Swami Rama Himalayan University

A BSTRACT Introduction Substance abuse issues are identified, in Uttarakhand, despite limited and outdated data. Thus, our study aims to assess the risk and prevalence of substance abuse (alcohol, tobacco, cannabis, cocaine, opioids, amphetamines, inhalants, sedatives, and hallucinogens) among teenagers and young people in the suburbs of Dehradun district of Uttarakhand. Methods A survey was conducted among 14,203 individuals aged 10–24 from Doiwala Block (6023 participants) and Sahaspur Block (8180 participants). The survey included participants from the community and schools/colleges and used the CRAFT and ASSIST questionnaire to establish risk scores for different drugs. Results In Doiwala block, the overall prevalence of substance use was 13.02%. The Risk Scoring for CRAFFT revealed that 58% of the 64 participants showed a high degree of risk of substance abuse. In Sahaspur Block, the overall prevalence of substance use was 8.14%. Among 10–17 years individuals (n = 107) using the CRAFFT questionnaire, 30% scored more than or equal to 2, which reflected a high potential risk. Discussion The growing epidemic of substance abuse is preventable in the community with collective efforts of the society, law enforcement department, community leaders, ASHA workers, school teachers, and health personnels. The best platform to achieve a difference in the community is at the school level, where the adolescents spend 6–7 hours of their time every day. Conclusion Addiction treatment programs that heavily emphasize inpatient treatment or hospitalization in addiction centers are unlikely to be able to keep up with the tremendous increase in the prevalence of substance abuse.

Background Immunotherapy that includes immune checkpoint inhibitors (ICI) is a revolutionary arm of the treatment of skin cancers like melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite this leap in clinical advances, a critically challenging area in this field is emerging resistance to immunotherapy that limits its efficaciousness in a profound segment of the population. This resistance can be classified as primary resistance, in which cancers fail to respond to initial regimen, or acquired resistance that develops after there is a favorable initial response. A comprehensive understanding of the basic mechanisms and figuring out novel strategies to combat resistance are necessary to improve patient outcomes. Methods A comprehensive review of recent studies was conducted with focus on preclinical and clinical evidence related to immunotherapy resistance in skin cancer with a wide literature search on databases such as PubMed, Cochrane, and Google Scholar with keywords, including “skin cancer,” “immunotherapy,” “malignant melanoma,” “drug resistance,” “mechanisms,” and “strategies” published in the last 15 years. Results This study aims to establish a review of the molecular and cellular mechanisms that contribute to development of drug resistance in skin cancer and to gauge emerging strategies to overcome these barriers. Insights into these mechanisms were classified into tumor‐intrinsic factors, like genetic and epigenetic changes, and tumor‐extrinsic factors, such as changes in tumor microenvironment (TME) and systemic immunosuppression. Therapeutic strategies that included combination therapies, newer checkpoint inhibitors, and modulation of the TME were evaluated. Key mechanisms leading to drug resistance identified include tumor‐intrinsic factors, including mutations in signaling pathways, tumor‐extrinsic factors, including immunosuppressive cells and changes in the TME, such as hypoxia that contributed to drug resistance. Upcoming strategies to counteract resistance included combination approaches, adoptive T‐cell therapy, and newer immunomodulatory agents that target resistance pathways. Conclusions There is a complex interplay of cancer and immune microenvironmental mechanisms that leads to development of immunotherapy resistance in skin tumor patients. A multi‐pronged approach with focus in fields of genomics and immunology as well as bioinformatics is required, along with combination therapies and novel immunomodulators, to tackle resistance and enhance clinical outcomes for patients suffering with skin tumors.

Objectives This study was aimed at identifying biofilm-producing carbapenem-resistant Acinetobacter baumannii (CRAB) from various clinical specimens and the possible relationship between biofilm formation and antimicrobial resistance at our clinical setup. Materials and Methods This observational study was conducted in the Department of Microbiology, HIMS, and Himalayan School of Biosciences at Swami Rama Himalayan University, Dehradun. A total of 72 CRAB were included and subjected to phenotypic microtiter plate assay and biofilm-forming gene detection using polymerase chain reaction. Statistical analysis The relationship between biofilm-forming CRAB and drug resistance was determined using a non-parametric statistical test. Results All 72 isolates of CRAB were uniformly found resistant to imipenem (100%) and meropenem (100%). A high level of resistance was observed against cefepime (100%), levofloxacin (99%), cotrimoxazole (70%), and minocycline (53%). Out of 72 CRAB isolates, 64 (89%) were identified phenotypically as biofilm producers and 8 (11%) as non-biofilm producers. All CRAB isolates harbored more than one biofilm-forming gene, including outer membrane protein A (ompA) (89%) and chaperon-usher pilus E (csuE) (68%). The most predominant gene, ompA, was carried by 56 (88%) biofilm producers and 8 (100%) non-biofilm producers. Conclusions A high frequency of biofilm-forming CRAB was identified in this study and found to variably carry ompA and csuE genes, suggesting the importance of implementation of biofilm eradication practices to reduce the burden of infection in critical settings.

The paradigm of cancer treatment has been shifting from traditional approaches to metal-based therapies; however, achieving effective and targeted treatments remains a significant challenge. The journey of metal-based drugs began with the serendipitous discovery of cisplatin, which paved the way for the development of various platinum derivatives. Additionally, other metals, such as ruthenium (Ru), nickel (Ni), zinc (Zn), and copper (Cu), have been explored for their therapeutic potential. Among these, ruthenium-based complexes stand out due to their unique redox properties, high selectivity, and remarkable chelation capabilities, making them promising candidates for cancer therapy. This Account aims to provide a comprehensive overview of the journey of ruthenium-based metal complexes, their current status, and their pharmacological and chemical classification. These pharmacophores enable the selective delivery of cytotoxic payloads to cancer cells while sparing healthy cells. Notably, the ruthenium complex IT-139 (formerly NKP-1339) has demonstrated significant promise in clinical studies for various cancer types, exhibiting a lower toxicity than platinum-based therapies. The Account also highlights other ruthenium-based complexes and their advances. It aims to provide readers with a detailed understanding of the role of ruthenium in metal-based drug development, its mechanisms of action, and its potential applications in personalized cancer treatments. This exploration underscores the potential of ruthenium complexes, both with and without active molecules, to emerge as safe and effective therapeutic candidates in clinical oncology. 1 Introduction 2 Importance of Ruthenium Metal and its Complexes 3 Synthesis of Ruthenium Complexes 4 Classification of Ruthenium Complex Antitumor Drugs Based on their Mode of Action 5 Classification of Ruthenium Complex Antitumor Drugs Based on their Structure and the Oxidation State of Ruthenium 6 Current Status of Drug Clinical Trials 7 Status and Applications of Metals Other than Ruthenium 8 Conclusion

Plasticized potato starch being a sustainable, renewable, and cost-effective reinforcement has been melt mixed in this study with nano-TiO2 and polypropylene (PP) and compression molded into test specimens. Starch concentration was kept at 20%, whereas nano-TiO2 was varied as 1, 3, and 5% in the hybrid composites. Investigations were done for the dispersion of TiO2 and starch in the base polymer, and studies for the impact of nano-TiO2 on the mechanical, electrical, and thermal characteristics were also done. No adversative degradation in the dry arc resistance and dielectric property of the PP composites was found even at high starch loading of 20%, whereas mechanical characterization revealed a decline in percentage elongation and flexural strength but nearly similar tensile and impact strengths. Dynamic mechanical analysis studies showed a decrease in the mechanical strength of the bio-composite PPST-20, which improved upon the fusion of nano-TiO2. Uniform dispersion of nano-TiO2 in the morphological structure was examined using scanning electron microscopy, whereas intact melting behavior and increased crystallization temperature indicating the nucleating effect of nanofiller were verified using differential scanning calorimeter studies. Two-stage degradation patterns due to biomaterial and PP were also evident in the thermo gravimetric analysis studies.

This study delves into sustainable bio-nanocomposite of polypropylene (PP) with thermoplastic starch and de-laminated nano-talc as filler. Synthesis and characterization were done in two stages, at first, thermoplastic starch in the PP matrix was kept at 15, 20, and 25% and bio-composite was investigated for their spectral, optical, mechanical, and thermal properties. Results revealed enhanced tensile strength, elongation, flexural strength, melt flow index, and melting point of the composite with 20% starch compared to other formulations. Thereafter, the PP matrix with 20% starch was taken as the base polymer, the concentration of nano-talc was kept at 1, 3, and 5%, and investigation of their mechanical properties revealed composite with 20% starch and 3% nano-talc to be better than those with 20% starch and nano-talc of 1 or 5%. Integration of 3% talc filling into the bio-composite material increased the tensile strength to 29.27 MPa and flexural modulus to 2964.6 MPa but, with marginal reduction in elongation and flexural strength to 1.03% and 40.59 Mpa, respectively. Increased mechanical properties can be attributed to the action of glycerol as a plasticizer and the uniform dispersion of fillers. X-ray diffraction study revealed uniform interplanar arrangement and crystal size whereas UV-Visio studies showed a decrease in ultraviolet absorbance. Differential scanning calorimetry and thermogravitational analysis studies revealed improved thermal stability.

Background Birth weight plays a vital role in an infant’s comprehensive development. Low birth weight (LBW) infants may go through several kinds of health complications in the early stages of their lives. This paper is an attempt to identify the predictors that significantly influence the likelihood of LBW through a model-based approach. Methodology Data for this hospital based cross sectional study includes 130 pregnant women during the years 2022-2023. We have applied logistic regression and the decision tree method for predicting LBW in pregnancies. The performance of these predictive models has been assessed through receiving operating characteristic curve (ROC). Results The findings revealed 38.5% prevalence of LBW in pregnancies. Factors such as age of mother, abortion, presence of co-morbidities, pregnancy complications, and gestational age have been identified as significant predictors ( P < 0.05) of LBW through logistic regression. The area under the ROC curve (AUC=0.881) for logistic regression and decision tree (AUC=0.814) indicates that the fitted models have better discrimination ability. Conclusions Logistic have better accuracy than decision tree model. Decision tree excels at capturing patterns but may overfit and hence should be used with caution. This study highlighted the need of targeted policy implementation on maternal and childhood care to reduce the risk of LBW.

Climate neutrality demands, therefore, not only a technological but also a change at the level of human behaviour. This chapter discusses the adaptation of behavioural economics in bringing about the desired change to promote sustainable practices and alleviate barriers to climate-neutral behaviour. Nudge theory, loss aversion, and social norms explain how cognitive bias, socioeconomic factors, and institutional constraints stand as barriers for sustainable behaviour. These challenges are counteracted by using the proposed INSPIRE framework, which combines strategies such as incentivization, nudges, feedback mechanisms, gamification, community-based interventions, reminders, and encouragement. Measurable impacts on carbon emissions have been seen in real-world examples such as programs for energy conservation, waste reduction, and adoption of renewable energy. Finally, the chapter addresses the policy implications of Behavioural Insights as a tool for integrating it with climate strategies, leveraging technologies like AI and IoT to scale interventions and promote cultural adaptability and inclusion. Methods of measuring intervention effects- challenges such as attribution and cultural differences are discussed along with recommendations for improved methodologies and multi-metric evaluation. Behavioural economics bridges the knowledge-action gap, offering effective tools for pro-environmental action. The book concludes with a call to policymakers, businesses, and communities to implement these insights to drive the transition to climate neutrality.

Healthcare workers (HCWs) actively involved in patient care at tertiary care hospitals face significant stress and workload, which may adversely impact their sympatho-vagal balance (SVB). Research has extensively investigated SVB using various techniques, such as heart rate variability (HRV). With its multifaceted approach, yoga has been suggested to influence autonomic nervous system function and, consequently, SVB. Thus, this study aims to investigate the efficacy of a 4-week yoga module on SVB among HCWs. This randomised controlled trial will involve 108 HCWs aged 19–60 years. Participants will be randomised to either (1) a yoga intervention group or (2) a medium-paced walking control group. The primary outcome is a change in HRV after 4 weeks of intervention. Secondary outcomes comprise immediate change in state anxiety, selective attention and HRV compared pre- and post-intervention on days 1, 14 and 28. Intention-to-treat and per-protocol analysis will be performed to gain a comprehensive understanding of the effects of intervention. Multivariate linear model will adjust covariates in baseline HRV data in both groups. Independent t-test will compare pre- and postdata on all outcomes between groups. Paired t-test will be used to compare pre- and postdata on all outcomes within the group. The study protocol is registered on the Clinical Trials Registry – India (CTRI) (CTRI/2024/09/074132).

The genital region is uniquely susceptible to both irritant and allergic contact dermatitis (ACD) due to its delicate anatomy, moist environment, and frequent exposure to potential irritants and allergens. Factors such as friction, maceration, and overuse of hygiene products significantly compromise the skin barrier, increasing the risk of dermatitis. The region’s sensitivity is further exacerbated by physiological changes, such as reduced estrogen levels in postmenopausal women, which heighten susceptibility to external agents. A detailed clinical history plays a critical role in diagnosing genital contact dermatitis (CD). Key elements include symptom onset, triggers, hygiene habits, and exposure to products used personally or by sexual partners. This thorough exploration often identifies potential irritants and allergens overlooked in a routine examination. Irritant CD (ICD) in the genital area typically presents as burning, stinging, and erythema soon after exposure to irritants. Chronic ICD may lead to scaling and lichenification. In contrast, ACD arises from delayed hypersensitivity to allergens, presenting as pruritus, erythema, and, in severe cases, vesiculobullous eruptions. Common agents implicated in ICD include soaps, urine, sweat, and certain hygiene sprays, while ACD is often triggered by allergens such as fragrances, topical medications, preservatives, and rubber components. Patch testing is a cornerstone of diagnosing genital ACD. It identifies specific allergens responsible for the dermatitis and helps in differentiating between relevant and incidental reactions. Expanding patch test series to include additional potential allergens, such as personal care products or items used by partners, enhances diagnostic accuracy. The repeat open application test is another valuable tool, particularly when patch testing yields inconclusive results. Management of genital CD primarily involves strict avoidance of identified irritants and allergens. Patients should cease using unnecessary topical medications and adopt hypoallergenic alternatives. Education on proper genital care, including the use of fragrance-free and dye-free products, is essential. Topical corticosteroids, calcineurin inhibitors, or phosphodiesterase-4 inhibitors may be prescribed for short-term relief.

Background Chronic myeloid leukemia [CML] is a common hematological malignancy where patients present with varied clinical symptoms and are usually diagnosed with incidentally detected elevated total leucocyte counts in hemogram. The presence of pelvic hematoma at the presentation of CML is an uncommon finding. Case Presentation Two male young adults presented with massive splenomegaly and pelvic hematoma. On evaluation for anemia and leukocytosis with massive splenomegaly, diagnosis of CML chronic phase [CML-CP] was made on peripheral smear, bone marrow examination including cytogenetic study and molecular methods [peripheral blood quantitative BCR: ABL1 by real-- time PCR]. The first patient underwent aspiration of hematoma, and the second patient presented late where the hematoma organized into a solid mass and no intervention could be possible. A basic available coagulation study revealed no abnormalities and was managed with tyrosine kinase inhibitors. Conclusion Initial manifestation of CML with pelvic hematoma is uncommon and should undergo aspiration or drainage to avoid organization of hematoma and compressive symptoms locally.

Individual around the globe faces enormous problems from illnesses of the neurological system and the cerebrum, including neurodegenerative conditions and brain tumours. There are still no demonstrated viable treatments for neurological conditions, despite advances in drug delivery technologies such as solid lipid nanoparticles, nanostructured lipid carriers, and nano‐liposomes. To address this, there is growing interest in leveraging naturally occurring bioactive substances for their therapeutic potential. However, challenges such as limited bioavailability and metabolism understanding hinder their efficacy, particularly in the brain. While various pharmaceutical interventions exist for neurodegenerative diseases, they often come with significant side effects, and there is currently no specific treatment to cure or slow down disease progression. Challenges such as the blood‐brain barrier and blood‐cerebrospinal fluid barrier present significant obstacles to deliver drugs into the brain. Strategies to improve drug penetration across these barriers include targeting specific transport systems and developing innovative drug delivery approaches. Hence, the development of nano‐carriers capable of targeting bioactive compounds to the brain represents a promising approach for neurodegenerative disease therapy. This review explores the potential of bioactive compound fortified nano‐delivery systems for treating neurodegenerative diseases, with various compounds offering unique avenues for investigating neurodegeneration pathways and strategies in overcoming associated challenges.

Carrageenan, a natural polysaccharide derived from red algae, has garnered significant attention for its versatile applications in biomedical, pharmaceutical, and material sciences because of its inherent biological and gelling nature. Moreover, its intrinsic properties, including gel-forming ability, biocompatibility, and tunable viscosity, make it a valuable material for drug delivery, tissue engineering, and food technology. However, these properties can be further enhanced or tailored through chemical and structural modifications per the requirements of biomedicine. This review explores various modifications of carrageenan, such as functional and ionic modifications, that alter its physiological and biomedical properties. Common changes in hydrophobicity were found through the addition of extra carbon chains and functional groups; moreover, ionic changes also affected hydrophobicity and cancer cell selectivity in the case of barium ions, which were analysed through the encapsulation of a water-insoluble drug. The conductivity was also enhanced by ionic changes as well as the addition of aromatic groups to carrageenan, which could be utilized for ionic moments in tissue engineering and ion-linked targeted drug delivery. Overall, all of these modifications were crucial for resolving the limitations of the parent polymer (toxicity, conductivity and excessive hydrophilicity), expanding its range of possible uses and expanding its use in targeted drug delivery, cancer therapy, wound healing, and smart material development. This review delves into the underlying mechanisms of these modifications and highlights their impact on the biomedical and material science applications of carrageenan, providing a pathway for future innovations in this field.

Mushrooms are crucial in the food and nutraceutical industries for their unique nutritional profile and versatile culinary applications. Despite numerous wild varieties offering substantial health benefits, they are underutilized. This study aims to comprehensively analyze Agaricus bisporus (AB) and Scleroderma texense (ST) to understand their distinct characteristics, aiding food processors in making informed ingredient decisions. Engineering properties of fresh mushrooms revealed significant variations. AB exhibited larger dimensions and lower moisture content compared to ST. Proximate analysis of mushroom flour indicated that AB possessed higher fat content (23.89%), energy and calorie value while ST inner mass had highest protein content (23.75%) compared to ST coat. ST coat demonstrated highest crude fibre content than AB along with superior flow and packing properties compared to AB and ST inner mass. Dried mushrooms had a shrunken strides-like structure, as observed by SEM. The levels of K, Ca, Fe, P, and Mg were significantly higher in ST than in AB, marking the first study to report the elemental composition of ST as revealed by EDX. Results obtained from FTIR revealed the presence of functional groups associated with fat (1740 cm−1), protein (1560 cm−1), polysaccharides (1500–750 cm−1), and moisture (3300 cm−1) in mushroom samples. AB had a higher total phenolic content (5.49 mg GAE g−1) and DPPH free scavenging activity (68.07%), while ST, demonstrated superior total flavonoid content (4.66 mg QE g−1) and ABTS scavenging activity (87.69%). The outcomes of this study offer a wealth of information that can be leveraged by food scientists, product developers, and the food industry as a whole.

Monkeypox has become a major worldwide health issue, which has brought attention to the necessity of having a thorough understanding of this zoonotic virus. An extensive examination of the monkeypox virus's taxonomy, morphology, replication cycle, transmission, clinical symptoms, and treatment options is given in this article. The review also addresses the possibility that, given the growing interconnection of human populations and the drop in smallpox vaccination rates, the monkeypox virus will take over the ecological niche once occupied by the smallpox virus.

The Ganga river, one of the largest and most culturally significant rivers in India, supports millions of people living along its banks. However, extensive use and untreated wastewater discharge have led to significant contamination. This study utilizes land use and land cover (LULC) analysis, along with regular water sampling from 2021 to 2222, to assess variations in physical, chemical, and biological characteristics and evaluate health risks posed by heavy metals across eight monitoring sites in the Ganga and Yamuna rivers, Prayagraj, India. Results were compared with drinking water standards established by the Bureau of Indian Standards (BIS) and the World Health Organization (WHO). The Water Quality Index (WQI) indicated substantial water quality degradation at sites S2 (Ganga) and S8 (Yamuna). Although heavy metal levels (Cu, Fe, Cd, Pb, Mn, Cr) fluctuated across sites, Pb and Cd frequently exceeded permissible limits. Health Risk Assessment (HRI) findings pointed to potential health risks at sites S4 (Ganga) and S8 (Yamuna) due to elevated Pb and Cd levels. The Heavy Metal Contamination Index (HMCI) ranged from 733.78 to 981.33, classifying all samples as highly polluted, with Heavy Metal Quality Index (HMQI) values also indicating high risk, especially at sites S4 and S8. Further analysis using principal component analysis (PCA) and cluster analysis highlighted correlations among water quality parameters, while Pearson's correlation matrix and heat maps indicated positive relationships for DO, pH, alkalinity, and SO4, with most heavy metals (except Zn and Mg) showing strong inter-correlations. These findings underline the urgent need for pollution control measures to safeguard public health in the region.

Proteasomes are the catalytic complexes in eukaryotic cells that decide the fate of proteins involved in various cellular processes in an energy‐dependent manner. The proteasomal system performs its function by selectively destroying the proteins labelled with the small protein ubiquitin. Dysfunctional proteasomal activity is allegedly involved in various clinical disorders such as cancer, neurodegenerative disorders, ageing, and so forth, making it an important therapeutic target. Notably, compared to healthy cells, cancer cells have a higher protein homeostasis requirement and a faster protein turnover rate. The ubiquitin‐proteasome system (UPS) helps cancer cells increase rapidly and experience less apoptotic cell death. Therefore, understanding UPS is essential to design and discover some effective inhibitors for cancer therapy. Hereby, we have focused on the role of the 26S proteasome complex, mainly the UPS, in carcinogenesis and seeking potential therapeutic targets in treating numerous cancers.