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Abstract Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5‐year follow‐up, confirming NETs as interesting therapeutic targets in metastatic breast cancer. Administration of DNase I is one strategy to eliminate NETs but long‐term treatment requires repeated injections and species‐specific versions of the enzyme. To enhance administration and therapeutic efficacy, we have developed an adeno‐associated virus (AAV) vector system for delivery of murine DNase I and addressed its potential to counteract cancer‐associated pathology in the murine MMTV‐PyMT model for metastatic mammary carcinoma. The AAV vector is comprised of capsid KP1 and an expression cassette encoding hyperactive murine DNase I (AAV‐mDNase I) under the control of a liver‐specific promotor. This AAV‐mDNase I vector could support elevated expression and serum activity of murine DNase I over at least 8 months. Neutrophil Gelatinase‐Associated Lipocalin (NGAL), a biomarker for kidney hypoperfusion that is upregulated in urine from MMTV‐PyMT mice, was suppressed in mice receiving AAV‐mDNase I compared to an AAV‐null control group. Furthermore, the proportion of mice that developed lung metastasis was reduced in the AAV‐mDNase I group. Altogether, our data indicate that AAV‐mDNase I has the potential to reduce cancer‐associated impairment of renal function and development of metastasis. We conclude that AAV‐mDNase I could represent a promising therapeutic strategy in metastatic breast cancer.

Abstract Individuals infected with SARS-CoV-2 may develop post-acute sequelae of COVID-19 (“long COVID”) even after asymptomatic or mild acute illness. Including time varying COVID symptom severity can provide more informative burden estimates for public health response. Using a compartmental model driven by confirmed cases, this study estimated long COVID burden by age group (0–4, 5–17, 18–49, 50–64, 65+) in California as measured by the cumulative and severity-specific proportion of quality-adjusted life years (QALYs) lost. Long COVID symptoms were grouped into severe, moderate, and mild categories based on estimates from the Global Burden of Disease study, and symptoms were assumed to decrease in severity in the model before full recovery. All 10,945,079 confirmed COVID-19 cases reported to the California Department of Public Health between March 1, 2020, and December 31, 2022, were included in the analysis. Most estimated long COVID-specific QALYs [59,514 (range: 10,372–180,257)] lost in California were concentrated in adults 18–49 (31,592; 53.1%). Relative to other age groups, older adults (65+) lost proportionally more QALYs from severe long COVID (1,366/6,984; 20%). Due to changing case ascertainment over time, this analysis might underestimate the actual total burden. In global sensitivity analysis, estimates of QALYs lost were most sensitive to the proportion of individuals that developed long COVID and proportion of cases with each initial level of long COVID symptom severity (mild/moderate/severe). Models like this analysis can help translate observable metrics such as cases and hospitalizations into quantitative estimates of long COVID burden that are currently difficult to directly measure. Unlike the observed relationship between age and incident severe outcomes for COVID-19, this study points to the potential cumulative impact of mild long COVID symptoms in younger individuals.

Introduction: Reconstruction of a cloacal defect in a girl is often difficult and complicated.[1] This is most often done either by the sacro-perineal route or through the posterior sagittal route.[2] The procedures may involve total mobilization of the cloaca with or without the creation of a lower vagina with the help of a loop of vascularized bowel.[3] In our approach, such defects can be corrected using the lower anorectum for the creation of a lower vagina and abdominoperineal pull-through of the proximal divided bowel. This method can be used both in short and long common channel cloaca. Materials and Methods: We have used this procedure in one patient of posterior cloaca and four patients of anterior cloaca. These operations were done in patients of 1 year and 6 months to 4 years. Only one patient is waiting for the closure of the colostomy. Results: In all the cases, the urethra, the vagina, and the anus were successfully separated. Conclusion: This operation restores normal pelvic anatomy and physiology with minimal mutilation of the pelvic floor.

Introduction: Fixation plays an important role in fixing the cells, making them amenable for evaluation. Ethanol (95%) has been used as a standard cytological fixative. Honey can be introduced as a natural fixative. Objectives: 1. To study cytomorphological features of smears fixed in 20% unprocessed honey. 2. To study the efficacy of honey as a fixative when compared with ethanol in both hematoxylin and eosin (H and E) stain and Papanicolaou (PAP) stain for cytological samples. Materials and Methods: A cross-sectional study was done in the Department of Pathology for 2 months on 100 cytological samples consisting of body fluids (peritoneal and pleural), cervical smears, and FNACs. These smears were fixed separately in 95% ethanol and 20% unprocessed honey for 5 minutes and were stained with both PAP and H and E stain. The cytomorphologies of both the smears were compared based on five parameters, clarity of staining, uniformity of staining, overall morphology, nuclear details, and cytoplasmic details, and the final score was calculated by adding all the scores: Total Score ≤2, poor score; 3–4, good score; 5, excellent score. Results: Cervical smears fixed in honey showed similar features to ethanol-fixed smears. Fluid smears fixed in honey and stained with PAP yielded superior results compared to those stained with H and E, as shown by a kappa value of 0.259. However, neither of the smears demonstrated statistical significance. The FNAC samples stained with H and E and PAP exhibited nearly identical results, with a kappa value of 0.688 and 0.647, respectively. FNAC and PAP smears were the next two most successful cytological smear types, with cervical smears exhibiting the best results of the three. Conclusion: In honey-fixed smears, we can easily observe all cellular features with clarity. It enhances safety and the working environment in the laboratory. Honey can serve as an effective substitute in situations where resources are limited.

Background: This study was carried out to compare the concurrent validity of the Kaufman Brief Intelligence Test – Second Edition (KBIT-2) with that of two Wechsler Intelligence Scales (Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V) and the Wechsler Preschool and Primary Scale of Intelligence – Fourth Edition (WPPSI-IV)) in an Asian setting. Methods: A retrospective study reviewed the medical records of 101 children with developmental disorders who were being followed up at a tertiary child development unit. Pearson product moment correlation coefficients were calculated between the KBIT-2 and Wechsler assessment scores. Simple regression analysis was used to calculate standard errors of estimation to assess the accuracy of predicting Wechsler scores using KBIT-2 scores. Results: A strong positive correlation was observed between KBIT-2's Intelligence Quotient (IQ) Composite and WISC-V's Full-Scale IQ (FSIQ) scores (r = 0.722, p

Nonextraction approach in correcting Class II malocclusion has gained a lot of attention over the past few years. Clinicians prefer intraoral appliances as compared to extraoral appliances to achieve distal molar movement; the reason being intraoral appliances depends minimally on patient cooperation. In this article, a case report was presented in which a patient was treated with modified rapid maxillary expander, a concept designed from Veltri distalizer considering its advantages. Molar distalization of 4 mm was achieved with minimal anchorage loss on premolars and anteriors. Class I molar, canine relation was achieved with 2 mm of overjet and overbite. Modified appliance when used at appropriate timing was found to be an effective and conservative approach in distalization of maxillary first molars.

Background and aim: To compare the marginal and internal adaptation of full veneer crowns cast from wax patterns fabricated by three-dimensional printing and conventional wax-up technique employing two different convergence angles.Material and methods: Two metal master dies, each with a convergence angle of 6 and 12-degrees, were duplicated 24 times to obtain 48 stone dies. Twelve dies from each group were randomly chosen for conventional wax-up (Group A) and the other twelve for the three-dimensional printed wax pattern (Group B) fabrication. Cobalt-chromium full veneer crowns were cemented onto the dies using glass ionomer cement. The cemented crowns and dies were sectioned in the midline buccolingually to measure the marginal and internal gaps using a stereomicroscope and digital image analysis software (Image J). Data obtained were recorded in microns, and an independent 't' test was used to compare quantitative parameters between categories.Results: Group B showed a statistically significant reduction in marginal discrepancy in crowns with a 6-degree taper (114.4 ± 37.5) compared to Group A (160.4 ±58.1). Group B did not demonstrate any significant difference when the 6-degree and 12-degree tapers were compared, but Group A showed a significant improvement in marginal and internal adaptation with the 12-degree taper.Conclusions: For the 6-degree taper, three-dimensional printing resulted in better marginal and internal fit than conventional wax patterns. Conventional and three-dimensional Printing offered similar accuracy within the acceptable range for a 12-degree taper.

Aims: Closure of congenital body wall defects in children can be a challenging task for the pediatric Surgeon. Biological prosthesis has been increasingly used for high-risk wound closure in adult patients with excellent outcomes and use in the pediatric population has also been reported. Here, we aim to study the outcome of abdominal wound repair with a tissue-engineered acellular bovine pericardial patch. Methods: Over a period of 21 months, a total of 15 children had undergone abdominal wound repair with bioprostheses, i.e., bovine pericardial patch at our institute. Patient demographics, cause of defect, an indication of patch use, rate of infection, postoperative recovery, recurrence, and outcome were studied. Results: A total of 15 patients underwent abdominal wall closure with acellular bovine pericardial patch. Nine out of 15 patients were neonates, of whom five had gastroschisis, two had a congenital diaphragmatic hernia, and two had ruptured omphalocele major. Of the rest 6 patients, 2 were patients of bladder exstrophy, 2 were older children of congenital diaphragmatic hernia with incisional hernias, and 2 were older children with omphalocele major. Out of the five patients with gastroschisis, two died during the early postoperative period due to sepsis. The wound healed in the rest 13 patients with mild skin dehiscence in two patients. Only one child had a recurrence. Conclusion: Reconstruction with acellular bovine pericardial patch is a viable option in children with high-risk abdominal wounds as it allows tensionless repair with excellent healing and minimal complications. Recurrence, if any, may disappear with time as remodeling of the prosthesis occurs along with the growth of the body wall of the child.

The rapid increase in soil and water pollution is primarily attributed to anthropogenic factors, notably the mismanagement of post-consumer plastics on a global scale. This exploratory research design evaluated the effectiveness of natural hydrophobic cattail (Typha Latifolia) fibres (CFs) as bio-adsorbents of microplastic particles (MPPs) from wastewater. The study investigates how the composition of the adsorption environment affects the adsorption rate. Straightforward batch adsorption tests were conducted to evaluate the “spontaneous” sorption of MPPs onto CFs. Five MPP materials (PVC, PP, LDPE, HDPE, and Nylon 6) were evaluated. Industrial wastewater (PW) and Type II Distilled Water (DW) were employed as adsorption environments. The batch test results show that CFs are effective in removing five MPP materials from DW and PW. However, a higher removal percentage of MPPs was observed in PW, ranging from 89% to 100% for PVC, PP, LDPE, and HDPE, while the adsorption of Nylon 6 increased to 29.9%, a removal increase of 50%. These findings indicate that hydrophobic interactions drive the “spontaneous and instantaneous” adsorption process and that adjusting the adsorption environment can effectively enhance the MPP removal rate. This research highlights the significant role that bio-substrates can play in mitigating environmental pollution, serving as efficient, sustainable, non-toxic, biodegradable, low-cost, and reliable adsorbents for the removal of MPPs from wastewaters.

Summary: Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.

An experiment was conducted to study the effect of dietary supplementation of Azolla on the performance of Japanese quail broilers. Day old Japanese quails (135) were divided into three treatment groups with three replicates per treatment and 15 quails in each replicate. The feeding of birds was done in two phases from 1-3 weeks and 4-5 weeks. Azolla was included at 0%, 5% and 10% levels in T0 (control), T1 and T2 groups, respectively. Azolla inclusion did not show any significant effect on the feed intake up to 5 weeks of age. Body weight gain and PCV%, total protein and albumin were significantly higher at 5% level whereas no significant difference was observed at 10% level of Azolla inclusion. Azolla at both 5% and 10% level significantly reduced serum cholesterol concentration and the highest net profit was in 10% Azolla supplemented group. So, Azolla can be included effectively at 10% level in diet of Japanese quail broiler.

Separation and quantification of highly polar metformin (MTF) alone or in combination with dipeptidyl peptidase-4 inhibitors, such as evogliptin (EVG), sitagliptin, saxagliptin, vildagliptin, linagliptin and teneligliptin, specifically from human plasma and pharmaceutical products is still difficult in mostly preferred ODS based RP-HPLC techniques. Since, owing to weak retention of MTF in ODS, it elutes together with the biological fluid components and drug excipients. Therefore, in this study, alternative to ODS based RP-HPLC, comparatively less known analytical techniques like strong cation exchange chromatography (SCX-3), hydrophilic interaction liquid chromatography (HILIC) and mix-mode chromatography (MMC) were comprehensively evaluated for their potentials and limitations in simultaneous quantification of newly approved EVG and MTF combination (Valera-M). In results, prolonged application of SCX-3, exhibits irreproducible and irreversible retention of MTF and EVG. While in HILIC with Cyano column, excessive acetonitrile as eluent developed the precipitation of MTF and column back pressure. Comparatively, the Acclaimed® mix-mode HILIC-1, demonstrated much promising and reproducible results for MTF and EVG separation and importantly, it can be used either reverse phase or HILIC mode. Considering the overall benefits of Acclaimed® mix-mode HILIC-1, it was used in estimation of MTF and EVG from human plasma and pharmaceutical formulations.

Background: Sepsis is responsible for 30-40% neonatal deaths which can be attributed to various maternal, neonatal and sociocultural risk factors. Objective: To recognize the clinical and laboratory risk factors of mortality in extramural neonatal sepsis. Material and methods: Prospective observational study was conducted for duration of one year on extramural neonates with suspected sepsis. Maternal, neonatal and sociocultural factors were analyzed. Results: Average duration of hospital stay was shorter in non-survival compared to survival neonates (p=0.01). On univariate analysis preterm (p 18 hours were the significant risk factors of mortality. Those neonates admitted with lethargy (p=0.04), hypothermia (p=0.01), respiratory distress (p

Introduction: Kidney diseases have shown a rising upward trend in the last few decades due to the increase in incidence of associated chronic diseases like diabetes, hypertension. However the frequency and spectrum of renal pathology in autopsy specimens is not well documented or overlooked by physicians as well as pathologists. Aim: To analyse the spectrum of various types of renal pathologies, based on the histopathological analysis of renal tissue where autopsies were performed routinely with no history of renal diseases. Materials and Methods: This cross-sectional study was carried out over a period of two years from June 2021 to June 2023 in the Department of Pathology of SCB Medical College and Hospital, Cuttack, Odisha, India, and consisted of 84 cases of well-preserved renal autopsies. The autopsy samples were routinely processed and stained by Haematoxylin and Eosin (H&E) and then reported. Special stain of Periodic Acid Schiff (PAS) was done. Gross and microscopic findings were studied. The study was compared with other relevant studies. The data was analysed using Microsoft Excel 2019. Results: A total of 84 cases were included in the study. The male:female ratio was 1.27:1. The age group with the highest number of cases (35 cases) was 21-40 years. Among the 84 cases the commonest pathology was seen in tubules (40 cases, 47.62%) and glomeruli (7 cases, 8.33%), followed by vascular pathologies (5 cases, 5.95%) and interstitial lesions (4 cases, 4.76%). Renal cell carcinoma was incidentally detected in two cases and Wilms tumour in one case. Five cases had normal histology. Conclusion: The study illuminates the various renal lesions on autopsy and showed tubular lesions were more common than glomerular lesions in renal autopsy. Renal lesions are more common in males. The focus should be to develop more effective diagnostic methods for renal lesions so that intervention can be fast and sharp resulting in less mortality.

Background: Akara, Ukara, Makara (OUM) chanting regulates emotions and removes negative emotions by inactivating the processing in the amygdala. At the same time, the prefrontal complex was inhibited followed by chanting OUM. Further, there was an increase in the oxygenation levels followed by chanting OUM. Hence, OUM chanting has multiple benefits and offers improvement in the quality of life. Though there are multiple benefits followed by chanting OUM, the scientific evidence for the same is comparatively less. Hence, there is a need for more studies in this area. Aims and Objectives: The present study aimed to find out the variations in the perceived stress, negative affectivity, and social inhibition in pre-hypertensive individuals and also to observe the effectiveness of Om chanting on perceived stress, negative affectivity, and social inhibition in pre-hypertensive individuals. Materials and Methods: The present study was conducted at the St Peter’s Medical College Hospital and Research Institute, Hosur, Tamil Nadu, India. A total of 50 young adults with pre-hypertension were recruited in the study after obtaining written informed consent. Age- and gender-matched 50 healthy participants were recruited after obtaining the voluntary, informed consent. Diamond digital sphygmomanometer was used to record the blood pressure. All the parameters were recorded at 9 am for the convenience of the participants and also to avoid diurnal variation. The perceived stress scale was used to assess the stress levels. Negative affectivity and social inhibition were recorded using a type D (DS-14) questionnaire. Cases practiced the OUM chanting for 6 weeks after they were trained by an expert yoga therapist. Results: Perceived stress scores were significantly decreased followed by the OUM chanting. There was a significant decrease in the scores of negative affectivity of cases after the intervention when compared with control group participants. There was a significant decrease in the scores of social inhibition of cases after the intervention when compared with control group participants. Conclusion: Perceived stress, negative affectivity, and social inhibition were significantly higher in the pre-hypertensive individuals. The study results provide further evidence that practicing OUM chanting causes stress relief and also decreases the negative emotions that is negative affectivity and social inhibition in pre-hypertensive individuals.

Background: According to ongoing research, assessing nuchal translucency (NT) in ultrasound pictures can help to identify fetal development that deviates from the norm. The chance of chromosomal abnormalities in a newborn is predicted by the nuchal translucency (NT) width in ultrasound sonography pictures performed on the child between 11 and 14 weeks of gestation. Method: Deeply learned convolutional networks have recently significantly improved NT region detection performance. This paper discusses a novel approach to learning a cutting-edge NT Region identification algorithm. To address the difficulty of improving the accuracy of NT recognition in various lighting and posture conditions, a Framework Learning Network (F-LNET) is employed. Discussion: The limitations of the current NT estimating technique include findings that are unpredictable and intra-personal, inter-personal, and inter-variation restrictions. On the other hand, existing solutions have a high processing overhead and are, hence, unsuitable for rapid NT limiting and localization, which is critical for reliable recognition. However, current methods could be better for quick NT limiting and localization, which is essential for trustworthy identification schemes because of their significant processing overhead. The suggested automated clinical finding approach, which computes the error between human and automated measurements, is very beneficial to both doctors and society at large. Conclusion: The suggested way reduces the error to 0.42, whereas the error of other methods ranges from 0.8 to 1.1.

Abstract Genome-wide association studies suggest significant overlaps in Parkinson’s disease (PD) and schizophrenia (SZ) risks, but the underlying mechanisms remain elusive. The protein-protein interaction network (‘interactome’) plays a crucial role in PD and SZ and can incorporate their spatiotemporal specificities. Therefore, to study the linked biology of PD and SZ, we compiled PD- and SZ-associated genes from the DisGeNET database, and constructed their interactomes using BioGRID and HPRD. We examined the interactomes using clustering and enrichment analyses, in conjunction with the transcriptomic data of 26 brain regions spanning foetal stages to adulthood available in the BrainSpan Atlas. PD and SZ interactomes formed four gene clusters with distinct temporal identities (Disease Gene Networks or ‘DGNs’1-4). DGN1 had unique SZ interactome genes highly expressed across developmental stages, corresponding to a neurodevelopmental SZ subtype. DGN2, containing unique SZ interactome genes expressed from early infancy to adulthood, correlated with an inflammation-driven SZ subtype and adult SZ risk. DGN3 contained unique PD interactome genes expressed in late infancy, early and late childhood, and adulthood, and involved in mitochondrial pathways. DGN4, containing prenatally-expressed genes common to both the interactomes, involved in stem cell pluripotency and overlapping with the interactome of 22q11 deletion syndrome (comorbid psychosis and Parkinsonism), potentially regulates neurodevelopmental mechanisms in PD-SZ comorbidity. Our findings suggest that disrupted neurodevelopment (regulated by DGN4) could expose risk windows in PD and SZ, later elevating disease risk through inflammation (DGN2). Alternatively, variant clustering in DGNs may produce disease subtypes, e.g., PD-SZ comorbidity with DGN4, and early/late-onset SZ with DGN1/DGN2.

The search for effective antidiabetic agents, both synthetic and natural, has intensified over the years. This review provides a comprehensive examination of xanthone compounds as potential antidiabetic agents, exploring their sources, chemical structures, and pharmacological properties. Xanthones have been shown to enhance insulin sensitivity, modulate glucose metabolism, and mitigate oxidative stress and inflammation through various mechanisms. Key molecular targets include AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), α-amylase, and α-glucosidase.The review details in vitro studies demonstrating that xanthones like γ-mangostin and mangiferin inhibit α-amylase and α-glucosidase with IC50 values of 3.2 μM and 5.6 μM, respectively, highlighting their potential to improve glucose metabolism. In vivo studies have shown that xanthones improve glucose homeostasis, lipid profiles, and overall glycemic control in diabetic models. For instance, mangiferin administration in streptozotocin-induced diabetic rats resulted in lower fasting blood glucose levels and improved HDL levels.Moreover, the safety profile and potential side effects associated with xanthone usage are discussed, providing a balanced view of their therapeutic potential. This review consolidates current knowledge on xanthones' antidiabetic properties and serves as a valuable resource for further research and development of these compounds as antidiabetic agents.

Talinum triangulare (water leaf) is an important herbaceous vegetable with medicinal importance. It has been used in traditional medicine for the management of diabetes, cancer, stroke, obesity, and measles. Popularly considered a weed, it is an unconventional food plant (UFP) with many nutritional and socio-economic potentials that needs to be rescued for invasive farming. The plant is a reservoir of various phytoconstituents belonging to flavonoids and lignans, alkaloids, and benzoic acid derivatives, which are known for their wide range of pharmacological effects. There is tremendous therapeutic potential in this cosmopolitan leafy vegetable plant, which has antidiabetic, antioxidative, hepatoprotective, and anticancer activity, along with a plethora of other pharmacological activities. This article reviews the traditional uses, phytochemistry, and pharmacology aspects of this underutilized food plant based on an extensive literature search which was available from 1976 to 2024 using a variety of electronic search engines. A network pharmacology-based approach was used for validation of the traditional claims as well as for exploring its therapeutic potential against diabetes for future research directions. This review intends to sensitize the scientific community to further research on this promising plant to bring it to commercial utilization as well as broaden the scope of this underutilized food plant.

Nanohybrid cerasomes represent a significant advancement in the field of drug delivery systems, offering a superior alternative to traditional cerasomes and liposomes. Cerasomes are biocompatible colloidal nanoparticles characterized by an additional polyorganosiloxane network layer that enhances their stability compared to conventional liposomes. The novel hybrid liposomal cerasome, featuring a partial ceramic or silica coating, has garnered substantial interest due to its unique structure. This structure provides better morphological stability than traditional liposomes and, in comparison to silica nanoparticles, significantly reduces overall stiffness and density. By incorporating liposomal architecture, cerasomes achieve greater biocompatibility than silica nanoparticles. This unique combination leverages the benefits of both liposomes and silica nanoparticles while mitigating their respective drawbacks, positioning cerasomes as an optimal drug delivery system. Nanohybrid cerasomes offer extended circulation residence time, enabling more efficient drug delivery to disease sites and facilitating the targeting of specific disease cells. Their potential as intracellular delivery vehicles for proteins, peptides, antisense compounds, ribozymes, and DNA is particularly noteworthy. The presence of a liposomal bilayer structure in cerasomes reduces rigidity and density, enhancing their stability and effectiveness as drug and gene delivery vehicles. This article reviews the techniques for preparing cerasomes and explores their applications in targeted drug and gene delivery systems, highlighting their advantages over conventional liposomes and silica nanoparticles.

The consumption of a high-sodium diet (HSD) is injurious and known to elevate blood pressure (BP), especially in obesity. Acute infusion studies depict a functional interdependency between angiotensin-II type 2 receptor (AT2R) and receptor Mas (MasR). Hence, we hypothesize that the subacute blockade of MasR should reverse AT2R-mediated renoprotection in obese Zucker rats (OZRs). Male OZRs were fed an HSD (for 14 days) and treated with the AT2R agonist C21 (100 ng/min) without or with a MasR antagonist A779 (1,000 ng/min). The indices of oxidative stress, proteinuria, kidney injury, and BP were measured before and after, along with the terminal measurements of an array of inflammatory and kidney injury markers. The HSD significantly decreased the estimated glomerular filtration rate and urinary osmolality and increased thirst, diuresis, natriuresis, kaliuresis, plasma creatinine, urinary excretion of H2O2, proteinuria, renal expression and urinary excretion of kidney injury markers (NGAL and KIM-1), and BP indexes. The HSD feeding showed early changes in the renal expression of CRP, ICAM-1, and galectin-1. The C21 treatment prevented these pathological changes. The MasR antagonist A779 attenuated C21-mediated effects on the urinary excretion and renal expression of NGAL and oxidative stress in the absence of inflammation and BP changes. Overall, we conclude that the subacute functional interactions between AT2R and MasR are weak or transient and that the beneficial effects of AT2R activation are independent of the MasR blockade in the kidney of male obese rats fed an HSD.

The tremendous speed and security that Free Space Optical Communication (FSOC) technology provides have led to its rapid expansion. This opens up a plethora of possibilities for terrestrial communication with small ranges of up to a few kilometers, such as multi-campus and building-to-building communication. However, the ever-varying nature of atmospheric channels poses a major challenge degrading the optical signal strength. Several constituents of atmospheric channels like fog, dust, smoke, rain, and wind turbulence will influence the performance of an FSOC channel. In this paper, we present a system model focusing on adverse atmospheric channels, primarily by replicating varying fog conditions. Additionally, we showcase the successful real-time implementation of diverse forward error correction (FEC) codes in adverse atmospheric conditions, specifically varying levels of fog, using a dedicated test bed. Our experiments demonstrate the capability to recover erroneous data up to 50% Bit Error Rates (BER). Furthermore, we delve into the selection of suitable FEC codes tailored to different fog conditions, aiming to optimize time efficiency with the encoded bitrate.

Background: HtrA2, a pro-apoptotic protease, plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol. Prior studies in ischemic cells have indicated that cytosolic HtrA2 triggers cFLIP degradation, plausibly through direct interaction. In this study, we have characterized the cFLIP protein, validated its interaction with HtrA2, and demonstrated that cFLIP is also a substrate of HtrA2. Methods: We have identified the probable cleavage sites of cFLIP through gel-based assays and mass spectrometric analysis of the cleaved fragments. Results: Our findings shed light on a key protein-protein interaction involving pro-apoptotic HtrA2, confirming cFLIP as its interacting partner and substrate. Conclusion: Understanding the nuances of HtrA2's interaction with cFLIP (a decoy protein of the initiator procaspase-8 in the extrinsic apoptotic pathway) and deciphering the cFLIP's mode of cleavage, would provide an excellent alternative to modulate the pathway for therapeutic benefits toward diseases like ischemia and cancer.

Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-mediated cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS® (mavacamten, MYK-461), a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment, was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression in vitro, suggesting its promise as a treatment for HFpEF.

Infectious keratitis is commonly encountered in the ophthalmology emergency department. Streptococcus pneumoniae causing bacterial keratitis is a cause of concern in developing countries, owing to its complication of irreversible corneal scarring. This is a rare case report of a 25-year-old immunocompromised patient who presented to the Ophthalmology Department in a tertiary care hospital in India with complaints of diminution of vision in the left eye with pain, redness and watering, along with a history of vesicular painful rashes involving the left side of the forehead, the tip of the nose and the supraciliary area. Gram-positive lanceolate diplococci and plenty of pus cells were seen on the Gram staining of the corneal abscess scrape. The clinical presentation of the patient led to a provisional clinical diagnosis of secondary bacterial infection in Herpes Zoster Opthalmicus (HZO), corneal abscess with herpetic keratitis. Quellung reaction yielded an 18C serotype of the isolated pneumococci. Prompt treatment was required to prevent rapidly progressive complications.

Abstract Background India has rolled out Early Infant Diagnosis (EID) program for HIV infection in all states. EID program consists of testing of Infants exposed to HIV periodically over 18 months of age which is a multi-step complex testing cascade. Caregivers represent the primary beneficiary of EID program i.e., infants exposed to HIV and face multiple challenges to access EID services. As part of national EID program outcome assessment study, this study narrates caregivers’ perspectives on barriers and facilitators to access and utilize EID services. Methods The study was conducted in 31 integrated counselling and testing centres (ICTCs) located in 11 high burden HIV states. A total of 66 in-depth interviews were conducted with caregivers’ of infants enrolled in EID program. Thematic analysis was carried out to help identify themes underlying barriers and facilitators to access EID services and utilization from caregivers’ perspectives. Results The stigma and discrimination prevalent in society about HIV remains a key demand side (caregiver-level) barrier. Non-disclosure or selective disclosure of HIV status led to missed or delayed EID tests and delayed HIV diagnosis and initiation of Anti-Retroviral Therapy (ART) for infants exposed to HIV. On supply side (health system-level), accessibility of healthcare facility with EID services was reported as a key barrier. The distance, time and cost were key concerns. Many caregivers faced difficulties to remember the details of complex EID test schedule and relied on a phone call from ICTC counsellor for next due EID test. Delayed EID test results and lack of communication of test results to caregiver were reported as primary barriers for completing the EID test cascade. Discussion The study reports caregiver-level and health system-level barriers and facilitators for access to EID services from the caregivers’ perspectives. While, decentralisation and single window approaches can improve the access, timely communication of test results to the caregiver also need to be built in with appropriate use of technology. A holistic intervention including PLHIV support networks and the peer-led support mechanisms would be useful to address societal factors. Conclusion The study findings have high significance for developing program implementation strategies to improve access and to build right-based and patient-centred EID services.

Background and Aims: Multiple sources of medical oxygen, namely liquid medical oxygen (LMO) tanks, pressure swing adsorption (PSA) plants, concentrators, and gaseous cylinders, are available at different healthcare facilities. These sources of oxygen have varying installation and operational costs. In low-resource settings, it is imperative to utilise these assets optimally. This study investigated the operational costs of multiple oxygen sources available at a healthcare facility. Methods: A Microsoft (MS) Excel-based model was developed to analyse and compare the oxygen manufacturing costs (in ₹/m3) using PSA plants and procurement costs (in ₹/m3) of LMO and third-party vendor-refilled cylinders. Results: The oxygen manufacturing costs for PSA plants of different capacities and running times on electricity and diesel generators (DGs) as a power source were calculated. This study highlights the cost-benefit of using PSA plants over LMO and third-party vendor-refilled cylinders as a source of oxygen. PSA plants are most economical when they are of higher capacity and used to their maximum capacity on electricity as the power source. On the contrary, they are most expensive when used on a DG set as a power source. Furthermore, this study provides evidence of PSA plants being more cost-effective for refilling cylinders using a booster compressor unit when compared to third-party vendor-cylinder refilling. Conclusion: Given their cost-effectiveness and low third-party dependence, they should be utilised to their maximum capacity as medical oxygen sources at healthcare facilities.

Purpose: To assess the accuracy of freehand cervical C1 C2 screws placement by knock and drill (K and D) technique in craniovertebral anomalous bony anatomy. Materials and Methods: From January 2017 to December 2022, 682 consecutive C1 C2 screws in 215 patients with craniovertebral junction (CVJ) anomalies were enrolled. All patients underwent posterior fixation with K and D technique without any fluoroscopic guidance. The patient's demographic details, clinical details, radiological details, major intraoperative events, and postoperative complications were noted. The screws malposition grades and direction on CT images in the axial and sagittal plane were defined as new per proposed “SGPGI accuracy criteria.” All patients had a clinical evaluation at 3-month follow-up. Results: Total 682 C1, C2 screws were placed in 215 patients for CVJ anomalies using K and D technique. The accuracy of screws placement by freehand technique was 84.46% (576/682). So with technique explained the rate of malplacement in simple (16.35%) and complex (15.19%) groups were almost comparable and comparison difference was not significant (P = 0.7005). Conclusion: The freehand technique, as described, is effective in cases of anomalous bony anatomy, and it is mandatory in complex CVJ anomalies. The accuracy of screw placement and VA injury is comparable with major studies. This technique is supposedly cost-effective and less hazardous to both health-care workers and patients.

Abstract Background Cardiac repair and remodeling following myocardial infarction (MI) is a multifactorial process involving pro-reparative inflammation, angiogenesis and fibrosis. Noninvasive imaging using a radiotracer targeting these processes could be used to elucidate cardiac wound healing mechanisms. The alpha7 nicotinic acetylcholine receptor (ɑ7nAChR) stimulates pro-reparative macrophage activity and angiogenesis, making it a potential imaging biomarker in this context. We investigated this by assessing in vitro cellular expression of ɑ7nAChR, and by using a tritiated version of the PET radiotracer [18F]NS14490 in tissue autoradiography studies. Results ɑ7nAChR expression in human monocyte-derived macrophages and vascular cells showed the highest relative expression was within macrophages, but only endothelial cells exhibited a proliferation and hypoxia-driven increase in expression. Using a mouse model of inflammatory angiogenesis following sponge implantation, specific binding of [3H]NS14490 increased from 3.6 ± 0.2 µCi/g at day 3 post-implantation to 4.9 ± 0.2 µCi/g at day 7 (n = 4, P

Introduction: Ocular manifestations of Haemodialysis (HD) are one of the important causes of morbidity in End-stage Renal Disease (ESRD) patients. According to studies, the incidence rate of glaucoma in the dialysis group was higher than that in the non dialysis group. Angle-closure glaucoma was found to be more common, which depends on anterior chamber morphology. Aim: To assess the effect of HD on Intraocular Pressure (IOP), Anterior Chamber Depth (ACD), and Lens Thickness (LT) in patients with ESRD. Materials and Methods: This was a single-centre crosssectional observational study conducted in the Department of Ophthalmology on 170 eyes of 87 patients undergoing HD for at least three months. The study was conducted between October 2020 and October 2022 at the Dialysis Centre of Bharati Vidyapeeth (DTU) Medical College and Hospital, Pune, Maharashtra, India. These patients underwent ophthalmological evaluation pre- and postdialysis. IOP, ACD, and LT were measured 30 minutes prior to and 30 minutes after the HD session. The paired t-test was used to compare differences in means, and a p-value of

The integration of three-dimensional (3D) printing techniques into the domains of biomedical research and personalized medicine highlights the evolving paradigm shifts within contemporary healthcare. This technological advancement signifies potential breakthroughs in patient-specific therapeutic interventions and innovations. This systematic review offers a critical assessment of the existing literature, elucidating the present status, inherent challenges, and prospective avenues of 3D printing in augmenting biomedical applications and formulating tailored medical strategies. Based on an exhaustive literature analysis comprising empirical studies, case studies, and extensive reviews from the past decade, pivotal sectors including tissue engineering, prosthetic development, drug delivery systems, and customized medical apparatuses are delineated. The advent of 3D printing provides precision in the fabrication of patient-centric implants, bio-structures, and devices, thereby mitigating associated risks. Concurrently, it facilitates the ideation of individualized drug delivery paradigms to optimize therapeutic outcomes. Notwithstanding these advancements, issues concerning material biocompatibility, regulatory compliance, and the economic implications of avant-garde printing techniques persist. To fully harness the transformative potential of 3D printing in healthcare, collaborative endeavors amongst academicians, clinicians, industrial entities, and regulatory bodies are paramount. With continued research and innovation, 3D printing is poised to redefine the trajectories of biomedical science and patient-centric care. The paper aims to justify the research objective of whether to what extent the integration of 3D printing technology in biomedicine enhances patient-specific treatment and contributes to improved healthcare outcomes.

Abstract Objective Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high‐risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center. Methods A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re‐appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging. Results Patients with relapsed HB had a 5‐year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16–4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783–149.091; p = 0.013) compared to only chemotherapy. Conclusions This study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

Abstract Anxiety disorders (ADs) are the most common form of mental disorder that affects millions of individuals worldwide. Although physiological studies have revealed the neural circuits related to AD symptoms, how AD-associated genes are spatiotemporally expressed in the human brain still remains unclear. In this study, we integrated genome-wide association studies of four human AD subtypes—generalized anxiety disorder, social anxiety disorder, panic disorder, and obsessive-compulsive disorder—with spatial gene expression patterns. Our investigation uncovered a novel division among AD-associated genes, marked by significant and distinct expression enrichments in the cerebral nuclei, limbic, and midbrain regions. Each gene cluster was associated with specific anxiety-related behaviors, signaling pathways, region-specific gene networks, and cell types. Notably, we observed a significant negative correlation in the temporal expression patterns of these gene clusters during various developmental stages. Moreover, the specific brain regions enriched in each gene group aligned with neural circuits previously associated with negative decision-making and anxious temperament. These results suggest that the two distinct gene clusters may underlie separate neural systems involved in anxiety. As a result, our findings bridge the gap between genes and neural circuitry, shedding light on the mechanisms underlying AD-associated behaviors.

In this paper, we determine the distance Laplacian and distance signless Laplacian spectrum of generalized wheel graphs and a new class of graphs called dumbbell graphs.

Introduction: Atraumatic extraction is necessary when a patient undergoes dental implant rehabilitation. Various tooth extraction systems are used and regularly upgraded. The periotome is a tool that severes the Periodontal Ligaments (PDL) and aids in atraumatic extraction while preserving the socket. Aim: To evaluate the efficacy of conventional forceps versus periotome extractions of single-rooted maxillary teeth in terms of socket preservation, procedure duration, and postoperative pain. Materials and Methods: This was a single-blinded randomised clinical trial conducted at Department of Oral and Maxillofacial Surgery, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharastra, India from December 2020 to March 2021 involved 42 patients aged 18-60 years who required extraction of maxillary single-rooted teeth that had failed endodontic treatment. The patients were randomly divided into two groups: a periotome group and a conventional forceps group. Clinical assessment was conducted to evaluate socket preservation, extraction time, postoperative pain, and any complications related to the extraction procedure. Statistical analysis was performed using the Mann-Whitney U test, Chi-square test, and unpaired t-test. Results: The majority of patients were within the age group of 51-60 years, with 13 males and 29 females. The difference in extraction time between the two groups was not statistically significant (p=0.368). The periotome group exhibited a significantly lower incidence of buccal cortical plate fractures compared to the conventional forceps group (p=0.048). Regarding the severity of postoperative pain, the periotome group demonstrated a significantly lower value than the conventional forceps group (p=0.028). Conclusions: The periotome proved to be a more efficient choice for preserving the socket in endodontically non treatable teeth requiring extraction, as compared to conventional forceps.

Background: Globally, oral cavity lesions are a serious public health issue. Premalignant lesions of the oral cavity, such as leukoplakia, erythroplakia, and oral submucous fibrosis, are common in India and are strongly associated with tobacco and betel nut use. These lesions have the potential to transform into malignancies, with squamous cell carcinoma (SCC) being the predominant type of oral cancer. Early detection and effective management of early malignant lesions are crucial to improving the prognosis for patients. Histopathological examination is a standard procedure used to identify these lesions. Aims and Objectives: The objective of this study is to examine the histopathology of premalignant and malignant lesions of the oral cavity, taking into account age, sex, site distribution, and their association with tobacco consumption. Materials and Methods: The study was a prospective, observational study carried out over a period of 3 years on patients with lesions of the oral cavity in a Government Medical College of Northern Odisha. Biopsies were obtained, fixed, and routinely processed. Sections were stained with Hematoxylin and Eosin. The final diagnosis was based on clinical, gross, and microscopic findings. The data was collected and analyzed. Results: Out of a total of 197 oral biopsies, 79 cases were malignant lesions, and 35 cases were pre-malignant lesions. The highest incidence of both pre-malignant and malignant lesions was observed in the age group of 51–60 years, with a male predominance. The buccal mucosa was the most affected site. The most frequent type of malignant lesion was well-differentiated SCC, while hyperkeratosis without dysplasia was the most common type of pre-malignant lesion. Conclusion: Cancers of the oral cavity are surface malignancies whose signs and symptoms can be recognized early. The most common subsite of cancer is the gingivobuccal complex, and site-specific carcinoma is often due to the use of tobacco and betel quid, as they are typically placed in the gingivobuccal sulcus. The occurrence of carcinoma can be minimized by creating public awareness regarding high-risk habits.

Sensescape, predominantly explored from the viewpoint of viewscape and soundscape, needs investigation from other senses such as smell, a vital part of place experience. The place experience not only depends on senses but also on how senses act within the context. Cities across developing countries, with dynamic tension of coexistence between traditional and modern, are experiencing transformations, inducing major alterations in urban land-use systems and have started to impact upon urban place experience and urban smellscapes diversities. Smellscape is a complex phenomenon posing challenges to the reductionist approach for better insight, hence requiring an effective conceptual framework for analyzing the smellscape with reference to the transformations in cities. Four urban node precinct typologies, as representative cases from developing countries, namely, traditional, partially transformed, transformed and majorly transformed urban nodes, are assessed and presented in this paper. The smellscape and urban place experience, their interconnectedness, and interdependency are investigated in this paper. Based on interpretive epistemology from the cognition framework, the paper posits that the smellscape has a vital role in urban place experience, it correlates and influences urban place liking, and provides clues for theory building for the assessment of smellscape, an underexplored intangible aspect of sensory place experience.

The current study aims to degrade Procion Golden Yellow H-R through ultrasound-induced cavitation coupled with various oxidants. A comprehensive investigation was conducted to examine the impact of parameters, specifically pH, power, and frequency, on the extent of degradation. The primary aim was to optimize degradation by solely utilizing a cavitation reactor where only 23.8% degradation was observed under the established optimum conditions of pH 2.5, frequency of 22 kHz, and power of 200 W. The investigation of the combined process of cavitation with H2O2, Fenton reagent (H2O2/Fe2+), NaOCl, and potassium persulphate (KPS) was subsequently conducted under optimized conditions. The combined operations greatly enhanced degradation with the use of H2O2 loading of 0.1 g/L leading to 53.3% degradation and the H2O2/Fe2+ ratio of 1:0.25 resulting in 94.6% degradation, while the NaOCl quantum of 0.075 g/L yielded 90% degradation and the KPS quantity of 2 g/L resulted in 97.5% degradation in the specific combinations. A toxicity test on two bacterial strains, Staphylococcus aureus and Escherichia coli, was carried out using the original dye solution and after treatment. The various individual and combination processes were compared using the parameters of cavitational yield and total treatment cost. The study elucidates that combining ultrasonic cavitation with KPS is an effective method for treating wastewater containing Procion Golden Yellow H-R dye, especially when implemented at a larger scale of operation.