Evolution of the atomic and electronic structures of CuO clusters: a comprehensive study using the DFT approach.

One of the most fundamental aspects of cluster science is to understand the structural evolution at the atomic scale. In this connection, here we report a comprehensive study of the atomic and electronic structures of (CuO)n clusters for n = 1 to 12 using DFT-based formalisms. Both the plane wave-based pseudo-potential approach and LCAO-MO-based method have been employed to obtain the ground state geometries of neutral, cation and anion copper oxide clusters. The results reveal that neutral copper oxide clusters favor a planar ring structure up to heptamer and from octamer onwards they adopt a three-dimensional motif with (CuO)9 and (CuO)12 forming a barrel-shaped layered structure. Detailed electronic structure analysis reveals that the transition of the atomic structure from 2D to 3D is guided by the energy balance of the Cu-O (d-p) and Cu-Cu (d-d) bonds. The removal of one electron from the cluster (cation) results in slightly stretched bonds while the addition of one electron (anion) showed compression in the overall geometries. The thermodynamic and electronic stability of these clusters has been analyzed by estimating their binding energy, ionization energy and electron affinity as a function of size. Remarkably, among these clusters, the octamer (CuO)8 and dodecamer (CuO)12 show higher binding energy and electron affinity (∼6.5 eV) with lower ionization energy (5.5-6.0 eV). This unique feature of the octamer and dodecamer indicates that they are very promising candidates for both oxidizing and reducing agents in different important chemical reactions.

Effect of experimental modulation of mood on exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually-induced mood shifts on exertional dyspnoea in individuals with COPD. METHODS: Following familiarization, 20 participants with mild to severe COPD (age 57-79 years) attended three experimental sessions on separate days, performing two 5-min treadmill exercise tests separated by a 30-min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0-10). Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were measured at 1-min intervals during each test. Mood valence ratings were obtained using Self-Assessment Manikin (SAM) scale (1-9). RESULTS: Mood valence ratings were significantly higher when viewing positive (end-exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty-five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. CONCLUSION: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

A review on marine source as anticancer agents.

This review investigates the potential of natural compounds obtained from marine sources for the treatment of cancer. The oceans are believed to contain physiologically active compounds, such as alkaloids, nucleosides, macrolides, and polyketides, which have shown promising effects in slowing human tumor cells both in vivo and in vitro. Various marine species, including algae, mollusks, actinomycetes, fungi, sponges, and soft corals, have been studied for their bioactive metabolites with diverse chemical structures. The review explores the therapeutic potential of various marine-derived substances and discusses their possible applications in cancer treatment.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Wavelength dependent photoionisation of ethanol clusters: generation of hydrogen like C5+ ions at terawatt laser intensity.

Photoionisation of ethanol clusters has been investigated at different laser wavelengths over the intensity range of ∼1012-1013 W cm-2. Under 266 nm ionisation, singly charged fragments and protonated cluster ions (up to (C2H5OH)9H+) were observed in the mass spectrum. Moreover, small ion signals corresponding to doubly charged carbon ions (C2+) were also observed. At longer laser wavelengths (i.e. 355, 532 and 1064 nm), the charge states of multiply charged ions of C and O were found to increase systematically and the maximum observed charge states were C5+ and O6+ at 1064 nm. Generation of C5+ ions (IE: 392 eV) is noteworthy as it requires removal of a core shell electron from a carbon atom. A comprehensive study has been carried out to appreciate the ionisation mechanism of such higher charge state formation in an ethanol cluster at terawatt laser intensity. A laser power dependency study suggests the role of multiphoton ionsation in creating initial charge centres within the cluster. Subsequently the ionised electrons produced upon multiphoton ionisation gain energy from the laser field and cause further ionisation via electron impact ionisation. Energisation of electrons and generation of multiply charged atomic ions were found to depend on the stability of clusters in the laser field which in turn is related to intermolecular interactions of ethanol clusters. Moreover, anionic fragment ions were observed in the ionisation of ethanol clusters at ∼1012 W cm-2 which also influences the ionisation dynamics of the cluster.

A journey of celecoxib from pain to cancer.

The most enthralling and versatile class of drugs called the Non-steroidal anti-inflammatory (NSAIDs) showed its therapeutic utility in inflammation, beginning from the era of classic drug 'Aspirin'. NSAIDs and their well-established action based on inhibiting the COX-1 and COX-2 enzyme leads to blockage of prostaglandin pathway. They further categorized into first generation (non-selective inhibitor) and second generation (selective COX-2 inhibitors). Selective COX-2 inhibitors has advantage over non-selective in terms of their improved safety profile of gastro-intestinal tract. Rejuvenating and recent avenues for COXIBS (selective COX-2 inhibitors) explains its integrated role in identification of biochemical pain signaling as well as its pivotal key role in cancer chemotherapy. A key role player in this class is the Celecoxib (only FDA approved COXIB) a member of Biopharmaceutical classification system (BCS) II. Low solubility and bioavailability issues related with celecoxib lead to the development and advancement in the discovery and research of some possible formulation administered either orally, topically or via transdermal route. This review article intent to draw the bead on Celecoxib and it clearly explain extensive knowledge of its disposition profile, its dynamic role in cancer at cellular level and cardiovascular risk assessment. Some of the possible formulations approaches with celecoxib and its improvement aspects are also briefly discussed.

Experimental modulation of mood by acoustic stimulation and its effect on exertional dyspnoea.

We examined the interactions between acoustically driven mood modulation and dyspnoea. Following familiarisation, 18 healthy participants attended three experimental sessions on separate days performing two 5 min treadmill tests with a 30 min interval per session while listening to either a positive, negative or neutral set of standardised International Affective Digitised Sounds (IADS). Participants rated intensity and affective domains of dyspnoea during the first exercise test and mood during the second. Mood valence was significantly higher when listening to positive (mean (95% CI): 6.5 (5.9-7.2)) compared with negative sounds (3.6 (2.9-4.4); p<0.001). Dyspnoea intensity and affect were statistically significantly lower when listening to positive (2.4 (1.8-2.9) and 1.3 (0.7-1.9)) compared with negative IADS (3.2 (2.3-3.7), p=0.013 and 2.3 (1.3-3.3), p=0.009). These findings indicate that acoustically induced mood changes influence exertional dyspnoea.

Essential Yet Neglected Role of Primary Care Physicians in Palliation Team.

Quality home-based care for patients with the end-stage disease is increasingly being preferred. Responding to disease associated symptoms and complications may pose an array of challenges in evolving palliative care systems, as no formal institutional mechanism exists to respond to patient and caregiver's wishes. Family and primary care physicians can play an instrumental role in such scenarios by bridging the gaps between cancer specialists and patient and caregivers expectations.

Mass spectrometric and charge density studies of organometallic clusters photoionized by gigawatt laser pulses.

Clusters on exposure to nanosecond laser pulses of gigawatt intensity exhibit a variety of photo-chemical processes such as fragmentation, intracluster reaction, ionization, Coulomb explosion, etc. Present article summarizes the experimental results obtained in our laboratory utilizing time-of-flight mass spectrometer which deal with one such aspect of cluster photochemistry related to generation of multiply charged atomic ions upon excessive ionization of cluster constituents (Coulomb explosion) at low intensity laser field (∼109 W/cm2 ). To understand the mechanism of laser-cluster interaction, laser as well as cluster parameters were varied. Mass spectrometric studies were carried out at different laser wavelength as well as varying the nature of cluster constituents, backup pressure, nozzle diameter, etc. In addition, charge density measurements were also preformed to get information about the total number of ions generated upon laser-cluster interaction as a function of laser wavelength. In case of pure molecular clusters, the charge state of atomic ions as well as charge density was observed to enhance with increasing laser wavelength, signifying efficient coupling of the cluster medium with nanosecond laser pulse at longer wavelength. While in case of clusters doped with species having comparatively lower ionization energy, the efficiency of laser-cluster interaction was less, in contrast to studies carried out using femtosecond lasers. Results obtained in the present work have been rationalized on the basis of proposed three-stage cluster ionization mechanism, that is, multiphoton ionization ignited-inverse Bremsstrahlung heating and electron ionization. © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:188-212, 2017.

(TMT)n clusters as dilute debris-free tin source for generation of multiply charged tin ions-of relevance in extreme ultraviolet (EUV) lithography, under intense laser irradiation.

RATIONALE: Multiply charged tin ions ([Sn]8+ to [Sn]13+ ) are considered as ideal-emitters at extreme ultraviolet (EUV) wavelength ~ 13.5 nm, pertinent to advanced micro-electronic device fabrication. Solid tin targets have been widely explored for the generation of these ions, but debris generation has restricted their utilization. Tin-containing molecular clusters have, however, the potential to act as dilute and debris-free sources for the generation of tin ions, as investigated in the present study. METHODS: Efficient coupling of laser energy with clusters has been utilized for the generation of multiply charged tin ions. The ions generated have been characterized using time-of-flight mass spectrometry. By varying experimental parameters, the yield of multiply charged tin ions has been manipulated, for tetramethyltin (TMT) clusters. In addition, the energetic electrons and photons liberated upon laser-cluster interaction have been probed utilizing an in-house developed retarding field analyser. RESULTS: Interaction of tetramethyltin clusters with 1064 nm picosecond laser pulses of intensity ~ 1013 W/cm2 leads to the generation of multiply charged tin ions (up to [Sn]14+ ) and carbon ions (up to [C]4+ ). Efficient laser-cluster interaction is evident from the generation of multiply charged tin ions with ionization energy ~ 282 eV ([Sn]14+ ). By varying the experimental conditions, the distribution of multiply charged tin ions can be influenced to obtain significant relative ion yield of multiply charged tin ions from [Sn]8+ to [Sn]13+ . CONCLUSIONS: Tetramethyltin clusters have the potential to act as dilute and debris-free source for EUV lithographic applications, in contrast to bulk tin targets. The inherent properties of clusters, such as higher local density and the pulsed nature of the cluster source, are appropriate for EUV lithographic applications.

A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.

Pharmacotherapy of Insomnia and Current Updates.

Insomnia is highly prevalent and is associated with a range of psychological, psychiatric, and medical conditions. Insomnia affects health by influencing cognitive, emotional and social functioning. Circadian and sleep homeostatic processes play an important role in insomnia development and its maintenance. Several efficacious treatments, both pharmacologic and non-pharmacologic, exist for the management of insomnia. Among non-pharmacologic treatments including stimulus control therapy, sleep restriction, relaxation, sleep hygiene and cognitive therapy have been shown to be efficacious. Pharmacological treatment acts as adjuvant to cognitive behavioural treatment. Despite availability of various classes drugs for insomnia treatment, none can be considered as an ideal agent. Novel therapies are still being explored and tested to arrive at a hypnotic that has acceptable side effects and tolerability profile while still being efficacious.

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients.

Indian College of Physicians Position Statement: Addictive Disorders Among Persons with Diabetes Mellitus.

OBJECTIVES: Migraine, a common primary headache disorder which can be severely disabling, associated with poor health-related quality of life (HRQoL) amongst affected patients. The present study was performed to provide adequate clinical data on migraine and the management practices in India. MATERIAL AND METHODS: A cross-sectional study was designed to assess disease burden, HRQoL, symptom profile, management trends and comorbidities associated with migraine patients across ten centres in India. This study assessed HRQoL using Migraine Specific Quality of life (MSQ) and Migraine Disability Assessment Scores (MIDAS) questionnaire. Categorical variables were summarized as frequency, and percentage and continuous variables as mean and standard deviation respectively. RESULTS: A total of 705 patients were enrolled with a mean age of 35.2 years. Hypertension (7.0%) was the highest co-morbid illness associated with migraine. A higher MSQ score was observed in females as compared to males (39.3±12.4 and 37.4±11.6) while MIDAS showed a comparable score (27.7±47.6 and 27.2±35.4). Majority of migraine patients were unemployed (61.6%) and in profession, females had poor HRQoL than males by MIDAS and MSQ. Majority of patients had pulsating, bilateral attacks for the duration of 4h to 72 h. Paracetamol (47.1%) and propranolol (50.9%) was most commonly prescribed drugs for acute attack and prophylaxis, respectively. CONCLUSION: The quality of life was superior in males as compared to females amongst migraine patients in India. Hypertension was the commonest comorbidity associated with migraine. KEY MESSAGES: Migraine is associated with substantial disability with higher prevalence in females and older people (age >40 years). NSAIDs and propanol was widely prescribed drug in acute attacks and prophylaxis of migraine respectively. Cardiovascular diseases, diabetes mellitus and anxiety were common comorbidities associated with migraine.

Kheri (Acacia chundra, family: Mimosaceae) gum: Characterization using analytical, mathematical and pharmaceutical approaches.

BACKGROUND: Natural polymers have been used in medical, pharmaceutical, cosmetic and food industry. They should be characterized before their possible applications in different industries. OBJECTIVES: The objective of this study was to characterize Kheri (Acacia chundra, family: Mimosaceae) gum using analytical, mathematical and pharmaceutical approaches. MATERIAL AND METHODS: Crude Kheri gum (KG) was purified using distilled water as a solvent and ethanol as a precipitating agent. KG was characterized in terms of phytochemical screening, micromeritic properties, microbial load, ash value, rheological behavior, solid state 1H nuclear magnetic resonance (NMR), mass spectra and Fourier-transform infrared spectroscopy (FTIR) studies for their possible applications in food, cosmetics and pharmaceutical industry. RESULTS: Studies show that KG contains carbohydrates, while protein, fat, volatile oils, alkaloids and glycosides are absent. 1% aqueous solution of polysaccharide showed 25.58 × 103 kJ/kg activation energy and 1.39 Reynold's number. Viscosity average molecular weight of purified gum was found 1.73 × 105 D. Thermodynamic parameters, i.e., change in enthalpy ΔHv and change in enthalpy ΔHv, were found to be 12.26 × 103 kJ/mol and 24.47 kJ/mol, respectively. Mathematical approach also determined the rod shaped conformation of KG in aqueous solution. IR spectroscopic study shows the presence of free (COO-) and esterified (COO-R) carboxylic acid, ether (C-O stretching), galacturonic acid and mannose in polysaccharide 1H NMR study predicts presence of tetrahydropyran hydrogen in molecule. Furthermore, KG was also characterized as a suspending agent using paracetamol as a model drug. Flow rate, pH, particle size and settling behavior of suspensions were evaluated. Initial particle size of dispersed phase particles does not change significantly after 45 days. CONCLUSIONS: From the findings of the research it can be concluded that KG can be used as an excipient in cosmaceuticals and pharmaceuticals and its characteristic rheological behavior may attract rheologists.

Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids.

New isatin-triazole based hybrids have been synthesized and evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds. Z-1-[3-(1H-1,2,4-Triazol-1-yl)propyl]-5-bromo-3-[2-(4-methoxyphenyl)hydrazono]indolin-2-one (19) with an IC50 = 20 µM and 89% ICAM-1 inhibition with MTD at 200 µM was found to be the most potent of all the synthesized derivatives. Introduction of 1,2,4-triazole ring and electron-donating methoxy group on the phenylhydrazone moiety resulted in four-fold increase of the anti-inflammatory activity.

Transrectal ultrasonography (TRUS)-guided pelvic plexus block to reduce pain during prostate biopsy: a randomised controlled trial.

OBJECTIVE: To assess the role of pelvic plexus block (PPB) in reducing pain during transrectal ultrasonography(TRUS)-guided prostate biopsy, compared with the conventional periprostatic nerve block (PNB). PATIENTS AND METHODS: A prospective, double-blind observational study was conducted with patients being randomised into three groups. Group-1 (47 patients) received intrarectal local anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group-2 (46 patients) received IRLA with periprostatic nerve block (PNB). Group-3 (46 patients) received only IRLA without any type of nerve block. The patients were requested to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two time points: VAS-1: during biopsy procedure and VAS-2: 30 min after the procedure. RESULTS: The mean age of the patients, mean volume of the prostates and mean serum PSA values were comparable among the three groups. The mean pain score during biopsy was significantly less in the PPB group [mean (range) sore of 2.91 (2-4)] compared with the PNB group [mean (range) score of 4 (3-5)], and both these groups were superior to the no nerve block group [mean score of 5.4 (3-7)]. There was no significant difference between the mean pain scores, 30 min after the procedure among the three groups with the mean (range) scores being 2.75 (2-4), 2.83 (2-4) and 2.85 (2-4), respectively. CONCLUSION: PPB is superior to conventional periprostatic nerve block (PNB) for pain control during TRUS-guided biopsy and both are in turn superior to no nerve block.

Efficient coupling of nanosecond laser pulses with the cluster medium: Generation of hydrogen-like [C](5+) atomic ions.

RATIONALE: Clusters exhibit diverse photochemical behavior as a function of laser parameters, i.e. wavelength, pulse duration and intensity. One such aspect of cluster photochemistry is the generation of energetic multiply charged atomic ions, upon efficient interaction of clusters with intense laser pulses. In the present work, mass spectrometric investigations have been carried out on clusters of tetrahydrofuran (THF, C4 H8 O) - a saturated cyclic ether - subjected to nanosecond laser pulse (spanning from UV to IR wavelength range) with the aim of shedding light on the complex mechanism of laser-cluster interactions, which is still ambiguous. METHODS: THF clusters, generated via supersonic expansion of room-temperature THF vapours seeded in argon, were subjected to gigawatt intensity laser pulses (355, 532 and 1064 nm) obtained from a nanosecond Nd:YAG laser. The ions generated upon laser-cluster interaction were characterized using a time-of-flight mass spectrometer. RESULTS: At 355 nm, THF clusters exhibit the usual multiphoton dissociation/ionization behavior while, at 532 nm, observation of multiply charged atomic ions of carbon (up to [C](4+) ) and oxygen (up to [O](3+) ) was ascribed to Coulomb explosion of THF clusters. For studies carried out at 1064 nm, multiply charged atomic ions of carbon up to [C](5+) having an ionization energy of ~392 eV were observed, at a laser intensity of 10(10) W/cm(2) . CONCLUSIONS: The observation of [C](5+) atomic ions signifies efficient coupling of the laser energy with the cluster medium, using a nanosecond laser pulse. The results have been rationalized on the basis of a three-stage cluster ionization mechanism, suggesting the crucial role of the threshold laser intensity for initiating ionization within the cluster and generation of optimum charge centers for efficient extraction of energy from the laser pulse.