Novel perspective of therapeutic modules to overcome motor and nonmotor symptoms in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons, which leads to motor and non-motor symptoms that have a significant impact. The pathophysiology of PD is complex and involves environmental and genetic factors that contribute to alpha-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. The current treatments of PD primarily focus on symptom management and have limitations in addressing disease progression and non-motor symptoms. Epidemiological data indicates a rise in PD cases worldwide, which highlights the need for effective treatments. Pathophysiological insights point out the involvement of various factors in PD progression, such as dopamine dysregulation, genetic mutations, oxidative stress, mitochondrial damage, alpha-synuclein aggregation, and neuroinflammation. Although current treatments, which include dopamine precursors, monoamine oxidase (MAO) inhibitors, and non-dopaminergic drugs, can alleviate motor symptoms, they are not effective in preventing disease progression or managing non-motor symptoms. Additionally, they can lead to adverse effects and become less effective over time. Novel therapeutic approaches, including cell-based therapies, gene therapies, targeted drug delivery therapies, and magnetic field therapies, are promising in improving symptom management and providing personalized treatment. Additionally, emerging therapies that target alpha-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation may have potential disease-modifying effects. To sum up, for dealing with the multiple aspects of PD, there is a great need to come up with new and creative therapeutic approaches that not only relieve symptoms, but also prevent the progression of disease and non-motor symptoms. The progress made in comprehending the underlying mechanisms of PD provides optimism for developing successful treatments that can enhance the outcomes and quality of life.

Phyllodes Tumors of the Breast-Experience in a Tertiary Care Center.

Phyllodes tumors (PTs) are rare neoplasms of the breast that are a challenge in clinical practice. Though mostly benign, they are notorious for local recurrence, requiring adjuvant treatments. This study was planned to report the clinicopathological features and outcomes of patients with PT treated at our center. Details of all patients who underwent surgery for PT in the last 6 years (December 2017-December 2023) were obtained from our prospectively maintained database. The demographic, clinical, radiological, pathological, and follow-up details were recorded and analyzed. Statistical analyses were carried out with Jamovi version 2.3.18. Out of 61 suspected PTs by triple assessment, 9 were excluded due to a non-phyllodes diagnosis on histopathology. We included 52 women with a mean age of 38.2 ± 11.0 years, most of whom were premenopausal (57.7%). BI-RADS 4 was the most common finding on radiological assessment (65.4%). Core needle biopsy (CNB) was the most frequently employed modality for histological diagnosis preoperatively (65.4% of cases). Wide local excisions (WLE) and mastectomies were done in 63.5% and 36.5% of patients, respectively. Benign, borderline, and malignant phyllodes constituted 67.3%, 15.4%, and 17.3% of tumors, respectively. Patients undergoing breast conservation surgery (BCS) had a significantly smaller mean tumor diameter than those who underwent a mastectomy (p < 0.001). Overall, the margin positivity rate was 34.6%. Patients undergoing mastectomy developed more local recurrence compared to WLE, although the difference was not significant (p = 0.400). The outcome following surgical excisions of large PTs in terms of margin positivity and local recurrence is the same, irrespective of whether BCS or mastectomy is done. A negative pathological margin width of > 1 mm appears acceptable. Malignant phyllodes with positive margins are associated with a higher rate of recurrence but positive margins in patients with other subtypes may not translate into recurrence, at least in the short term.

Plant growth promoting bacteria (PGPB)-induced plant adaptations to stresses: an updated review.

Plants and bacteria are co-evolving and interact with one another in a continuous process. This interaction enables the plant to assimilate the nutrients and acquire protection with the help of beneficial bacteria known as plant growth-promoting bacteria (PGPB). These beneficial bacteria naturally produce bioactive compounds that can assist plants' stress tolerance. Moreover, they employ various direct and indirect processes to induce plant growth and protect plants against pathogens. The direct mechanisms involve phytohormone production, phosphate solubilization, zinc solubilization, potassium solubilization, ammonia production, and nitrogen fixation while, the production of siderophores, lytic enzymes, hydrogen cyanide, and antibiotics are included under indirect mechanisms. This property can be exploited to prepare bioformulants for biofertilizers, biopesticides, and biofungicides, which are convenient alternatives for chemical-based products to achieve sustainable agricultural practices. However, the application and importance of PGPB in sustainable agriculture are still debatable despite its immense diversity and plant growth-supporting activities. Moreover, the performance of PGPB varies greatly and is dictated by the environmental factors affecting plant growth and development. This review emphasizes the role of PGPB in plant growth-promoting activities (stress tolerance, production of bioactive compounds and phytohormones) and summarises new formulations and opportunities.

An updated view of bacterial endophytes as antimicrobial agents against plant and human pathogens.

Bacterial endophytes are a crucial component of the phytomicrobiome, playing an essential role in agriculture and industries. Endophytes are a rich source of bioactive compounds, serving as natural antibiotics that can be effective in combating antibiotic resistance in pathogens. These bacteria interact with host plants through various processes such as quorum sensing, chemotaxis, antibiosis, and enzymatic activity. The current paper focuses on how plants benefit extensively from endophytic bacteria and their symbiotic relationship in which the microbes enhance plant growth, nitrogen fixation, increase nutrient uptake, improve defense mechanisms, and act as antimicrobial agents against pathogens. Moreover, it highlights some of the bioactive compounds produced by endophytes.

In vitro larvicidal efficacy of Lantana camara essential oil and its nanoemulsion and enzyme inhibition kinetics against Anopheles culicifacies.

Mosquitoes are important vectors for the transmission of several infectious diseases that lead to huge morbidity and mortality. The exhaustive use of synthetic insecticides has led to widespread resistance and environmental pollution. Using essential oils and nano-emulsions as novel insecticides is a promising alternative approach for controlling vector borne diseases. In the current study, Lantana camara EO and NE were evaluated for their larvicidal and pupicidal activities against Anopheles culicifacies. The inhibitory effect of EO and NE on AChE, NSE (α/ß), and GST was also evaluated and compared. GC-MS analysis of oil displayed 61 major peaks. The stable nano-emulsion with an observed hydrodynamic diameter of 147.62 nm was formed using the o/w method. The nano-emulsion exhibited good larvicidal (LC50 50.35 ppm and LC90 222.84 ppm) and pupicidal (LC50 54.82 ppm and LC90 174.58 ppm) activities. Biochemical evaluations revealed that LCEO and LCNE inhibited AChE, NSE (α/ß), and GST, displaying LCNE to be a potent binder to AChE and NSE enzyme, whereas LCEO showed higher binding potency towards GST. The nano-emulsion provides us with novel opportunities to target different mosquito enzymes with improved insecticidal efficacy. Due to its natural origin, it can be further developed as a safer and more potent larvicide/insecticide capable of combating emerging insecticide resistance.

Sentinel lymph node biopsy in early breast carcinoma using fluorescein sodium and methylene blue dye: A validation study.

The availability of radioisotopes for sentinel lymph node biopsy (SLNB) in breast carcinoma is limited in low- and middle-income countries and thus the need for other reliable tracers exists. We aimed to validate the effectiveness of fluorescein sodium (FS) together with methylene blue dye (MBD) for patients with node-negative early breast carcinoma in a prospective cross-sectional study. Patients underwent SLNB using FS and MBD followed by axillary dissection to validate results. Sentinel lymph node (SLN) identification rate and false negative rate were assessed for all three tracers/combinations (MBD, FS, and MBD + FS). We concluded that SLNB using a combination of FS and MBD has an acceptable rate of SLN identification but the addition of FS provided no additional benefit.

Microbiota-brain axis: Exploring the role of gut microbiota in psychiatric disorders - A comprehensive review.

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.

Wild edible vegetables of ethnic communities of Mizoram (Northeast India): an ethnobotanical study in thrust of marketing potential.

BACKGROUND: Assessment of wild edible vegetables (WEVs) from the ethnobotanical approach is a significant key to understanding indigenous knowledge systems. The available literature has revealed a tremendous decline in knowledge of WEVs over the last few decades. The main purpose of this study was to document and analyse the traditional knowledge of WEVs among the two major ethnic groups of Mizoram regarding their use and the diversity associated with the importance of traditional medicines. Secondly, a market survey will be conducted to determine the status of available WEVs. METHODS: This study conducted an ethnobotanical survey among 72 informants through semi-structured interviews and questionnaires besides direct field observations. The documented data were quantitatively analysed using various ethnobotanical indices, including Informant's consensus factor (ICF), Fidelity level value (Fl), and Direct matrix ranking (DMR). A marketing survey was conducted in the Bara Bazar, Mizoram's most prominent local market. A total of 38 vendor informants were interviewed to observe and collect the price of commonly sold WEVs. RESULTS: A total of 70 WEVs, distributed in 58 genera under 36 families, were documented and identified. Of these, 33 WEVs were of medicinal importance. Leafy vegetables were documented as the most frequently consumed parts (55.71%). The majority (44.29%) of the plants documented were consumed in fried form. The highest level of agreement among informants for food used categories was observed for plants combined with dry fish (ICF = 1). The Informant's consensus factor (ICF) of disease categories ranges from 0.75 to 1, with the highest being reported for convulsion (ICF = 1), sleep inducer (ICF = 1), and antiseptic (ICF = 1). Picria fel-terrae was the most preferred plant for hypertension treatment (100% FL). Direct matrix ranking (DMR) indicated that Dysoxylum excelsum was highly utilized by the inhabitant for multipurpose species (DMR = 64). Jaccard similarity index (JI) between the two ethnic groups was revealed at 1.26. Forty-seven WEVs were found to be commercialized in the Bara Bazar market, Aizawl, with a price range from 0.1 to 2.4 USD. Ensete superbum was reported as near threatened per the IUCN Red List of Threatened Species. CONCLUSION: This work highlighted the importance and rich diversity of WEVs in Mizoram, which are presently used among different age groups for food and medicine. Informants have good knowledge of WEVs, which was shared to a great extent among the inhabitants; this legacy of traditional culture must be conserved. This study further suggests a priority setting for conserving multipurpose WEVs in human-inhabited sites, investigating the recorded species' nutritional properties and pharmacological activities.

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

INTRODUCTION: Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. AIMS AND METHODS: We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. RESULTS: If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. CONCLUSIONS: Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. IMPLICATIONS: This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

Bacterial diversity and biopotentials of Hamtah glacier cryoconites, Himalaya.

Cryoconite is a granular structure present on the glaciers and ice sheets found in polar regions including the Himalayas. It is composed of organic and inorganic matter which absorb solar radiations and reduce ice surface albedo, therefore impacting the melting and retreat of glaciers. Though climate warming has a serious impact on Himalayan glaciers, the biodiversity of sub-glacier ecosystems is poorly understood. Moreover, cryoconite holes are unique habitats for psychrophile biodiversity hotspots in the NW Himalayas, but unfortunately, studies on the microbial diversity of such habitats remain elusive. Therefore, the current study was designed to explore the bacterial diversity of the Hamtah Glacier Himalaya using both culturable and non-culturable approaches. The culturable bacterial count ranged from 2.0 × 103 to 8.8 × 105 colony-forming units (CFUs)/g at the different locations of the glacier. A total of 88 bacterial isolates were isolated using the culturable approach. Based on the 16S ribosomal RNA gene (16S rRNA), the identified species belong to seven genera, namely, Cryobacterium, Duganella, Janthinobacterium, Pseudomonas, Peribacillus, Psychrobacter, and Sphingomonas. In the non-culturable approach, high-throughput sequencing of 16S rRNA genes (using MiSeq) showed unique bacterial community profiles and represented 440 genera belonging to 20 phyla, namely, Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, Chloroflexi, Acidobacteria, Planctomycetes, Cyanobacteria, Verrucomicrobia, Spirochaetes, Elusimicrobia, Armatimonadetes, Gemmatimonadetes, Deinococcus-Thermus, Nitrospirae, Chlamydiae, Chlorobi, Deferribacteres, Fusobacteria, Lentisphaerae, and others. High relative abundances of Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were observed in the samples. Phototrophic (Cyanobacteria and Chloroflexi) and nitrifier (Nitrospirae) in bacterial populations indicated sustenance of the micro-ecosystem in the oligotrophic glacier environment. The isolates varied in their phenotypic characteristics, enzyme activities, and antibiotic sensitivity. Furthermore, the fatty acid profiles of bacterial isolates indicate the predominance of branched fatty acids. Iso-, anteiso-, unsaturated and saturated fatty acids together constituted a major proportion of the total fatty acid composition. High cold-adapted enzyme activities such as lipase and cellulase expressed by Cryobacterium arcticum (KY783365) and protease and cellulase activities by Pseudomonas sp. strains (KY783373, KY783377-79, KY783382) provide evidence of the possible applications of these organisms. Additionally, antibiotic tests indicated that most isolates were sensitive to antibiotics. In conclusion, the present study contributed for the first time to bacterial diversity and biopotentials of cryoconites of Hamtah Glacier, Himalayas. Furthermore, the cold-adapted enzymes and polyunsaturated fatty acids (PUFAs) may provide an opportunity for biotechnology in the Himalayas. Inductively coupled plasma mass spectrometry (ICPMS) analyses showed the presence of several elements in cryoconites, providing a clue for the accelerating melting and retreating of the Hamtah glacier.

Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.

Optimizing methanol synthesis from CO2 using graphene-based heterogeneous photocatalyst under RSM and ANN-driven parametric optimization for achieving better suitability.

Assessment of the performance of linear and nonlinear regression-based methods for estimating in situ catalytic CO2 transformations employing TiO2/Cu coupled with hydrogen exfoliation graphene (HEG) has been investigated. The yield of methanol was thoroughly optimized and predicted using response surface methodology (RSM) and artificial neural network (ANN) model after rigorous experimentation and comparison. Amongst the different types of HEG loading from 10 to 40 wt%, the 30 wt% in the HEG-TiO2/Cu assisted photosynthetic catalyst was found to be successful in providing the highest conversion efficiency of methanol from CO2. The most influencing parameters, HEG dosing and inflow rate of CO2, were found to affect the conversion rate in the acidic reaction regime (at pH of 3). According to RSM and ANN, the optimum methanol yields were 36.3 mg g-1 of catalyst and 37.3 mg g-1 of catalyst, respectively. Through the comparison of performances using the least squared error analysis, the nonlinear regression-based ANN showed a better determination coefficient (overall R2 > 0.985) than the linear regression-based RSM model (overall R2 ∼ 0.97). Even though both models performed well, ANN, consisting of 9 neurons in the input and 1 hidden layer, could predict optimum results closer to RSM in terms of agreement with the experimental outcome.

An overview of techniques for monitoring and compensating tool wear in micro-electrical discharge machining.

Micro-electrical discharge machining (µEDM) is severely affected by tool wear and its process variants, which can lead to compromised precision and dimensional disruptions in micro-part production. Several attempts have been made to address this problem by suggesting offline and online (real-time) tool wear compensation strategies. Research efforts in this area have intensified over the last 20 years. However, most methods proposed were applicable only for a few work-tool combinations and in limited input process parametric settings. Instead of tool wear compensation, several research articles have focused on strategies to reduce the negative impact of tool wear on the quality of fabricated parts. The present study systematically reviews various investigations conducted in this area and aims to add cutting-edge compensation for tool wear to future inquiries. The articles reviewed here are explored in detail. Critical findings/innovations are classified into four categories: tool wear in µEDM, tool wear compensation techniques, and offline and online compensation methods.

How Does Tobacco Use Affect the Cognition of Older Adults? A Propensity Score Matching Analysis Based on a Large-Scale Survey.

INTRODUCTION: Tobacco is a well-established risk factor for cancer, but its association with other morbidities needs consideration. The low-income and middle-income countries (LMICs) with unprecedented demographic transformation lack evidence on tobacco use and its impact on cognitive health. AIMS AND METHODS: Using a propensity score matching approach, we utilized data from the Longitudinal Ageing Study of India. Study employed 1:1 nearest neighbor matching with the replacement methodology. We estimated the odds of the poor cognitive score and tobacco use among older adults based on five different models for ever tobacco user, former tobacco user, current tobacco user, current smokers, and current smokeless tobacco users with reference to never tobacco users. RESULTS: The estimated average treatment effect for the treated and the untreated group has shown a higher likelihood of cognitive decline among ever (OR -0.26; 95%CI -0.43 to -0.09), current (OR -0.28; 95%CI -0.45 to -0.10), and former (OR -0.53; 95%CI -0.87 to -0.19) tobacco users compared to never tobacco users. The finding further suggests the odds of lower cognitive scores among older adults who were smokers (OR -0.53; 95%CI -0.87 to -0.19) and smokeless tobacco users (OR -0.22; 95%CI -0.43 to -0.01) as compared to never tobacco users. CONCLUSIONS: Interventions designed to prevent the incidence of cognitive impairment should focus on limiting the use of tobacco. Strategies under the tobacco-free generation initiative should be amplified in order to prevent future generations from productivity loss, premature ageing and to promote healthy aging. IMPLICATIONS: Evidence of a definitive association between tobacco consumption and cognition among older adults is sporadic in LMICs. Though tobacco is a risk factor for various diseases including cancer, the extent of its impact on cognitive health among the older population is limited. This study contributes to the existing literature by highlighting poor cognitive outcomes among older adults who smoke tobacco and/or consume smokeless tobacco as compared to never-tobacco users. Our findings emphasize the need to accelerate programmes related to tobacco-free generation in LMICs to reach a higher quality of life and healthy aging in pursuit of achieving the sustainable development goal of "good health and well-being."

From concept to reality: Transforming agriculture through innovative rhizosphere engineering for plant health and productivity.

The plant rhizosphere is regarded as a microbial hotspot due to a wide array of root exudates. These root exudates comprise diverse organic compounds such as phenolic, polysaccharides, flavonoids, fatty acids, and amino acids that showed chemotactic responses towards microbial communities and mediate significant roles in root colonization. The rhizospheric microbiome is a crucial driver of plant growth and productivity, contributing directly or indirectly by facilitating nutrient acquisition, phytohormone modulation, and phosphate solubilization under normal and stressful conditions. Moreover, these microbial candidates protect plants from pathogen invasion by secreting antimicrobial and volatile organic compounds. To enhance plant fitness and yield, rhizospheric microbes are frequently employed as microbial inoculants. However, recent developments have shifted towards targeted rhizosphere engineering or microbial recruitments as a practical approach to constructing desired plant rhizospheres for specific outcomes. The rhizosphere, composed of plants, microbes, and soil, can be modified in several ways to improve inoculant efficiency. Rhizosphere engineering is achieved through three essential mechanisms: a) plant-mediated modifications involving genetic engineering, transgenics, and gene editing of plants; b) microbe-mediated modifications involving genetic alterations of microbes through upstream or downstream methodologies; and c) soil amendments. These mechanisms shape the rhizospheric microbiome, making plants more productive and resilient under different stress conditions. This review paper comprehensively summarizes the various aspects of rhizosphere engineering and their potential applications in maintaining plant health and achieving optimum agricultural productivity.