Benign to Malignant Hepatic Lesion Transformation in Abernethy Malformation.

Abernethy malformation or congenital extrahepatic portosystemic shunt is an extremely rare condition whereby the portomesenteric blood drains into a systemic vein and bypasses the liver through a complete or partial shunt. Severe complications include hyperammonemia and encephalopathy, benign and malignant liver tumors, and hepatopulmonary syndrome. We describe a case where a female adult diagnosed with congenital extrahepatic portosystemic shunt subsequently developed focal nodular hyperplasia and then hepatocellular carcinoma.

Occurrence of Depression and its Association with Oral Health in Elderly People Living in Old Age Homes of Mathura.

Introduction: Depression can affect oral health as a result of neglecting oral hygiene procedures which leads to an increased risk of dental caries and periodontal disease. Aim: To determine relationship between oral health and depression among elder people residing in old age homes of Mathura city. Materials and Methods: The study was conducted among 500 subjects aged ≥60 years where dental condition, number of missing teeth, removable denture wearing, teeth mobility, periodontal condition, pocket depth, loss of attachment, and depression according to the Patient Health Questionnaire-9 scale were assessed. Results: Regression analysis showed a positive relationship of the PHQ-9 value with DMFT and MT. Conclusion: Among people aged 60 years and over, severity of depression increased with higher number of MT and DT.

Demystifying Fogging in Lyophilized Products: Impact of Pharmaceutical Processing.

A commonly encountered challenge with freeze-dried drug products is glass vial fogging. Fogging is characterized by a thin layer of product deposited upon the inner surface of the vial above the lyophilized cake. While considered to be a routine cosmetic defect in many instances, fogging around the shoulder and neck of the vial may potentially impact container closure integrity and reject rates during inspection. In this work, the influence of processing conditions i.e. vial pre-treatment, lyophilization cycle modifications and filling conditions on fogging was evaluated. A battery of analytical techniques was employed to investigate factors affecting glass vial fogging. A fogging score was used to quantify its severity in freeze-dried products. Additionally, a dye-based method was used to study solution upcreep (Marangoni flow) following product filling. Our lab-scale results indicate measurable improvement in fogging following the addition of an annealing step in the lyophilization cycle. Pre-freeze isothermal holding of the vials (at 5°C on the lyophilizer shelf) for an extended duration indicated a reduction in fogging whereas an increase in the freezing time exhibited no effect on fogging. Vial pre-treatment conditions were critical determinants of fogging for Type 1 vials whereas they had no impact on fogging in TopLyo® vials. The headspace relative humidity (RH) investigation also indicated sufficient increase in the water vapor pressure inside the vial to be conducive to the formulation of a hydration film - the precursor to Marangoni flow.

Impact of Medicaid Expansion on Surgical Care and Outcomes for Hepatobiliary Malignancies.

BACKGROUND: As part of the Patient Protection and Affordable Care Act, some states expanded Medicaid eligibility to adults with incomes below 138% of the federal poverty line. While this resulted in an increased proportion of insured residents, its impact on the diagnosis and treatment of hepatopancreaticobiliary (HPB) cancers has not been studied. STUDY DESIGN: The National Cancer Database (NCDB) from 2010 to 2017 was used. Patients diagnosed with HPB malignancies in states which expanded in 2014 were compared to patients in non-expansion states. Subset analyses of patients who underwent surgery and those in high-risk socioeconomic groups were performed. Outcomes studied included initiation of treatment within 30 days of diagnosis, stage at diagnosis, care at high volume or academic center, perioperative outcomes, and overall survival. Adjusted difference-in-differences analysis was performed. RESULTS: A total of 345,684 patients were included, of whom 55% resided in non-expansion states and 54% were diagnosed with pancreatic cancer. Overall survival was higher in states with Medicaid expansion (HR .90, 95% CI [.88-.92], P < .01). There were also better postoperative outcomes including 30-day mortality (.67 [.57-.80], P < .01) and 30-day readmissions (.87 [.78-.97], P = .02) as well as increased likelihood of having surgery in a high-volume center (1.42 [1.32-1.53], P < .01). However, there were lower odds of initiating care within 30 days of diagnosis (.77 [.75-.80], P < .01) and higher likelihood of diagnosis with stage IV disease (1.09 [1.06-1.12], P < .01) in expansion states. CONCLUSION: While operative outcomes and overall survival from HPB cancers were better in states with Medicaid expansion, there was no improvement in timeliness of initiating care or stage at diagnosis.

Endoplasmic reticulum stress and its role in various neurodegenerative diseases.

The Endoplasmic reticulum (ER), a critical cellular organelle, maintains cellular homeostasis by regulating calcium levels and orchestrating essential functions such as protein synthesis, folding, and lipid production. A pivotal aspect of ER function is its role in protein quality control. When misfolded proteins accumulate within the ER due to factors like protein folding chaperone dysfunction, toxicity, oxidative stress, or inflammation, it triggers the Unfolded protein response (UPR). The UPR involves the activation of chaperones like calnexin, calreticulin, glucose-regulating protein 78 (GRP78), and Glucose-regulating protein 94 (GRP94), along with oxidoreductases like protein disulphide isomerases (PDIs). Cells employ the Endoplasmic reticulum-associated degradation (ERAD) mechanism to counteract protein misfolding. ERAD disruption causes the detachment of GRP78 from transmembrane proteins, initiating a cascade involving Inositol-requiring kinase/endoribonuclease 1 (IRE1), Activating transcription factor 6 (ATF6), and Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathways. The accumulation and deposition of misfolded proteins within the cell are hallmarks of numerous neurodegenerative diseases. These aberrant proteins disrupt normal neuronal signalling and contribute to impaired cellular homeostasis, including oxidative stress and compromised protein degradation pathways. In essence, ER stress is defined as the cellular response to the accumulation of misfolded proteins in the endoplasmic reticulum, encompassing a series of signalling pathways and molecular events that aim to restore cellular homeostasis. This comprehensive review explores ER stress and its profound implications for the pathogenesis and progression of neurodegenerative diseases.

Metal Oxide Nanowire-Based Sensor Array for Hydrogen Detection.

Accurate hydrogen leakage detection is a major requirement for the safe and widespread integration of this fuel in modern energy production devices, such as fuel cells. Quasi-1D nanowires of seven different metal oxides (CuO, WO3, Nb-added WO3, SnO2, ZnO, α-Bi2O3, NiO) were integrated into a conductometric sensor array to evaluate the hydrogen-sensing performances in the presence of interfering gaseous compounds, namely carbon monoxide, nitrogen dioxide, methane, acetone, and ethanol, at different operating temperatures (200-400 °C). Principal component analysis (PCA) was applied to data extracted from the array, demonstrating the ability to discriminate hydrogen over other interferent compounds. Moreover, a reduced array formed by only five sensors is proposed. This compact array may be easily implementable into artificial olfaction systems used in real hydrogen detection applications.

Marginal bone loss around implants with platform switching and platform matched connection: A systematic review.

STATEMENT OF PROBLEM: Platform switching using narrower abutments than the implant platform has been used to reduce marginal bone loss (MBL) surrounding dental implants. While platform switching has been reported to prevent initial peri-implant bone loss, available data regarding the use of the platform-switching implant abutment configuration with long-term follow-up has been sparse; thus, the systematic review was planned to evaluate the best available evidence for the use of the platform switching technique. PURPOSE: The purpose of this systematic review was to answer the specific question, "Is there a difference between platform-matching implant abutment configurations and platform-switching implant abutment configurations in terms of MBL changes around endosseous implants"? MATERIAL AND METHODS: The PubMed/Medline, Scopus, Google Scholar, and Lilac databases were searched by 2 independent reviewers for articles published between January 2000 and July 2022. Platform-switched versus platform-matched implants were examined for changes in MBL in human randomized clinical trials (RCTs) and potential clinically controlled cohort studies (PCCS). RESULTS: Overall, 4 eligible studies were included and critically evaluated to summarize their findings. The follow-up period of the included studies was between 5 and 10 years. Two of the included studies showed a mean ±standard deviation of 0.6 ±0.20 mm MBL at 5 years and 1.20 ±0.21 mm at 10 years for the platform switched (PS) technique and 1.1 ±0.3 mm and 1.24 ±0.39 mm MBL for the platform matched (PM) technique. Another study showed marginal bone level changes for the platform-switched technique to be 0.18 ±0.14 mm as compared with the platform matched technique (0.80 ±0.40 mm). In one of the studies published in 2019, the mean estimated difference in the marginal bone levels of PS- and PM-restored implants after 5 years was reported to be 0.29 mm. The descriptive analysis of 4 RCTs indicated that platform-switched implant-to-abutment connections reduced average marginal bone loss surrounding implants compared with platform-matched implant-to-abutment connections, favoring the platform-switched approach. CONCLUSIONS: Platform switching appears to be a beneficial approach for retaining the crestal bone around dental implants.

Detrimental influence of industrial effluents, especially heavy metals, on limnological parameters of water and nutritional profile in addition to enzymatic activities of fish, Sperata seenghala (Sykes, 1839) from diverse Ramsar sites, India (Punjab).

The present research was designed to determine the nutritive value of the liver and intestine of fish, Sperata seenghala, the impact of effluence load on limnological parameters of water and proximate composition of fish organs, especially on fatty acids, liver enzymatic activities, seasonal variations in the nutritional profile of fish, and to check and compare the pollution status of Ramsar sites in Punjab by calculating the water quality index, heavy metal pollution index, and metal index from June 2018 to August 2020. WQI of Harike wetland was found to be 53.95, which depicts that water quality in this region is "poor". At Nangal wetland, water quality index was reported to be "excellent" quality water and fit for the whole ecological unit. Overall heavy metal pollution index for Harike wetland was reported 174.569, whereas for Nangal wetland it was 5.994, depicting massive contaminant loads in a polluted region. MI value was also recorded as being higher (6.9336) in polluted habitat than in control habitat (0.8175). In fish liver, significant (p < 0.05) higher mean total lipids (6.73%), total proteins (3.98%), moisture (77.69%), ash (3.56%), and carbohydrates (3.79%) were observed in the samples from Nangal wetland than Harike wetland. A similar trend was reported in all biochemical contents of the fish intestine. Enzyme activities such as aspartate-aminotransferase and alanine-aminotransferase were significantly elevated (p < 0.05) in the specimens collected from the polluted region. The mean total n-3 (except in spring), n-6 polyunsaturated fatty acids (except in winter), and average monounsaturated and saturated fatty acids diminished significantly (p < 0.05) in the liver of fish from contaminated habitat than control site. In the intestine of fish collected from the polluted region, significant reductions in the mean total n-3 (except in autumn as well as summer), total n-6 PUFAs (in autumn and winter), and total SFAs were reported than control site.

Cucurbita pepo seeds improve peripheral neuropathy in diabetic rats by modulating the inflammation and oxidative stress in rats.

BACKGROUND: Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats. MATERIALS AND METHODS: Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60th day of STZ/NAD administration and continued upto 90th day. RESULTS: CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-ß and IL-1ß was found to be significantly attenuated in experimental animals. CONCLUSION: Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain.

Identification of Bile Acid-Derived Chemical Chaperone(s) Targeting E46K-Mutated Alpha-Synuclein Protein to Treat Parkinson's Disease: Molecular Modelling, Docking, ADME, and Simulation Studies.

Aggregated α-synuclein (α-syn) present inside small cytoplasmic inclusions in the substantia nigra region marks the major pathological hallmark of Parkinson's disease (PD) and makes it an attractive target for the drug development process. Certain small-molecule chaperones (such as DCA, UDCA, TUDCA) presented the ability to prevent misfolding and aggregation of α-syn as well as to disentangle mature α-syn amyloid fibrils. However, due to toxicity constraints, these small molecules could not be translated into clinical settings. Computational biology methods and bioinformatics approaches allow virtual screening of a large number of molecules, with reduced side effects and better efficacy. In the present study, a library of 10,928 derivatives was generated using DCA, UDCA, and TUDCA bile acid scaffolds and analysed for their binding affinity, pharmacokinetic properties, and drug likeliness profile, to come up with promising compounds with reduced toxicity and better chaperone ability. Molecular docking revealed that with respect to their free binding energy, C1-C25 have the lowest binding energy and bind significantly to recombinantly assembled E46K α-syn fibrils (PDB ID-6UFR). In silico ADME predictions revealed that all these compounds had minimal toxic effects and had good absorption as well as solubility characteristics. Simulation studies further showed that the imidazole ring-based TUDCA derivatives interacted better with the protein in comparison to the others. The proposed study has identified potent chemical chaperones (C2 and C3) as effective therapeutic agents for Parkinson's disease, and further in vitro and in vivo testing will be undertaken to substantiate their potential as novel drugs.

Characteristics of acid attacks involving children in India.

Aim: To examine the characteristics of acid attack survivors who were aged ≤16 years at the time of the assault. Methods: Case files from the Chhanv and the Laxmi Foundations in India were accessioned for cases of acid attacks involving children and adolescents (≤16 years). Details of the age, sex, reason for the attack, injuries sustained and possible outcomes were recorded. Results: Ten cases were identified that involved eight girls (aged 3-16 years) and two boys (12 and 14 years). The head and neck were the primary targets in all cases. The primary reasons for the attacks involving adolescent girls were punishment for refusing sexual advances from older males and family violence/child abuse. The two male victims were assaulted as part of property dispute and gang violence. Penalties varied greatly with prison sentences (when handed down) ranging from <1 year to 10 years. Conclusion: The number of cases of paediatric acid attacks appear small, with motivations for the attacks including responses to spurned sexual advances, domestic violence/child abuse, criminal gang activities and ostensibly at random. Nongovernment organisations are vital in the rehabilitation of victims. It is of concern that dissemination on social networks and publicity through the media may lead to an increase in number of cases.

Multifaceted Carbon Dots: toward pH-Responsive Delivery of 5-Fluorouracil for In Vitro Antiproliferative Activity.

The synthesis of smart hybrid material to assimilate diagnosis and treatment is crucial in nanomedicine. Herein, we present a simple and facile method to synthesize multitalented blue-emissive nitrogen-doped carbon dots N@PEGCDs. The as-prepared carbon dots N@PEGCDs show enhanced biocompatibility, small size, high fluorescence, and high quantum yield. The N@PEGCDs are used as a drug carrier for 5-fluorouracil (5-FU) with more release at acidic pH. Furthermore, the mode of action of drug-loaded CD (5FU-N@PEGCDs) has also been explored by performing wound healing assay, DCFDA assay for ROS generation, and Hoechst staining. The drug loaded with carbon dots showed less toxicity to normal cells compared to cancer cells, making it a perfect candidate to be studied for designing next-generation drug delivery systems.

To evaluate eosinophilia (tissue eosinophilia, blood eosinophilia and tissue eosinophilia/blood eosinophilia ratio) in increasing grades/ severity of oral neoplastic lesions.

Oral squamous cell carcinoma (OSCC) is the most common cause of morbidity and mortality in India. Buccal mucosa is the most common site because of tobacco quid. Several parameters for the assessment of OSCC have been studied like lymph node metastasis, tumor stage, grade, and perineural invasion. Tumor-associated tissue eosinophilia is another parameter, on which several studies have been done because of its favorable and unfavorable prognosis. The aim of our study is to study quantitative and qualitative eosinophilia in premalignant and malignant lesions of squamous origin in oral cavity with respect to tumor-associated blood eosinophilia. A retrospective study was done at Tertiary care hospital between January 2016 and December 2016. A total of 150 cases of premalignant (oral leukoplakia and dysplasia) and malignant oral squamous cell carcinoma (of various grades) along with blood pictures were evaluated.

Tobacco Smoking among the Online Respondent Dental Students of a Dental College: A Descriptive Cross-sectional Study.

Introduction: Smoking tobacco is most common nowadays among dental students due to stress induced by practical workloads and exams. There is limited data regarding tobacco smoking among dental students. The aim of this study was to determine the prevalence of tobacco smoking among online respondent dental students of a dental college. Methods: This was a descriptive cross-sectional study conducted on dental students from 15 July 2021 to 15 August 2021. Ethical approval was obtained from the Institutional Review Committee of K.D. Dental College and Hospital (Reference number: KDDC/Admin/2021/9990A). Data was collected through a structured questionnaire and responses were gathered using an online Google form survey with informed consent. A convenience sampling method was used. Point estimate and 95% confidence interval were calculated. Results: Among 60 online respondents, the prevalence of tobacco smoking was found to be 11 (18.33%) (17.04-24.56, 95% Confidence Interval). The percentage of participants who wanted to stop smoking now was 11 (18.33%). Conclusions: The prevalence of tobacco smoking among the online dental respondents of a dental college was similar to the other studies done in similar settings. Keywords: dental students; smoking; tobacco cessation.

Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.

Free energy perturbation is a computational technique that can be used to predict how small changes to an inhibitor structure will affect the binding free energy to its target. In this paper, we describe the utility of free energy perturbation with FEP+ in the hit-to-lead stage of a drug discovery project targeting soluble adenyl cyclase. The project was structurally enabled by X-ray crystallography throughout. We employed free energy perturbation to first scaffold hop to a preferable chemotype and then optimize the binding affinity to sub-nanomolar levels while retaining druglike properties. The results illustrate that effective use of free energy perturbation can enable a drug discovery campaign to progress rapidly from hit to lead, facilitating proof-of-concept studies that enable target validation.

A dual-purpose polymerase engineered for direct sequencing of pseudouridine and queuosine.

More than 170 posttranscriptional RNA modifications are so far known on both coding and noncoding RNA species. Within this group, pseudouridine (Ψ) and queuosine (Q) represent conserved RNA modifications with fundamental functional roles in regulating translation. Current detection methods of these modifications, which both are reverse transcription (RT)-silent, are mostly based on the chemical treatment of RNA prior to analysis. To overcome the drawbacks associated with indirect detection strategies, we have engineered an RT-active DNA polymerase variant called RT-KTq I614Y that produces error RT signatures specific for Ψ or Q without prior chemical treatment of the RNA samples. Combining this polymerase with next-generation sequencing techniques allows the direct identification of Ψ and Q sites of untreated RNA samples using a single enzymatic tool.

Congenital Heart Disease: Would It Be the Key Driver of Infant Survival During Amrit Kaal (2022-2047)?

Post-independence, we made significant strides in childhood survival. However, there is an abysmal improvement in survival due to birth defects. Globally, India contributes the largest proportion of under-5 deaths, overall as well as due to birth defects. Congenital heart disease (CHD) is the single most common cause of birth-defect related deaths, and is the 7th most common cause of infant deaths. Scarcity of pediatric cardiac care professionals and pediatric cardiac centers has led to a huge demand-supply gap. Understanding the burden of CHD and taking imperative steps at primary, secondary and tertiary levels are essential during Amrit Kaal (2022-2047). Coverage of management of CHD under Janani Shishu Suraksha Karyakram, Rashtriya Bal Suraksha Karyakram and Ayushman Bharat programs offers a huge promise, as shown by the experience from Hridayam program in Kerala.

Living donor liver paired exchange between pediatric and adult recipients due to donor graft size mismatch.

Living donor liver transplantation is an effective means to decrease organ shortage. However, many potential living donors are currently being denied due to ABO incompatibility or inadequate donor liver volume. Liver paired exchange (LPE) provides a practical solution to overcome these obstacles, and yet the first case of LPE in the United States was only recently reported in 2020. Here, we report world's first case of LPE involving pediatric and adult recipients to avoid surgical complexity of the pediatric recipient and to increase the graft-to-recipient weight ratio of the adult recipient between 2 ABO compatible pairs. As living donor liver transplantation becomes more widely adopted, the need for pair exchange to improve surgical safety and postoperative outcomes between 2 ABO compatible pairs is likely to increase.