the pandemic, from April 2020 to June 2020. Of these, 92 patients who underwent chest CT scans were included in the final analysis. The incidence of APE, clinical presentations, radiological patterns, and patient outcomes were assessed and compared against those for patients without PE. The incidence of APE was 22% [95% confidence interval (95% CI): 19%-39%], detected by chest CT. Men constituted 85.0% of patients, with a mean age of 48.9 ± 16.7 years. For most patients with APE, risk factors for thromboembolism were established but did not differ significantly from those without PE. The mean D-dimer level of 9.1 (range 7.0-10.2) was significantly higher among patients diagnosed with APE (OR: 1.021; 95% CI: 1.012-1.028; P = 0.001) compared with that in patients without PE. Moreover, the mean levels of lactate dehydrogenase (LDH, 628.5; range: 494.0-928.3; OR: 1.002; 95% CI: 1.000-1.003; P = 0.02), C-reactive protein (CRP; 158.5; range: 105.3-204.5; OR: 1.025; 95% CI: 1.015-1.035; P = 0.001), and cardiac troponin (3.5; range; 2.6-3.8; OR: 1.016; 95% CI: 0.971-1.067; P = 0.01) were also significantly higher in patients with APE than those in patients with PE. The chest CT presentations of APE included massive, segmental, and sub-segmental APE. The need for Intensive Care Unit admission was higher among patients diagnosed with APE, who presented a fatality rate of 10%.. Our study pointed to the incidence and predictors of APE in COVID-19 patients. High levels of D-dimer, CRP, cardiac troponin, and LDH should alert the clinician to the possibility of APE in COVID-19 patients..

Locus Coeruleus Acid-Sensing Ion Channels Modulate Sleep-Wakefulness and State Transition from NREM to REM Sleep in the Rat.

The locus coeruleus (LC) is one of the essential chemoregulatory and sleep-wake (S-W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement (REM) sleep. LC neurons are also involved in CO2-dependent modulation of the respiratory drive. Acid-sensing ion channels (ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM (NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S-W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S-W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized. Microinjections of amiloride (an ASIC blocker) and APETx2 (a blocker of ASIC-2 and -3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S-W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.

Locus Coeruleus Acid-Sensing Ion Channels Modulate Sleep–Wakefulness and State Transition from NREM to REM Sleep in the Rat / 神经科学通报·英文版

The locus coeruleus (LC) is one of the essential chemoregulatory and sleep–wake (S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement (REM) sleep. LC neurons are also involved in CO