Yellapragada Subbarow: A Pioneer in Biomedical Research and the Unsung Hero of Modern Medicine.

Yellapragada Subbarow, an often overlooked yet monumental figure in biomedical research, made groundbreaking contributions that have profoundly shaped modern medicine. Born in 1895 in Andhra Pradesh, India, Subbarow's journey from humble beginnings to a pioneering biochemist is a testament to his relentless determination and intellectual prowess. His discoveries, including the elucidation of adenosine triphosphate (ATP), the development of folic acid, and the introduction of methotrexate and tetracycline antibiotics, have had a lasting impact on various fields such as biochemistry, oncology, and infectious disease treatment. Despite his significant scientific achievements, Subbarow's name remains relatively obscure outside academic circles. This review highlights his pivotal contributions and explores the reasons behind his underrecognition. By examining his life's work, this article seeks to celebrate Subbarow's enduring legacy and advocate for greater recognition of his contributions to medical science. His story enriches our understanding of scientific progress and is an inspiring example of the profound impact of perseverance and innovation in advancing human health. Through this review, we hope to honor Subbarow's remarkable achievements and bring deserved attention to one of the unsung heroes of modern medicine.

Global citizenship identity mediates the relationship of knowledge, cognitive, and socio-emotional skills with engagement towards global issues.

The UN Sustainable Development Goals (SDGs) provide a unified framework to address interconnected global issues, emphasizing the need for collective action across all sectors of society to achieve a sustainable future for all. In this paper, we empirically investigate how knowledge (awareness of global issues), cognitive skills (critical inquiry), and socio-emotional skills (cognitive empathy) relate to engagement towards global issues, and whether global citizenship identification mediates these relationships. Mediation analysis of data from 249 participants revealed that both awareness of global issues and cognitive empathy directly predict higher engagement levels. In contrast, no direct effect of critical inquiry was observed. Global citizenship identification significantly mediated the relationships between all three predictors and engagement: accounting for 70.7% of the effect of critical inquiry, 39.9% of the effect of awareness, and 33.6% of the effect of cognitive empathy. Our findings highlight that global citizenship identification plays a crucial role in translating knowledge and skills into active engagement. The results highlight the potential effectiveness of identity-based interventions in fostering more engaged communities and advancing efforts toward achieving the SDGs.

From Transfusion Medicine to Vaccines: The Enduring Impact of Karl Landsteiner.

This is the biography of the Nobel Prize winner Karl Landsteiner who divided human blood into groups according to the presence of naturally occurring agglutinating antibodies. His research eventually led to the establishment of safe transfusion practices. Before his discovery, transfusions of blood were given to patients in need from animals like sheep or randomly chosen human donors, often with disastrous results. Millions of lives were genuinely saved by Landsteiner's discovery. He established the foundation for the creation of the polio vaccine by determining that a microbe causes poliomyelitis. Additionally, Landsteiner contributed to the identification of the syphilis-causing microbes. This biography is a tribute to the legend Karl Landsteiner.

A Review of Infant and Young Child Feeding Practices and Their Challenges in India.

This review focuses on infant and young child feeding (IYCF) practices in India, aiming to offer information on its trends, challenges, and opportunities for improvement. The overview starts by exploring the importance of IYCF practices and their results on child health, growth, and development. It delves into cultural norms, conventional practices, and local variations that impact feeding behaviors, acknowledging the range of nutritional habits across communities. The role of healthcare systems and community interventions in promoting the most desirable feeding practices is mentioned, addressing issues consisting of different breastfeeding practices, well-timed introduction of complementary meals, and micronutrient supplementation. By making this assessment, the goal of this review is to make healthcare professionals, policymakers, and researchers aware of the current trends of IYCF and its demanding situations, and regions for development in India. It gives an understanding of the improvement of strategies and interventions that can make contributions to the increase and improvement of infant and young child nutrients, thereby nurturing the Upcoming generations.

Selective Dissolution of Calcium Pyrophosphate Dihydrate Crystals Using a Pyrophosphate Specific Receptor.

Pseudo-gout is caused by the deposition of highly insoluble calcium pyrophosphate dihydrate (CPPD) crystals in the joints of sufferers. This leads to inflammation and ultimately joint damage. The insolubility of CPPD is driven by the strong attraction of di-cationic calcium ions with tetra-anionic pyrophosphate ions. One of the challenges of dissolving CPPD is that a related mineral, hydroxy apatite (HA) is present in larger amounts in the form of bone and also contains strongly interacting calcium and phosphate ions. Our aim in this work was to selectively dissolve CPPD in preference to HA. To accomplish this, we used a known receptor for pyrophosphate that contains two complexed zinc ions that are ideally spaced to interact with the tetra-anion of pyrophosphate. We hypothesized that such a molecule could act as a preorganized tetra-cation that would be able to outcompete the two calcium ions present in the crystal lattice of CPPD. We demonstrate both visually and through analysis of released phosphorous that this molecule is able to preferentially dissolve CPPD over the closely related HA and thus can form the basis for a possible approach for the treatment of pseudo-gout.

Louis Pasteur: A Legacy Unmasked.

Louis Pasteur is perhaps the most globally recognized French scientist. His groundbreaking discoveries in molecular chirality and advancements in fermentation greatly benefited brewers and winemakers. Pasteur introduced the process of pasteurization to sterilize wines and significantly contributed to the development of germ theory, which made Joseph Lister's antiseptic surgical techniques possible. Despite initially disproving Antoine Béchamp's theory that silkworm disease was caused by a microbial infection, Pasteur tackled this issue effectively. Building on the work of Henri Toussaint and Pierre Victor Galtier, he developed vaccines for pig erysipelas, chicken cholera, anthrax, and rabies. Pasteur also coined the term "vaccination," which Richard Dunning had used before Edward Jenner expanded upon it. Although Robert Koch criticized Pasteur's vaccination methods as ambiguous, historians have clarified many of the myths surrounding Pasteur. This review explores Pasteur's career, his undeniable achievements, and the realities behind the legendary figure who strove to make a significant impact on science and medicine.

Exploring the Global Health Legacy of Dr. Vulimiri Ramalingaswami: A Review of His Life and Contributions.

Dr. Vulimiri Ramalingaswami was an Indian biomedical scientist who rose to fame in the 20th century. He became well-known during his lifetime. Possessing a sharp mind, well-developed communication skills, a love of research and teaching, and a strong commitment to public welfare, he set an unwavering path to success in any field he decided to pursue. He broke new ground in administration, public service, research, and medical education. He was endowed with an enigmatic charm that won the respect of everyone he encountered. He made his students and coworkers leaders by setting a good example. As a result, he excelled in representing Indian biomedical research abroad. He was well known for his ability to think clearly, to present ideas and thoughts either orally or in writing with eloquence, and to do so in a straightforward manner.

Assessing Cardiometabolic Disease Risk Factors Among Healthcare Workers in a Rural Tertiary Care Hospital in Wardha, India: A Study Protocol.

Background Cardiometabolic diseases pose a significant public health challenge globally, particularly among healthcare workers, who often face heightened occupational stress and lifestyle challenges. This study aims to assess the prevalence of cardiometabolic risk factors and their determinants among healthcare workers at Acharya Vinoba Bhave Rural Hospital, a tertiary care hospital in rural Wardha, Maharashtra, India. Methods A cross-sectional study design was employed, involving the recruitment of healthcare workers from various job roles. Data on demographic characteristics, behavioral risk factors, anthropometric measurements, biochemical parameters, and mental health status was collected using standardized instruments and procedures. Statistical analysis included descriptive statistics, inferential tests, and multivariate analyses to identify significant associations and predictors of cardiometabolic risk factors. Expected results Anticipated findings include a notable prevalence of cardiometabolic risk factors among healthcare workers, including elevated BMI, fasting blood glucose, dyslipidemia, and hypertension. Behavioral risk factors such as physical inactivity, unhealthy dietary habits, tobacco use, and alcohol consumption are expected to be prevalent. Additionally, varying degrees of psychological distress, including depression, anxiety, and stress, are anticipated. Significant associations between cardiometabolic risk factors and demographic variables are expected to be identified. Conclusion The study findings provide valuable insights into the prevalence and determinants of cardiometabolic risk factors among healthcare workers in a rural setting. These insights can inform targeted interventions and public health strategies aimed at improving the cardiovascular health and overall well-being of healthcare workers, ultimately contributing to the enhancement of healthcare delivery and outcomes in rural areas.

Number of serotonergic neurons in the subthalamic nucleus and globus pallidus internus could influence the effects of deep brain stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is a standard treatment for Parkinson's disease (PD), with both regions exhibiting similar treatment effectiveness. However, posttreatment neuropsychiatric side effects, such as severe depression, are common, primarily due to the loss of serotonergic cells. Identifying a region with fewer serotonergic neurons could potentially reduce these side effects. This study aimed to quantify the number of serotonergic neurons in the STN and GPi. Both regions were analyzed using hematoxylin and eosin staining and immunohistochemistry. The GPi exhibited a significantly lower number and H-score of serotonergic neurons than the STN. Within the STN, the number and H-score of serotonergic neurons were higher in the medial aspect than in the lateral aspect. Three different types of neurons, large and small, were observed. In STN, large neurons were concentrated in the center and small neurons in the periphery. This distribution was not observed in GPi. In addition, the concentration of the serotonergic neurons is less in GPi. These findings suggest that the GPi may be a safer target region, potentially reducing the incidence of post-DBS depression.

Pneumomediastinum and pneumothorax in coronavirus disease-2019: Description of a case series and a matched cohort study.

Objective: To describe the characteristics of COVID-19 patients with pneumothorax and pneumomediastinum (PTX/PM) and their association with patient outcomes. Patients and methods: Adults admitted to five Mayo Clinic hospitals with COVID-19 between 03/2020-01/2022 were evaluated. PTX/PM was defined by imaging. Descriptive analyses and a matched (age, sex, admission month, COVID-19 severity) cohort comparison was performed. Hospital mortality, length of stay (LOS), and predisposing factors were assessed. Results: Among 6663 patients, 197 had PTX/PM (3 %) (75 PM, 40 PTX, 82 both). The median age was 59, with 71 % males. Exposure to invasive and non-invasive mechanical ventilation and high-flow nasal cannula before PTX/PM were 42 %, 17 %, and 20 %, respectively. Among isolated PTX and PM/PTX patients 70 % and 53.7 % underwent an intervention, respectively, while 96 % of the PM-only group was followed conservatively.A total of 171 patients with PTX/PM were compared to 171 matched controls. PTX/PM patients had more underlying lung disease (40.9 vs. 23.4 %, p < 0.001) and lower median body mass index (BMI) (29.5 vs. 31.3 kg/m2, p = .007) than controls. Among patients with available data, PTX/PM patients had higher median positive end-expiratory and plateau pressures than controls; however, differences were not significant (10 vs. 8 cmH2O; p = 0.38 and 28 vs. 22 cmH2O; p = 0.11, respectively). PTX/PM patients had a higher odds of mortality (adjusted odds ratio [95%CI]: 3.37 [1.61-7.07]) and longer mean LOS (percent change [95%CI]: 39 [9-77]) than controls. Conclusion: In COVID-19 patients with similar severity, PTX/PM patients had more underlying lung disease and lower BMI. They had significantly increased mortality and LOS.

Neonatal hyperoxia exposure leads to developmental programming of cardiovascular and renal disease in adult rats.

Premature infants are often exposed to hyperoxia. However, there is limited data regarding the mechanistic underpinnings linking neonatal hyperoxia exposure and its contribution to cardio-renal dysfunction in adults born preterm. Our objective was to determine whether neonatal hyperoxia induces systemic vascular stiffness and cardio-renal dysfunction in adulthood. Newborn rats were randomly assigned to room air (RA) or hyperoxia (85% O2) from postnatal day 1 to 14, then recovered in RA until 1 year of life. Arterial stiffness, cardio-renal histomorphometry, and fibrosis in the aorta, heart, and kidney were assessed. RNA-sequencing (RNA-seq) of the aorta and kidney was also done. Adult rats exposed to neonatal hyperoxia had increased aortic and mesenteric artery stiffness as demonstrated by wire and pressure myography. They also had cardiomyocyte hypertrophy, glomerulomegaly, and tubular injury. Hyperoxia exposure altered the transcriptome profile associated with fibrosis and matrix remodeling in the aorta and kidney. There was also increased TGF-ß1 levels and fibrosis in the aorta, left ventricle, and kidney. In conclusion, neonatal hyperoxia exposure was associated with systemic vascular and cardio-renal alterations in 1-year-old rats. Further studies to determine how targeted therapies could reprogram cardio-renal injury after neonatal hyperoxia exposure are indicated.

OpenMedLM: prompt engineering can out-perform fine-tuning in medical question-answering with open-source large language models.

LLMs can accomplish specialized medical knowledge tasks, however, equitable access is hindered by the extensive fine-tuning, specialized medical data requirement, and limited access to proprietary models. Open-source (OS) medical LLMs show performance improvements and provide the transparency and compliance required in healthcare. We present OpenMedLM, a prompting platform delivering state-of-the-art (SOTA) performance for OS LLMs on medical benchmarks. We evaluated OS foundation LLMs (7B-70B) on medical benchmarks (MedQA, MedMCQA, PubMedQA, MMLU medical-subset) and selected Yi34B for developing OpenMedLM. Prompting strategies included zero-shot, few-shot, chain-of-thought, and ensemble/self-consistency voting. OpenMedLM delivered OS SOTA results on three medical LLM benchmarks, surpassing previous best-performing OS models that leveraged costly and extensive fine-tuning. OpenMedLM displays the first results to date demonstrating the ability of OS foundation models to optimize performance, absent specialized fine-tuning. The model achieved 72.6% accuracy on MedQA, outperforming the previous SOTA by 2.4%, and 81.7% accuracy on MMLU medical-subset, establishing itself as the first OS LLM to surpass 80% accuracy on this benchmark. Our results highlight medical-specific emergent properties in OS LLMs not documented elsewhere to date and validate the ability of OS models to accomplish healthcare tasks, highlighting the benefits of prompt engineering to improve performance of accessible LLMs for medical applications.

A Comprehensive Review on Trends and Patterns of Non-communicable Disease Risk Factors in India.

This review explores the trends and patterns of non-communicable disease (NCD) risk factors in India, with a focus on tobacco use, unhealthy diet, physical inactivity, and air pollution. Drawing upon existing literature and data, the review highlights the substantial burden imposed by NCDs and their associated risk factors on public health and healthcare systems in India. Key findings reveal the widespread prevalence of these risk factors, particularly among certain demographic groups and in urban areas. Socioeconomic disparities also play a significant role in shaping the distribution of NCD risk factors across the population. The review underscores the importance of addressing NCD risk factors through evidence-based interventions and policies tailored to the Indian context. Furthermore, it emphasizes the need for multi-sectoral collaboration among government agencies, healthcare providers, civil society organizations, academia, industry partners, and communities to mitigate the NCD epidemic effectively. By mobilizing collective efforts and resources, India can make significant strides in preventing and controlling NCDs, thereby enhancing population health and well-being.

Development of engineered transferosomal gel containing meloxicam for the treatment of osteoarthritis.

OBJECTIVE: .In this study, we investigated the potential of meloxicam (MLX) developed as transferosomal gel as a novel lipidic drug delivery system to address osteoarthritis (OTA), a degenerative joint disease that causes pain and stiffness. By incorporating meloxicam into a transferosomal gel, our aim was to provide a targeted and efficient delivery system capable of alleviating symptoms and slowing down the progression of OTA. MATERIAL AND METHODS: Classical lipid film hydration technique was utilized to formulate different transferosomal formulations. Different transferosomal formulations were prepared by varying the molar ratio of phospholipon-90H (phosphodylcholine) to DSPE (50:50, 60:40, 70:30, 80:20, and 90:10) and per batch, 80mg of total lipid was used. The quality control parameters such as entrapment efficiency, particle size and morphology, polydispersity and surface electric charge, in vitro drug release, ex vivo permeation and stability were measured. RESULTS: The optimized transferosomal formulations revealed a small vesicle size (121±12nm) and greater MLX entrapment (68.98±2.3%). Transferosomes mediated gel formulation MLX34 displayed pH (6.3±0.2), viscosity (6236±12.3 cps), spreadability (13.77±1.77 gm.cm/sec) and also displayed sustained release pattern of drug release (81.76±7.87% MLX released from Carbopol-934 gel matrix in 24h). MLX34 revealed close to substantial anti-inflammatory response, with ∼81% inhibition of TNF-α in 48h. Physical stability analysis concluded that refrigerator temperature was the preferred temperature to store transferosomal gel. CONCLUSION: MLX loaded transferosomes containing gel improved the skin penetration and therefore resulted into increased inhibition of TNF-α level.

Comparison of Various Commonly Used Luting Cements on the Success of Composite Inlays Assessed by the Levels of the Microleakage-An In vitro Study.

Introduction: Indirect composite restoration is one of the commonly followed procedures in the posterior teeth. The success of this is dependent on many factors, one being the luting cement. Hence, the current study explores the microleakage of the two luting cements at 2 different times. Materials and Methods: Eighty extracted human teeth were taken, and class II cavities were made that were to receive the composite inlays. They were grouped as supragingival and subgingival, which for further divided as were further subdivided to be observed for marginal leakage at cervical and occlusal margins, at the end of a day and 1 month. Each group had ten specimens. The luting cements that were evaluated were Variolink N and RelyX Unicem. After the composite inlay restoration was done for all the specimens, the sections were put on slides, and a stereomicroscope was used to measure the amount of dye penetration. Leakage was evaluated and compared using Mann-Whitney U test. Results: At the end of 1 day, there was no significant alteration in the microleakage in the occlusal or cervical regions for either region supragingivally or subgingivally between the two luting cements. Significant difference between the two cements at the cervical borders at the end of a month was seen for both the margins. When compared supragingivally and subgingivally at the end of 1 day or at the end of 1 month, there was not a significant difference for any of the cements. Conclusion: Within the constraints of the current investigation, it can be said that there was similar microleakage for both Variolink N and RelyX Unicem at the conclusion of a day's storage time. After a 1-month storage period, RelyX Unicem showed more cervical microleakage than Variolink N.

Comparison of Different Betadine and Saline Combinations on Microorganisms: An Original Research.

Introduction: Pathogenic bacteria in the oral cavity or a physiological microbiome imbalance can cause or maintain disease. Thus, this work examined a novel betadine-saline combination for antibacterial and antifungal activities. Materials and Methods: This study was in vitro. Betadine, saline, and their mixtures were tested for Bacillus subtilis, Staphylococcus aureus (gram-positive), Pseudomonas aeruginosa, Escherichia coli, and Aspergillus niger (gram-negative). Pour plate and disc diffusion methods were used to test CFUs, DZI, and RZI for various agent combinations. Results: For Lactobacillus acidophilus, Betadine 90% + saline 10% had the greatest DZI and RZI at 24 and 12 mm, respectively. For E. coli, Betadine 50% + saline 50% had the highest at 16 and 8 mm. Betadine 60% + saline 40% had 14 mm RZI and the highest antifungal activity. Conclusion: The novel betadine-saline antibacterial and antifungal combination performed well. In vivo research should confirm the existing findings.

Comparison of the Conventional and Laser Etching on the Bonding of the Orthodontic Brackets: An Original Research.

Background: Acid etching enamel improves resin-enamel adhesion and adhesive characteristics, but has pros and cons. The effects of laser etching on the bonding of orthodontic brackets vary depending on the wavelength, power output, exposure duration, and energy delivered. Materials and Methods: This study used a new 1064-nm diode laser to irradiate 30 freshly extracted human premolars. They were divided into three groups: group A, group B, and group C. Acid etching was used for 1 min to bond bracket to tooth surface, and Indian ink was used for 30 s. Group C uses acid etching for 1 min following 30 s of laser irradiation with Indian ink. Results: In comparison to the other groups, group C's acid etching after laser irradiation has considerably stronger bond strength (P = 0.05). Orthodontic brackets in group B exhibited considerably poorer shear bond strength than those in the other groups. Conclusion: Acid etching improves the adhesion of orthodontic composite resin to human enamel following laser irradiation, but can interfere with the adhesion of composite resin.

Auto-PAP Titration Efficacy in Obstructive Sleep Apnea: A Single-Center Experience.

Introduction: Obstructive sleep apnea, often known as OSA, is a sleep-related breathing disease that, if not treated, can lead to serious disabilities or even death. Continuous positive airway pressure (CPAP) is the therapy technique that is suggested for treating severe and moderate OSA. An auto/manual CPAP titration study can be used to determine the appropriate pressure that must be maintained to treat this condition. The motive of this research is to appraise the effectiveness among OSA patients for the auto-PAP titrations. Methodology: A cross-sectional clinical prospective study was conducted at the tertiary care center. Subjects who underwent auto-PAP titration and had a diagnosis of moderate and sever OSA were included. They were evaluated for the efficacy of auto-PAP titration and other demographic features and their association with the titration efficacy. The values were compared for statistical significance. Results: The findings of the study showed that fifty percent of the cohort showed optimal titration, forty percent showed good titration, ten percent showed suitable titration, and none fell into the unacceptable group. Conclusion: According to the findings, using auto-PAP was associated with positive results in those with moderate and severe OSA. There is evidence to suggest that unattended auto-PAP titration is a very successful technique that might be regarded as a substitute for attended CPAP titrations. This would result in a reduction in the amount of labor required and the price.

Role of bio-flavonols and their derivatives in improving mitochondrial dysfunctions associated with pancreatic tumorigenesis.

Mitochondria, a cellular metabolic center, efficiently fulfill cellular energy needs and regulate crucial metabolic processes, including cellular proliferation, differentiation, apoptosis, and generation of reactive oxygen species. Alteration in the mitochondrial functions leads to metabolic imbalances and altered extracellular matrix dynamics in the host, utilized by solid tumors like pancreatic cancer (PC) to get energy benefits for fast-growing cancer cells. PC is highly heterogeneous and remains unidentified for a longer time because of its complex pathophysiology, retroperitoneal position, and lack of efficient diagnostic approaches, which is the foremost reason for accounting for the seventh leading cause of cancer-related deaths worldwide. PC cells often respond poorly to current therapeutics because of dense stromal barriers in the pancreatic tumor microenvironment, which limit the drug delivery and distribution of antitumor immune cell populations. As an alternative approach, various natural compounds like flavonoids are reported to possess potent antioxidant and anticancerous properties and are less toxic than current chemotherapeutic drugs. Therefore, we aim to summarize the current state of knowledge regarding the pharmacological properties of flavonols in PC in this review from the perspective of mitigating mitochondrial dysfunctions associated with cancer cells. Our literature survey indicates that flavonols efficiently regulate cellular metabolism by scavenging reactive oxygen species, mitigating inflammation, and arresting the cell cycle to promote apoptosis in tumor cells via intrinsic mitochondrial pathways. In particular, flavonols proficiently inhibit the cancer-associated proliferation and inflammatory pathways such as EGFR/MAPK, PI3K/Akt, and nuclear factor κB in PC. Overall, this review provides in-depth evidence about the therapeutic potential of flavonols for future anticancer strategies against PC; still, more multidisciplinary human interventional studies are required to dissect their pharmacological effect accurately.