In-vitro Analysis of Different Trichoderma spp. Against Fusarium Rhizome Rot of Ginger (Zingiber officinale Roscoe)

This study evaluated the effectiveness of four isolates of Trichoderma spp. obtained from various plant protection divisions and commercial products for the biocontrol of Fusarium rhizome rot of ginger (Zingiber officinale Roscoe). Experiments were designed in a completely randomized design (CRD) with five treatments and ten replications. The National Agriculture Research Council (NARC) isolates of Trichoderma spp. were multiplied through direct inoculation on PDA media. Meanwhile, the commercial products of T. harzianum (TRICHO-HR) and T. viride (Biocide Trivi) were prepared as spore suspension. The dual culture technique was used to evaluate the interaction between Trichoderma spp. and Fusarium pathogen. The radial diameter of both Trichoderma and Fusarium was measured every 24 h for 7 days. The experiments in dual cultures demonstrated that various Trichoderma isolates and commercial products significantly inhibited Fusarium mycelial growth. Among the isolates tested, T1-NARC showed the highest efficacy at 57.91% growth inhibition, followed by T2-RPPL (52.50%) and T4-Biocide Trivi (40.98%). However, T3-TRICHO HR displayed lower performance with an inhibition rate of 24.75%. These findings offer valuable insights for the use of Trichoderma spp. as biocontrol agents in ginger cultivation, contributing to improved disease control and enhanced crop health. The observed differences in performance could be attributed to the genetic variations among the isolates

Analysis of profitability and effect of factors of production in paddy cultivation in Morang, Nepal

Paddy is one of the principal food crops in Nepal. Most of the Nepalese farmers are currently utilizing inputs in an unscientific manner due to lack of information about the most efficient use of resources, resulting in low yield and efficiency. This study was conducted for the analysis of profitability and effect of factors of production in paddy cultivation in Morang district of Nepal. A sample of 120 paddy growers were selected from 4350 paddy farmers registered in PMAMP, Rice zone, Morang using Simple Random Sampling Technique. Primary and secondary data were collected using face-to-face interview schedule and reviewing different articles and journals. Data collected were entered, tabulated and analyzed using MS-Excel and Statistical Package for the Social Sciences (SPSS). Descriptive statistics such as mean, frequency, and percentage were used to study farmer's socio-economic characteristics while inferential statistics was used in analysing the influence of production factors using Cobb-Douglas production function. The total cost of paddy production, gross income, and net income per hectare was found to be Rs.70,082.65, Rs.1,11,171.23 and Rs.41,088.57 respectively whereas productivity of paddy was found to be 4.32 MT/ha. The BC ratio 1.66 indicates that it is a profitable enterprise. The labor cost contributed most to the variable cost with 45.48%. Moreover, independent variables such as seed, labor and mechanical power contributed significantly to the yield. Therefore, paddy farming should be encouraged among farmers by increasing the availability and affordability of inputs while also improving food security

Efficacy of chemical fungicides against the fusarium rhizome rot of Ginger (Zingiber officinale)

The present investigation was conducted to analyze efficacy of different commercially available fungicides against the Fusarium spp. causing rhizome rot of ginger adopting poison food technique. The experiment was carried out in a completely randomized design (CRD) with 8 treatment and 3 replications. The fungicides SAAF (Carbendazim 12% WP + Mancozeb WP 63%), Nativo (Tebuconazole 50% WP + Trifloxystrobin 25% WP), Caviet (Tebuconazole 25% WP), Kingsin M (Thiophanate –methyl 70%WP), Moximate (Cymoxil 8% WP + Mancozeb 64% WP), Custodia (Azoxystrobin 11% SC + Tebuconazole 18.3% SC), Melody duo (Iprovalicarp 5.5% WP + Probineb 61.5% WP) were used as a treatment for poison food technique. The results of this study indicated that there was a highly significant difference (p≤0.001) among the treatments in mycelial growth of the pathogen and inhibition of pathogen by different fungicides. The maximum mycelial growth of pathogen was observed on control plate (79.67mm) which was followed by melody duo and Moximate with the radial mycelial growth of 57.33mm and 55.83mm, respectively. Whereas the least mycelial growth of pathogen was recorded in SAAF (0.00mm) which was followed by Nativo, Custodia, Caviet and Kingsin M with the radial mycelial growth of 10.33mm, 14.83mm, 15.50, 21.83mm, respectively. Therefore, SAAF fully inhibited the growth of pathogen and found most effective which was followed by Nativo, Custodia, and Caviet with 87.04%, 81.40%, 80.55%, respectively

IMPACT OF TINNITUS IN PRIMARY AUDITORY CORTEX IN A RAT MODEL OF TINNITUS: NICOTINIC ACETYLCHOLINE RECEPTORS AS POSSIBLE THERAPEUTIC TARGETS.

Tinnitus, ringing in the ears, is a phantom sound percept affecting roughly 10-20% of the total world population. Tinnitus severely impacts the quality of life of 10% of tinnitus sufferers, affecting their sleep, concentration, emotion, social enjoyment, and sometimes leading to depression and suicidal tendencies. In humans, most forms of tinnitus are associated with noise-exposure, leading to compensatory maladaptive plasticity of central auditory neurons. Human and animal studies suggest that tinnitus alters normal adult attentional resources. Human studies by McKenna, Hallam and Surlock 1996, suggested tinnitus-related impairment in sustained attention, vigilance, visual conceptualization and visuo-motor memory. Additionally, tinnitus may impact aspects of selective or divided attention as well as working and long-term memory. The involvement of primary auditory cortex and nicotinic signaling in selective attention, working and long-term memory has been well established. Neuronal nicotinic acetylcholine receptors (nAChRs) are present on presynaptic and postsynaptic inputs that innervate neurons across layers of primary auditory cortex (A1). Layer 5 pyramidal neurons (PNs) in the A1 are major output neurons, conveying auditory information to corticocortical and subcortical nuclei. The excitation of PNs is regulated by a complex microcircuitory of inhibitory neurons with vasointestinal peptide positive (VIP) neurons playing a key role in regulating the excitation. The focus of present studies was to: 1) Characterize tinnitus-related changes in the physiology and nAChR signaling of layer 5 PNs and VIP neurons in the A1 and 2) Determine the ability of nAChR partial/desensitizing agonists to ameliorate tinnitus pathology in subcellular studies. Wild-type, ChAT-Cre and VIP-Cre:Rosa26-loxP-stop-loxP-tdTomato (VIP-Cre:Rosa-tdTomato Long-Evans rats were used in the present study. CHAT-Cre rats allowed us to selectively express cre-inducible AAV-EF1a-DIO-hChR2(H134R)-EYFP and stimulate the cholinergic neurons of basal forebrain (BF). VIP-Cre:Rosa-tdTomato express fluorescent tdTomato protein in the VIP positive neurons allowing us to identify them under fluorescence microscopy using 550 nm wavelength. An established noise-exposure (one hour of 116 dB narrowband noise centered at 16 kHz) was used to induce behavioral tinnitus in a rat model. Approximately 50-60% noise-exposed animals (53/92) exhibited behavioral evidence of tinnitus with significant shifts in hearing threshold contiguous to the exposure frequency. Animals were classified as control, exposed tinnitus and non-tinnitus. In vitro whole-cell patch clamp recordings were performed in control and tinnitus animals. Results: Numerous tinnitus-related changes in the physiology of layer 5 PNs and VIP neurons, and changes in the activity of excitatory and inhibitory input neurons were observed. The resting membrane potential of A1 layer 5 PNs from tinnitus animals was significantly depolarized compared to PNs from unexposed controls. PNs from the A1 of animals with behavioral evidence of tinnitus showed increases in the frequency of excitatory and decreases in frequency of inhibitory spontaneous postsynaptic currents, which directly correlated with the rat’s tinnitus score. Optical stimulation of thalamocortical terminals from PNs in tinnitus animals evoked significantly larger excitatory/inward currents than in currents evoked in PNs from controls. A1 layer 5 PNs showed tinnitus-related decreases in postsynaptic gamma-amino butyric acid (GABA) signaling suggestive of GABA-A receptors (GABA-ARs) subunit switches or loss of GABA-ARs. VIP neurons favoring excitation of layer 5 PNs via disinhibition, were depolarized with significantly lower current to evoke action potentials (rheobase current). The excitability of VIP neurons was significantly increased, with this increase being strongly correlated to the rat’s tinnitus score. Tinnitus-related changes in nAChR signaling were then tested in layer 5 PNs and VIP neurons. Both PNs and VIP neurons receive cholinergic input from basal forebrain and were highly sensitive to nicotinic stimulation. Optical stimulation of basal forebrain (BF) terminals evoked a depolarizing current from VIP neurons. In tinnitus animals, layer 5 PNs showed a significant loss of nAChR signaling, while, VIP neurons showed tinnitus-related increase in responses to nicotinic stimulation. Most of the nAChR responses in auditory cortex are believed to be mediated via volume transmission of acetylcholine (ACh). Continuous voltage clamped recordings were used to examine the activity of excitatory and inhibitory neurons impacting PNs in the presence of bath applied ACh. We observed significant tinnitus-related changes in nAChR signaling with layer 5 PNs showing significantly larger GABAergic input after prolonged bath application of ACh. This led us to hypothesize that desensitization of nAChRs could increase/normalize the activity of GABAergic input neurons. To test this hypothesis, nAChR partial desensitizing agonists sazetidine-A and varenicline were used in cellular and behavioral studies. Immediately after bath application of sazetidine-A or varenicline, a dramatic increase in the activity of inhibitory input neurons onto PNs was observed. In a behavioral tinnitus test, both sazetidine-A and varenicline were effective in lowering the tinnitus-like behavior. In conclusion, we identified a significant tinnitus-related disruption in intrinsic physiology of layer 5 PNs and VIP neurons, with strong evidence of dysregulated cholinergic signaling. Partial/desensitizing agonists sazetidine-A and varenicline increased the activity of inhibitory input neurons, showing therapeutic potential in both subcellular and behavioral studies

Thromboprophylaxis with apixaban and the risk of pulmonary embolism in patients undergoing knee replacement surgery

Background: Apixaban, a novel oral anticoagulant, is also used for deep vein thrombosis (DVT) prophylaxis. In this study, we sought to critically evaluate the differences in the rates of symptomatic DVT and bleeding, and analyze the rates of pulmonary embolism (PE) in subgroups of patients from ADVANCE I and II trials given their similar indication and design. Methods: Studies were identified through electronic literature searches of MEDLINE, clinicaltrial.gov, SCOPUS, and EMBASE up to January 2014. Phase III RCTs involving use of apixaban and enoxaparin for thromboprophylaxis in patients undergoing total knee or hip replacement were included. Study-specific odds ratios were calculated and between-study heterogeneity was assessed using the I 2 statistics. Results: In three studies involving 11,659 patients, the risk of symptomatic DVT (pooled OR 0.38, 95% CI 0.16–0.90, I 2=0%, p=0.03) and bleeding (pooled OR 0.87, 95% CI 0.77–0.99, I 2=0%, p=0.03) was less in apixaban group compared to the enoxaparin group. However, it was interesting to note that on subgroup analysis, the risk of PE was higher with apixaban when used for thromboprophylaxis in knee replacement surgery (pooled OR 2.58, 95% CI 1.10–6.04, I 2=0%, p=0.03). Conclusion: Apixaban was found to be associated with lower risk of symptomatic DVT and bleeding compared to enoxaparin when used for thromboprophylaxis in patients undergoing knee and hip replacement surgeries. However, it was associated with higher risk of PE in patients undergoing knee replacement

Artemisinin derivatives as potential drug candidates against <i>Mycobacterium tuberculosis</i>: insights from molecular docking, MD simulations, PCA, MM/GBSA and ADMET analysis

Tuberculosis, one of the most ancient and formidable infectious diseases, primarily arises from the pathogenic bacterium Mycobacterium tuberculosis (Mtb). Phosphoenolpyruvate carboxykinase (Pck), a potential drug target, is essential for the growth of Mtb that involves in the pathway of gluconeogenesis at the centre of phosphoenolpyruvate-pyruvate-oxaloacetate node. This study aims to understand drug-like properties of the compounds derived from artemisinin, and to investigate their inhibitory roles against Mtb. Molecular docking was performed on a set of 56 artemisinin compounds to identify their binding efficacy to the Mtb protein target. Subsequently, the selected top three complexes were subjected to molecular dynamics simulations. By the trajectory analysis, root mean square deviation and radius of gyration indicated the compactness of the systems without much fluctuation. The principal component analysis revealed that the complexes were less dynamic and energetically more favourable, and Gibbs energy landscape revealed the favourable energetic transitions between conformations. The artemisinin dimer primary alcohol holding good bioavailability scores appears highly stable in complex with Pck (MM/GBSA of −37.67 kcal/mol) that stands as a potential inhibitor of the Mtb target. However, further preclinical experiments and investigations are necessary to evaluate the intrinsic properties and to confirm effectiveness of the drug candidate.</p

Rituximab-induced serum sickness: A systematic review.

OBJECTIVES: To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. METHODS: A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0. RESULTS: In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögren\u27s syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d. CONCLUSION: It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms

Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in elderly elective postarthroplasty patients.

The risk of venous thromboembolism (VTE) increases with age. New oral anticoagulants (NOACs) have been increasingly studied for VTE prophylaxis in patients with elective postarthroplasty. Although the elderly population accounts for a significant proportion of patients requiring VTE prophylaxis, safety and efficacy of NOACs in this subgroup for VTE prophylaxis has not been well studied. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov (from inception to 12 August 2014). Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE prophylaxis in patients with elective postarthroplasty were included. We defined our elderly population as adults of at least 75 years and assessed the reported safety and efficacy outcomes with NOACs in this population. Study-specific odds ratios (ORs) were calculated and between-study heterogeneity was assessed using the I statistic. In nine trials involving 29 403 patients, the risk of VTE or VTE-related deaths in elderly patients with elective postarthroplasty was similar with NOACs compared with LMWH (OR 0.62, 95% confidence interval 0.30-1.26; P = 0.18; I = 44%) but bleeding risk was significantly lower (OR 0.71, 95% confidence interval 0.53-0.94; P = 0.02; I = 0%). Analysis of individual NOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients with elective postarthroplasty, NOACs have similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis