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Background: Examining small bowel loops within the peritoneal cavity poses significant challenges because of their length and overlapping nature. Aims and Objectives: This study aimed to evaluate the utility of computed tomography enteroclysis (CTE) in diagnosing small intestinal diseases and to understand its clinical application. Materials and Methods: The study was conducted from November 2019 to October 2021 in 30 patients undergoing CTE treatment. The day before treatment, bowel preparation included a low-residue diet, lots of fluids, an overnight fast of 8–12 h, and laxatives. A 16-slice Aquilion Lightning computed tomography (CT) scanner was used in general hospitals, and a 128-slice GE Healthcare helical CT scanner was used in multispecialty hospitals. Results: Among the 30 patients, 20 (66.7%) were male, and 10 (33.3%) were female, predominantly aged between 30 and 60 years old. Positive findings were noted in 23 patients (76.7%), including intestinal tuberculosis, inflammatory bowel disease, small bowel obstruction, and neoplastic lesions. Various small intestinal pathologies, such as non-specific edema, intussusception, and ischemic bowel disease, were also identified. Conclusion: This raises the standard of current small bowel imaging by delivering suitable intestinal distension using the enteral volume challenge principle and helps identify and characterize small-bowel problems.

Abstract The repeatability of two biometers (Lenstar-LS900 and Eyestar-900) to measure ocular parameters and intraocular lens (IOL) power calculation, and their agreement were evaluated. 134 eyes of 134 participants were measured thrice with each biometer. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT) and keratometry (K) were evaluated. The IOL power was calculated using different formulas. The repeatability limit (RLimit), the mean differences (MD) and the limits of agreement (LoA) were calculated. The RLimits for all parameters were higher with Lenstar compared to Eyestar. RLimits were lower than 0.50 D except for Barrett Universal II (0.54 D) and Haigis (0.51 D) formulas with the Lenstar. Mean differences were lower than 0.01 mm for AL, ACD and LT, and lower than 0.03 D for K. MD ranged from 0 to 0.02 D for all formulas except for Barrett and Hill. When dividing the sample into subgroups (short, normal and long eyes), the MDs were similar for the IOL power and were lower than 0.03 D, except for the Barrett and Hill formulas. Both biometers provide repeatable biometry and IOL power calculations. The LoA interval for the IOL power calculation was between 0.75 and 1.50D, which was similar among the subgroups.

Abstract Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Background According to the UN Committee Against Torture, all state parties to the Torture Convention have a responsibility to meet the rehabilitation needs of torture victims who have sought asylum within their borders. General practitioners (GPs) can play a crucial role in identifying torture victims and securing rehabilitation when needed. There is a pressing knowledge gap on the knowledge and practices of GPs vis-à-vis potentially tortured patients, and an urgent need for research that investigates GPs’ practices of identification, referral, and rehabilitation – in Norway and beyond. This article presents an exploratory qualitative pilot study that investigates the experiences of GPs in Oslo vis-à-vis this patient group.Methods Semi-structured interviews with five experienced GPs in the greater Oslo area. Interview data was analyzed through thematic analysis and discussed within a theoretical framework seeing GPs as street-level bureaucrats.Results Issues that emerged in the pilot involve a consistent professional confidence and a particular concern for victims of sexual violence and sexualized torture. The pilot also found a troubling commonsensical reasoning about identification in the asylum process. The GPs asked for the re-establishment of specialist rehabilitation centers for refugees and torture victims to consult in case of need. Alas, the study also confirmed that GPs are a difficult profession to recruit for research.Conclusions This study indicates that GPs are important actors in terms of identifying torture victims after resettlement, but that there are shortcomings in their training and knowledge, in the overall organization of the healthcare system, and in specialized healthcare, that limit prospects for rehabilitation.

Background: Benzodiazepines (BZDs) are recommended as the initial therapy of choice in status epilepticus (SE). The age-old second-line treatment for BZD refractory convulsive SE is intravenous phenytoin (PHT) based predominantly on nonrandomized clinical trial data. We did this study to compare the efficacy and safety of intravenous levetiracetam (LEV) and PHT as second-line antiseizure medication (ASM) for children with SE. Methodology: A prospective, randomized controlled, open-label study was conducted in children 3 months to 15 years of age with SE in Pediatric Emergency. A total of 41 children were randomly allocated to either group 1 (Levetiracetam) or group 2 (Phenytoin) on the basis of computer-generated randomization. Children who were already on antiseizure medications, either LEV or PHT, or receiving these drugs outside for SE were excluded. Data analysis was done by SPSS V25 Results: The most common age group presenting with SE was 12 months to 5 years. Clinical cessation of seizure 5 minutes after the completion of drugs was 85% (17/20) in Levetiracetam group and 90.5% (19/21) in Phenytoin group. Recurrence of seizure within 24 hours was noted in 35% (7/20) in Levetiracetam group and 38.1% (8/21) in Phenytoin group. There was no statistically significant difference noted in both the groups in terms of seizure cessation, adverse events, and recurrence. Conclusion: The efficacy and safety of LEV were found to be comparable to those of PHT in controlling seizure as second-line ASM in SE.

Nonunion represents a crucial challenge in orthopedic medicine, demanding innovative solutions beyond the scope of traditional bone grafting methods. Among the various strategies available, magnesium (Mg) implants have been recognized for their biocompatibility and biodegradability. However, their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering (BTE), particularly in the development of Mg-incorporated biocomposite scaffolds. These scaffolds gradually release Mg2+, which enhances immunomodulation, osteogenesis, and angiogenesis, thus facilitating effective bone regeneration. This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds, including electrospinning, three-dimensional printing, and sol-gel synthesis. Despite these advancements, the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability. These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds. This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.

Introduction: The mobile phone has evolved into an indispensable accessory carried by everyone. With its increasing usage, there is a parallel rise in mobile phone addictions. Nomophobia, short for no mobile phone phobia, is characterized as a fear specific to the absence of mobile phones. Objectives: (1) To assess the prevalence of nomophobia among adolescents and adults residing in semi-urban Chennai. (2) To understand the patterns of mobile phone usage and explore the health-related consequences of nomophobia. Methods: This cross-sectional study was conducted among adolescents and adults (15–50 years) in semi-urban Chennai from July to September 2022. The sample size was 220, and the study utilized the Test of Mobile Phone Dependence Brief as an assessment tool. Participants scoring >30 were identified as nomophobic, indicating mobile phone dependence. Results: Among the 220 study participants, there was an almost equal distribution between males and females, with a majority falling within the 21–25 age group. Approximately 26.1% belonged to the upper middle class and 89.1% were married. The prevalence of nomophobia was notably high at 68.6% (151 out of 220). A significant association was found between social class and mobile phone addiction, with the middle class exhibiting higher levels of addiction. Conclusion: The study highlights that a substantial majority of adults exhibit mobile phone addiction, almost two-thirds of the participants. There is a pressing need for health awareness programmes targeting adults to educate them about the adverse effects of mobile phone addiction. Additionally, reinforcing strategies for effective and time-restricted mobile phone usage is essential.

IntroductionQualitative data provides deep insights into an individual's behaviors and beliefs, and the contextual factors that may shape these. Big qualitative data analysis is an emerging field that aims to identify trends and patterns in large qualitative datasets. The purpose of this review was to identify the methods used to analyse large bodies of qualitative data, their cited strengths and limitations and comparisons between manual and digital analysis approaches.MethodsA multifaceted approach has been taken to develop the review relying on academic, gray and media-based literature, using approaches such as iterative analysis, frequency analysis, text network analysis and team discussion.ResultsThe review identified 520 articles that detailed analysis approaches of big qualitative data. From these publications a diverse range of methods and software used for analysis were identified, with thematic analysis and basic software being most common. Studies were most commonly conducted in high-income countries, and the most common data sources were open-ended survey responses, interview transcripts, and first-person narratives.DiscussionWe identified an emerging trend to expand the sources of qualitative data (e.g., using social media data, images, or videos), and develop new methods and software for analysis. As the qualitative analysis field may continue to change, it will be necessary to conduct further research to compare the utility of different big qualitative analysis methods and to develop standardized guidelines to raise awareness and support researchers in the use of more novel approaches for big qualitative analysis.Systematic review registrationhttps://osf.io/hbvsy/?view_only=.

Summary: Astroglia play crucial neuroprotective roles by internalizing pathogenic aggregates and facilitating their degradation. Here, we show that α-SYN protofibril-induced organelle toxicities and reactive oxygen species (ROS) cause premature cellular senescence in astrocytes and astrocyte-derived cancer cells, resulting in a transient increase in the biogenesis of tunneling nanotubes (TNTs). TNT-biogenesis and TNT-mediated cell-to-cell transfer lead to clearance of α-SYN-induced organelle toxicities, reduction in cellular ROS levels, and reversal of cellular senescence. Enhanced cell proliferation is seen in the post-recovered cells after recovering from α-SYN-induced organelle toxicities. Further, we show that α-SYN-induced senescence promotes the transient localization of focal adhesion kinase (FAK) in the nucleus. FAK-mediated regulation of Rho-associated kinases plays a significant role in the biogenesis of TNTs and their subsequent proliferation. Our study emphasizes that TNT biogenesis has a potential role in the clearance of α-SYN-induced cellular toxicities, the consequences of which cause enhanced proliferation in the post-recovered astroglia cells.

PurposeThis study aims to evaluate the repeatability of anterior segment optical coherence tomography (AS-OCT) in diverse ocular surface disorder (OSD) cohorts, exploring various anterior segment parameters and their accuracy in different disease groups.MethodsA total of 239 participants across six distinct OSD groups and healthy controls underwent nonmydriatic AS-OCT imaging using the Tomey CASIA 2 device. Anterior segment parameters including anterior chamber depth, width, angle metrics, corneal thickness, keratometry, lens vault, and others were meticulously assessed. Statistical analyses determined repeatability limits and coefficients of variation for each parameter within the different OSD cohorts.ResultsRepeatability for anterior chamber and corneal parameters remained consistent across all OSD groups, indicating minimal impact of ocular surface disease on accuracy. The coefficient of variation (CoV) for the trabecular iris-space area was about 20% for all cohorts. Ocular surface inflammation emerged as a key factor in dry eye, affecting immune-mediated and non-immune conditions alongside age-related ocular surface changes. While anterior chamber depth measurements showed variations, particularly in immune (CoV = 2.5%) and non-immune (CoV = 3.8%) OSD groups, parameters like anterior chamber width and angle to angle showed similar values among the cohorts. Keratometry measures remained stable despite OSD (CoV lower than 1%).ConclusionThe Tomey CASIA 2 demonstrated reliable repeatability for measuring anterior segment parameters in diverse OSD cohorts. Despite challenges posed by dry eye conditions, this technology holds promise in assessing OSD, suggesting potential clinical protocols similar to those in healthy controls.

Cardiac dysfunction in thyrotoxicosis is believed to arise from changes in preload, afterload, heart rate, and contractility. Cardiomyopathy is a less frequent cardiac complication linked to thyrotoxicosis. Here, we present a rare case of thyrotoxicosis induced cardiomyopathy in a 30-year-old male, where dilated cardiomyopathy manifested as the initial sign of thyrotoxicosis. The patient was treated with antithyroid drugs, diuretics and beta blockers. General surgery opinion obtained and planned to do thyroidectomy after euthyroid status. Patient was followed up and after 6 weeks was symptomatically better and was found to be euthyroid and repeat 2D ECHO showed an improvement in systolic function with EF of 55% and the patient was planned for thyroidectomy. In the management of thyrotoxicosis induced cardiomyopathy, pharmacological interventions involve the use of specific thyroid therapies such as thionamides (methimazole, carbimazole, propylthiouracil) and beta-blockers, coupled with heart failure management.

Lhermitte–Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is an uncommon hamartomatous lesion found in the cerebellar cortex. First described by French physicians Lhermitte and Duclos in 1920, this condition involves enlarged cerebellar folia containing abnormal ganglion cells. Clinical manifestations typically include headaches, visual disturbances, and cerebellar dysfunction. While imaging techniques like computed tomography (CT) scans may indicate the presence of mass lesions, magnetic resonance imaging (MRI) is crucial for accurate delineation of the lesion's boundaries and characterization of tissue involvement. Surgical intervention, typically in the form of respective surgery, remains the cornerstone of treatment for LDD. Despite advancements in imaging technologies and surgical techniques, the management of LDD remains fraught with complexities. The prognosis can be variable, and in some cases, despite appropriate therapeutic interventions guided by MRI-assisted surgical planning and confirmation through CT screening, the outcome may be unfavorable, as observed in this instance with the demise of the 50-year-old male patient. Further research and a deeper understanding of the pathophysiology underlying LDD are imperative to enhance diagnostic accuracy, refine treatment modalities, and potentially improve patient outcomes. This case underscores the challenges in managing this rare neurological condition and highlights the need for continued exploration into more effective therapeutic avenues.

Abstract We assessed the repeatability and agreement of ganglion cell complex (GCC) in the macular area and the peripapillary retinal nerve fiber layer (ppRNFL) with individual and combined macula and disc scans. The macular GCC and ppRNFL thicknesses from 34 control eyes and 43 eyes with glaucoma were measured with the Canon Optical Coherence Tomography (OCT) HS-100. Two repeated measurements were performed with both scan modes. The repeatability limit (Rlim) and agreement analysis were performed. The individual scan showed better repeatability than the combined scan in both groups. However, the differences in the Rlim for the GCC in most sectors were lower than 3 μm (axial resolution of the OCT), and this was larger than 3 μm for most of the ppRNFL sectors. The mean differences in the thickness between both scan modes for the GCC and ppRNFL measurements were less than 3 and 6 μm, respectively. The interval of the limits of agreement was about 10 μm in some sectors for the GCC, and about 40 and 60 μm in some sectors in controls and glaucoma eyes, respectively. Both scan modes showed good repeatability in both groups. The agreement results suggest that the scan modes cannot be used interchangeably.

AbstractPrevious research suggests that individuals with 22q11.2 deletion syndrome (DS) have an increased risk of bleeding following cardiac surgery. However, current guidelines for management of patients with 22q11.2DS do not provide specific recommendations for perioperative management. This study sought to identify specific risk factors for bleeding in this patient population. Examine the factors determining bleeding and transfusion requirements in patients with 22q11.2DS undergoing cardiac surgery. This was a single center review of patients who underwent cardiac surgery at the Children’s Hospital of Philadelphia from 2000 to 2016. Data was extracted from the medical record. Frequency of bleeding events, laboratory values, and transfusion requirements were compared. We included 226 patients with 22q11.2DS and 506 controls. Bleeding events were identified in 13 patients with 22q11.2DS (5.8%) and 27 controls (5.3%). Platelet counts were lower among patients with 22q11.2DS than in control patients, but not statistically different comparing bleeding to not bleeding. Patients with 22q11.2DS received more transfusions (regardless of bleeding status). However, multivariate analysis showed only procedure type was associated with increased risk of bleeding (p = .012). The overall risk of bleeding when undergoing cardiac surgery is not different in patients with 22q11.2DS compared to non-deleted patients. Though platelet counts were lower in patients with 22q11.2DS, only procedure type was significantly associated with an increased risk of bleeding.

Abstract As the demand for higher-strength of concrete is increasing, the research on Ultra-High Strength Concrete (UHSC) has the spectacular development in recent years. The purpose of this paper is to compare and summarize the properties of UHSC with different raw materials based on the published research and share it with researchers involved in the study of UHSC. Thus, papers relevant to UHSC were identified through a systematic literature search. The use of supplementary cementitious materials such as silica fume (SF), fly ash (FA), ground granulated blast furnace slag (GGBS), nanomaterials and fibers that were widely used in UHSC was investigated. This results in UHSC with promising compressive strength and better workability. Curing under high temperatures found denser microstructure and higher strength than standard curing.

Abstract By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)‐induced osteoporosis. Results confirm OVX‐induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole‐body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor‐BB and leukemia inhibitory factor, with downregulation of interleukin‐1 R6, and receptor activator of nuclear factor kappa‐B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor‐beta/SMAD, and Wingless‐related integration site/be‐catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo‐osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX‐induced bone loss.

Neurogenin 2 (NGN2), a neuronal transcription factor, can expedite differentiation of stem cells into mature glutamatergic neurons. We have utilized an allelic series of previously published and characterized isogenic Huntington's disease (IsoHD) human embryonic stem cell lines (Ooi et al., 2019), carrying different CAG repeat lengths in the first exon of the huntingtin gene. These IsoHDs were modified using CRISPR/Cas9 to insert NGN2 under the TET-ON doxycycline inducible promoter. The resulting IsoHD-NGN2 cell lines retained pluripotency in the absence of doxycycline (DOX), and via addition of DOX to the culturing media differentiation to neurons was achieved within 14 days.

Purpose: Waste and waste disposal is a universal problem and attention is required in all ways. The plant generated waste (leaf litter) is also a type of organic waste that creates multiple issues in urban areas.Method: Vermicomposting is a suitable alternative safe, hygienic, and cost-effective disposal of organic solid waste with the help of earthworms. The present study focussed on the conversion of leaf litter of Lagerstroemia speciosa trees from the local places to beneficial vermicompost. Vermicompost was prepared using leaf litter (LL) supplemented with cattle dung (CD), food waste, and earthworms. The study also explored the physical factors like temperature, pH, moisture, and biomass reduction of the vermicompost (100% & 50% LL) and CD.Results: An alkaline pH (8.97±0.04), nominal temperature (22.63±0.26°C) and high moisture content (72±2.75%), as well as increased biomass reduction (7.45±0.69 cm) was observed at the end of the vermicompost process. The study also performed plant growth analysis using vermicompost as manure. Increased growth, germination, and pest resistance were observed in the plants in which compost was utilized.Conclusion: The current study paves the way to create a green environment by reducing and converting leaf litter into vermicompost which will act as a circular economy.

Introduction: Lectures are traditional sources of learning and are effective with face-to-face interactions but lack efficacy because of distractions and the lack of attentiveness of students to lecture. This study aimed to assess the preference for learning methods among medical students and the utility and usefulness of learning methods among medical students. Methods: A cross-sectional study was conducted among 566 medical students in a tertiary care teaching hospital all over Tamilnadu, South India using web-based platforms for 4 months (December 2021 to March 2022). Participants were selected by using a convenience sampling method. A pre-tested and semi-structured questionnaire was used to collect the data on sociodemographic details (gender, age, level of degree, time spent on learning) and preference of learning methods for their university examination and competitive exam. The data was analyzed by using an independent t-test, Chi-square test, and Binary logistic regression, and the data was represented as Mean, Standard Deviation (SD), Frequency, and Percentage. Results: The mean (SD) age of the participants was 22.78 (2.62) years. Among the 566 responses, the offline mode 438 (73%) of education was preferred among medical students over the online mode of education 128 (23%). More than half of the participants preferred textbooks 406 (71.7%) followed by 327 (57.8%) written notes in offline mode and nearly half of them preferred the Google/internet search 346 (61.1%) followed by YouTube 315 (55.7%) in online mode. Age [AOR:0.88 95%CI (0.80-0.96)]is the only predictor of the preference for online learning and which is statistically significant (p-0.038) Conclusion: Traditional offline learning methods are well accepted than online learning methods among medical students in Tamil N?du. By emphasizing the importance of e-learning and incorporating it effectively into the curriculum, institutions can cater to the diverse learning needs of medical students in Tamil Nadu.

Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- β-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

Astrocytes are increasingly recognized for their important role in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). In ALS, astrocytes shift from their primary function of providing neuronal homeostatic support towards a reactive and toxic role, which overall contributes to neuronal toxicity and cell death. Currently, our knowledge on these processes is incomplete, and time-efficient and reproducible model systems in a human context are therefore required to understand and therapeutically modulate the toxic astrocytic response for future treatment options. Here, we present an efficient and straightforward protocol to generate human induced pluripotent stem cell (hiPSC)-derived astrocytes implementing a differentiation scheme based on small molecules. Through an initial 25 days, hiPSCs are differentiated into astrocytes, which are matured for 4+ weeks. The hiPSC-derived astrocytes can be cryopreserved at every passage during differentiation and maturation. This provides convenient pauses in the protocol as well as cell banking opportunities, thereby limiting the need to continuously start from hiPSCs. The protocol has already proven valuable in ALS research but can be adapted to any desired research field where astrocytes are of interest.Key features• This protocol requires preexisting experience in hiPSC culturing for a successful outcome.• The protocol relies on a small molecule differentiation scheme and an easy-to-follow methodology, which can be paused at several time points.• The protocol generates >50 × 106 astrocytes per differentiation, which can be cryopreserved at every passage, ensuring a large-scale experimental output.Graphical overview

Abstract Background and objective Postpartum Depression (PPD) is a frequently ignored birth-related consequence. Social network analysis can be used to address this issue because social media network serves as a platform for their users to communicate with their friends and share their opinions, photos, and videos, which reflect their moods, feelings, and sentiments. In this work, the depression of delivered mothers is identified using the PPD score and segregated into control and depressed groups. Recently, to detect depression, deep learning methods have played a vital role. However, these methods still do not clarify why some people have been identified as depressed. Methods We have developed Attribute Selection Hybrid Network (ASHN) to detect the postpartum depression diagnoses framework. Later analysis of the post of mothers who have been confirmed with the score calculated by the experts of the field using physiological questionnaire score. The model works on the analysis of the attributes of the negative Facebook posts for Depressed user Diagnosis, which is a large general forum. This framework explains the process of analyzing posts containing Sentiment, depressive symptoms, and reflective thinking and suggests psycho-linguistic and stylistic attributes of depression in posts. Results The experimental results show that ASHN works well and is easy to understand. Here, four attribute networks based on psychological studies were used to analyze the different parts of posts by depressed users. The results of the experiments show the extraction of psycho-linguistic markers-based attributes, the recording of assessment metrics including Precision, Recall and F1 score and visualization of those attributes were used title-wise as well as words wise and compared with daily life, depression and postpartum depressed people using Word cloud. Furthermore, a comparison to a reference with Baseline and ASHN model was carried out. Conclusions Attribute Selection Hybrid Network (ASHN) mimics the importance of attributes in social media posts to predict depressed mothers. Those mothers were anticipated to be depressed by answering a questionnaire designed by domain experts with prior knowledge of depression. This work will help researchers look at social media posts to find useful evidence for other depressive symptoms.

Abstract Background Tumours on the scalp are diverse and often exhibit site- and histology-specific characteristics. Reconstructing the scalp after oncological resection has always been challenging because of its unique anatomy. Methodology A retrospective review of patients with malignant scalp tumour operated on at a single institution over 10 years was performed. Data were collected and analysed regarding the scalp tumour profile, treatment, and the outcome of these procedures. Results Of the 66 patients in our study, 33 (50%) had SCC. In addition to this, 21% were sarcomas, 17% were appendageal carcinomas, 11% were BCCs, and 1% was neuroendocrine carcinoma. Cortical erosion was observed in 6 patients in the CT imaging, all with SCC histology. Among the eight patients with pathological nodal involvement, three had angiosarcoma, three had SCC, one had appendageal carcinoma, and one had neuroendocrine carcinoma. The mean surgical defect size was 67.4 cm2. The surgical defect was reconstructed with local flaps in 58% of patients and primary closure in 27%. Local and systemic recurrence was noted in 25% of patients. Tumour size more than 6 cm, tumour histology (SCC & sarcoma), unplanned margin-positive excision, and residual disease in re-excision had higher recurrence, even though the p-value was not significant. Conclusion Scalp tumours are heterogeneous in their clinical profiles. Often, its tumour biology and microscopic extent are underestimated. High suspicion, histological diagnosis, and clear surgical margins are all requirements in successfully treating scalp tumours. In order to minimize morbidity and restore an aesthetic and functional outcome, it is critical to use the simplest scalp reconstruction whenever possible.

Background and Purpose: India witnessed an explosive rise in mucormycosis following COVID-19 infection. While rhino orbital mucormycosis was the most common presentation, pulmonary mucormycosis was closely followed. The need for advanced resources and lack of clinical suspicion for COVID-19-associated pulmonary mucormycosis led to widespread underdiagnosis and poor response to late therapy. The study aimed to assess the prevalence of pulmonary mucormycosis in COVID-19-associated rhino-orbital mucormycosis using non-invasive techniques like sputum microscopy and chest imaging. Materials and methods: A prospective observational study was conducted at the Institute of Internal Medicine, Rajiv Gandhi Government General Hospital between June 2021 and July 2021. All hospitalised patients with proven rhino orbital mucormycosis with or without cerebral involvement within three months of confirmed COVID-19 infection having clinical symptoms compatible with pulmonary mucormycosis were included in the study. These patients were screened for probable and possible COVID-19-associated pulmonary mucormycosis using CT chest imaging and sputum microscopy within 48 hours of hospital admission.Results: Out of 50 patients with rhino-orbital mucormycosis, 16% had associated possible or probable pulmonary mucormycosis. All 8 patients were diabetics and had characteristic CT chest findings while only half had positive sputum microscopy. A higher prevalence of disseminated COVID-19-associated mucormycosis was noted among 51-60 years males with the use of corticosteroids and oxygen for COVID-19 therapy. The mortality was 100% in probably disseminated mucormycosis, 50% in possible disseminated mucormycosis and only 9.5% in isolated rhino-orbital mucormycosis. Conclusion: Hence, non-invasive and feasible methods such as sputum microscopy and chest imaging can be considered for early screening and intensive management of probably disseminated mucormycosis to improve prognosis.

Mediastinal venolymphatic malformations (VLM) are rare tumours, with very few reported cases in the literature. Arising often from the anterior mediastinum, VLM manifests symptoms based on invaded surrounding structures. Masses from the anterior and superior mediastinum pose an anaesthetic challenge for airway and hemodynamic management. A 7-month-old male child presented with a progressively growing mass over the left anterior chest wall for one month, about 4x4 cm, with diffuse margins and now expanded to involve the root of the neck and into the axilla. The patient was free from any apparent systemic illness. The breathing difficulty worsened in the past week with noisy respiration associated with feeding difficulty and hence sought medical admission to the paediatrics emergency unit. In conclusion, such huge mediastinal masses are managed better under spontaneous ventilation with an adequate surgical depth of anaesthesia to maintain appropriate respiratory compliance and necessitate lower peak inspiratory pressure. Given rare cases reported in the literature, similar topics would help choose the modus of ventilation and their safe management.

This work reports the development of novel curcuminoid-based electrochemical sensors for the detection of environmental pollutants from water. In this study, the first set of electrochemical experiments was carried out using curcumin-conjugated multi-walled carbon nanotubes (MWCNT–CM) for 1,4-dioxane detection. The MWCNT–CM/GCE showed good sensitivity (103.25 nA nM−1 cm−2 in the linear range 1 nM to 1 µM), with LOD of 35.71 pM and LOQ of 108.21 pM. The second set of electrochemical experiments was carried out with bisdemethoxy curcumin analog quantum dots (BDMCAQD) for hydrazine detection. The BDMCAQD/GCE exhibited good sensitivity (74.96 nA nM−1 cm−2 in the linear range 100 nM to 1 µM), with LOD of 10 nM and LOQ of 44.93 nM. Thus, this work will serve as a reference for the fabrication of metal-free electrochemical sensors using curcuminoids as the redox mediator for the enhanced detection of environmental pollutants.

Abstract Radiotherapy is a critical component of cancer care but can cause osteoporosis and pathological insufficiency fractures in surrounding and otherwise healthy bone. Presently, no effective countermeasure exists, and ionizing radiation-induced bone damage continues to be a substantial source of pain and morbidity. The purpose of this study was to investigate a small molecule aminopropyl carbazole named P7C3 as a novel radioprotective strategy. Our studies revealed that P7C3 repressed ionizing radiation (IR)-induced osteoclastic activity, inhibited adipogenesis, and promoted osteoblastogenesis and mineral deposition in vitro. We also demonstrated that rodents exposed to clinically equivalent hypofractionated levels of IR in vivo develop weakened, osteoporotic bone. However, the administration of P7C3 significantly inhibited osteoclastic activity, lipid formation and bone marrow adiposity and mitigated tissue loss such that bone maintained its area, architecture, and mechanical strength. Our findings revealed significant enhancement of cellular macromolecule metabolic processes, myeloid cell differentiation, and the proteins LRP-4, TAGLN, ILK, and Tollip, with downregulation of GDF-3, SH2B1, and CD200. These proteins are key in favoring osteoblast over adipogenic progenitor differentiation, cell matrix interactions, and shape and motility, facilitating inflammatory resolution, and suppressing osteoclastogenesis, potentially via Wnt/β-catenin signaling. A concern was whether P7C3 afforded similar protection to cancer cells. Preliminarily, and remarkably, at the same protective P7C3 dose, a significant reduction in triple-negative breast cancer and osteosarcoma cell metabolic activity was found in vitro. Together, these results indicate that P7C3 is a previously undiscovered key regulator of adipo-osteogenic progenitor lineage commitment and may serve as a novel multifunctional therapeutic strategy, leaving IR an effective clinical tool while diminishing the risk of adverse post-IR complications. Our data uncover a new approach for the prevention of radiation-induced bone damage, and further work is needed to investigate its ability to selectively drive cancer cell death.

Abstract Background To evaluate the repeatability of a fully automated swept-source optical coherence tomography (SS-OCT) and its agreement with an optical low coherence reflectometry (OLCR) for several biometric parameters. Methods In this study, 74 eyes of 74 patients were measured using the Eyestar 900 SS-OCT and Lenstar LS 900 OLCR. Flat keratometry (K1) and steep keratometry (K2), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) were measured three times with each device. The repeatability was analyzed with the intrasubject standard deviation, coefficient of variability (CoV), and coefficient of repeatability (CoR) for each instrument. The agreement between the instruments was evaluated with Bland-Altman analysis. Results K1, K2 and CCT CoV values were

Abstract Phishing attacks have become one of the powerful sources for cyber criminals to impose various forms of security attacks in which fake website Uniform Resource Locators (URL) are circulated around the Internet community in the form of email, messages etc., in order to deceive users, resulting in the loss of their valuable assets. The phishing URLs are predicted using several blacklist‐based traditional phishing website detection techniques. However, numerous phishing websites are frequently constructed and launched on the Internet over time; these blacklist‐based traditional methods do not accurately predict most phishing websites. In order to effectively identify malicious URLs, an enhanced deep learning‐based phishing detection approach has been proposed by integrating the strength of Variational Autoencoders (VAE) and deep neural networks (DNN). In the proposed framework, the inherent features of a raw URL are automatically extracted by the VAE model by reconstructing the original input URL to enhance phishing URL detection. For experimentation, around 1 lakh URLs were crawled from two publicly available datasets, namely ISCX‐URL‐2016 dataset and Kaggle dataset. The experimental results suggested that the proposed model has reached a maximum accuracy of 97.45% and exhibits a quicker response time of 1.9 s, which is better when compared to all the other experimented models.

The unmet need for family planning is a pervasive public health concern in many low- and middle-income countries (LMICs). Mobile health (mHealth) interventions have been designed and implemented in LMIC settings to address this issue through health information dissemination via voice calls, apps, and short message services (SMS). Although the impact of mHealth programmes on postpartum family planning outcomes have been systematically reviewed, the contexts, conditions, and mechanisms underpinning programme engagement and their impact on outcomes remain unclear. This study aims to formulate hypotheses in the form of context-mechanism-outcome configurations (CMOCs) of whether, how, why, for whom, and in what contexts mHealth interventions implemented in LMICs influence postpartum family planning (PPFP) outcomes. We conducted a realist review of peer-reviewed and grey literature. Peer-reviewed literature was identified through MEDLINE, Embase, Global Health, Web of Science, and Google Scholar. Grey Literature was identified through The National Grey Literature Conference, FHI 360, Guttmacher Institute, Population Council, and MSI Reproductive Choices. Inclusion criteria were updated as the review progressed. Narrative data were analysed using dimensional analysis to build CMOCs. Two overarching concepts (underpinned by 12 CMOCs) emerged from the 37 included records: mobile phone access, use, and ownership as well as women's motivation. Women's confidence to independently own, access, and operate a mobile phone was a central mechanism leading to mHealth programme engagement and subsequent change in PPFP knowledge, awareness, and outcomes. Receiving family and social support positively interacted with this while low digital literacy and harmful gender norms pertaining to prescribed domestic duties and women's household influence were barriers to programme engagement. Intrinsic motivation for health improvement functioned at times both as a context and potential mechanism influencing mHealth programme engagement and PPFP outcomes. However, these contexts rarely occur in isolation and need to be evaluated as co-occurring phenomena. (Review registration: PROSPERO CRD42023386841).

Researchers worldwide are working hard to develop nanoparticles that can be used for the photocatalytic degradation of dangerous substances and antibiotics. In this report, we present a study on how to make yttrium-incorporated magnesium oxide nanoparticles using hydrothermal and calcination methods. These particles measure around 50 nm and have excellent photocatalytic properties. We analyzed them using various physiochemical techniques like X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy with EDAX, transmission electron microscopy, X-ray photoelectron spectroscopy, and ultra-violet diffused reflectance spectroscopy. The nanohexagons created in this study showed reduced band gap energy from 4.8 eV to 3.8 eV when yttrium was incorporated into MgO nanohexagons resulting in an unusual increase in light absorption within the visible light region. Experimental reports show these synthesized nanoparticles could degrade about 66.5 % antibiotic Ciprofloxacin (CIP) and 79 % Methylene Blue (MB) dye respectively with .O2– playing a significant role at every step during the degradation process. This study demonstrates that these synthesized nanohexagons have practical applications as promising photocatalysts for treating toxic contaminants found in industrial effluents.

Forkhead box P3 (FOXP3) is an essential transcription factor for regulatory T cell (Treg) function. Defects in Tregs mediate many immune diseases including the monogenic autoimmune disease immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), which is caused by FOXP3 mutations. Treg cell products are a promising modality to induce allograft tolerance or reduce the use of immunosuppressive drugs to prevent rejection, as well as in the treatment of acquired autoimmune diseases. We have recently opened a phase I clinical trial for IPEX patients using autologous engineered Treg-like cells, CD4LVFOXP3. To facilitate the pre-clinical studies, a novel humanized-mouse (hu-mouse) model was developed whereby immune-deficient mice were transplanted with human hematopoietic stem progenitor cells (HSPCs) in which the FOXP3 gene was knocked out (FOXP3KO) using CRISPR-Cas9. Mice transplanted with FOXP3KO HSPCs had impaired survival, developed lymphoproliferation 10–12 weeks post-transplant and T cell infiltration of the gut, resembling human IPEX. Strikingly, injection of CD4LVFOXP3 into the FOXP3KO hu-mice restored in vivo regulatory functions, including control of lymphoproliferation and inhibition of T cell infiltration in the colon. This hu-mouse disease model can be reproducibly established and constitutes an ideal model to assess pre-clinical efficacy of human Treg cell investigational products.

Abstract Background A pigmented lesion that progressively increases in size anywhere in the body is a matter of concern, and when it presents in the ear, it has various differential diagnosis, one among them being a benign nevus. In this case report, we present a rare and interesting case of a pigmented lesion in the aural concha and review the literature of the same. Case presentation A 40-year-old male presented with pigmented right aural conchal growth with easy bruising of 1-year duration. Initial evaluation reported as a possible hemangioma, and excision biopsy revealed a compound nevus. Conclusion Despite its rarity, we should consider compound nevus as a differential diagnosis of pigmented external ear lesions. Histopathological examination is considered confirmatory; hence, excision biopsy is the treatment of choice.

Abstract Due to the rise in our aging population, a disproportionate demand for total joint arthroplasty (TJA) in the elderly is forecast. Periprosthetic joint infection (PJI) represents one of the most challenging complications that can occur following TJA, and as the number of primary and revision TJAs continues to rise, an increasing PJI burden is projected. Despite advances in operating room sterility, antiseptic protocols, and surgical techniques, approaches to prevent and treat PJI remain difficult, primarily due to the formation of microbial biofilms. This difficulty motivates researchers to continue searching for an effective antimicrobial strategy. The dextrorotatory-isoforms of amino acids (D-AAs) are essential components of peptidoglycan within the bacterial cell wall, providing strength and structural integrity in a diverse range of species. Among many tasks, D-AAs regulate cell morphology, spore germination, and bacterial survival, evasion, subversion, and adhesion in the host immune system. When administered exogenously, accumulating data have demonstrated that D-AAs play a pivotal role against bacterial adhesion to abiotic surfaces and subsequent biofilm formation; furthermore, D-AAs have substantial efficacy in promoting biofilm disassembly. This presents D-AAs as promising and novel targets for future therapeutic approaches. Despite their emerging antibacterial efficacy, their role in disrupting PJI biofilm formation, the disassembly of established TJA biofilm, and the host bone tissue response remains largely unexplored. This review aims to examine the role of D-AAs in the context of TJAs. Data to date suggest that D-AA bioengineering may serve as a promising future strategy in the prevention and treatment of PJI.

Abstract Objectives To three-dimensionally analyse the stress distribution and displacement pattern in the maxillofacial complex following intrusion and distalization of the maxillary arch using finite element analysis in skeletal class II malocclusion with prognathic maxilla and vertical maxillary excess using miniplates and mini-implants. Materials and methods Finite Element models of a skull, Y-shaped stainless steel miniplate, mini-implant and a posted arch were generated. Three force levels (1) 200 g (2) 300 g and (3) 500 g per side were applied to the assembly. The models were pre-processed and the analysis was performed using ANSYS version 18.1 software. Alterations in von mises stress, principal maximum stress, principal minimum stress and compressive stress were analysed around the sutures and surface landmarks. Results With miniplates, there was a maximum stress concentration at the zygomatic buttress with even stress distribution at the fronto-maxillary, zygomatico-temporal, zygomatico-frontal and pterygomaxillary sutures along with anatomical landmarks such as frontal process of maxilla, ANS, Point A, prosthion and maxillary process of zygoma. First molars experienced greater distalization effects with buccal flaring when miniplates were used. With mini-implants, canine and premolars also exhibited greater distalization effects. In the root apices, lateral incisors showed increased lingual root movement with mini-implants. Conclusion Miniplates provide a greater distalizing effect while mini-implants produce increased intrusive effect. The distalizing effect is greater when 500 g of force is applied using miniplates with significantly even stress distribution and displacement pattern.

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

Leiomyomas are benign tumours of smooth muscle origin and can occur in any part of the body with adrenal gland being an uncommon site. Ganglioneuromas of adrenal gland are benign neural crest-derived tumours. Both of these tumours are usually detected incidentally. Hereby, the authors report an unusual case of a 31-year-old woman, who presented with paroxysmal attacks of headache, palpitations and flushing pointing towards a hormone secreting adrenal tumour. However, functional adrenal markers were normal. Radiological investigations revealed 8×3 cm heterogeneously enhancing left suprarenal mass with calcification and extension to left renal vein. Patient underwent left nephrectomy and adrenalectomy with a high clinical suspicion of malignancy because of tumour extension to the renal vein. The histopathological examination revealed a leiomyoma arising in a background of ganglioneuroma which was later on confirmed using immunohistochemistry. Authors have presented the present case because of atypical presentation as a hormone secreting adrenal tumour with radiological features of malignancy and the unique histomorphology of the combined occurrence of leiomyoma and ganglioneuromatous area in the adrenal gland. To the best of author’s knowledge, this is the first case report of such an occurrence in the adrenal gland.