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Abstract Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown. These populations of direct and indirect pathway-projecting spiny projection neurons (SPNs) have classically been thought to promote or suppress actions, respectively, leading to a long-held hypothesis that increased output of direct relative to indirect pathway promotes compulsive behavior. Contrary to this hypothesis, here we find that indirect pathway hyperactivity is associated with compulsive grooming in the Sapap3-knockout mouse model of OCD-relevant behavior. Furthermore, we show that suppression of indirect pathway activity using optogenetics or treatment with the first-line OCD pharmacotherapy fluoxetine is associated with reduced grooming in Sapap3-knockouts. Together, these findings highlight the striatal indirect pathway as a potential treatment target for compulsive behavior.

Summary: Lung cancer varies between Caucasians and Asians. There have been differences recorded in the epidemiology, genomics, standard therapies and outcomes, with variations according to the geography and ethnicity which affect the decision for optimal treatment of the patients. To better understand the profile of lung cancer in Southeast Asia, with a focus on India, we have comprehensively reviewed the available data, and discuss the challenges and the way forward. A substantial proportion of patients with lung cancer in Southeast Asia are neversmokers, and adenocarcinoma is the common histopathologic subtype, found in approximately a third of the patients. EGFR mutations are noted in 23–30% of patients, and ALK rearrangements are noted in 5–7%. Therapies are similar to global standards, although access to newer modalities and molecules is a challenge. Collaborative research, political will with various policy changes and patient advocacy are urgently needed.

Background: Early childhood caries is one of the most serious and high-priced oral health conditions among young children. With advancing dental sciences, the focus of dental caries treatment is shifted from restorative procedures to preventive measures, and a modality grabbing attention is probiotics. Probiotics exert their effects in many ways as chemical inhibition of pathogenic bacteria and stimulation of the immune response through the production of immunoglobulin A and many more. Objective: This systematic review aims to explore the efficacy and safety of probiotics in dental caries in preschool children. Methodology: The study was registered in the PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42020159058). The search was done for randomized control trials in electronic databases such as Cochrane, PubMed, ClinicalTrials.gov, Medline, and Embase. It has further included manual searches of journals, conference abstracts, and books. Three reviewers done the selection of the study as per the criteria and also did the risk of bias assessment independently and wherever required, a fourth reviewer resolved the discrepancy in case of disagreement. Results: The nine randomized control trials were included in the study, and the pooled analysis revealed probiotics as an effective intervention in preschool children with dental caries. Conclusion: The results about the efficacy of probiotics in the prevention of dental caries are very encouraging, though the level of evidence is still inadequate.

In the present scenario, research on Thermal Barrier Coatings (TBCs) is attracting significant attention in high-temperature applications due to the rising demand in industrial applications, such as gas turbine blades and internal combustion engine components. To meet these demands, it is essential to enhance the mechanical and oxidation properties of thermal barrier coatings. The atmospheric plasma spray methodology for producing these coatings has become a central focus in recent times. In this work, TBCs were prepared by blending pure alumina and Yttria-Stabilized Zirconia (YSZ) in equal proportions. Extensive study of TBCs carried out under high-temperature conditions through thermal cycle tests at elevated temperatures, around 850 °C. A total of 350 thermal cycles were conducted, and microstructures of the coating surface were examined at 150, 250, and 350 cycles. High-temperature stress, generated due to the sintering of the coating, also influences the life of the coatings. Specimen with a topcoat thickness of 300 μm, exhibited good thermal shock resistance compared to the specimens with topcoats of thickness of 100 μm and 200 μm. The effects of process parameters, porosity, and thermal shock resistance are presented in detail. The topcoat with a thickness of 300 μm demonstrated excellent thermal shock resistance and reduced formation of thermally grown oxide (TGO). The porosity of the coating, found to be between 2% and 3%, contributed to its dense nature, effectively reducing oxidation rates and enhancing the coating's lifespan under cyclic high-temperature conditions.

IntroductionRapid urbanization in coastal areas worldwide, combined with intense precipitation events and coastal flooding exacerbated by climate change, poses an existential challenge for many coastal communities. Floodwater in coastal urban areas contains non-point source pollutants, such as trace metals and fecal coliforms, but the presence of fecal coliforms resistant to antibiotics poses an additional threat to human health and has yet to be reported.MethodsIn this study, floodwater samples were collected from four locations in Charleston, SC, a medium-sized coastal city in the southeastern United States. All sites were impacted by flooding: two by tidal and rainfall flooding, one by tidal flooding, and one by stormwater runoff. Since ampicillin is a commonly-prescribed antibiotic for both humans and animals, this study aimed to analyze the patterns of ampicillin-resistant coliform (AmpRC) concentrations as correlated to flood-source and land-use patterns.ResultsFloodwater from all areas contained AmpRC and trace metals, with varying contaminant concentrations based on the flood source. No correlations were observed between coliform and trace metal concentrations. Analysis of land-use patterns demonstrated a positive correlation between percent coverage of impervious surfaces and coliform concentrations at all the sites.DiscussionOverall, the results suggest that land-use patterns increase the prevalence of antibiotic-resistant coliforms and increase the likelihood of human exposure to these potential pathogens. Climate change is expected to exacerbate the presence of antibiotic-resistant bacteria in floodwater generated from rainfall and tidal flooding in coastal cities. Cities like Charleston, SC are experiencing rapid urbanization and increased coastal flooding, making this research particularly relevant.

A dual-band antenna with pattern similarity using the energy-squeezing mechanism of an epsilon-near-zero (ENZ) metamaterial is designed, and experimental results are presented with simulated data. To achieve high gain and pattern similarity, a waveguide-based ENZ metamaterial property is adopted in a planar microstrip form at the upper band. The designed dual-band antenna is resonating at 4.3 GHz and 9.8 GHz frequencies with the desired radiation pattern. A metamaterial unit cell with ENZ characteristics at 9.8 GHz is designed to improve the antenna’s performance. The permittivity and permeability of the unit cell are characterized using the Nicolson–Ross–Weir method. By adding a square ring structure, the antenna geometry exhibits ENZ characteristics. Using the ENZ material’s energy-squeezing mechanism, a 12-dB gain improvement is achieved in the upper band without affecting the lower band radiation characteristics without increasing the complexity. It can be used in C- and X-band applications, such as mobile, military, defense, and radar communication. The dual-band antenna with ENZ material is fabricated, and the measured results show a good match with the simulated results. The proposed antenna size at 4.3 GHz is 0.58λ × 0.58λ × 0.02λ.

Dragon fruit [Hylocereus undatus (Haworth) Britton and Rose] is an exotic super fruit introduced in India. It can be naturally propagated through seeds and stem cuttings. Present study was carried out during 2018 to 2021 at Main Horticultural Research and Extension Centre (MHREC), College of Horticulture, University of Horticultural Sciences, Bagalkote, Karnataka to improve the efficiency of seed germination and seedling growth in dragon fruit using PGRs. The results showed that, there were significant differences among various treatments. Treatment 100 ppm GA3 recorded as the best treatment with respect to the parameters, viz. days taken for germination (10.60 days), germination percentage (87.00%), shoot length (10.27 cm), root length (8.06 cm), number of roots (6.20), seedling length (18.33 cm), seedling fresh weight (3.26 g), seedling dry weight (1.22 g) respectively at 90 days after sowing (DAS) and survival percentage (48%) than other treatments.

In this study, we develop novel tetrazole compounds based on dibenzyl amine (DBA) and investigate their potential as antioxidants. The aforementioned compounds were synthesised by the Ugi multicomponent reaction, which involved the simultaneous addition of four systems, i.e., DBA, cyclohexyl isocyanide, TMSN3 and aromatic aldehyde in ethanol media under RT. The different isocyanides effect in the progress of the TMSN3 based Ugi reaction was studied. The tetrazoles that were changed with DBA were studied using several techniques, including FTIR, 1H NMR, 13C NMR, and MS. The antioxidant properties of the produced compounds (4a-4j) were subsequently tested in a controlled laboratory setting using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical assay. When compared to ascorbic acid, the antioxidant efficacy of all of the produced compounds was high. The obtained results for all prepared compounds were good as an antioxidant in comparison with ascorbic acid. The electron withdrawing effect of the substituents (halogens and nitro groups) on the aromatic side enhanced the antioxidant activity of the newly derived motifs. Their molecular docking investigation with the myeloperoxidase (MPO) enzyme revealed a strong relationship between their binding modalities and the antioxidant properties they displayed.

Three approaches for determining the thermodynamic stability of irreversible processes are described in generalized formulations. The simplest is the Gibbs–Duhem theory, specialized to irreversible trajectories, which uses the concept of virtual displacement in the reverse direction. Its only drawback is that even a trajectory leading to an explosion is identified as a thermodynamically stable motion. In the second approach, we use a thermodynamic Lyapunov function and its time rate from the Lyapunov thermodynamic stability theory (LTS, previously known as CTTSIP). In doing so, we demonstrate that the second differential of entropy, a frequently used Lyapunov function, is useful only for investigating the stability of equilibrium states. Nonequilibrium steady states do not qualify. Without using explicit perturbation coordinates, we further identify asymptotic thermodynamic stability and thermodynamic stability under constantly acting disturbances of unperturbed trajectories as well as of nonequilibrium steady states. The third approach is also based on the Lyapunov function from LTS, but here we additionally use the rates of perturbation coordinates, based on the Gibbs relations and without using their explicit expressions, to identify not only asymptotic thermodynamic stability but also thermodynamic stability under constantly acting disturbances. Only those trajectories leading to an infinite rate of entropy production (unstable states) are excluded from this conclusion. Finally, we use these findings to formulate the Fourth Law of thermodynamics based on the thermodynamic stability. It is a comprehensive statement covering all nonequilibrium trajectories, close to as well as far from equilibrium. Unlike previous suggested “fourth laws”, this one meets the same level of generality that is associated with the original zeroth to third laws. The above is illustrated using the Schlögl reaction with its multiple steady states in certain regions of operation.

Cabozantinib is a tyrosine kinase inhibitor that has been approved as therapy for several solid tumors, including metastatic renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid cancer. To prepare this review, we comprehensively searched various websites, including the United States Food and Drug Administration, the European Medicine Agency Drug Manual, PubMed, Science Direct, and UpToDate using the search terms, “cabozantinib,” “renal cell carcinoma,” “hepatocellular carcinoma,” “differentiated thyroid cancer,” and “medullary thyroid cancer.” We shortlisted all the full-text articles published between 2011 and 2022. Out of a total of 788 manuscripts identified, we included 52. This review of cabozantinib details the pharmacodynamics, pharmacokinetics, clinical indications, adverse effects, safety, and the key research trials that investigated the use of cabozantinib. We have discussed the available clinical trial data and real-world outcomes, both with respect to the efficacy and safety of cabozantinib.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune fibrosclerotic inflammatory condition with distinctive histopathological findings affecting various organ systems. The disease can be tumefactive or “mass-like” in morphology, or less commonly, infiltrative. Many historic and well-known disease entities are manifestations of IgG4-RD in different organs. Radiologists need to be aware of this multifaceted disorder and its systemic nature. We searched Pubmed and Embase using the keywords “head and neck,” “IgG4-related disease,” and “imaging.” We included the relevant review articles published in the English language from 1997 to 2021, whose major area of discussion was IgG4-RD manifestations in the head-and-neck. Filters applied for inclusion were: “full text,” “humans,” “English,” “cancer,” article type: “review,” “meta-analysis,” “systematic review,” and “guideline.” In this review article, we have discussed the wide spectrum of manifestations of this disease at different head-and-neck subsites to familiarize radiologists with this interesting disease entity.

Abstract Kumar Prabhash Background The development of immune-related adverse effects (irAEs) can corroborate with the response to immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD1) inhibitors. However, there is extremely limited data on the association of irAEs with survival in patients who have shown a response to ICIs. Patients and Methods This study is a retrospective audit of the prospectively collected database of patients who received PD1 inhibitors for advanced solid tumors. Responders were defined as patients who attained the best response of either complete response or partial response. Time-to-event analysis was done using the Kaplan–Meier estimator, and the hazard ratio (HR) was calculated by using Cox proportional model. A point-biserial correlation was used to find out the potential influence of irAEs on overall survival (OS). Results A total of 155 patients (49% lung cancer, 31% head and neck cancer) who received ICI during the specified period were evaluated for this study. The overall response rate was 19.4% and disease control rate was 43.2%. The median (OS) for patients who developed irAE was 12.3 months (95% confidence interval [CI]: 8.9–15.6), while it was not reached for patients without irAE (HR: 10.5, 95% CI: 1.2–NR, p = 0.007). One-year OS for the corresponding group of patients was 53.6% (standard deviation [SD]: 15.6) versus 92.9% (SD: 6.9), respectively. Among responders, 12 (40%) developed at least grade 1 irAE, while among nonresponders, 38 (30.4%) developed irAE (p = 0.312). Conclusions In our study, we found significant improvement in survival of solid tumor patients treated with ICIs who developed irAEs on treatment as compared with those who did not. On specifically analyzing patients who responded to ICIs, there was no difference in OS who developed irAEs versus those who did not. However, this needs to be studied in a larger sample to reach a definite conclusion.

Abstract Akhil Kapoor Introduction The prognosis of anaplastic lymphoma kinase (ALK) fusion-positive metastatic non-small cell lung cancer (mNSCLC) patients has improved drastically since the introduction of targeted therapies. Apart from age, performance status, and type of driver mutation in a mNSCLC, prognosis also depends on baseline metastatic sites number as well as location with liver metastases being a poor prognostic factor. However, the clinical and prognostic association of baseline liver metastases in ALK fusion-positive mNSCLC is not well known. Material and Methods We performed a retrospective analysis of ALK fusion-positive mNSCLC patients to assess prognostic impact of liver metastases. Records were obtained from lung cancer audit database and electronic medical records. Patients were started on either chemotherapy, ALK-directed tyrosine kinase inhibitors, or given best supportive care as per the clinical scenario. Radiological response was assessed every 2 to 3 months or earlier at clinical suspicion of progressive disease. Adverse events were evaluated as per Common Terminology Criteria for Adverse Events v4.02. Results A total of 441 patients were screened, out of which 76 had baseline liver metastases. Median age was 49 years with 64.5% males. Median progression-free survival (mPFS) was 14.2 months (95% confidence interval [CI] 8.9–19.4) in patients with baseline liver metastases. In patients who received first-line ALK inhibitor therapy versus who received first-line chemotherapy, mPFS was significantly better in the ALK-directed therapy subgroup, 15.3 months (95% CI 11.7–18.9) versus 5.9 months (95% CI 2.7–9.1), respectively (hazard ratio [HR] 0.3 [95% CI 0.17–0.54]; p

Background: The high-speed resistance of microbial pathogens and enfeeble of antibiotic therapy competence specifically with the rise in healthcare-associated infections (HAIs) eventually brought several thousand deaths each year. Nanoparticles have gained a lot of interest in recent years for their antibacterial and cytotoxic potential, very distinctly the copper oxide nanoparticles. Methods: Methodology involves the green synthesis of Cu2O NPs using kiwi fruit juice followed by characterization viz., XRD, SEM, UV-visible, FT-IR, particle size and zeta potential techniques. Toxicity evaluation was done by exposing HEK-293 and MCF-7 cell lines to Cu2O NPs and further testing the potency of nanoparticles against S. aureus, E.coli, A.niger and C.albicans. Results: The SEM-EDX analysis showed that Cu2O NPs are spherical in nature and pure. Half of the Cu2O NPs particles size was about 100 nm. IC50values observed for HEK-293 and MCF-7 cells were 20.51±0.52 ug mL−1and 6.25±0.27 ug mL−1. The distinct selectivity index (3.28) of the Cu2O NPS against human breast cancer cells (MCF-7) was observed. In the antimicrobial test, the zone of inhibitions were 20, 18, 14, 15 mm on S. aureus, E.coli, A.niger and C.albicans respectively. Conclusion: The Cu2O nanoparticles manifested excellent cytotoxicity against HEK-293 and MCF-7 cell lines and their antimicrobial activity was superlative with exceptional zones of inhibition against S. aureus (20 mm), E. coli (18 mm), C. albicans (14 mm) and A. niger (15 mm) revealing outstanding effectiveness at minimal concentrations.

Background: Head-and-neck squamous cell cancers (HNSCC) are common in India. Recurrent and metastatic HNSCC carry a poor prognosis. The chemotherapy options are limited, and the median survival is measured in months. The addition of targeted antibodies and immunotherapy improves overall survival (OS). In resource-limited settings, chemotherapy remains the only option in advanced HNSCC. Objectives: We aimed to assess the efficacy and safety of the combination of paclitaxel and Mycidac-C (heat-killed Mycobacterium w) in the palliative setting for advanced HNSCC. Materials and Methods: This was a retrospective study conducted in the Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India in patients with relapsed/refractory or metastatic HNSCC who received the combination of paclitaxel and Mycidac-C between August 2019 and May 2020. Patients were treated until progression or unacceptable toxicity. The study was approved by the Institutional Ethics Committee, and the requirement for written informed consent was waived. Results: We included 28 patients in the study. Most of the patients (22, 78.6%) had oral cavity cancers and had platinum-refractory disease (25 patients, 96.4%). The median age was 51 years (range, 31-70), 26 (92.9%) patients were male, and 25 (89.3%) had a performance status of 0-1. At least two lines of previous therapies had been administered to 23 (82.1%) patients. The median duration of follow-up was 3.4 months (range, 0.2-18.1). The median numbers of cycles of paclitaxel and Mycidac-C administered were 3 (range, 1-6) and 2.5 (range, 1-6), respectively. The median progression-free survival (PFS) and OS were 2.9 months (95% confidence interval [CI], 2.36-3.48) and 4.9 months (95% CI, 3.78-5.99), respectively. The most common adverse effects were anemia in 26 (93.9%) patients and increased alanine aminotransferase and aspartate aminotransferase levels in five (17.9%) and four (14.3%) patients, respectively. Four (14.3%) patients developed neutropenia, two (7.1%) developed diarrhea, and two (7.1%) developed peripheral neuropathy. Conclusion: In resource-limited settings, the combination of paclitaxel and Mycidac-C can be considered a therapeutic option for patients with advanced relapsed/metastatic HNSCC.

Skull bone graft failure is a potential complication of autologous cranioplasty after decompressive craniectomy (DC). Our objective was to investigate the association of graft size with subsequent bone graft failure after autologous cranioplasty. This single-center retrospective cohort study included patients age ?18 years who underwent primary autologous cranioplasty between 2010 and 2017. The primary outcome was bone flap failure requiring graft removal. Demographic, clinical, and radiographic factors were recorded; three-dimensional (3D) reconstructive imaging was used to perform accurate measurements. Univariate and multi-variate regression analysis were performed to identify risk factors for the primary outcome. Of the 131 patients who underwent primary autologous cranioplasty, 25 (19.0%) underwent removal of the graft after identification of bone flap necrosis on computed tomography (CT); 16 (64%) of these were culture positive. The mean surface area of craniectomy defect was 128.5?cm2 for patients with bone necrosis and 114.9?cm2 for those without bone necrosis. Linear regression analysis demonstrated that size of craniectomy defect was independently associated with subsequent bone flap failure; logistic regression analysis demonstrated a defect area >125?cm2 was independently associated with failure (odds ratio [OR] 3.29; confidence interval [CI]: 0.249-2.135). Patient- and operation-specific variables were not significant predictors of bone necrosis. Our results showed that increased size of antecedent DC is an independent risk factor for bone flap failure after autologous cranioplasty. Given these findings, clinicians should consider the increased potential of bone flap failure after autologous cranioplasty among patients whose initial DC was >125?cm2.

Density (ρ) and speed of sound (u) values of L-Citrulline in aqueous solution, 0.06 mol·kg−1 aqueous Urea and aqueous 0.06 mol·kg−1 Dextrose solutions have been measured at T = (288.15, 293.15, 298.15, 303.15, 308.15, 313.15 and 318.15) K within the concentration range of (0.02 to 0.2) mol·kg−1.These measurements have been performed to evaluate some important parameters, viz, apparent molar volume of solute (Vϕ), limiting apparent molar volume of solute (Vϕ0), limiting apparent molar volume of transfer (ΔtrVϕ0), limiting apparent molar expansivity(Eϕ0), thermal expansion coefficient (α*), Hepler's constant (∂2Vϕ0∂T2), isentropic compressibility (κs), apparent molar compressibility (Ks,ϕ), limiting apparent molar compressibility (Ks,ϕ0), limiting apparent molar isentropic compressibility of transfer (ΔtrKs,ϕ0)and hydration number(ηH) . The results have been interpreted in terms of different interactions taking place in aqueous solutions.

Summary: Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) has activity in glioma both in-vivo and in-vitro, and is well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: In this phase II randomized open-label trial, adult patients with ECOG PS 0–3, with recurrent GBM who were not eligible for re-radiation, were randomized 1:1 to the CCNU-MBZ and TMZ-MBZ arms. CCNU was administered at 110 mg/m2 every 6 weeks with MBZ 800 mg thrice daily and TMZ was administered at 200 mg/m2 once daily on days 1–5 of a 28 days cycle with MBZ 1600 mg thrice daily. The primary endpoint was OS at 9 months. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. OS was analyzed using intention to treat (ITT) and per-protocol (PP) analyses. Per-protocol analysis was used for safety analysis. Clinical Trials Registry-India number, CTRI/2018/01/011542. Findings: Participants were recruited from 14th March 2019 to 18th June 2021, 44 patients were randomised on each arm. At 17.4 months, 68 events for OS analysis had occurred, 33 in the TMZ-MBZ and 35 in the CCNU-MBZ arm. The 9-month OS was 36.6% (95% CI 22.3–51.0) and 45% (95% CI 29.6–59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively, in the ITT population. ECOG PS was the only independent prognostic factor impacting OS (HR-0.48, 95% CI 0.27–0.85; P = 0.012). Grade 3–5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. There were no treatment related deaths. Interpretation: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients having poor PS of 2–3. Funding: Brain Tumor Foundation (BTF) of India, Indian Cooperative Oncology Network (ICON), and India Cancer Research Consortium (ICRC) under ICMR (Indian Council of Medical Research).

Remi Shrivastava,1 Megha Vijay,2 Nathalie Maneby,1 Ravishekhar Shrivastava1 1VITROBIO Research Institute, Issoire, 63500, France; 2Mudra Clincare, Navi Mumbai, IndiaCorrespondence: Ravishekhar Shrivastava Email rs@vitrobio.comBackground: Covid-19 infection is a multifactorial disease where the virus mainly enters through the nasal cavity, grows, triggers inflammation, and destroys nasal mucosa cells, allowing systemic virus entry and infection of other organs. When symptoms appear, the disease physiopathology is already established. The immune system tries to control the infection but if the infection persists, it gets tired, fatigued, stressed, and finally, there is burnout. Therefore, an effective treatment should be multi-targeted and should not focus only on one parameter. Minimizing virus concentration, reducing nasal mucosa inflammation, and keeping the nasal surface clean should lessen systemic infection and the probability of developing severe respiratory distress. We evaluated clinical efficacy and safety of an osmotic nasal surface cleaning, virus and cytokine trapping polymeric film, in early-stage Covid-19 positive symptomatic patients.Methods: A randomized, multicentric, observational study was performed to evaluate the efficacy and safety of the osmotic film in 213 patients, randomized in 2 equal arms, and confined for 14-days just after the RT-PCR+ test. Due to ethical reasons, all patients received symptomatic treatments (ST). In addition, the patients in Arm-1 received the test product (ST+TP, 2– 3 sprays, 4– 5 times/day) for 14-days. Leicester Cough Questionnaire, Visual Analogue Scale, and Covid-19-associated symptoms such as fever, pain, taste, smell, and headache were evaluated daily. Home-confined patients were immediately hospitalized in case of aggravation of any life-threatening clinical sign.Results: Among 213 patients, 98 in the ST and 102 in the ST+TP group completed the study. Thirteen patients did not complete the study as 8 in the ST group and 5 in the ST+TP group were hospitalized during the study due to low blood oxygen levels or sudden health deterioration and were excluded from the study. In the remaining control standard treatment group (n=98), clinical signs sharply aggravated on day 1– 2 followed by stabilisation between days 3– 6 and progressive reduction thereafter. In the test product group (n=102), symptoms were stabilized just after the first application and improved progressively. Only 42/102 patients in the test product group presented nasal discharge or irritation due to the osmotic properties of the product.Conclusion: The continuous multi-target approach of detaching and neutralizing virus particles and pro-inflammatory cytokines from the nasal surface to minimize systemic virus exposure is a very logical and efficient approach to avoid Covid-19-induced systemic pathology.Keywords: clinical trial, Covid-19, osmotic filmogen barrier

Abstract Background Acute oral mucositis has been infrequently studied in the patients with head and neck squamous cell carcinoma (HNSCC) receiving once-weekly cisplatin-based chemoradiotherapy (CRT). Hence, this analysis was conducted to explore the various aspects of the same. Results The overall incidence of mucositis was 96.9% (n = 508) and of grade 3–5 mucositis was 61.3% (n = 321). The overall incidence of oral mucositis was similar in both the arms (CCRT and NCRT) (p value = 0.58) while grade 3–5 mucositis was more common in the NCRT arm (p value = 0.01). Out of all factors listed, the presence of nimotuzumab was the only significant risk factor for the development of grade 3 or more oral mucositis (p value = 0.01); (OR = 1.64, 95%CI 1.15–2.32). Delays in the treatment delivery were similar in both the arms. Conclusion Acute oral mucositis is a common occurrence in locally advanced-HNSCC patients receiving chemoradiotherapy. Nimotuzumab is a significant factor for development of grade 3 and above oral mucositis.

The unprecedented Covid-19 pandemic has resulted in more than 14.75 million infections and 6, 10, 839 deaths in 212 countries. Appropriate interventions can decrease the rate of Covid-19 related mortality. Fast track clinical trials around the world are addressing the efficacy of individual pharmaceutical agent acting at various stages of pathogenesis. However, lessons learnt while dealing with past viral epidemics mandates, simultaneous use of such drugs in combination amongst different populations. Mathematical modelling studies can be extremely helpful in understanding the efficacy of drugs both individually and in combination. The current within-host mathematical model studies the natural history of Covid-19 in terms of complex interplay of virus replication and behaviour of host immune response. Additionally it studies the role of various drugs at various stages of pathogenesis. The model was validated by generating two-parameter heat plots, representing the characteristics of Covid-19, the sensitivity analysis identified the crucial parameters. The efficacy of interventions was assessed by optimal control problem. The model dynamics exhibited disease-free equilibrium and the infected equilibrium with their stability, based on the reproduction number R0, the transcritical bifurcation observed at R0=1. The burst rate and the natural death rate of the virus were observed as most significant parameters in the life-threatening Covid-19 pneumonia. The antiviral drugs affecting viral replication and those modulating the immune response, reduce the infected cells and viral load significantly. However, the yield was optimal and most effective when the combination therapy involving one or more antiviral and one or more immunomodulating drugs were administered together. These findings may help physicians with early decision making in treatment of life-threatening Covid-19 infection.

Background: Neutrophils, the most abundant white blood cells are known to play a major role in the fundamental physiological response to tackle with microbial infections via different mechanisms. A series of assays have been developed that mimic neutrophil functions both in vivo and in vitro to look at specific deficiencies of neutrophil function. There is need to develop method to have defined normal range for these tests to differentiate between health and disease. We aim to define normal range for panel of screening assays in healthy adult Indian participants. Materials and Methods: The study included 30 male and 30 female adult healthy participants. A volume of 10 ml of blood was collected from each participant. Four different assays that included chemotaxis, phagocytosis, intracellular killing (candidacidal assay), and nitroblue tetrazolium (NBT) test were performed. For defined range was established for all the assays. Simultaneously controls were set up for all the tests. Results: For NBT assay, the mean values for control and test were 13.58 and 58.90 respectively. The mean values for the control and test for phagocytosis assay were 1.77 and 4.49. Similarly, the values for candidacidal assay were 11.67% and 34.98. Finally, the values for chemotaxis test were 2.13 cm for Formyl-Methionyl-Leucyl-Phenylalanine, 0.54 cm for participant's serum and 0.48 cm for the medium. Conclusion: Based on the data generated, the values produced in the present investigation should be considered as normal range for adult population between the age group of 25–50 years for the protocols followed in the study.

Background: Cancer-related fatigue (CRF) has a high prevalence in individuals with cancer, especially in those with central nervous system (CNS) tumors, and impacts the quality of life (QOL). However, there are limited data on CRF in Indian patients with CNS tumors. Objective: We aimed to estimate the CRF scores in patients with CNS tumors. Materials and Methods: This cross-sectional study was conducted in the Department of Medical Oncology of the Tata Memorial Hospital in Mumbai, India, between May 2019 and August 2019. Patients with CNS tumors aged ≥18 years, who presented to the Neuro-Oncology Disease Management Group, were enrolled in the study. The Functional Assessment of Chronic Illness Therapy Fatigue Scale was used to collect data related to well-being and fatigue. Data were captured in a single visit. Descriptive statistics and multiple regression analyses were performed to identify the factors associated with a high fatigue score. Results: There were 100 patients in our cohort with a median age of 40 (range, 18–64) years. The median fatigue score was 36. The median physical well-being, social well-being, emotional well-being, functional well-being, and Functional Assessment of Cancer Therapy-General (FACT-G) scores were 19, 19.9, 18, 17, and 72, respectively. There was a significant correlation between the fatigue score and the various subscales of FACT-G (P < 0.0001). The associated risk factors for CRF were age (P = 0.021), poor Eastern Cooperative Oncology Group-Performance Status (ECOG PS) (2–3) (P < 0.0001), general category based on the payment ability of the patient (P = 0.004), ongoing treatment status (P = 0.0003), and the presence of recurrent disease (P = 0.001). Conclusion: CRF is common in patients with CNS tumors and impacts all aspect of the QOL. It is affected by age, ECOG PS, payment ability, treatment status, and disease recurrence status.

Background: Polypharmacy and the use of potentially inappropriate medications (PIMs) are important issues in older patients with cancer. Objectives: We aimed to study the prevalence of polypharmacy, and the use of PIMs, including the peri-chemotherapy supportive care regimens in older Indian patients with cancer. Materials and Methods: This was an analysis of a prospective observational study of patients aged 60 years and over with a diagnosis of malignancy who were assessed in the geriatric oncology clinic at the Tata Memorial Hospital (Mumbai, India). Patients on five or more medications were considered to have polypharmacy; excessive polypharmacy was defined as ten or more medications and PIMs were defined and categorized according to the Beers criteria. Results: Between June 2018 and October 2020, 285 patients were enrolled in the study. Polypharmacy was noted in 55% of the patients and excessive polypharmacy in 13%. Polypharmacy was noted in 70% of the patients with lung cancer, compared to 45% for other malignancies, P < 0.001. Unindicated medications such as vitamins and calcium were being taken by 20% of the patients and 23% were taking alternative medications (ayurvedic/homeopathic/naturopathic). Eighty percent of the patients were taking PIMs, commonly proton-pump inhibitors (33%) and tramadol (30%). The median number of PIMs was 2 (interquartile range, 1–2). Of the peri-chemotherapy supportive care medications, 53% were potentially inappropriate, commonly intravenous antihistamines in 39%, histamine H2 blockers in 15%, and steroids in 12%. Conclusions: Polypharmacy and PIM use are common problems in older Indian patients with cancer. Recognizing the problem and taking steps to ensure safe medication prescription practices should be a priority.

Background: Methicillin- resistant Staphylococcus aureus (MRSA) strains are predominantly significant because they are leading healthcare- associated infections worldwide and even majorly emerged as community associated infections. Methods: A total of 40 S. aureus isolates were collected from Navodaya Institute of Medical Sciences, Raichur Institute of Medical Sciences, and Mid Tech Diagnostic Laboratory, Raichur, and analyzed for mecA, Panton–Valentine leukocidin (PVL), and staphylococcal cassette chromosome mec (SCCmec) typing by gradient and Multiplex polymerase chain reaction (PCR). Results: Out of 40 S. aureus isolates, 7 (17.8%) were resistant and 33 (82.8%) were sensitive for methicillin antibiotic. The seven isolates showed positive for Vancomycin /cefoxitin Ezy MIC strip and oxacillin antibiotic MIC was ≥ 8μg/ml respectively PCR detection has revealed, seven isolates were positive for mecA and SCCmec typing, but none of the isolates has shown positive for PVL genes. The study shows the presence of SCCmec Type II and III was confirmed by multiplex PCR in hospital-acquired MRSA isolate and mecA gene positive of seven strains of MRSA Conclusion: The study demonstrated high specificity and positive prediction of the detection of MRSA from clinical samples.

Purpose/Aim: To evaluate adherence to medication in chronic illnesses during pregnancy and to identify factors responsible for non-adherence. Methods: This was a prospective, cross-sectional, questionnaire based study initiated after approval of the institutional ethics committee. Pregnant women suffering from any chronic illness (except HIV) were questioned to evaluate adherence to medication in chronic illnesses during pregnancy and to detect factors responsible for non-adherence using a semi-structured, open-ended questionnaire. Adherence to medication was also assessed using 4-item Morisky's medication adherence scale. Results: Rate of high adherence was significantly more (58.77%) with medications for chronic illness compared to medications for normal pregnancy (15.78%). Majority of women were more concerned about the chronic illness and believed that keeping the chronic illness under control is more important for normal growth of the baby. Unawareness about usefulness of each medicine and forgetfulness were the most common reasons for non-adherence to medications. Not taking prescribed dose was the most common type of non-adherence. Level of adherence positively correlated with level of education while it was inversely related to number of tablets per day. Conclusion: Higher adherence to medications for chronic illnesses during pregnancy is an encouraging finding but at the same time poor adherence to medications for normal pregnancy is a matter of concern. Most of the issues responsible for non-adherence to medication as reported in this study can be resolved to a significant extent by planning and implementing interventions aimed at improving adherence to treatment during pregnancy in which health professionals play a major role.

A solitary median maxillary central incisor (SMMCI) is a rare anomaly that can occur alone or be associated with other systemic abnormalities. Early diagnosis of SMMCI is crucial as it might indicate the presence of an associated congenital or developmental abnormality. The prevalence of live-born children with SMMCI is determined to be 1:50,000 and is more common among females. The purpose of this paper was to report an unusual case of a 9-year-old girl with SMMCI who had no growth deficiency or any other systemic involvement. Since pediatricians and dentists are the first professionals to evaluate an SMMCI's patient in most cases, it is important that they be aware of the possibility of other related systemic problems that require systemic care. Appropriate treatment, diagnosis, and referral should also include neuropediatric evaluation, genetic testing, and craniofacial profile analysis along with multidisciplinary approach.

Background: Although the multidimensional geriatric assessment (GA) is considered the standard of care, it is not uniformly practiced. In older patients with cancer, shared decision-making requires a clear understanding of the goals of therapy. Objectives: We aimed to understand the perceptions of health-care professionals of the need to assess the various domains in the GA and what would constitute worthwhile outcomes in older patients with cancer. Materials and Methods: An online questionnaire survey was conducted by the geriatric oncology group of the Department of Medical Oncology at the Tata Memorial Hospital in Mumbai, India. Participants in the survey included various health professionals with an interest in the care of older patients with cancer. Data were collected in Microsoft Excel and basic descriptive statistics were performed. Results: Between July and August 2020, 234 health-care professionals responded to the survey. The respondents included predominantly medical oncologists (146, 70.9%), practicing in academic centers (148, 65.6%) from India (168, 87%). According to 46% of the respondents, over 30% of the patients in their practices were in the geriatric age group; yet, 144 (73.8%) respondents reported that they referred

It has been demonstrated by using generalized phenomenological irreversible thermodynamic theory (GPITT) that by replacing the conventional composition variables {xk} by the quantum level composition variables {x˜k,j} corresponding to the nonequilibrium population of the quantum states, the resultant description remains well within the local thermodynamic equilibrium (LTE) domain. The next attempt is to replace the quantum level composition variables by their respective macroscopic manifestations as variables. For example, these manifestations are, say, the observance of fluorescence and phosphorescence, existence of physical fluxes, and ability to register various spectra (microwave, IR, UV-VIS, ESR, NMR, etc.). This exercise results in a framework that resembles with the thermodynamics with internal variables (TIV), which too is obtained as a framework within the LTE domain. This TIV-type framework is easily transformed to an extended irreversible thermodynamics (EIT) type framework, which uses physical fluxes as additional variables. The GPITT in EIT version is also obtained well within the LTE domain. Thus, GPITT becomes a complete version of classical irreversible thermodynamics (CIT). It is demonstrated that LTE is much more flexible than what CIT impresses upon. This conclusion is based on the realization that the spatial uniformity for each tiny pocket (cell) of a spatially non-uniform system remains intact while developing GPITT and obviously in its other versions.

Staphylococcus aureus protein A (SpA) is an IgG Fc-binding virulence factor that is widely used in antibody purification and as a scaffold to develop affinity molecules. A cyclized SpA Z domain could offer exopeptidase resistance, reduced chromatographic ligand leaching after single-site endopeptidase cleavage, and enhanced IgG binding properties by preorganization, potentially reducing conformational entropy loss upon binding. In this work, a Z domain trimer (Z3) was cyclized using protein intein splicing. Interactions of cyclic and linear Z3 with human IgG1 were characterized by differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC). DSF showed a 5 ℃ increase in IgG1 melting temperature when bound by each Z3 variant. SPR showed the dissociation constants of linear and cyclized Z3 with IgG1 to be 2.9 nM and 3.3 nM, respectively. ITC gave association enthalpies for linear and cyclic Z3 with IgG1 of −33.0 kcal/mol and −32.7 kcal/mol, and −T∆S of association 21.2 kcal/mol and 21.6 kcal/mol, respectively. The compact cyclic Z3 protein contains 2 functional binding sites and exhibits carboxypeptidase Y-resistance. The results suggest cyclization as a potential approach toward more stable SpA-based affinity ligands, and this analysis may advance our understanding of protein engineering for ligand and drug development.

Abstract Background The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology’s central role; this may have future negative consequences for resource allocation. Methods, findings and interpretation This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the healthcare value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined.

Abstract Background The objective of present research work is to design and characterize camptothecin gel using Carbopol-934 for the treatment of epidermoid carcinoma. Optimized herbal gel formulations were evaluated for homogeneity and appearance, viscosity, extrudability, spreadability, drug content, drug release, pH, and in vitro skin cancer activity on A431 cell lines. Results Mass and Infrared Spectra respectively conforms molecular weight and functional groups present in camptothecin. All the formulations F1 to F5 showed good homogeneity, pH from 6.68 to 6.90, spreadability in the range of 15.81–23.37 gm.cm/s, extrudability 85.51–90.45% w/w, drug content 89.12–96.64%, and in vitro diffusion 88.36–98.40%, respectively. The drug release study showed that all the formulations followed a diffusion-controlled, zero-order release mechanism. Anticancer activity results indicate that camptothecin gel induce cell death in A-439 cells having IC50 48.03 μg and % apoptosis 54.67 ± 4.58. Conclusion Topical delivery of camptothecin alleviates the side effects caused by systemic chemotherapy; hence, the developed herbal gel formulation can be effectively useful to deliver camptothecin in the treatment of epidermoid carcinoma on A-431 cells.

Abstract Background Relapsed high‐grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in‐vitro and in‐vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. Methods We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re‐irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1‐5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. Findings 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). Interpretation The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide‐radiation combination while the dose of 800 mg TDS needs to be used with single‐agent CCNU.

The development of reliable measures of health in ageing organisms is a need in ageing research. Using atomic force microscopy, here, the authors assess whole body stiffness of worms and show that it reflects organismal fitness.

Background: Apart from disease management and the toxicities of systemic therapy, financial burden is an additional liability in patients with brain tumors receiving systemic therapy. However, currently, there is a paucity of data on the financial toxicities incurred by these patients. Objectives: In this study, we aimed to assess the perceived financial toxicity and the quality of life (QOL) of patients with brain tumors receiving systemic therapy and to evaluate the factors affecting it. Materials and Methods: This single-center, cross-sectional study was conducted in the Department of Medical Oncology at the Tata Memorial Hospital in Mumbai, India, between January 2019 and March 2019. The financial toxicity scores (FTSs) were captured at a single visit from the patients with primary brain tumors with or without recurrence who visited the Neuro Medical Oncology Outpatient Department. The Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy and Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaires were used to collect data on the FTS and QOL, respectively. Pearson correlation coefficient was used to determine the correlation between FTS and the various domains of QOL. Multiple linear regression was used to determine the factors that influence FTS, and P < 0.05 was considered statistically significant. Results: A total of 147 patients were included in the study; the median age of the cohort was 38 years (range, 16–67). Of them, 102 (67.5%) were men and 48 (32.5%) were women. The median monthly income was ₹7000 ($92.75). The median FTS was 13 (interquartile range [IQR], 6–21). The associated risk factors for financial toxicity were age (beta = 0.242,P = 0.001), category under which the patient availed treatment – private (regular cost) or general (discounted cost) (beta = 0.398, P < 0.001), and disease status (beta = −0.151,P = 0.043). The median FACT-General score, FACT-Br Trial Outcome Index score, and FACT-Br Total score were 77.2 (IQR, 64-91.7), 92.89 (IQR, 73.16–107), and 131.5 (IQR, 107.33–150.9), respectively, and were significantly associated with FTS ( P < 0.001). Conclusions: Financial distress was found to be severe in patients with brain tumors receiving systemic therapy. The age, payment category under which the patients availed treatment, and the disease status were found to be contributory factors. These, along with the QOL, were significantly associated with FTS.

Introduction: Diabetics face a series of challenges that affect all aspects of their daily life. Diabetes related complications adversely affect patient’s health-related quality of life (HRQoL). Knowledge and self-care skills of diabetics are corner stones to improve their HRQoL. Objective: To assess the impact of pharmacist-supervised intervention on HRQoL of newly diagnosed diabetics using an Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire. Materials and Methods: A pre-post comparison study was conducted among the control group (CG), test 1 group (T1G) and test 2 group (T2G) patients with three treatment arms to explore the impact of pharmacist-supervised intervention on HRQoL of newly diagnosed diabetics for 18 months. Patients’ HRQoL scores were determined using ADDQoL questionnaire at baseline, 3, 6, 9 and 12-months. T1G patients received pharmacist’s intervention whereas T2G patients received diabetic kit demonstration in addition to pharmacist’s intervention. CG patients were deprived of pharmacist intervention and diabetic kit demonstration, and only received care from attending physician/nurses. Non-parametric tests were used to find the differences in an average weighted impact scores (AWIS) among the groups before and after the intervention at P ≤ 0.05. Results: Friedman test identified significant (P < 0.001) improvement in AWIS among the test groups’ patients. Differences in scores were significant between T1G and T2G at 6-months (P = 0.033), 9-months (P < 0.001) and 12-months (P < 0.001); between CG and T1G at 12-months (P < 0.001) and between CG and T2G at 9-months (P < 0.001) and 12-months (P < 0.0010) on Mann.Whitney U test. Conclusion: Pharmacist’s intervention improved AWIS of test groups’ diabetics. Diabetic kit demonstration strengthened the disease understanding and selfcare skills of T2G patients. Disease and self-care awareness among diabetics should be increased in Nepali healthcare system by involving pharmacists for better patient’s related outcomes.