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Combined treatment modalities for age related macular degeneration

Das RA, Romano A, Chiosi F, Menzione M, Rinaldi M

Curr Drug Targets, 2011 Feb;12(2):182-9.
PMID: 20887244

BACKGROUND: Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50.
OBJECTIVES: The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD.
DATA SOURCES: Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs).
RESULTS: The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease.
CONCLUSIONS: Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.
Fulltext The Toxic Truth About Carbon Nanotubes in Water Purification: a Perspective View

Das R, Leo BF, Murphy F

Nanoscale Res Lett, 2018 Jun 18;13(1):183.
PMID: 29915874 DOI: 10.1186/s11671-018-2589-z

Without nanosafety guidelines, the long-term sustainability of carbon nanotubes (CNTs) for water purifications is questionable. Current risk measurements of CNTs are overshadowed by uncertainties. New risks associated with CNTs are evolving through different waste water purification routes, and there are knowledge gaps in the risk assessment of CNTs based on their physical properties. Although scientific efforts to design risk estimates are evolving, there remains a paucity of knowledge on the unknown health risks of CNTs. The absence of universal CNT safety guidelines is a specific hindrance. In this paper, we close these gaps and suggested several new risk analysis roots and framework extrapolations from CNT-based water purification technologies. We propose a CNT safety clock that will help assess risk appraisal and management. We suggest that this could form the basis of an acceptable CNT safety guideline. We pay particular emphasis on measuring risks based on CNT physico-chemical properties such as diameter, length, aspect ratio, type, charge, hydrophobicity, functionalities and so on which determine CNT behaviour in waste water treatment plants and subsequent release into the environment.
Synergic effect of tungstophosphoric acid and sonication for rapid synthesis of crystalline nanocellulose

Hamid SB, Zain SK, Das R, Centi G

Carbohydr Polym, 2016 Mar 15;138:349-55.
PMID: 26794771 DOI: 10.1016/j.carbpol.2015.10.023

The utilization of sonication in combination with tungstophosphoric acid (PWA) catalyst reduces dramatically the time of operations from 30h to 10min by using an optimum sonication power of 225W. The basic cellulosic structure is maintained, allowing preparing high-quality nanocellulose. The size of the nanocellulose obtained was in the range from 15 to 35nm in diameter and several hundred nanometers in length, with a high crystallinity of about 88%. The nanocellulose shows a surface charge of -38.2mV which allows to obtaina stable colloidal suspension. The surface tension of the stable, swollen aqueous nanocellulose was close to that of water. These characteristics, together with the fast procedure allowed from the synergic combination of PWA and sonication, evidence the high potential of the proposed method for the industrial production of nanocellulose having the properties required in many applications.
Fulltext Highly Efficient and Stable Novel NanoBiohybrid Catalyst to Avert 3,4-Dihydroxybenzoic Acid Pollutant in Water

Das R, Hamid SB, Annuar MS

Sci Rep, 2016 10 10;6:33572.
PMID: 27721429 DOI: 10.1038/srep33572

The present study reported for the first time covalent immobilization of protocatechuate 3,4-dioxygenase (3,4-POD) onto functionalized multi-walled carbon nanotubes (F-MWCNT) for degrading the toxic 3,4-dihydroxybenzoic acid (3,4-DHBA) pollutant in water. The F-MWCNTs had a maximum 3,4-POD loading of 1060 μg/mg. Immobilized 3,4 POD had 44% of relative structural changes to its free configurations. Nevertheless, >90% of relative activity and about 50% of catalytic efficiency were retained to the free enzyme. Immobilized 3,4-POD demonstrated higher alkaline stability and thermostability than the free 3,4-POD. The free and immobilized 3,4-POD lost 82% and 66% of relative activities, respectively after 180 min of incubations at 90 °C. Excellent shelf-life was observed for the immobilized 3,4-POD with residual activity of 56% compared with 41% and 39% of the free 3,4-POD at 4 °C and 25 °C over 30 days storage. Immobilized 3,4-POD showed >60% of catalytic activity retention even after ten-cycle uses, defraying the expenses of free 3,4-POD productions for long term uses. Finally, the immobilized 3,4-POD removed 71% of 3,4-DHBA from water in <4 h, paving its future application for water purification with reduced costs and time.
Fulltext Chronic musculoskeletal pain among elderly individuals in a rural area of West Bengal: A mixed-method study

Sengupta T, Paul B, Banerjee A, Das R, Halder R

Malays Fam Physician, 2023;18:25.
PMID: 37205144 DOI: 10.51866/oa.232

INTRODUCTION: The high prevalence among elderly individuals and potential adverse impact on their overall life quality make chronic musculoskeletal pain a significant public health concern. Chronic musculoskeletal pain is an important cause of self-medication, which must be addressed to avoid various side effects and improve elderly health. This study aimed to determine the prevalence of chronic musculoskeletal pain and its associated factors among individuals (age ≥60 years) in rural West Bengal and explore their perspectives and perceived barriers regarding pain and its management.
METHOD: This mixed-method study was conducted in rural West Bengal from December 2021 to June 2022. The quantitative strand was conducted by interviewing 255 elderly participants (age ≥60 years) using a structured questionnaire. The qualitative strand was conducted via in-depth interviews of 10 patients with chronic pain. Quantitative data were analyzed using SPSS version 16, and chronic pain-related factors were analyzed using logistic regression models. Qualitative data were analyzed thematically.
RESULTS: Among the participants, 56.8% reported chronic musculoskeletal pain. The most frequently affected site was the knee joint. Comorbidity (adjusted odds ratio [aOR]=7.47, 95% confidence interval [CI]=3.2-17.5), age (aOR=5.16, 95% CI=2.2-13.5), depression (aOR=2.96, 95% CI=1.2-6.7) and over-the-counter drug usage (aOR=2.51, 95% CI=1.1-6.4) were significantly associated with chronic pain. Analgesic dependency, lack of motivation to adopt lifestyle modifications, lack of knowledge on analgesic side effects were considered pain management barriers.
CONCLUSION: Managing comorbidities, providing mental support, generating awareness of analgesic side effects, strengthening healthcare facilities should be prioritized for holistic chronic musculoskeletal pain management.
Fulltext Utilisation of adolescent reproductive and sexual health services in a rural area of West Bengal: A mixed-method study

Banerjee A, Paul B, Das R, Bandyopadhyay L, Bhattacharyya M

Malays Fam Physician, 2023;18:26.
PMID: 37205146 DOI: 10.51866/oa.224

INTRODUCTION: Despite policy actions and strategic efforts for improving the reproductive and sexual health of adolescents by promoting the uptake of adolescent reproductive and sexual health (ARSH) services, the utilisation rate remains significantly low, especially in rural areas of India. This study aimed to assess the utilisation of these services by adolescents in rural West Bengal and its associated determinants.
METHOD: This mixed-method study was conducted from May to September 2021 in the Gosaba rural block of South 24 Parganas, West Bengal. Quantitative data were collected from 326 adolescents using a pre-tested structured questionnaire. Qualitative data were collected via four focus group discussions among 30 adolescents and key-informant interviews among six healthcare workers. Quantitative data were analysed using SPSS, while qualitative data were analysed thematically.
RESULTS: Ninety-six (29.4%) adolescents had utilised ARSH services at least once during adolescence. The factors associated with non-utilisation of ARSH services were younger age, female sex, increasing reproductive health stigma and decreasing parent-adolescent communication related to sexual health. Qualitative exploration revealed that unawareness regarding services, perceived lack of privacy and confidentiality at healthcare facilities and disruption of services post-emergence of the COVID-19 pandemic were some major barriers to ARSH service utilisation.
CONCLUSION: A multi-component strategy, including promotion of adolescent-friendly health clinics, community support interventions associated with motivation and counselling of parents regarding the importance of adolescent reproductive health, is needed to improve the utilisation of ARSH services. Necessary steps to correct the deficiencies at the facility level should also be prioritised.
Counterpoint. Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine

Bhattachary-Chatterjee M, Nath Baral R, Chatterjee SK, Das R, Zeytin H, Chakraborty M, et al.

Cancer Immunol Immunother, 2000 Jun;49(3):133-41.
PMID: 10881692

Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.
Fulltext In silico-based vaccine design against Ebola virus glycoprotein

Dash R, Das R, Junaid M, Akash MF, Islam A, Hosen SZ

Adv Appl Bioinform Chem, 2017;10:11-28.
PMID: 28356762 DOI: 10.2147/AABC.S115859

Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154-162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.
Population genetic variation of SLC6A4 gene, associated with neurophysiological development

Hande SH, Krishna SM, Sahote KK, Dev N, Erl TP, Ramakrishna K, et al.

J Genet, 2021;100.
PMID: 33764333

The serotonin transporter 5-HTT is encoded by a single gene SLC6A4. Polymorphisms in SLC6A4 has been associated with a wide variety of neurological and psychiatric disorders including increased risk of posttraumatic stress disorder, higher likelihood for depression, obsessive-compulsive disorder (OCD), increased hostility and criminal behaviour. Genes associated with complex diseases often exhibit strong signatures of purifying selection compared to others. Further, discernible population specific variation in the signature of natural selection have been observed for several complex disease-related genes. In this project we aimed to investigate the population genetic variation of the serotonin transporter gene (SLC6A4), focussing on the single nucleotide polymorphisms (SNPs). To this end, we employed 2504 individuals around the globe available in 1000 Genome project Phase III data and classified them into five ethnic groups: Americans (AMR), Europeans (EUR), Africans (AFR), East Asians (EAS) and South Asians (SAS). Principal component analysis (PCA) performed on all annotated SNPs of SLC6A4 depicted clear clustering between Africans and the rest of the world along PC1, and East Asians and other non-African populations along PC2. Further, these SNPs were found to be under strong selection pressure especially among East Asian populations with significantly high positive cross-population extended haplotype homozygosity scores compared to Africans, indicating that SLC6A4 has likely undergone a strong selective sweep among the East Asians in the recent past. Our study can potentially explain the association between polymorphisms in SLC6A4, and major depression and suicidal tendencies among people of East Asian ancestry and the absence of such associations among people of European ancestry.
The formation of hybrid carbon nanomaterial by chemical vapor deposition: an efficient adsorbent for enhanced removal of methylene blue from aqueous solution

Alayan HM, Alsaadi MA, Das R, Abo-Hamad A, Ibrahim RK, AlOmar MK, et al.

Water Sci Technol, 2018 Mar;77(5-6):1714-1723.
PMID: 29595174 DOI: 10.2166/wst.2018.057

In this study, carbon species were grown on the surface of Ni-impregnated powder activated carbon to form a novel hybrid carbon nanomaterial by chemical vapor deposition. The carbon nanomaterial was obtained by the precipitation of the methane elemental carbon atoms on the surface of the Ni catalyst. The physiochemical properties of the hybrid material were characterized to illustrate the successful growth of carbon species on the carbon substrate. The response surface methodology was used for the evaluation of adsorption parameters effect such as pH, adsorbent dose and contact time on the percentage removal of MB dye from aqueous solution. The optimum conditions were found to be pH = 11, adsorbent dose = 15 mg and contact time of 120 min. The material we prepared showed excellent removal efficiency of 96% for initial MB concentration of 50 mg/L. The adsorption of MB was described accurately by the pseudo-second-order model with R2 of 0.998 and qe of 163.93 (mg/g). The adsorption system showed the best agreement with Langmuir model with R2 of 0.989 and maximum adsorption capacity (Qm) of 250 mg/g.
Recent advances in nanomaterials for water protection and monitoring

Das R, Vecitis CD, Schulze A, Cao B, Ismail AF, Lu X, et al.

Chem Soc Rev, 2017 Sep 29.
PMID: 28959815 DOI: 10.1039/c6cs00921b

The efficient handling of wastewater pollutants is a must, since they are continuously defiling limited fresh water resources, seriously affecting the terrestrial, aquatic, and aerial flora and fauna. Our vision is to undertake an exhaustive examination of current research trends with a focus on nanomaterials (NMs) to considerably improve the performance of classical wastewater treatment technologies, e.g. adsorption, catalysis, separation, and disinfection. Additionally, NM-based sensor technologies are considered, since they have been significantly used for monitoring water contaminants. We also suggest future directions to inform investigators of potentially disruptive NM technologies that have to be investigated in more detail. The fate and environmental transformations of NMs, which need to be addressed before large-scale implementation of NMs for water purification, are also highlighted.
Fulltext Global and local mutations in Bangladeshi SARS-CoV-2 genomes

Hasan MM, Das R, Rasheduzzaman M, Hussain MH, Muzahid NH, Salauddin A, et al.

Virus Res, 2021 May;297:198390.
PMID: 33737154 DOI: 10.1016/j.virusres.2021.198390

Coronavirus Disease 2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations, and pathogenesis. Nearly 0.4 million mutations have been identified so far among the ∼60,000 SARS-CoV-2 genomic sequences. In this study, we compared a total of 371 SARS-CoV-2 published whole genomes reported from different parts of Bangladesh with 467 sequences reported globally to understand the origin of viruses, possible patterns of mutations, and availability of unique mutations. Phylogenetic analyses indicated that SARS-CoV-2 viruses might have transmitted through infected travelers from European countries, and the GR clade was found as predominant in Bangladesh. Our analyses revealed 4604 mutations at the RNA level including 2862 missense mutations, 1192 synonymous mutations, 25 insertions and deletions and 525 other types of mutation. In line with the global trend, D614G mutation in spike glycoprotein was predominantly high (98 %) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab, S, ORF3a, M, and N were significantly higher (p < 0.001) for sequences containing the G614 variant compared to those having D614. Previously reported frequent mutations, such as R203K, D614G, G204R, P4715L and I300F at protein levels were also prevalent in Bangladeshi isolates. Additionally, 34 unique amino acid changes were revealed and categorized as originating from different cities. These analyses may increase our understanding of variations in SARS-CoV-2 virus genomes, circulating in Bangladesh and elsewhere.
Primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region: a systematic review and meta-analysis

Kuo YT, Liou JM, El-Omar EM, Wu JY, Leow AHR, Goh KL, et al.

Lancet Gastroenterol Hepatol, 2017 10;2(10):707-715.
PMID: 28781119 DOI: 10.1016/S2468-1253(17)30219-4

BACKGROUND: So far, a comprehensive systematic review and meta-analysis has not been done of the prevalence of primary antibiotic resistance in Helicobacter pylori in the Asia-Pacific region. We aimed to assess the trends and regional differences in primary antibiotic resistance to H pylori in the Asia-Pacific region and to examine the relation between resistance and first-line eradication.
METHODS: We did a systematic review and meta-analysis of primary antibiotic resistance to H pylori and the efficacy of first-line regimens in the Asia-Pacific region. We searched PubMed, Embase, and the Cochrane Library for articles published between Jan 1, 1990, and Sept 30, 2016; we also searched abstracts from international conferences. Both observational studies and randomised controlled trials were eligible for inclusion in the analysis of primary antibiotic resistance, but only randomised controlled trials were eligible for inclusion in the analysis of efficacy of first-line therapies. Meta-analysis was by the random-effects model to account for the substantial variations in resistance across the region. We did subgroup analyses by country and study period (ie, before 2000, 2001-05, 2006-10, and 2011-15) to establish country-specific prevalences of primary antibiotic resistance and first-line eradication rates. This study is registered with PROSPERO, number CRD42017057905.
FINDINGS: 176 articles from 24 countries were included in our analysis of antibiotic resistance. The overall mean prevalences of primary H pylori resistance were 17% (95% CI 15-18) for clarithromycin, 44% (95% CI 39-48) for metronidazole, 18% (95% CI 15-22) for levofloxacin, 3% (95% CI 2-5) for amoxicillin, and 4% (95% CI 2-5) for tetracycline. Prevalence of resistance to clarithromycin and levofloxacin rose significantly over time during the period investigated, whereas resistance to other antibiotics remained stable. 170 articles from 16 countries were included in analysis of efficacy of first-line therapies. We noted unsatisfactory efficacy (ie, <80%) with clarithromycin-containing regimens in countries where the clarithromycin resistance rates were higher than 20%.
INTERPRETATION: The prevalence of primary antibiotic resistance varied greatly among countries in the Asia-Pacific region, and thus treatment strategy should be adapted relative to country-specific resistance patterns. Clarithromycin-containing regimens should be avoided in countries where the prevalence of clarithromycin resistance is higher than 20%.
FUNDING: Ministry of Health and Welfare of Taiwan, Ministry of Science and Technology of Taiwan, and Amity University.
Fulltext Optimization of the Synthesis of Superhydrophobic Carbon Nanomaterials by Chemical Vapor Deposition

Aljumaily MM, Alsaadi MA, Das R, Hamid SBA, Hashim NA, AlOmar MK, et al.

Sci Rep, 2018 02 09;8(1):2778.
PMID: 29426860 DOI: 10.1038/s41598-018-21051-3

Demand is increasing for superhydrophobic materials in many applications, such as membrane distillation, separation and special coating technologies. In this study, we report a chemical vapor deposition (CVD) process to fabricate superhydrophobic carbon nanomaterials (CNM) on nickel (Ni)-doped powder activated carbon (PAC). The reaction temperature, reaction time and H2/C2H2 gas ratio were optimized to achieve the optimum contact angle (CA) and carbon yield (CY). For the highest CY (380%) and CA (177°), the optimal reaction temperatures were 702 °C and 687 °C, respectively. However, both the reaction time (40 min) and gas ratio (1.0) were found to have similar effects on CY and CA. Based on the Field emission scanning electron microscopy and transmission electron microscopy images, the CNM could be categorized into two main groups: a) carbon spheres (CS) free carbon nanofibers (CNFs) and b) CS mixed with CNFs, which were formed at 650 and 750 °C, respectively. Raman spectroscopy and thermogravimetric analysis also support this finding. The hydrophobicity of the CNM, expressed by the CA, follows the trend of CS-mixed CNFs (CA: 177°) > CS-free CNFs (CA: 167°) > PAC/Ni (CA: 65°). This paves the way for future applications of synthesized CNM to fabricate water-repellent industrial-grade technologies.
Fulltext Tacrine Derivatives in Neurological Disorders: Focus on Molecular Mechanisms and Neurotherapeutic Potential

Mitra S, Muni M, Shawon NJ, Das R, Emran TB, Sharma R, et al.

Oxid Med Cell Longev, 2022;2022:7252882.
PMID: 36035218 DOI: 10.1155/2022/7252882

Tacrine is a drug used in the treatment of Alzheimer's disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer's disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers' interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer's disease, as well as other neurological disorders like Parkinson's disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
Fulltext Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer

Sullivan T, Thirthagiri E, Chong CE, Stauffer S, Reid S, Southon E, et al.

Hum Mutat, 2021 Feb;42(2):200-212.
PMID: 33314489 DOI: 10.1002/humu.24154

The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations. Here we report the characterization of novel variants in the Malaysian and Singaporean population that consist of different ethnic groups (Malays, Chinese, Indian, and other indigenous groups). We have evaluated the functional significance of 14 BRCA2 variants of uncertain clinical significance by using multiple in silico prediction tools and examined their frequency in a cohort of 7840 breast cancer cases and 7928 healthy controls. In addition, we have used a mouse embryonic stem cell (mESC)-based functional assay to assess the impact of these variants on BRCA2 function. We found these variants to be functionally indistinguishable from wild-type BRCA2. These variants could fully rescue the lethality of Brca2-null mESCs and exhibited no sensitivity to six different DNA damaging agents including a poly ADP ribose polymerase inhibitor. Our findings strongly suggest that all 14 evaluated variants are functionally neutral. Our findings should be valuable in risk assessment of individuals carrying these variants.

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