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Balini Balasubramaniam,1 Yu Jeat Chong,2 Matthew Azzopardi,3 Abison Logeswaran,4 Alastair K Denniston1 1Ophthalmology Department, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK; 2Birmingham & Midland Eye Centre, Birmingham, B18 7QH, UK; 3Ophthalmology Department, Royal London Hospital, Barts Health NHS Trust, London, E1 1BB, UK; 4Moorfields Eye Hospital NHS Foundation Trust, London, UKCorrespondence: Yu Jeat Chong, Birmingham & Midland Eye Centre, Dudley Road, Birmingham, B18 7QH, UK, Email yu.chong.2@city.ac.ukAbstract: Non-infectious uveitis represents a heterogenous group of immune-mediated ocular diseases, which can be associated with underlying systemic disease. While the initial choice of treatment of non-infectious uveitis depends on a number of factors such as anatomical location and degree of inflammation, topical therapies often remain the initial choice of non-invasive therapy. In this narrative review, we aim to describe the literature on non-infectious uveitis, with specific focus on the current perspective on topical anti-inflammatory therapy.Keywords: non-infectious uveitis, topical anti-inflammatory therapy, topical corticosteroids, topical non-steroid anti-inflammatory drugs, topical cycloplegics

Problem: Papua New Guinea (PNG) is situated in the Pacific Ocean and has experienced multiple natural disasters and disease outbreaks. However, PNG lacks the ability to rapidly and systematically deploy trained personnel to provide surge capacity in response to major national disasters. It was therefore decided to establish a national emergency medical team (EMT) in PNG. Context: PNG's responses to the 2018 earthquake in the Highlands Region and the coronavirus disease (COVID-19) pandemic required assistance from international EMTs. PNG began developing its own EMT in 2019, coinciding with the development of other Pacific EMTs. Action: PNG's EMT project was initiated in 2019 with the creation of a technical working group. By 2021, a focal point had been identified, standard operating procedures had been drafted and training of EMT members had been completed. Pilot deployments of the national EMT members contributed to the COVID-19 response during 2021. Outcome: Four major challenges were identified during the early phase of PNG's national EMT development: introducing the concept of EMTs in an EMT-naïve landscape; integrating the national EMT into existing PNG National Department of Health organizational structures; assembling adequate members at short notice to respond to disasters; and securing funding for deployment. Discussion: Solutions identified for these challenges included strengthening stakeholder involvement through engagement in the development process and participation in technical working groups and consultative group discussions, offering exposure to other Pacific-based EMTs, and creating incentive schemes for EMT members and their place of employment. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has various manifestations including neurological and musculoskeletal system involvement. COVID-19 infection causes peripheral nerve lesions including small fibre neuropathy. Complex regional pain syndrome is a debilitating neurological condition manifested by predominantly pain associated with other sensory, motor, autonomic and tropic involvement. Identification and early treatment of CRPS has better prognosis. Here, we report a 21-year-old woman presented with pain, hyperalgesia, and swelling of left upper and lower limb following SARS-CoV-2 infection managed as possible complex regional pain syndrome.

Background/Introduction: Papua New Guinea (PNG) is a Pacific nation of over nine million. It is one of the world's most diverse nations, with over 800 languages and geographic diversity that includes both tropical islands and highland mountains. Located on the Pacific "ring of fire," PNG is regularly struck by disasters and outbreaks. The COVID-19 pandemic triggered multiple deployments of international EMTs to PNG, which were coordinated through a national EMT Coordination Cell. To strengthen rapid, national response to future emergencies, the PNG Government through its National Department of Health is now developing the "PNG EMT." Objectives: To describe the development of the PNG EMT. Method/Description: PNG's national EMT development was inspired by multiple international EMT deployments, including the 2018 Highlands earthquake and multiple COVID-19 deployments. With support from WHO, PNG's National Department of Health led EMT coordination efforts in those responses, and recognized the need for similar capabilities to be developed for national response. Results/Outcomes: To develop the PNG EMT, a focal point was appointed, a national technical working group was formed, and SOPs have been drafted with support from WHO and partners. In consultation with PNG and other Pacific EMTs, WHO is procuring a tailored Pacific EMT cache, including items specifically selected for PNG's diverse geographic and climactic environments. PNG plans to train team members and be ready for self-sufficient national deployments by late 2022. Conclusion: PNG is strengthening readiness for future emergencies by developing a national EMT capable of rapid response to challenging and austere post-disaster environments. [ABSTRACT FROM AUTHOR]

Teratomas are uncommon tumors of the nervous system, the commonest site being the pineal region. Spinal teratomas are very rare apart from the sacrococcygeal variety. The authors report the occurrence of an intramedullary teratoma in an infant. The clinical features, imaging studies and the pathology are discussed. In addition the literature is also reviewed.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pregnancy is a physiological state in women which creates significant alterations in energy metabolism to provide energy supply to the foetus. The maternal fasting glucose level would be less than that of a non-pregnant state and in contrast plasma ketones and free fatty acids levels are elevated, resulting in a state of accelerated starvation. These metabolic alterations place a pregnant woman at a higher risk of developing euglycaemic ketoacidosis. We report a rare case of euglycaemic ketoacidosis causing severe increased anion gap metabolic acidosis in a pregnant woman.

Abstract Background Rural Indian tribes are anthropologically distinct with unique cultures, traditions and practices. Over the years, displacement and rapid acculturation of this population has led to dramatic changes in their socio-cultural and value systems. Due to a poor health infrastructure, high levels of poverty and ignorance, these communities are highly vulnerable to various health problems, especially, communicable diseases including HIV/AIDS. Our study sought to assess knowledge, attitudes and practices regarding sexuality, and the risk factors associated with the spread of HIV/AIDS and STDs among these communities. Methods A nested cross sectional study was undertaken as part of the on going Reproductive and Child Health Survey. A total of 5,690 participants age 18–44 were recruited for this study. Data were obtained through home interviews, and focused on socio-demographics, knowledge, attitudes and behaviors regarding sexuality, HIV/AIDS and other STDs. Results The study revealed that only 22% of adults had even heard of AIDS, and 18 % knew how it is transmitted. In addition, only 5% knew that STDs and AIDS were related to each other. AIDS awareness among women was lower compared to men (14% vs.30 %). Regarding sexual practices, 35% of the respondents reported having had extramarital sexual encounters, with more males than females reporting extramarital affairs. Conclusion Lack of awareness, permissiveness of tribal societies for premarital or extra-marital sexual relationships, and sexual mixing patterns predispose these communities to HIV/AIDS and STD infections. There is a dire need for targeted interventions in order to curtail the increasing threat of HIV and other STDs among these vulnerable populations.

Introduction: ApoE knockout (-/-) mice are a genetically modified model that holistically represents human physiology. It tends to gain weight innately and being fed a high-fat diet (Western diet) will accelerate the progression of fat accumulation. The promising drug, celastrol, has therapeutic properties to reduce weight in many animal models. This study aims to determine celastrol’s effect on body weight in the ApoE -/- mice fed the high-fat diet model. Methods: Two groups (n=5 per group) of mice at eight weeks of age were fed high-fat diet for 12 weeks. Mice were treated with celastrol daily at 2 mg/kg body weight (BW) intraperitoneally (IP). At the same time, the control group was treated with 2% DMSO as vehicle IP daily during the last four weeks of high-fat diet. Mice’s body weights were recorded weekly using an animal weighing scale with standardization in gram units. At 20 weeks, the mice were sacrificed with an anesthetic cocktail of ketamine-xylazine. Data were then analyzed using GraphPad Prism 10 (GraphPad Software, Inc., USA) using a paired t-test. Result: The result showed an increase in body weight for both groups that were fed with HFD, which is supported by many previous literatures on the effect of HFD on body weight. Interestingly, the celastrol administration reduced body weight in ApoE -/- mice fed high-fat diet significantly compared to the control group. by which most studies focus on different animal models, drug routes, and doses. Conclusion: More studies are required to elucidate the optimum dose of celastrol in this model, and the outcome could be extrapolated to those at a greater risk for weight gain. In addition to this, more studies are required to scrutinize the mechanism of celastrol. [ABSTRACT FROM AUTHOR]

Copper metalloenzymes ascorbate oxidase (AOase), amine oxidase (AmOase), and catechol oxidase (COase) possess copper(II) sites of coordination, which are trimeric, homodimeric, and dimeric, respectively. Two newly mononuclear copper(II) complexes, namely, [Cu(L)(bpy)](ClO 4 ) (1) and [Cu(L)(phen)](ClO 4 ) (2) where HL = Schiff base, have been synthesized. UV-visible, EPR and single-crystal X-ray diffraction examinations were used to validate the geometry in solution and solid state. For complex 1, the metal exhibits a coordination sphere between square pyramidal and trigonal bipyramidal geometry (τ, 0.49). A positive Cu II / I redox potential indicates a stable switching between Cu II and Cu I redox states. Despite the monomeric origin, both homogeneous catalysts (1 or 2) in MeOH were found to favor three distinct chemical transformations, namely, ascorbic acid (H 2 A) to dehydroascorbic acid (DA), benzylamine (Ph-CH 2 -NH 2 ) to benzaldehyde (Ph-CHO), and 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylquinone (3,5-DTBQ) [k cat : AOase, 9.6 (1) or 2.0 × 10 6  h -1 (2); AmOase, 13.4 (1) or 9.4 × 10 6  h -1 (2); COase, 2.0 (1) or 1.9 × 10 3  h -1 (2)]. They exhibit higher levels of AOase activity as indicated by their k cat values compared to the AOase enzyme. The k cat values for COase activity in buffer solution [5.93 (1) or 2.95 × 10 5  h -1 (2)] are one order lower than those of the enzymes. This is because of the labile nature of the coordinated donor, the flexibility of the ligand, the simplicity of the catalyst-substrate interaction, and the positive Cu II / I redox potential. Interestingly, more efficient catalysis is promoted by 1 and 2 concerning that of other mono- and dicopper(II) complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Subarachnoid block is the most common anesthetic technique for patients having corrective hip surgeries. However, adequate positioning for a successful subarachnoid block is a major challenge in this particular population of patients, owing to the site of fracture. Regional anesthesia, in the form of nerve blocks, is an effective means of alleviating such constraints and gives an added benefit of prolonged postoperative analgesia. The pericapsular nerve group (PENG) block and the fascia iliaca compartment block (FICB), under ultrasonography guidance, are a few examples of the commonly performed peripheral nerve blocks in such settings. However, the landmark-based techniques of nerve blockade still hold good in many resource poor settings, given the lack of ultrasonography facilities., Aim: To compare the ease of spinal positioning using the patient sitting satisfaction score between the landmark-guided FICB and PENG block., Materials and Methods: This study was done on 80 patients of the American Society of Anesthesiology (ASA) grade I or II with intertrochanteric fractures of the hip joint scheduled for proximal femoral nailing. Patients were allocated into two groups of 40 each through computer generated random numbers, to receive 30 ml of 0.5% ropivacaine via the landmark-guided technique of FICB in Group F and peripheral nerve stimulator assisted landmark-guided PENG block in Group P, 30 minutes prior to spinal positioning. Time to passive leg raise (PLR) to 15 degrees and time to PLR to 30 degrees with a standard goniometer guidance at visual analogue scale (VAS) score < 4 and ease of spinal positioning through the sitting satisfaction score at the 30th minute were assessed. Any adverse effects and events of failure were noted. The duration of postoperative analgesia was measured through the time to the first dose of paracetamol on arrival at the post-anesthesia care unit., Results: Statistical analysis was done using JASP version (0.18.3.0) using the independent samples t-test and significance was taken when p value was < 0.001. The time to PLR to 15 degrees and 30 degrees were achieved faster in the patients who received the PENG block in comparison to the patients who received the FICB, and the average patient sitting satisfaction score was significantly higher in Group P as compared to Group F (p < 0.001). While the overall amount of analgesics used in both groups was similar, the overall period of postoperative analgesia was prolonged in Group F compared to Group P (p < 0.001)., Conclusion: The landmark guided PENG block is feasible and superior to the landmark-guided FICB for preoperative positioning and analgesia. The FICB provides a longer duration of postoperative analgesia for patients with intertrochanteric fractures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. SRM Medical College Hospital - Institutional Ethics Committee - Students issued approval SRMIEC-ST0922-196. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pavithra et al.)

IgG4-related autoimmune pancreatitis (AIP) is a rare inflammatory condition characterized by elevated IgG4-positive plasma cells and lymphoplasmacytic infiltration in the pancreas. This disease responds to steroid therapy but can be challenging to differentiate from pancreatic cancer. In this paper, we present two cases of IgG4-related AIP presenting as pancreatic masses. Our aim is to highlight the diagnostic complexities of this condition and emphasize the need for a multidisciplinary approach to avoid unnecessary surgical interventions and ensure appropriate treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mohamed et al.)

Background and Aim: The aim of this study is to compare the effect of different lubricating agents used with the i-gel® laryngeal mask airway on the incidence of postoperative sore throat., Materials and Methods: After obtaining institutional ethics approval, this prospective trial was conducted on 150 patients who were scheduled for minor surgical procedures. The study population was placed in three groups of 50 each, after randomization with computer-generated random numbers, based on the lubricant used (Group LJ: with lignocaine jelly as the lubricant, Group WJ: with water-based jelly as a lubricant, Group NS: with 0.9% normal saline as a lubricant). The time taken to secure the airway (from insertion to the first end-tidal carbon dioxide (ETCO 2 ) tracing and five-point auscultation) and the number of attempts were noted. During extubation, blood staining was noted. In the postoperative period, sore throat was monitored with the numerical rating scale for the first 24 hours. Postoperative hoarseness of voice, cough and difficulty in swallowing were the other parameters noted. The results were entered in a standard spread sheet. Statistical analysis was done using JASP version 0.18.3.0 using the independent samples t-test and the Chi-square test for quantitative variables., Results: All three groups were comparable in terms of demography (p > 0.05). The time taken to insertion, number of attempts and securing of the airway were also comparable amongst the three groups (p > 0.05). Blood staining during LMA removal was comparable between the three groups (p > 0.05). In the postoperative period, sore throat was comparable between the three groups (p > 0.05). The incidence of hoarseness of voice in the postoperative period however was more significant in Group LJ when compared to the other two (p < 0.05). Postoperative swallowing discomfort was also significantly higher in Group LJ than in the other two groups (p < 0.05)., Conclusion: We conclude that lignocaine jelly, water-based jelly and normal saline used as lubricating agents on the i-gel airway did not show a difference in the incidence of postoperative sore throat. Lignocaine jelly was associated with a higher incidence of hoarseness of voice and swallowing discomfort when compared to the other lubricants., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. SRM Medical College Hospital Institutional Ethics Committee issued approval 8469(A)/IEC/2022. This double-blind trial was registered with the Clinical Trial Registry of India (CTRI/2023/02/049480). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Balachandran et al.)

This study aims to improve the quality of fuel with high calorific value namely Sfuel - a commercial high-quality refuse-derived fuel (RDF) from hazardous waste via modifying the process design and operating parameters of thermal conversion process. The study analyses key parameters of RDF quality, such as calorific value and heavy metal content, before and after process modifications based on the combination of experimental and simulation using Aspen Plus. In this study, the temperature and pressure of the simulation system are varied from 100 to 700 °C and from 1 to 5 bar, respectively. Findings indicate that there are a total of eleven heavy metals and 179 volatile compounds in the "Sfuels". The quality of the targeted product is greatly improved by the metal evaporation at high temperatures and pressures. However, the calorific value of RDF significantly decreases at 700 °C due to a large amount of the carbon content being evaporated. Although the carbon content at high temperatures is significantly lost, the heat from the vapour stream reactor outlet, which is reused to preheat the nitrogen gas stream supplied to the system, reduces energy consumption while improving the thermal conversion efficiency of the system. Besides, low pressure along with high temperature are not the optimal conditions for quality Sfuels improvement by thermal conversion. Results also indicate that electric heating is more economically efficient than natural gas heating., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study presents the binder-free synthesis of mixed metallic organic frameworks (MMOFs) supported on a ternary metal oxide (TMO) core as an innovative three-dimensional (3D) approach to enhance electron transport and mass transfer during the electrochemical charge-discharge process, resulting in high-performance hybrid supercapacitors. The research demonstrates that the choice of organic linkers can be used to tailor the morphology of these MMOFs, thus optimizing their electrochemical efficiency. Specifically, a NiCo-MOF@NiCoO 2 @Ni electrode, based on terephthalic linkers, exhibits highly ordered porosity and a vast internal surface area, achieving a maximum specific capacity of 2320 mC cm -2 , while maintaining excellent rate capability and cycle stability. With these performances, the hybrid supercapacitor (HSC) achieves a maximum specific capacitance of 424.6 mF cm -2 (specific capacity 653.8 mC cm -2 ) and 30.7 F cm -3 with energy density values of 10.1 mWh cm -3 at 167.4 mW cm -3 (139.8 µWh cm -2 at 2310 µW cm -2 ), which are higher than those of previously reported MMOFs based electrodes. This research introduces a novel approach for metal organic framework based HSC electrodes, diverging from the traditional emphasis on metal ions, in order to achieve the desired electrochemical performance., (© 2023 Wiley‐VCH GmbH.)

In this study, we investigate the communication networks of urban, suburban, and rural communities from three US Midwest counties through a stochastic model that simulates the diffusion of information over time in disaster and in normal situations. To understand information diffusion in communities, we investigate the interplay of information that individuals get from online social networks, local news, government sources, mainstream media, and print media. We utilize survey data collected from target communities and create graphs of each community to quantify node-to-node and source-to-node interactions, as well as trust patterns. Monte Carlo simulation results show the average time it takes for information to propagate to 90% of the population for each community. We conclude that rural, suburban, and urban communities have different inherent properties promoting the varied flow of information. Also, information sources affect information spread differently, causing degradation of information speed if any source becomes unavailable. Finally, we provide insights on the optimal investments to improve disaster communication based on community features and contexts., (© 2024. The Author(s).)

Introduction Laparotomy is associated with significant prolonged postoperative pain, which can cause an adverse neuroendocrine stress response. Intrathecal morphine (ITM) retains an important place in pain management after major laparotomy since it is easier to administer and has a relatively lesser possibility of failure and technical difficulty. Aim The study aims to compare the effect of the administration of ITM with intravenous (IV) morphine administered by a patient-controlled analgesia (PCA) pump on postoperative analgesia after elective laparotomy. The primary objective was to compare total morphine consumption while secondary objectives were to compare pain assessed by the visual analog scale (VAS) and adverse reactions to opioids. Methods Sixty patients who underwent elective laparotomy were enrolled in this study. Thirty patients were enrolled in the study group (ITM+PCA) where ITM (200 mcg) was administered before laparotomy and intravenous morphine was initiated with PCA postoperatively. In the control group, only intravenous morphine was given with PCA postoperatively for pain relief. Parameters in both groups were compared, where estimation of cumulative morphine dose was the primary outcome and pain as assessed by VAS and side effects of opioids were the secondary outcomes. Results Patients in the ITM (ITM+PCA) group required less morphine (6.6 ± 2.96 vs. 24.77 ± 6.79 mg of morphine, p < 0.001) compared to patients on PCA. There was no statistically significant difference in VAS score and adverse effects between both groups. Conclusion Preoperative ITM can be used as an effective and safe modality for alleviating immediate postoperative pain following laparotomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kuppusamy et al.)

This study investigates the potential use of circulating extracellular vesicles' (EVs) DNA and protein content as biomarkers for traumatic brain injury (TBI) in a mouse model. Despite an overall decrease in EVs count during the acute phase, there was an increased presence of exosomes (CD63 + EVs) during acute and an increase in microvesicles derived from microglia/macrophages (CD11b+ EVs) and astrocytes (ACSA-2+ EVs) in post-acute TBI phases, respectively. Notably, mtDNA exhibited an immediate elevation post-injury. Neuronal (NFL) and microglial (Iba1) markers increased in the acute, while the astrocyte marker (GFAP) increased in post-acute TBI phases. Novel protein biomarkers (SAA, Hp, VWF, CFD, CBG) specific to different TBI phases were also identified. Biostatistical modeling and machine learning identified mtDNA and SAA as decisive markers for TBI detection. These findings emphasize the importance of profiling EVs' content and their dynamic release as an innovative diagnostic approach for TBI in liquid biopsies., Competing Interests: The authors declare no competing interests.

The neural pathways of Caenorhabditis elegans play a crucial role in regulating host immunity and inflammation during pathogenic infections. To understand the major neuro-immune signaling pathways, this study aimed to identify the key regulatory proteins in the host C. elegans during C. sakazakii infection. We used high-throughput label-free quantitative proteomics and identified 69 differentially expressed proteins. KEGG analysis revealed that C. sakazakii elicited host immune signaling cascades primarily including mTOR signaling, axon regeneration, metabolic pathways ( let-363 and acox-1.4 ), calcium signaling (mlck-1) , and longevity regulating pathways ( ddl-2 ), respectively. The abrogation in functional loss of mTOR-associated players deciphered that C. sakazakii infection negatively regulated the lifespan of mutant worms ( akt-1 , let-363 and dlk-1 ), including physiological aberrations, such as reduced pharyngeal pumping and egg production. Additionally, the candidate pathway proteins were validated by transcriptional profiling of their corresponding genes. Furthermore, immunoblotting showed the downregulation of mTORC2/SGK-1 during the later hours of pathogen exposure. Overall, our findings profoundly provide an understanding of the specificity of proteome imbalance in affecting neuro-immune regulations during C. sakazakii infection.

Drug repositioning is a method of using authorized drugs for other unusually complex diseases. Compared to new drug development, this method is fast, low in cost, and effective. Through the use of outstanding bioinformatics tools, such as computer-aided drug design (CADD), computer strategies play a vital role in the re-transformation of drugs. The use of CADD's special strategy for target-based drug reuse is the most promising method, and its realization rate is high. In this review article, we have particularly focused on understanding the various technologies of CADD and the use of computer-aided drug design for target-based drug reuse, taking COVID-19 and cancer as examples. Finally, it is concluded that CADD technology is accelerating the development of repurposed drugs due to its many advantages, and there are many facts to prove that the new ligand-targeting strategy is a beneficial method and that it will gain momentum with the development of technology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

An infant with restricted mouth opening from birth had presented for cleft lip repair. He had an interalveolar gap of 6 mm and was diagnosed as a case of cleft palate lateral synechiae syndrome. Fibreoptic bronchoscope of appropriate size was not available at the time of the procedure, and we had to device an alternative plan. The case describes the common challenges that can arise while anaesthetising infants with this syndrome in a resource-limited setting and highlights the importance of adapting the protocol to the demands., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Lower gastrointestinal bleeding is a common presentation with little data concerning risk factors for adverse outcomes. The aim was to derive and validate a scoring system to stratify risk in lower gastrointestinal bleeding and compare it to the Oakland score., Methods: A total of 2385 consecutive patients (mean age 65 years, 1140 males) were used to derive the score using multivariate logistic regression modeling then internally and externally validated. The Oakland score was applied and area under receiver operating characteristic (AUROC) curves were calculated and compared. A score of <1 was compared with an Oakland score of <9 to assess 30-day rebleeding and mortality rates., Results: Rebleeding was associated with age, inpatient bleeding, syncope, malignancy, tachycardia, hypotension, lower hemoglobin and mortality with age, inpatient bleeding, liver/gastrointestinal disease, tachycardia, and hypotension. The area under the receiver operating characteristic curves was 0.742 for rebleeding and 0.802 for mortality. A score <1 was associated with rebleeding (0.0%-2.2%) and mortality (0%). The Oakland score had a significantly lower area under the receiver operating characteristic curve for rebleeding of 0.687 but not for mortality; 0.757. A score <1 was associated with a lower 30-day rebleeding risk compared to an Oakland score <9 (4/379 vs. 15/355, p = 0.009) but not mortality (0/365 vs. 1/355, p = 0.493)., Conclusions: Our score predicts 30-day rebleeding and mortality rate with low scores associated with very low risk. The Aberdeen score is superior to the Oakland score for predicting rebleeding. Prospective evaluation of both scores is required., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background Preoperative fasting for six hours and accepting clear fluids till two hours of surgery is followed as a regular practice. Carbohydrate-rich fluids antagonize catabolism and are claimed to be tolerated better. This study aims to compare the effect of carbohydrate-rich drinks on gastric volume and blood sugar control in diabetic and non-diabetic patients undergoing elective surgery with plain water. Methods Two hundred forty patients aged 40 to 65 undergoing elective surgery under regional anesthesia were randomized into diabetic control, diabetic study, non-diabetic control, and non-diabetic study. Control groups were given 400 ml of plain water, while the study group received 50 grams of dextrose dissolved in 400 ml of water two hours prior to surgery. Gastric volume was evaluated using USG, and thirst and discomfort were assessed using the Likert scale. Perioperatively, blood sugar values were monitored and kept under control using insulin. Results Mean gastric volume (ml) in diabetic control (35.3±12.95 ml), diabetic study (31.2±11.75 ml), non-diabetic control (29±11.42 ml), and non-diabetic study (30.4±9.12 ml) showed no statistically significant difference (p>0.05). Capillary blood glucose (CBG) values two hours post fluid intake showed a significant increase in CBG levels in the diabetic study (183.2±28.67 mg/dl) compared to the diabetic control group (138.66±15.81 mg/dl). The values returned to baseline within six hours. Thirst and discomfort were significantly lower in the study group of diabetic and non-diabetic populations. Conclusion We conclude that carbohydrate loading does not affect gastric volume in diabetics and non-diabetics. However, the sugar values do increase which may warrant hourly checking and administration of insulin in diabetics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vishak et al.)

Background: Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers providing conclusive evidence., Objectives: This study is aimed to determine the safety and efficacy of Pioglitazone in improving cognitive function in patients with mild-moderate Alzheimer's disease (AD)., Materials and Methods: Trials published in the last 12 years were identified from PubMed, Scopus, Cochrane Central, and other trial registries. Five hundred twenty-five records were obtained, from which five studies were included for quantitative analysis. Studies comparing Pioglitazone with a suitable placebo or other oral hypoglycemic agent were considered for review. Data was extracted using a pretested form, which was followed by a risk of bias assessment (ROB) with Cochrane's ROB assessment tool., Results: This meta-analysis included studies where Pioglitazone (15-30 mg) was compared to other oral hypoglycemic agents, placebo, or diabetic diet for a minimum duration of 6 months. Pioglitazone did not show a statistically significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores [mean difference (MD): -1.16; 95% confidence interval (CI): -4.14-1.81]. By conducting sensitivity analysis with the removal of one study, significant efficacy was obtained [MD: -2.75; 95% CI: -4.84--0.66]. The Wechsler Memory Scale-Revised logical memory I (WMS-R) scores had a significant improvement in the Pioglitazone group [MD: 2.02; 95% CI: 0.09-3.95]., Conclusion: Pioglitazone is a safe medication that has a promising effect in slowing the advancement of AD., Competing Interests: None

Problem: Papua New Guinea (PNG) is situated in the Pacific Ocean and has experienced multiple natural disasters and disease outbreaks. However, PNG lacks the ability to rapidly and systematically deploy trained personnel to provide surge capacity in response to major national disasters. It was therefore decided to establish a national emergency medical team (EMT) in PNG., Context: PNG's responses to the 2018 earthquake in the Highlands Region and the coronavirus disease (COVID-19) pandemic required assistance from international EMTs. PNG began developing its own EMT in 2019, coinciding with the development of other Pacific EMTs., Action: PNG's EMT project was initiated in 2019 with the creation of a technical working group. By 2021, a focal point had been identified, standard operating procedures had been drafted and training of EMT members had been completed. Pilot deployments of the national EMT members contributed to the COVID-19 response during 2021., Outcome: Four major challenges were identified during the early phase of PNG's national EMT development: introducing the concept of EMTs in an EMT-naïve landscape; integrating the national EMT into existing PNG National Department of Health organizational structures; assembling adequate members at short notice to respond to disasters; and securing funding for deployment., Discussion: Solutions identified for these challenges included strengthening stakeholder involvement through engagement in the development process and participation in technical working groups and consultative group discussions, offering exposure to other Pacific-based EMTs, and creating incentive schemes for EMT members and their place of employment., Competing Interests: The authors have no conflicts of interest to declare., ((c) 2023 The authors; licensee World Health Organization.)

Traditional rice is gaining popularity worldwide due to its high nutritional and pharmaceutical value, as well as its high resistance to abiotic and biotic stresses. This has attracted significant attention from breeders, nutritionists, and plant protection scientists in recent years. Hence, it is critical to investigate the grain metabolome to reveal germination and nutritional importance. This research aimed to explore non-targeted metabolites of five traditional rice varieties, viz ., Chinnar, Chithiraikar, Karunguruvai, Kichili samba, and Thooyamalli, for their nutritional and therapeutic properties. Approximately 149 metabolites were identified using the National Institute of Standards and Technology (NIST) library and Human Metabolome Database (HMDB) and were grouped into 34 chemical classes. Major classes include fatty acids (31.1-56.3%), steroids and their derivatives (1.80-22.4%), dihydrofurans (8.98-11.6%), prenol lipids (0.66-4.44%), organooxygen compounds (0.12-6.45%), benzene and substituted derivatives (0.53-3.73%), glycerolipids (0.36-2.28%), and hydroxy acids and derivatives (0.03-2.70%). Significant variations in metabolite composition among the rice varieties were also observed through the combination of univariate and multivariate statistical analyses. Principal component analysis (PCA) reduced the dimensionality of 149 metabolites into five principle components (PCs), which explained 96% of the total variance. Two clusters were revealed by hierarchical cluster analysis, indicating the distinctiveness of the traditional varieties. Additionally, a partial least squares-discriminant analysis (PLS-DA) found 17 variables important in the projection (VIP) scores of metabolites. The findings of this study reveal the biochemical intricate and distinctive metabolomes of the traditional therapeutic rice varieties. This will serve as the foundation for future research on developing new rice varieties with traditional rice grain metabolisms to increase grain quality and production with various nutritional and therapeutic benefits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Udhaya Nandhini, Venkatesan, Senthilraja, Janaki, Prabha, Sangamithra, Vaishnavi, Meena, Balakrishnan, Raveendran, Geethalakshmi and Somasundaram.)

Introduction Complete loss of natural teeth severely compromises the masticatory efficiency of geriatric patients and directly affects their general health. Biofunctional prosthetic system (BPS) has been developed as an alternate method of denture fabrication to match the higher expectations of patients. Studies comparing BPS dentures with injection-molded conventional complete dentures (IM-CCD) are lacking. Our study aimed to compare the masticatory efficiency and patient satisfaction of BPS dentures with IM-CCD. Methods This trial was designed as a randomized, prospective, single-center, double-blinded study with two parallel arms (BPS group and IM-CCD group) having an equal allocation (1:1). Completely edentulous patients aged 45-80 who visited our outpatient department between January and August 2018 were screened and enrolled according to our inclusion and exclusion criteria. Random sequence generation was done using an online randomization program. Allocation concealment was done using sequentially labeled opaque envelopes. The participants and the outcome assessors were blinded. A single operator performed all the clinical procedures in both groups under the guidance of the instructor. The age and gender of the patients were recorded for demographic data at baseline. Primary outcomes were assessed six weeks after denture insertion. The number of denture adjustments required during the first six weeks after denture delivery was recorded as the secondary outcome. Masticatory efficiency was evaluated by the volumetric single-sieve method. An abbreviated version of the Oral Health Impact Profile questionnaire for edentulous patients (OHIP-EDENT) was used for patient satisfaction scores. The total OHIP-EDENT score was calculated by adding all the responses to the 19 questions (ranging from 0 to 38). Individual domain scores were calculated by adding the response to all the questions in that domain. All the data obtained were tested for normality using the Kolmogorov-Smirnov test. Data were analyzed using either unpaired Student's T-test or Mann-Whitney U test for normal and non-normal data, respectively. The gender characteristics of the sample were compared using Chi-Square test. Results Two patients in the IM-CCD group and one patient in the BPS group were lost to follow-up. Hence only the secondary outcome data were analyzed for these patients. Primary outcome data of patients who were lost to follow-up were excluded from the analysis. No significant differences (p>0.05) were found between the two groups for age and gender characteristics of the samples. Masticatory efficiency for both peanut and carrot was found to be significantly higher (p<0.05) in the BPS group than in the IM-CCD group. No significant differences (p>0.05) in the mean scores were observed between the two groups for total OHIP-EDENT scores or the individual domain scores. No significant differences (p>0.05) were observed between the groups for the number of denture adjustments done. Conclusion Within the limitations of the trial, it can be concluded that the BPS dentures significantly improved the masticatory efficiency for both hard (carrots) and soft (peanuts) foods compared to the IM-CCD. However, there was no difference between the masticatory-related complaints domain scores between the two dentures. No significant differences were found between BPS dentures and IM-CCD with respect to overall patient satisfaction scores or post-insertion denture adjustments., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vivek et al.)

During embryogenesis the nascent Caenorhabditis elegans epidermis secretes an apical extracellular matrix (aECM) that serves as an external stabilizer, preventing deformation of the epidermis by mechanical forces exerted during morphogenesis. At present, the factors that contribute to aECM function are mostly unknown, including the aECM components themselves, their posttranslational regulators, and the pathways required for their secretion. Here we showed that two proteins previously linked to aECM function, SYM-3/FAM102A and SYM-4/WDR44, colocalize to intracellular and membrane-associated puncta and likely function in a complex. Proteomics experiments also suggested potential roles for SYM-3/FAM102A and SYM-4/WDR44 family proteins in intracellular trafficking. Nonetheless, we found no evidence to support a critical function for SYM-3 or SYM-4 in the apical deposition of two aECM components, NOAH-1 and FBN-1. Moreover, loss of a key splicing regulator of fbn-1, MEC-8/RBPMS2, had surprisingly little effect on the abundance or deposition of FBN-1. Using a focused screening approach, we identified 32 additional proteins that likely contribute to the structure and function of the embryonic aECM. We also characterized morphogenesis defects in embryos lacking mir-51 microRNA family members, which display a similar phenotype to mec-8; sym double mutants. Collectively, these findings add to our knowledge of factors controlling embryonic morphogenesis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Purpose: Risk for developing age-related macular degeneration (AMD) is linked to an overactive complement system. In the mouse model of laser-induced choroidal neovascularization (CNV), elevated levels of complement effector molecules, including complement C3, have been identified, and the alternative pathway (AP) is required for pathology. The main soluble AP regular is complement factor H (fH). We have previously shown that AP inhibition via subretinal AAV-mediated delivery of CR2-fH using a constitutive promoter is efficacious in reducing CNV. Here we ask whether the C3 promoter (pC3) effectively drives CR2-fH bioavailability for gene therapy., Methods: Truncated pC3 was used to generate plasmids pC3-mCherry/CR2-fH followed by production of corresponding AAV5 vectors. pC3 activation was determined in transiently transfected ARPE-19 cells stimulated with H2O2 or normal human serum (+/- antioxidant or humanized CR2-fH, respectively). CNV was analyzed in C57BL/6J mice treated subretinally with AAV5-pC3-mCherry/CR2-fH using imaging (optical coherence tomography [OCT] and fundus imaging), functional (electroretinography [ERG]), and molecular (protein expression) readouts., Results: Modulation of pC3 in vitro is complement and oxidative stress dependent, as shown by mCherry fluorescence. AAV5-pC3-CR2-fH were identified as safe and effective using OCT and ERG. CR2-fH expression significantly reduced CNV compared to mCherry and was correlated with reduced levels of C3dg/C3d in the retinal pigment epithelium/choroid fraction., Conclusions: We conclude that complement-dependent regulation of AP inhibition ameliorates AMD pathology as effectively as using a constitutive promoter., Translational Relevance: The goal of anticomplement therapy is to restore homeostatic levels of complement activation, which might be more easily achievable using a self-regulating system.

Background and Aim: This study evaluates the effectiveness of long-acting antihypertensive drugs (clonidine and enalaprilat) in blunting the intubation response. Also, the study seeks to determine how effectively clonidine and enalaprilat can maintain stable haemodynamics during a change in position., Methods: After ethical committee approval and trial registration, a double-blinded, randomised controlled trial was conducted with 71 consenting patients scheduled for elective spine surgery in a prone position under general anaesthesia. Group C received clonidine 2 μg/kg, and Group E received enalaprilat 1.25 mg diluted in normal saline as an intravenous infusion given over 10 min before induction of anaesthesia. The changes in heart rate (HR) and blood pressure (BP) in response to the infusion of the study drugs, induction, tracheal intubation and change in position were recorded. P value <0.05 was considered significant. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25., Results: Clonidine infusion caused a significant fall in heart rate post-infusion and post-induction with propofol (p value <0.05). Both clonidine and enalaprilat caused a significant fall in mean arterial pressure (MAP) post-infusion and post-induction (p value <0.05). Clonidine effectively blunted the intubation response with no increase in HR and MAP following intubation. Enalaprilat caused a significant rise in HR in response to intubation. On proning, there was a significant fall in MAP in both groups., Conclusion: Clonidine is effective in blunting the intubation response. Preoperative infusion of clonidine and enalaprilat causes hypotension during a change of position., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

The aim of this study was to investigate the flexural strength of heat cure acrylic resin reinforced with varying concentration copper nanoparticles. The study followed ISO 20795-1-2013 guidelines for estimating the flexural strength. Hundred samples of heat cure acrylic resin of dimension were fabricated. The study had five groups and each group had 20 samples. The samples were grouped as per the concentration of copper (Cu) nanoparticles in acrylic. Three-point bending flexural strength was evaluated with universal testing machine. The load was directed at the midpoint of the sample at a cross-sectional speed of 5 mm/min. The fractured load was recorded and flexural strength was estimated. The data were statistically analyzed with analysis of variance and the post hoc test. The results displayed improved flexural strength in lower Cu concentrations. The increase in flexural strength was observed in 1% (78.38 MPa), 2% (73.08 MPa), and 3% (73.08 MPa) of Cu nanoparticles and it decreased beyond 3% increase in Cu nanoparticles. The tests were statistically insignificant ( P <.05). The results concluded that the optimal concentration of Cu nanoparticles to be reinforced with heat cure PMMA is 1 gm. The flexural strength decreased with an increase in concentration of Cu nanoparticles., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Deep reinforcement learning (DRL) has empowered a variety of artificial intelligence fields, including pattern recognition, robotics, recommendation systems, and gaming. Similarly, graph neural networks (GNNs) have also demonstrated their superior performance in supervised learning for graph-structured data. In recent times, the fusion of GNN with DRL for graph-structured environments has attracted a lot of attention. This article provides a comprehensive review of these hybrid works. These works can be classified into two categories: 1) algorithmic contributions, where DRL and GNN complement each other with an objective of addressing each other's shortcomings and 2) application-specific contributions that leverage a combined GNN-DRL formulation to address problems specific to different applications. This fusion effectively addresses various complex problems in engineering and life sciences. Based on the review, we further analyze the applicability and benefits of fusing these two domains, especially in terms of increasing generalizability and reducing computational complexity. Finally, the key challenges in integrating DRL and GNN, and potential future research directions are highlighted, which will be of interest to the broader machine learning community.

Type 1 diabetes is an autoimmune disease with onset from early childhood. The insulin-producing pancreatic beta cells are destroyed by CD8 + cytotoxic T cells. The disease is challenging to study mechanistically in humans because it is not possible to biopsy the pancreatic islets and the disease is most active prior to the time of clinical diagnosis. The NOD mouse model, with many similarities to, but also some significant differences from human diabetes, provides an opportunity, in a single in-bred genotype, to explore pathogenic mechanisms in molecular detail. The pleiotropic cytokine IFN-γ is believed to contribute to pathogenesis of type 1 diabetes. Evidence of IFN-γ signaling in the islets, including activation of the JAK-STAT pathway and upregulation of MHC class I, are hallmarks of the disease. IFN-γ has a proinflammatory role that is important for homing of autoreactive T cells into islets and direct recognition of beta cells by CD8 + T cells. We recently showed that IFN-γ also controls proliferation of autoreactive T cells. Therefore, inhibition of IFN-γ does not prevent type 1 diabetes and is unlikely to be a good therapeutic target. In this manuscript we review the contrasting roles of IFN-γ in driving inflammation and regulating the number of antigen specific CD8 + T cells in type 1 diabetes. We also discuss the potential to use JAK inhibitors as therapy for type 1 diabetes, to inhibit both cytokine-mediated inflammation and proliferation of T cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De George, Ge, Krishnamurthy, Kay and Thomas.)

Background and Aim: Percutaneous nephrolithotomy (PCNL) under epidural anesthesia has been reported to have few advantages over general anesthesia, like lower postoperative pain and less need for analgesics. There are limited studies on PCNL being performed under neuraxial anesthesia in supine position. Hence the present study was conceived to compare hemodynamic parameters in patients undergoing percutaneous nephrolithotomy (PCNL) in the supine position under combined spinal-epidural with general anesthesia (GA)., Material and Methods: A prospective, randomized control trial was conducted among 90 patients who were posted to undergo elective percutaneous nephrolithotomy in the the supine position, after obtaining Institutional Ethical Committee (IEC) approval and CTRI (Clinical Trial Registry - India) registration. Patients were randomly allotted to undergo surgery either under general anesthesia (group GA) or combined spinal epidural anesthesia (group CSE) by computer-generated random number method. Hemodynamic parameters, postoperative analgesic requirement and incidence of blood transfusion were recorded and analyzed., Results: There was no significant difference between the two groups with respect to gender, ASA grade, surgery duration, calculus size and pulse rate. There was a statistically significant reduction in mean arterial pressure from 5 to 50 minutes of surgery and less incidence of blood transfusion in patients in the CSE group. Patients who underwent PCNL in the supine position under CSE required lesser analgesics postoperatively compared to those under general anesthesia., Conclusion: Combined spinal epidural analgesia can be used as an alternative to general anesthesia for patients undergoing PCNL in the supine position in view of less MAP and reduced postoperative analgesic and blood transfusion requirement., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Sankar et al.)

Introduction: The ultrasound-guided infraclavicular brachial plexus block by triple-point injection method was aimed at blocking the three individual cords in the infraclavicular region. Recently, a single-point injection method which does not require visualization of cords to produce nerve block has been introduced. This study compared the block onset time, performance time, patient's satisfaction, and complications between the ultrasound guided triple-point injection and single-point injection methods., Patients and Method: This randomized controlled trial was conducted in a tertiary care hospital. Sixty patients were divided into two groups - Group S: 30 patients received single-point injection method of infraclavicular block. Group T: 30 patients received triple-point injection method of infraclavicular block. Drugs used were 0.5% ropivacaine with 8 mg dexamethasone., Results: The sensory onset time was significantly longer in Group S (11.13 ±1.83 min) than Group T (6.20 ±1.19min). No statistically significant difference was found between the two groups regarding mean motor onset time. The composite sensorimotor onset time was similar between the groups. The mean time to perform the block was significantly lesser in Group S (1.35 ±0.38 min) when compared to group T (3.44 ±0.61min). The patient satisfaction score, conversion to general anesthesia and complications were not significant among the two groups., Conclusion: We concluded that single-point injection method had a shorter performance time and similar total onset time with less procedural complications compared with triple point injection method., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Vedavyas et al.)

Uveitis consists of a group of syndromes characterised by intraocular inflammation, accounting for up to 15% of visual loss in the western world and 10% worldwide. Assessment of intraocular inflammation has been limited to clinician-dependent, subjective grading. Developments in imaging technology, such as optical coherence tomography (OCT), have enabled the development of objective, quantitative measures of inflammatory activity. Important quantitative metrics including central macular thickness and vitreous signal intensity allow longitudinal monitoring of disease activity and can be used in conjunction with other imaging modalities enabling holistic assessment of ocular inflammation. Ongoing work into the validation of instrument-based measures alongside development of core outcome sets is crucial for standardisation of clinical trial endpoints and developing guidance for quantitative multi-modal imaging approaches. This review outlines methods of grading inflammation in the vitreous and retina, with a focus on the use of OCT as an objective measure of disease activity.

Objectives: To review radiation exposure during emergency ureteric stent insertion to identify differences based on operator experience, specialty operator and stone characteristics., Patients and Methods: A retrospective audit over 10 years was performed for patients who underwent emergency stent insertion for urolithiasis with intraoperative fluoroscopy. Outcomes measured included operator experience, radiation exposure (mGy), dose area product (Gy/cm 2 ), fluoroscopy time, stone characteristics and patient BMI. Analysis was performed in IBM SPSS Version 28. p  < 0.05 was considered statistically significant., Results: Four hundred ten patients were identified, with a median age of 57 years, 64.6% male and a median BMI of 30. Urolithiasis was left-sided in 50.8%, with a median size of 7 mm and predominantly proximal (49%) followed by mid (34.5%) and distal (12.1%) location. Median radiation exposure was 12.6 mGy, 2.94 Gy/cm 2 and fluoroscopy time 44.5 s, with no significant difference between consultants and registrars. No significant association between radiation exposure for subgroups of stone location, gender, size, laterality or specialty registrar (general surgery vs. urology)., Conclusion: No significant difference in radiation exposure was identified between registrars and consultants or between subspecialty registrars. We suggest formal radiation safety education for all health professionals involved with intra-operative fluoroscopy and personal dosimeters., Competing Interests: The authors declare no conflicts of interest in preparing this article., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background : Very early-onset inflammatory bowel disease (VEOIBD) is defined as IBD in children under six years of age. We present outcome data of hematopoietic stem cell transplantation (HSCT) in the above children. Patients and methods : We performed a retrospective study in children under six years of age who underwent HSCT for VEOIBD with an identified monogenic disorder from December 2012 to December 2020. Results : Of the 25 children included, the underlying diagnosis was IL10R deficiency (n = 4), Wiskott-Aldrich syndrome (n = 4), Leukocyte adhesion defect (n = 4), Hyper IgM syndrome (n = 3), Chronic granulomatous disease (n = 2), and one each with XIAP deficiency, severe congenital neutropenia, Omenn syndrome, Hyper IgE syndrome, Griscelli syndrome, MHC Class II deficiency, LRBA deficiency, and IPEX syndrome. Donors included a matched family donor in 10(40%); a matched unrelated donor in 8 (32%), haploidentical in 7 (28%) (T depleted 16%, T replete with post-transplant cyclophosphamide12%). Conditioning was myeloablative in 84% ofHSCTs. We documented engraftment in 22 (88%) children, primary graft failure in 2 children (8%), mixed chimerism in 6 (24%) children with mortality in 4/6 children. Children with a sustained chimerism of > 95% did not have recurrence of any features of IBD. Overall survival was 64%, with a median follow-up of 55 months. Mixed chimerism was associated with a significantly increased risk of mortality (p-value = 0.001). Conclusions : VEOIBD caused by monogenic disorders can be offered HSCT. Early recognition, optimal supportive care, and complete chimerism are essential components to achieving survival., Competing Interests: Conflict of InterestNone.Conflict of InterestThere are no conflicts of interest., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Extracellular vesicles (EVs) are membrane-derived, tiny vesicles produced by all cells that range from 50 to several hundreds of nanometers in diameter and are used as a means of intercellular communication. They are emerging as promising diagnostic and therapeutic tools for a variety of diseases. There are two main biogenesis processes used by cells to produce EVs with differences in size, composition, and content. Due to their high complexity in size, composition, and cell origin, their characterization requires a combination of analytical techniques. This project involves the development of a new generation of multiparametric analytical platforms with increased throughput for the characterization of subpopulations of EVs. To achieve this goal, the work starts from the nanobioanalytical platform (NBA) established by the group, which allows an original investigation of EVs based on a combination of multiplexed biosensing methods with metrological and morphomechanical analyses by atomic force microscopy (AFM) of vesicular targets trapped on a microarray biochip. The objective was to complete this EV investigation with a phenotypic and molecular analysis by Raman spectroscopy. These developments enable the proposal of a multimodal and easy-to-use analytical solution for the discrimination of EV subsets in biological fluids with clinical potential.

Heart rate variability (HRV) features support several clinical applications, including sleep staging, and ballistocardiograms (BCGs) can be used to unobtrusively estimate these features. Electrocardiography is the traditional clinical standard for HRV estimation, but BCGs and electrocardiograms (ECGs) yield different estimates for heartbeat intervals (HBIs), leading to differences in calculated HRV parameters. This study examines the viability of using BCG-based HRV features for sleep staging by quantifying the impact of these timing differences on the resulting parameters of interest. We introduced a range of synthetic time offsets to simulate the differences between BCG- and ECG-based heartbeat intervals, and the resulting HRV features are used to perform sleep staging. Subsequently, we draw a relationship between the mean absolute error in HBIs and the resulting sleep-staging performances. We also extend our previous work in heartbeat interval identification algorithms to demonstrate that our simulated timing jitters are close representatives of errors between heartbeat interval measurements. This work indicates that BCG-based sleep staging can produce accuracies comparable to ECG-based techniques such that at an HBI error range of up to 60 ms, the sleep-scoring error could increase from 17% to 25% based on one of the scenarios we examined.

Background Hypotension is a commonly encountered side effect in patients undergoing spinal anaesthesia, particularly in patients undergoing caesarean section. Phenylephrine is a widely used drug to treat spinal-induced hypotension and to maintain hemodynamic stability. Our aim is to evaluate the effectiveness of phenylephrine given through two different routes prophylactically in prevention of post-spinal hypotension in patients undergoing caesarean section. Methods A total of 150 healthy pregnant women undergoing elective caesarean section were randomly allocated into three groups: Group M (prophylactic intramuscular use of 2 mg phenylephrine), group V (prophylactic intravenous infusion of 30 mcg phenylephrine per minute), and group P (no prophylaxis), rescue phenylephrine 30 mcg IV and atropine 0.6 mg IV were used intraoperatively to treat bradycardia and hypotension in all three groups. The primary outcome was maternal hemodynamic changes. Results There was an insignificant difference in demographic data between the groups. Maternal systolic and diastolic blood pressure were more stable in group M compared to group V and group P. Heart rate was significantly lower only in group V. We did not observe any statistical difference between the groups in the APGAR score or the fetal arterial blood gas values. The incidence of nausea and vomiting was more in group P. Conclusion Preventive intramuscular phenylephrine exhibited a more stable maternal hemodynamics when compared with the prophylactic intravenous infusion of phenylephrine and placebo in elective caesarean under spinal anaesthesia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lakshmikanthan et al.)