Ion Channels and Metal Ions in Parkinson's Disease: Historical Perspective to the Current Scenario.

Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times. Hence, there is a need to look for new molecular targets that could be investigated both preclinically and clinically for PD treatment. Among these, several ion channels and metal ions are being studied for their effects on PD pathology and the functioning of dopaminergic neurons. Ion channels such as N-methyl-D-aspartate (NMDA), γ-aminobutyric acid A (GABAA), voltage-gated calcium channels, potassium channels, HCN channels, Hv1 proton channels, and voltage-gated sodium channels and metal ions such as mercury, zinc, copper, iron, manganese, calcium, and lead showed prominent involvement in PD. Pharmacological agents have been used to target these ion channels and metal ions to prevent or treat PD. Hence, in the present review, we summarize the pathophysiological events linked to PD with an emphasis on the role of ions and ion channels in PD pathology, and pharmacological agents targeting these ion channels have also been listed.

Shielded ionisation discharge (SID) probe for spatiotemporal profiling of pulsed molecular beam.

Intense pulsed supersonic molecular beams are used in many applications such as tokamak fueling, edge plasma diagnostics, ion beam profile monitors, laser cluster experiments, chemical kinetics, etc. Measurement of absolute density is required to optimize beam sources used in these experiments. Absolute density measurement of a continuous molecular beam is challenging due to its small size and rarefied flow, which makes it even more difficult for a pulsed molecular beam due to its transient nature. In this work, we demonstrate a novel probe to measure the spatiotemporal evolution of the absolute number density of a pulsed supersonic molecular beam. The probe is named the Shielded Ionization Discharge probe. It measures density using localized discharge within the molecular beam created by the thermionic emission of electrons from a hot filament. We describe the design, calibration, and characterization of the developed probe. The performance of the probe is demonstrated by measuring the spatial and temporal profiles of a pulsed supersonic molecular beam of 1.5 ms duration.

Possible high risk of transmission of the Nipah virus in South and South East Asia: a review.

Nipah virus (NiV) is a zoonotic, single-stranded RNA virus from the family Paramyxoviridae, genus Henipavirus. NiV is a biosafety-level-4 pathogen that is mostly spread by Pteropus species, which serve as its natural reservoir host. NiV is one of the major public health challenges in South and South East Asia. However, few molecular studies have been conducted to characterise NiV in a specific region. The main objective of this review is to understand the epidemiology, pathogenesis, molecular surveillance, transmission dynamics, genetic diversity, reservoir host, clinical characteristics, and phylogenetics of NiV. South and South East Asian nations have experienced NiV outbreaks. Phylogenetic analysis confirmed that two primary clades of NiV are in circulation. In humans, NiV causes severe respiratory illness and/or deadly encephalitis. NiV is mainly diagnosed by ELISA along with PCR. Therefore, we recommend that the governments of the region support the One Health approach to reducing the risk of zoonotic disease transmission in their respective countries.

Phosphorylation-mediated regulation of the Bacillus anthracis phosphoglycerate mutase by the Ser/Thr protein kinase PrkC.

Bacillus anthracis Ser/Thr protein kinase PrkC is necessary for phenotypic memory and spore germination, and the loss of PrkC-dependent phosphorylation events affect the spore development. During sporulation, Bacillus sp. can store 3-Phosphoglycerate (3-PGA) that will be required at the onset of germination when ATP will be necessary. The Phosphoglycerate mutase (Pgm) catalyzes the isomerization of 2-PGA and 3-PGA and is important for spore germination as a key metabolic enzyme that maintains 3-PGA pool at later events. Therefore, regulation of Pgm is important for an efficient spore germination process and metabolic switching. While the increased expression of Pgm in B. anthracis decreases spore germination efficiency, it remains unexplored if PrkC could directly influence Pgm activity. Here, we report the phosphorylation and regulation of Pgm by PrkC and its impact on Pgm stability and catalytic activity. Mass spectrometry revealed Pgm phosphorylation on seven threonine residues. In silico mutational analysis highlighted the role of Thr459 residue towards metal and substrate binding. Altogether, we demonstrated that PrkC-mediated Pgm phosphorylation negatively regulates its activity that is essential to maintain Pgm in its apo-like isoform before germination. This study advances the role of Pgm regulation that represents an important switch for B. anthracis resumption of metabolism and spore germination.

Spatial mapping of low pressure cluster jets using Rayleigh scattering.

In this work, we report evolution of atomic clusters in a highly under-expanded supersonic jet of Argon. A high resolution and sensitive Rayleigh scattering based experimental set-up is designed to overcome the limitations encountered in conventional set-ups. Further, the measurement range could be extended from a few nozzle diameters to 50 nozzle diameters. Simultaneously, we had been able to generate 2D profiles of the distribution of clusters inside the jet. This paves the way to track the growth of clusters along the flow direction experimentally, which until now was limited to few nozzle diameters. The results show that spatial distribution of clusters inside the supersonic core deviates considerably from the prediction of the free expansion model. We exploit this to estimate cluster growth along the expansion direction. Further, it is observed that the growth of the clusters gets saturated after a certain distance from the nozzle. At the jet boundary, we see substantial cluster strengthening immediately upstream of barrel shock while the normal shock exhibits disintegration of clusters. These observations are noticed for the first time, which, we believe will further the understanding of cluster dynamics in a supersonic jet.

Exploring the superhydrophilicity of nanosecond laser textured silicon: a Raman analysis.

We present Raman analysis of nanosecond laser textured silicon. The samples have also been characterized by field emission scanning electron microscopy (FESEM) and x ray diffraction. Contact angles (CAs) are measured to trace the hydrophilic nature. Characterization of the textured samples in argon and air shows that cleavage cracks are developed during texturing. CA measurements reveal the superhydrophilic nature of textured samples obtained in the presence of ambient oxygen and argon. In vacuum, however, the hydrophilicity is decreased. Micro-Raman analysis indicates the formation of nano-sized cleavage cracks that impart stable superhydrophilic properties to textured silicon is supported from FESEM images also. On the other hand, in vacuum textured silicon, evidence of such cracks is not noticed, which is also supported by Raman analysis. Further, the hydrophilicity is decreased. A definitive trend appears to exist between Raman signatures and hydrophilicity. We believe that the study will further the understanding of the mechanistic aspect in designing textured silicon with a high degree of self-cleaning capability.

Understanding COVID-19 Situation in Nepal and Implications for SARS-CoV-2 Transmission and Management.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19), one of the most infectious diseases in the modern history, is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and has had a profound health and economic toll, globally. This paper identifies the overall health status associated with COVID-19 pandemic in all 7 provinces of Nepal, a developing country in South Asia, analyzing data from January 2020 to February 2022. It focuses on the SARS-CoV-2 prevalence, transmission through wastewater and other routes, diagnostics, treatment options, and alternative medicines, thereby offering key perspectives for its management. Materials and Methods: Studies regarding coronavirus spanning the 2017 to 2022 period were searched on the web, Nepalese database, and Web of Science. Refined criteria included SARS-CoV-2 in wastewater of Nepal or worldwide. Demographic data (sex, age-group, and geographic location) were also obtained from websites and relevant reports of the Ministry of Health and Population (MOHP) of Nepal, ranging from January 2020 to February 2022. Moreover, trends concerning lockdown, business, and border activities in Nepal between February 2020 and October 2020 were evaluated. The viral dissemination pathways, diagnosis, and available treatment options, including the Ayurvedic medicine, were also examined. Results: Aerosols generated during the hospital, industrial, recreational, and household activities were found to contribute to the propagation of SARS-CoV-2 into environmental wastewater, thereby putting the surrounding communities at risk of infection. When lockdown ended and businesses opened in October 2020, the number of active cases of COVID-19 increased exponentially. Bagmati Province had the highest number of cases (53.84%), while the remaining 6 provinces tallied 46.16%. Kathmandu district had the highest number of COVID-19 cases (138, 319 cases), while Manang district had the smallest number of infections (81 cases). The male population was found to be predominantly infected (58.7%). The most affected age groups were the 31 to 40 years old males (25.92%) and the 21 to 30 years old females (26.85%). Conclusion: The pandemic impacted the public health and economic growth in our study duration. SARS-CoV-2 was prevalent in the wastewater of Nepal. The Terai districts and the megacities were mostly affected by SARS-CoV-2 infections. Working-age groups and males were identified as the highest risk groups. More investigations on the therapeutic and alternative cures are recommended. These findings may guide the researchers and professionals with handling the COVID-19 challenges in developing countries such as Nepal and better prepare for future pandemics.

Förster Resonance Energy Transfer between Fluorescent Organic Semiconductors: Poly(9,9-dioctylfluorene-alt-benzothiadiazole) and 6,13-Bis(triisopropylsilylethynyl)pentacene.

In the present study, an investigation of the electronic excitation energy transfer between two p-type fluorescent semiconductors, F8BT [poly(9,9-dioctylfluorene-alcohol-benzothiadiazole] and TIPS-P [6,13-bis(triisopropylsilylethynyl)pentacene], has been carried out in a chloroform solution using steady-state and time-domain fluorescence techniques. The spectral overlap integral between donor (F8BT) emission and acceptor (TIPS-P) absorption is 2.04 × 1015 nm4/(M cm), and the corresponding critical transfer distance is 53.12 Å. In donor decay dynamics, at the lower acceptor concentrations, the observed results deviate from the Förster theory due to the combined effect of diffusion and energy migration. However, it does not exhibit energy migration and distribution for higher acceptor concentrations, and the system follows the Förster model of resonance excitation energy transfer (FRET). The higher value of the donor-acceptor interaction strength than self-interaction (donor-donor interaction) appears to be responsible for this behavior. Further, in acceptor decay, the appearance of the rise time and its decrease with the acceptor concentration confirms FRET from F8BT to TIPS-P.

Outcomes of dexmedetomidine sedation for drug-induced sleep ciné magnetic resonance imaging studies in pediatric obstructive sleep apnea patients.

BACKGROUND: Dexmedetomidine is utilized as a sedative agent for drug-induced sleep cine magnetic resonance imaging studies due to its ability to mimic natural sleep and lack of respiratory depressant effects. The outcomes of dexmedetomidine sedation such as respiratory complications and unplanned admissions in obstructive sleep apnea patients undergoing these studies are currently unknown. AIM: To describe the outcomes of dexmedetomidine sedation for outpatient drug-induced sleep magnetic resonance imaging in pediatric patients with obstructive sleep apnea. METHODS: This is a retrospective chart review conducted in pediatric patients with obstructive sleep apnea undergoing outpatient drug-induced sleep ciné magnetic resonance imaging studies with dexmedetomidine sedation. Demographics, comorbidities, polysomnography study results, vital signs, respiratory complications, airway interventions, successful completion of the scan, and unplanned hospital admissions were measured. MAIN RESULTS: We analyzed 337 patients aged 2-18 years (median age of 11 years). The imaging was completed with dexmedetomidine as the sole sedative agent in 61% (N = 207) patients. Ketamine was administered as additional sedative agent in 36% (N = 122) of the patients. There was no difference in sedation-related adverse events and respiratory complications with regard to the severity of sleep apnea with the exception of mild desaturation episodes (SpO2 85%-90%). Patients who received additional sedative agents had significantly longer recovery room stay (71.5 [44] vs 55 [39] minutes; 95% CI of difference [9 to 23 min], p < 0.001) and total periprocedural stay (164.5 [52] vs 138 [64] minutes; 95% CI of difference [17 to 35 min], p < .001). CONCLUSIONS: Dexmedetomidine alone or along with ketamine provided acceptable sedation in majority of the patients with obstructive sleep apnea undergoing outpatient diagnostic sleep magnetic resonance imaging studies without significant respiratory adverse events regardless of the severity of sleep apnea. Sedation failure and unplanned admissions are rare, and routine planned admission may not be required for this patient population.

Inter-provincial disparity of COVID-19 transmission and control in Nepal.

Despite the global efforts to mitigate the ongoing COVID-19 pandemic, the disease transmission and the effective controls still remain uncertain as the outcome of the epidemic varies from place to place. In this regard, the province-wise data from Nepal provides a unique opportunity to study the effective control strategies. This is because (a) some provinces of Nepal share an open-border with India, resulting in a significantly high inflow of COVID-19 cases from India; (b) despite the inflow of a considerable number of cases, the local spread was quite controlled until mid-June of 2020, presumably due to control policies implemented; and (c) the relaxation of policies caused a rapid surge of the COVID-19 cases, providing a multi-phasic trend of disease dynamics. In this study, we used this unique data set to explore the inter-provincial disparities of the important indicators, such as epidemic trend, epidemic growth rate, and reproduction numbers. Furthermore, we extended our analysis to identify prevention and control policies that are effective in altering these indicators. Our analysis identified a noticeable inter-province variation in the epidemic trend (3 per day to 104 per day linear increase during third surge period), the median daily growth rate (1 to 4% per day exponential growth), the basic reproduction number (0.71 to 1.21), and the effective reproduction number (maximum values ranging from 1.20 to 2.86). Importantly, results from our modeling show that the type and number of control strategies that are effective in altering the indicators vary among provinces, underscoring the need for province-focused strategies along with the national-level strategy in order to ensure the control of a local spread.

Excited-State Intramolecular Proton Transfer: A Short Introductory Review.

In this short review, we attempt to unfold various aspects of excited-state intramolecular proton transfer (ESIPT) from the studies that are available up to date. Since Weller's discovery of ESIPT in salicylic acid (SA) and its derivative methyl salicylate (MS), numerous studies have emerged on the topic and it has become an attractive field of research because of its manifold applications. Here, we discuss some critical aspects of ESIPT and tautomerization from the mechanistic viewpoint. We address excitation wavelength dependence, anti-Kasha ESIPT, fast and slow ESIPT, reversibility and irreversibility of ESIPT, hydrogen bonding and geometrical factors, excited-state double proton transfer (ESDPT), concerted and stepwise ESDPT.

Modeling transmission dynamics of rabies in Nepal.

Even though vaccines against rabies are available, rabies still remains a burden killing a significant number of humans as well as domestic and wild animals in many parts of the world, including Nepal. In this study, we develop a mathematical model to describe transmission dynamics of rabies in Nepal. In particular, an indirect interspecies transmission from jackals to humans through dogs, which is relevant to the context of Nepal, is one of the novel features of our model. Our model utilizes annual dog-bite data collected from Nepal for a decade long period, allowing us to reasonably estimate parameters related to rabies transmission in Nepal. Using our model, we calculated the basic reproduction number ( R 0 = 1.16 ) as well as intraspecies basic reproduction numbers of dogs ( R 0 D = 1.14 ) and jackals ( R 0 J = 0.07 ) for Nepal, and identified that the dog-related parameters are primary contributors to R 0 . Our results show that, along with dogs, jackals may also play an important role, albeit lesser extent, in the persistence of rabies in Nepal. Our model also suggests that control strategies may help reduce the prevalence significantly but the jackal vaccination may not be as effective as dog-related preventive strategies. To get deeper insight into the role of intraspecies and interspecies transmission between dog and jackal populations in the persistence of rabies, we also extended our model analysis into a wider parameter range. Interestingly, for some feasible parameters, even though rabies is theoretically controlled in each dog and jackal populations ( R 0 D < 1 , R 0 J < 1 ) if isolated, the rabies epidemic may still occur ( R 0 > 1 ) due to interspecies transmission. These results may be useful to design effective prevention and control strategies for mitigating rabies burden in Nepal and other parts of the world.

Observation of ion acceleration in nanosecond laser generated plasma on a nickel thin film under rear ablation geometry.

In this article we report acceleration observed for the ions produced in a 50-nm-thick nickel film coated on a quartz substrate, under nanosecond laser ablation, in the rear ablation geometry. A detailed study with varying background pressure and laser energy is done. Spectroscopic study including spectroscopic time of flight (STOF) measurements of ionic and other neutral transitions from the plasma has been undertaken. The STOF spectra recorded for ionic transition clearly show an enhancement in the velocity of the slow component as the background pressure increases. In addition, a large asymmetric spectral broadening in the 712.22-nm neutral line is observed, which increases with background pressure. While these observations have similarity to some of the reported studies on the acceleration of ionic species through double-layer formation, the electric fields calculated from the measured acceleration appear to be anomalously higher, and a double-layer concept seems to be inadequate. Moreover, the large asymmetry observed in the neutral line profile is indicative of microelectric fields present inside the laser produced plasma plume, which may play a role in the continuous acceleration of the ions. Interestingly, this asymmetry in spectral broadening exhibits temporal and spatial dependence, which indicates that significant electric field is present in the plasma plume even for longer duration and larger distance from the target. These spectroscopic observations of acceleration have also been complemented by triple Langmuir probe measurements. To the best of our information, such observations regarding large ion acceleration for the rather low laser intensities as used in this experiment have not been reported in literature so far.

Therapeutic potential of pharmacological agents targeting TRP channels in CNS disorders.

Central nervous system (CNS) disorders like Alzheimer's disease (AD), Parkinson disease (PD), stroke, epilepsy, depression, and bipolar disorder have a high impact on both medical and social problems due to the surge in their prevalence. All of these neuronal disorders share some common etiologies including disruption of Ca2+ homeostasis and accumulation of misfolded proteins. These misfolded proteins further disrupt the intracellular Ca2+ homeostasis by disrupting the activity of several ion channels including transient receptor potential (TRP) channels. TRP channel families include non-selective Ca2+ permeable channels, which act as cellular sensors activated by various physio-chemical stimuli, exogenous, and endogenous ligands responsible for maintaining the intracellular Ca2+ homeostasis. TRP channels are abundantly expressed in the neuronal cells and disturbance in their activity leads to various neuronal diseases. Under the pathological conditions when the activity of TRP channels is perturbed, there is a disruption of the neuronal homeostasis through increased inflammatory response, generation of reactive oxygen species, and mitochondrial dysfunction. Therefore, there is a potential of pharmacological interventions targeting TRP channels in CNS disorders. This review focuses on the role of TRP channels in neurological diseases; also, we have highlighted the current insights into the pharmacological modulators targeting TRP channels.

Comment on ""Where does the fluorescing moiety reside in a carbon dot?"- Investigations based on fluorescence anisotropy decay and resonance energy transfer dynamics" by A. Das, D. Roy, C. K. De and P. K. Mandal, Phys. Chem. Chem. Phys., 2018, 20, 2251.

In a recent paper published in Physical Chemistry Chemical Physics (Phys. Chem. Chem. Phys., 2018, 20, 2251-2259), Förster resonance energy transfer (FRET) between carbon dots and rhodamine 123 has been reported. The FRET rates and hence donor acceptor distances estimated from acceptor rise time for various acceptor concentrations appear to be incorrect. In the present comment need for a correct analysis in the case of such a scenario is addressed.

Chronic Pain and Associated Factors in India and Nepal: A Pilot Study of the Vanderbilt Global Pain Survey.

BACKGROUND: Evaluation and treatment of chronic pain worldwide are limited by the lack of standardized assessment tools incorporating consistent definitions of pain chronicity and specific queries of known social and psychological risk factors for chronic pain. The Vanderbilt Global Pain Survey (VGPS) was developed as a tool to address these concerns, specifically in the low- and middle-income countries where global burden is highest. METHODS: The VGPS was developed using standardized and cross-culturally validated metrics, including the Brief Pain Inventory and World Health Organization Disability Assessment Scale, as well as the Pain Catastrophizing Scale, the Fibromyalgia Survey Questionnaire along with queries about pain attitudes to assess the prevalence of chronic pain and disability along with its psychosocial and emotional associations. The VGPS was piloted in both Nepal and India over a 1-month period in 2014, allowing for evaluation of this tool in 2 distinctly diverse cultures. RESULTS: Prevalence of chronic pain in Nepal and India was consistent with published data. The Nepali cohort displayed a pain point prevalence of 48%-50% along with some form of disability present in approximately one third of the past 30 days. Additionally, 11% of Nepalis recorded pain in 2 somatic sites and 39% of those surveyed documented a history of a traumatic event. In the Indian cohort, pain point prevalence was approximately 24% to 41% based on the question phrasing, and any form of disability was present in 6 of the last 30 days. Of the Indians surveyed, 11% reported pain in 2 somatic sites, with only 4% reporting a previous traumatic event. Overall, Nepal had significantly higher chronic pain prevalence, symptom severity, widespread pain, and self-reported previous traumatic events, yet lower reported pain severity. CONCLUSIONS: Our findings confirm prevalent chronic pain, while revealing pertinent cultural differences and survey limitations that will inform future assessment strategies. Specific areas for improvement identified in this VGPS pilot study included survey translation methodology, redundancy of embedded metrics and cultural limitations in representative sampling and in detecting the prevalence of mental health illness, catastrophizing behavior, and previous traumatic events. International expert consensus is needed.

Comment on the article "Investigation of Fluorescence Resonance Energy Transfer between Fluorescein and Rhodamine 6G".

In this comment we, report the missing of relevant literature regarding Forster energy transfer (FRET) between fluorescein and rhodamine 6G in a recent paper (Spectrochim. Acta A, 149 (2015) 143-149). In this paper, the authors claim that "a new FRET pair" has been identified, which is absolutely incorrect. In fact, studies on FRET in this dye pair under different conditions have been done earlier. Further, the estimated critical transfer distance may have uncertainty because of donor quantum yield which is not clarified in the paper.

Slow excited state phototautomerization in 3-hydroxyisoquinoline.

In the present work we report the spectral and photophysical properties of 3-hydroxyisoquinoline in various protic/aprotic solvents. Our steady state and time resolved fluorescence data indicates that in the monomer form of 3HIQ phototautomerization can take place in the excited state through excited state intramolecular proton, while as per earlier suggestions phototautomerization in 3HIQ occurs in dimer or complex (in the presence of acetic acid) form. Moreover, we find rather slow tautomerization (occurring on the nanosecond scale). It is found that proton transfer occurs both in the ground as well as excited states and is controlled by the polarity of the solvent.

Economic recession and headache-related hospital admissions.

Incidence of headaches across different regions and its relationship to unemployment rates in the United States before and during an economic recession was evaluated. Years 2008 and 2009 were determined as recessionary period. Headache-related admissions, particularly the uncomplicated headaches, increased significantly during recession. Proportion of women with headaches has increased and the age group of 25-54 years was the most affected during the recession. The hospital charges have increased even though the average length and charge of stay decreased. These findings are consistent with our understanding of effects of stress and unemployment on psychological and physical health.

Photochemistry and excited state prototropic behaviour of 8-amino 2-naphthol.

In the present work, photophysical behaviour of 8-amino 2-naphthol in various solvents as well as at various pH values has been investigated. Various ground and excited state species are noticed. It exhibits a completely different photo prototropic behaviour as compared to its parent molecule 2-naphthol. The spectral and transient studies indicate that at lower pH values, equilibrium between cation and neutral exists in the excited state. At neutral pH some peculiar behaviour in its spectral properties is noticed.