Emerging 2D Nanomaterials-Integrated Hydrogels: Advancements in Designing Theragenerative Materials for Bone Regeneration and Disease Therapy.

This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D-material integrated hydrogels, with a focus on their performance in bone-related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near-infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D-material-based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug-loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D-materials -infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug-resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio-imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real-time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D-materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials.

Biosensors with left ventricular assist devices.

Heart failure imposes a significant global health burden, standing as a primary contributor to mortality. Various indicators and physiological shifts within the body may hint at distinct cardiac conditions. Specific biosensors have the capability to identify these changes. Integrating or embedding these biosensors into mechanical circulatory support devices (MCSDs), such as left ventricular assist devices (LVADs), becomes crucial for monitoring alterations in biochemical and physiological factors subsequent to an MCSD implantation. Detecting abnormal changes early in the course of disease progression will allow for improved patient outcomes and prognosis following an MCSD implantation. The aim of this review is to explore the available biosensors that may be coupled or implanted alongside LVADs to monitor biomarkers and changes in physiological parameters. Different fabrication materials for the biosensors are discussed, including their advantages and disadvantages. This review also examines the feasibility of integrating feedback control mechanisms into LVAD systems using data from the biosensors. Challenges facing this emerging technology and future directions for research and development are outlined as well. The overarching goal is to provide an overview of how implanted biosensors may improve the performance and outcomes of LVADs through continuous monitoring and closed-loop control.

Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-ß (TGF-ß) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-ß levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-ß should be evaluated further as a biomarker.

Iron-deficiency anemia following herpetic esophagitis in a previously healthy female.

Introduction: Herpetic Esophagitis is caused by the Herpes Simplex virus, which generally affects immunocompromised individuals and is rarely seen in healthy individuals. Symptoms are usually self-limiting. Case presentation: We report the case of a 68-year-old female who presented with odynophagia, dysphagia, and epigastric pain with no other underlying disease. Endoscopic findings of soft, nodular, and friable growths just above the squamocolumnar junction with diffuse ulcerations in the distal esophagus, led to the diagnosis. It was confirmed with a histopathological report which revealed multinucleated giant cells with eosinophilic intranuclear inclusions. During follow-up, laboratory investigations revealed iron deficiency anemia, which was the consequence of GI bleeding. Clinical discussion: Herpes Simplex virus esophagitis can occur in immunocompetent individuals and even it can cause food impaction and GI bleeding, which can lead to Iron deficiency anemia. Conclusion: Hence, follow-up of patients is important for early diagnosis and intervention of any complications that may arise.

Single Ventricle With Hypoplastic Left Heart Syndrome in a 22-Year-Old Male: A Rare Case Report.

Uni-ventricle transposition of great arteries with ductus-dependent pulmonary circulations with hypoplastic pulmonary atresia (PA) represents rare cardiac malformations. We are presenting a unique case of a 22-year-old male who complained of dizziness since morning with numbness of the left lower and upper limbs. He also complained of palpitations on and off for two to three years with episodes of cyanosis on exertion. He gave a history of cough with frothy pink sputum at the same time. At birth, he was diagnosed to have cyanotic congenital heart disease (CCHD), for which he was prescribed a combination of ambrisentan 5 mg and tadalafil 20 mg and tablet aspirin 75mg along with some lifesaving modalities like proper hydration and phlebotomy as and when required. He was told to go for high-risk surgery like Blalock Taussig shunt or bidirectional Glenn. A Blalock Taussig shunt is a short tube only a few mm wide, which makes a path for blood to go from the arterial circulation to the lungs and bidirectional Glenn sends blood directly from the upper body to the lungs. Strict compliance with drug therapy is implied for the patient for a better outcome.

Emerging 0D, 1D, 2D, and 3D nanostructures for efficient point-of-care biosensing.

The recent COVID-19 infection outbreak has raised the demand for rapid, highly sensitive POC biosensing technology for intelligent health and wellness. In this direction, efforts are being made to explore high-performance nano-systems for developing novel sensing technologies capable of functioning at point-of-care (POC) applications for quick diagnosis, data acquisition, and disease management. A combination of nanostructures [i.e., 0D (nanoparticles & quantum dots), 1D (nanorods, nanofibers, nanopillars, & nanowires), 2D (nanosheets, nanoplates, nanopores) & 3D nanomaterials (nanocomposites and complex hierarchical structures)], biosensing prototype, and micro-electronics makes biosensing suitable for early diagnosis, detection & prevention of life-threatening diseases. However, a knowledge gap associated with the potential of 0D, 1D, 2D, and 3D nanostructures for the design and development of efficient POC sensing is yet to be explored carefully and critically. With this focus, this review highlights the latest engineered 0D, 1D, 2D, and 3D nanomaterials for developing next-generation miniaturized, portable POC biosensors development to achieve high sensitivity with potential integration with the internet of medical things (IoMT, for miniaturization and data collection, security, and sharing), artificial intelligence (AI, for desired analytics), etc. for better diagnosis and disease management at the personalized level.

Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures.

Breast cancer is a global cause for concern owing to its high incidence around the world. The alarming increase in breast cancer cases emphasizes the management of disease at multiple levels. The management should start from the beginning that includes stringent cancer screening or cancer registry to effective diagnostic and treatment strategies. Breast cancer is highly heterogeneous at morphology as well as molecular levels and needs different therapeutic regimens based on the molecular subtype. Breast cancer patients with respective subtype have different clinical outcome prognoses. Breast cancer heterogeneity emphasizes the advanced molecular testing that will help on-time diagnosis and improved survival. Emerging fields such as liquid biopsy and artificial intelligence would help to under the complexity of breast cancer disease and decide the therapeutic regimen that helps in breast cancer management. In this review, we have discussed various risk factors and advanced technology available for breast cancer diagnosis to combat the worst breast cancer status and areas that need to be focused for the better management of breast cancer.

Obesity, Thyroid and OSA: An Intriguing Triangle.

The complex relationship between BMI, thyroid and its effects on OSA raises a question on how patients with suspected OSA should be evaluated. Some studies have described an association between thyroid disorders and OSA. Whether this is a direct effect of thyroid disorders, or it is indirectly related to BMI values is an important point to ponder. The aim of this study was to estimate the prevalence of thyroid disorders in relation to BMI in newly diagnosed patients with OSA (AHI > 5/h on diagnostic Polysomnography) at sleep lab of our tertiary care centre. In addition, we compared baseline characteristics of OSA patients with thyroid parameters. MATERIAL: In this hospital based observational study, recently diagnosed OSA on the basis of PSG showing AHI > 5/ h according to the AASM 2012 scoring rules and age more than 18 years were recruited from OPD and in-patients of SMS Medical College Jaipur. Patients on previous CPAP treatment, mixed or predominantly central sleep apnea, known diabetics and language barriers or cognitive or psychiatric disorders that made informed consent difficult to obtain were excluded. OBSERVATION: During the study period, 65 patients with treatment naïve OSA and a mean age of 52.28±10.92 year, a mean body mass index (BMI) of 34.73±7.20 kg/m2 underwent thyroid function tests. In the OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was 12.3%. In Mild OSA the mean FT3 (ng/ml), FT4 (ng/dl), TSH (mIU/l) and mean AHI score was 3.10±0.71, 1.37±0.58, 3.64±1.37 and 7.74±3.55 respectively. Similarly, mean FT3 (ng/ml), FT4 (ng/dl), TSH (mIU/l) and mean AHI score were 2.97±0.93, 1.46±0.79, 6.33±8.05 and 17.42±88.90 respectively in moderate OSA and 3.32±0.58, 1.23±0.46, 3.55±1.82 and 45.54±21.38 respectively in severe OSA. There was a statistically significant difference between mild moderate and severe OSA regarding thyroid profile as well as BMI with p of <0.05. CONCLUSION: The prevalence of hypothyroidism was common among patients with OSA and the severity of OSA correlated with thyroid function tests and BMI.

Pancytopenia: Etiology and it's Variables.

Current study intends to study the etiological profile of Pancytopenia and to identify the complete blood count (CBC), peripheral smear (PS) findings which are helpful in narrowing the differential diagnosis and in planning the additional investigations to arrive at a specific diagnosis. MATERIAL: Hospital based observational study being conducted at tertiary centre, Jaipur. INCLUSION CRITERIA: Patients >18 years, CBC on admission fulfilling criteria of pancytopenia as mentioned in definition. EXCLUSION CRITERIA: Patients > 80 years, Patients on radiotherapy and chemotherapy., Observation :Mean age of patients was 35.42 years with majority (29.90%) patients with majority of patients were in 2nd and 3r decade of their life with male preponderance Male: female ratio is 1.15:1). Vitamin B-12 deficiency (34.02%), folate deficiency (18.55%) CLD (9.27%) were the most common cause of pancytopenia. CONCLUSION: Detailed clinical history and meticulous physical examination along with baseline hematological investigations, provides invaluable information in the complete workup of pancytopenic patients, helping in systematic planning of further investigations to diagnose and ascertain the cause.

Carrier frequency of Spino-muscular atrophy in individuals of a reproductive age group from North India.

Introduction: Spinal muscular atrophy (SMA) is a neuro-muscular disorder caused by biallelic variations in Survival Motor Neuron 1 gene (SMN1) located on chromosome 5q13.2. It is the most common hereditary cause of neonatal death. Ethnicity specific studies are desirable for estimating the prevalence of carrier status of this disease in a population. Objectives: To estimate the carrier frequency of SMA among individuals of a reproductive age group in a North Indian cohort. Methods: SMA carrier screening was offered to individuals of a reproductive age group (>18 years) visiting a tertiary care center. Multiplex ligation-dependent probe amplification (MLPA) and quantitative real-time polymerase chain reaction (PCR) were the molecular techniques used to detect the carrier status. Results: A total of 198 individuals without a family history of SMA were screened in this study. The carrier frequency of heterozygous deletion of SMN1 gene in our cohort was found to be 1 in 30 (~3/100). Conclusion: The carrier frequency of SMA is high in our country. The data from the study emphasize the need of a population carrier screening program on SMA in India.

Coding roles of long non-coding RNAs in breast cancer: Emerging molecular diagnostic biomarkers and potential therapeutic targets with special reference to chemotherapy resistance.

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes.