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Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses. The technology improved vaccine manufacturing, rendering it more efficient and economical. These vaccines have multiple advantages compared to conventional vaccines. The pandemic has heightened awareness of the advantages of these vaccine technologies; trust and acceptance of these vaccines are steadily growing globally. This work offers an overview of the prospects and advantages associated with recombinant vaccines. Additionally, it discusses some of the challenges likely to arise in the future. Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases (especially vector-borne and emerging diseases) and hurdles faced throughout the vaccine development process, especially in enhancing the effectiveness of these vaccines. Moreover, their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects. This review also reviewed the hurdles faced throughout the vaccine development process, especially in enhancing the effectiveness of these vaccines against vector-borne diseases, emerging diseases, and untreatable diseases with high mortality rates like AIDS as well as cancer.

Introduction: Nasoendotracheal (NET) tubes are exposed to various external forces, handling, slippage, and accidental extubation, with the potential for fatal complications. In the modern era, several techniques have been developed to reduce the complication rate of Nasoendotracheal Intubation (NTI). NET tubes can be secured using twill or cotton tape, adhesive tape, gauze, or a manufactured device, either individually or in combination. In present study, a transcolumellar stitch and transeptal stitch were designed with 2-0 silk suture material and utilised by many anaesthetists and surgeons to secure the NET, providing good stability but sometimes leading to columellar ischaemia and cutting through. Aim: To compare the intraoperative stability of Nasoendotracheal Tubes (NETT) secured by a transept flower stitch with those secured using a simple surgical knot in patients undergoing NET Intubation (NETI) for open reduction and internal fixation of maxillofacial trauma. Materials and Methods: This cross-sectional study was conducted in the Department of Oral and Maxillofacial Surgery at Sharad Pawar Dental College and Hospital and Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha, Maharashtra, India, over a period of six months from March 2023 to August 2023. The study involved 30 patients with maxillofacial fractures who were divided into two groups. Preoperative assessments included case history, physical examinations, and maxillofacial evaluations. Patients were divided into two groups: Group A underwent simple surgical knot using 2-0 silk suture (odd-numbered patients), while patients in Group B underwent transseptal flower stitch using 2-0 silk suture (even-numbered patients). All parameters were recorded by the same surgeon at the beginning and end of the procedure. The data was collected, tabulated, and statistically analysed using Statistical Package for the Social Sciences (SPSS) statistical software version 23.0. Results: Out of the total 30 patients enrolled in the study, 24 (80%) were male and 6 (20%) were female. The comparison between the two groups regarding the duration of surgery showed no statistically significant difference. Three parameters, namely the amount of NETT displacement, nasal tip laceration, and tip ischaemia, were evaluated and recorded both preoperatively and immediately after extubation. The amount of NETT displacement (p-value=0.031) and nasal tip laceration, haemorrhage, or necrosis (p-value=0.049) were shown to differ statistically significantly between the groups. Conclusion: The present study highlighted that the flower stitch method is an extremely beneficial approach. It offers advantages in terms of better stability and is associated with fewer complications and lower morbidity when compared to the simple surgical knot group.

Abstract A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Abstract Background Rare disorders comprise of ~ 7500 different conditions affecting multiple systems. Diagnosis of rare diseases is complex due to dearth of specialized medical professionals, testing labs and limited therapeutic options. There is scarcity of data on the prevalence of rare diseases in different populations. India being home to a large population comprising of 4600 population groups, of which several thousand are endogamous, is likely to have a high burden of rare diseases. The present study provides a retrospective overview of a cohort of patients with rare genetic diseases identified at a tertiary genetic test centre in India. Results Overall, 3294 patients with 305 rare diseases were identified in the present study cohort. These were categorized into 14 disease groups based on the major organ/ organ system affected. Highest number of rare diseases (D = 149/305, 48.9%) were identified in the neuromuscular and neurodevelopmental (NMND) group followed by inborn errors of metabolism (IEM) (D = 47/305; 15.4%). Majority patients in the present cohort (N = 1992, 61%) were diagnosed under IEM group, of which Gaucher disease constituted maximum cases (N = 224, 11.2%). Under the NMND group, Duchenne muscular dystrophy (N = 291/885, 32.9%), trinucleotide repeat expansion disorders (N = 242/885; 27.3%) and spinal muscular atrophy (N = 141/885, 15.9%) were the most common. Majority cases of β-thalassemia (N = 120/149, 80.5%) and cystic fibrosis (N = 74/75, 98.7%) under the haematological and pulmonary groups were observed, respectively. Founder variants were identified for Tay-Sachs disease and mucopolysaccharidosis IVA diseases. Recurrent variants for Gaucher disease (GBA:c.1448T > C), β-thalassemia (HBB:c.92.+5G > C), non-syndromic hearing loss (GJB2:c.71G > A), albinism (TYR:c.832 C > T), congenital adrenal hyperplasia (CYP21A2:c.29–13 C > G) and progressive pseudo rheumatoid dysplasia (CCN6:c.298T > A) were observed in the present study. Conclusion The present retrospective study of rare disease patients diagnosed at a tertiary genetic test centre provides first insight into the distribution of rare genetic diseases across the country. This information will likely aid in drafting future health policies, including newborn screening programs, development of target specific panel for affordable diagnosis of rare diseases and eventually build a platform for devising novel treatment strategies for rare diseases.

Introduction: Plantar fasciitis is the most common cause of heel and foot pain, leading individuals to use compensatory techniques to alleviate their pain, resulting in an antalgic gait. These compensations alter the feeling of joint position and muscle activation, making it challenging to maintain an upright posture within the base of support. According to Mulligan's concept, rigid tape allows painful or restricted movements with quick pain relief and increased range of motion while correcting positional faults and reducing tensile tension on the fascia, thereby decreasing inflammation and microscopic tears. Currently, there is a scarcity of data studying the effect of Mulligan’s calcaneal taping on dynamic balance. Aim: To evaluate the effect of Mulligan’s calcaneal taping on dynamic balance and functional performance in subjects with plantar fasciitis. Materials and Methods: The study was a prospective cohort study conducted at D.Y. Patil Hospital and Research Centre, Navi Mumbai, Maharashtra, India. It began in March 2023 and concluded in March 2024, spanning one year. Thirty-six subjects were randomly divided into group A (n=18) and group B (n=18). Subjects experiencing pain for more than six weeks, aged between 18-60 years, with a positive Windlass test, plantar medial heel pain, and abnormal foot posture index (between +6 to +9) were included in the study. The experimental group received Mulligan’s calcaneal taping along with conventional physiotherapy exercises, while the control group received only conventional physiotherapy exercises. Pre-post assessments were conducted using the star excursion balance test for dynamic balance assessment and the Foot Function Index (FFI) for functional performance. Results: Statistically significant differences were found among the medial (p-value=0.0212), posteromedial (p-value=0.0199), and posterior (p-value=0.0091) directions of the star excursion balance test. Both groups did not show statistically significant differences in the FFI score. However, with effect size, there was good clinical significance for the FFI score and all directions of the star excursion balance test except the posterolateral direction. Conclusion: Mulligan calcaneal taping has been shown to be more effective in improving dynamic balance in subjects with plantar fasciitis.

Abstract Background Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. Results 903 smMIPs were designed to target exon and exon–intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. Conclusion We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Introduction: Neonatal Sepsis (NS) is a major cause of morbidity and mortality worldwide, especially in developing countries like India. The role of antimicrobials is life-saving in NS. To achieve a good prognosis, early diagnosis and appropriate treatment are required. Data related to the irrational use of antimicrobials in neonates are limited. Aim: To evaluate the drug usage pattern and Adverse Drug Reactions (ADRs) of antimicrobials in NS. Materials and Methods: A prospective observational study was conducted among 350 neonates who were admitted and diagnosed with NS from January to December 2021 in the Neonatal Intensive Care Unit (NICU) of PDU Medical College and Civil Hospital, Rajkot, Gujarat, India. Demographic data such as age, sex, birth weight, and clinical data such as type of delivery, type of sepsis, culture-sensitivity status, and antimicrobials used were recorded. Suspected ADRs were reported in the pharmacovigilance database. Categorical data were analysed in percentage, whereas some clinical data were analysed with mean and median using Microsoft Office Excel-2019. Results: In the present study, 172 (49.15%) male and 178 (50.85%) female neonates were almost equally affected. The mean gestational age and birth weight were 35±3.6 weeks and 2±0.7 kg, respectively. Early-Onset Neonatal Sepsis (EONS) cases were more at 273 (78%) compared to Late-Onset Neonatal Sepsis (LONS). Seventeen different antimicrobials were used. The average number of antimicrobials used per case was 2.9. The Piperacillin Tazobactam was the most commonly used antimicrobial in 173 cases (49.43%) in early-onset sepsis, while Meropenem was used in 40 cases (11.43%) in late-onset sepsis. Coagulase-negative Staphylococcus was the most commonly isolated organism in 15 cases (4.2%), followed by Klebsiella Pneumoniae in 13 cases (3.7%). Twelve out of 17 antimicrobials (70.59%) were not included in the first list of essential medicines for children of India in 2011. Six ADRs were reported in the present study. Conclusion: In all admitted cases of sepsis, empirical therapy was given, but variations from standard recommendations were observed in dose and frequency. A periodic survey of antimicrobial use patterns in NS will be useful in the rational selection of empirical therapy.

The present research investigates the potential of activated vetiver root powder as a bioadsorbent for removing chloride ions from saline aqueous environments, especially relevant for addressing agricultural water scarcity. Factors such as pH, biomass dosage, contact duration, and initial salt ion concentration were examined. Thermodynamic analysis provided insights into the adsorption process, demonstrating the feasibility, non-spontaneous behavior, and exothermic nature of chloride ion adsorption onto activated vetiver root powder. The batch adsorption of chlorides adhered to the Langmuir equation and a pseudo-second-order kinetic model, demonstrating a monolayer adsorption capacity of 17.58 mg/g for activated vetiver powder. An artificial neural network (ANN) was used to develop a predictive model for estimating the percentage removal of chloride ions. The values of R2 and mean squared error were used to determine the predictive performance of the ANN. In the near term, prospective commercial uses of activated vetiver powder merit further investigation through in-depth research using real wastewater containing salinity-inducing ion. HIGHLIGHTS This study focused on vetiver root powder's efficacy in removing chloride ions under varied conditions.; It explored the contrast between linear and nonlinear regression in isotherm and kinetics analyses.; Thermodynamic assessment revealed a non-spontaneous and exothermic bioadsorption process.; This study introduced an ANN model that predicts chloride ion removal, highlighting its potential in biosorption studies.;

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been demonstrated to limit the host interferon response; however, the underlying mechanism remains unclear. Here, we found that SARS-CoV-2 infection upregulated the E3 ubiquitin ligase Huwe1, which in turn facilitated the degradation of the transcription factor Miz1. The degradation of Miz1 hampered interferon alpha and gamma responses, consequently fostering viral replication and impeding viral clearance. Conversely, silencing or inhibiting Huwe1 enhanced the interferon responses, effectively curbing viral replication. Consistently, overexpressing Miz1 augmented the interferon responses and limited viral replication, whereas silencing Miz1 had the opposite effect. Targeting Huwe1 or overexpressing Miz1 elicited transcriptomic alterations characterized by enriched functions associated with bolstered antiviral response and diminished virus replication. Further study revealed Miz1 exerted epigenetic control over the transcription of specific interferon signaling molecules, which acted as common upstream regulators responsible for the observed transcriptomic changes following Huwe1 or Miz1 targeting. These findings underscore the critical role of the Huwe1-Miz1 axis in governing the host antiviral response, with its dysregulation contributing to the impaired interferon response observed during COVID-19.

Abstract Lysosomal storage disorders (LSDs) in adults have milder phenotype and variable age at presentation. Several studies have described the phenotype, genotype and treatment outcomes for adult‐onset LSDs like Gaucher, Fabry, Pompe disease and others. We describe the first systematic study on the occurrence of LSDs in an adult population from India. It describes, the key clinical signs seen in these patients and those from literature review that can aid in early detection. Of 2102 biochemically diagnosed LSDs cases, 32 adult patients were identified with LSDs. Based on the clinical suspicion, screening test and enzyme study was carried out. Twenty‐two patients were subjected to a genetic study to identify the causative variant in a respective gene. Of the 32 adult patients, we observed a maximum percentage of 37.5% (n = 12) cases with Gaucher disease, followed by 13% (n = 4) with Fabry disease. We found 10% of cases with MPS IVA and MPS I, and 9% cases with Pompe. Single case of adult mucolipidosis III and two cases each of Type 1 Sialidosis, Niemann‐Pick disease B and metachromatic leukodystrophy were identified. We observed two common variants p.Leu483Pro and p.Ala487Thr in the GBA1 gene in 23% of Indian patients with adult Gaucher disease. No common variants were observed in other aforementioned LSDs. Study identified 50% of Fabry patients and 4% of Gaucher patients diagnosed at our centre to be adults. The prevalence of adult Pompe patients was low (3.4%) as compared to 80% reported in the Caucasian population. Adult LSDs such as, MPS III, GM1/GM2 gangliosidosis and Krabbe disease were not identified in our cohort.

Introduction: For crafting complete dentures, Polymethylmethacrylate (PMMA) has long been the material of choice. Various reinforcements are being used to enhance the properties of PMMA and minimise denture fracture. Aim: The present in-vitro study compared the flexural strength of PMMA resin samples reinforced with Silver Nanoparticles (Ag NP), siwak, and fluconazole. Materials and Methods: The present in-vitro experiment was conducted from July to August 2017 at the Prosthodontics Department of a Dental College with technical support from the Centre for Scientific Research and Development (CSRD), affiliated with People’s University in Bhopal, Madhya Pradesh, India. Flexural testing was conducted at the Central Institute of Plastic Engineering and Technology (CIPET), Bhopal. A total of 120 acrylic resin samples, each measuring 65 mm in length, 10 mm in width, and 2.5 mm in thickness, were fabricated in accordance with American Dental Association (ADA) Specification No. 12. These specimens were categorised into four distinct groups. The first group consisted of only PMMA resin (Group A), while the remaining three groups comprised PMMA resin enhanced with AgNP (Group B), Siwak (Group C), and Fluconazole (Group D), respectively, with each group containing 30 samples. Subsequently, these specimens underwent a flexural strength assessment through a 3-point flexural test. The statistical analysis to assess and compare the mean flexural strength of the samples was conducted. The present analysis was performed first by applying an Analysis of Variance (ANOVA) test, followed by pairwise comparisons with Tukey’s Post-hoc test. A p-value less than 0.05 was used to determine statistical significance. Results: The mean flexural strength (±Standard Deviation) in N/mm2 for PMMA; PMMA+AgNP; PMMA+Siwak and PMMA+ Fluconazole was 82.33±5.18; 80.55±5.67; 71.50±10.15; and 74.03±10.84, respectively. The mean flexural strengths of the PMMA and PMMA+AgNP groups were similar (p=0.842). However, the flexural strength of the Siwak+PMMA and Fluconazole+PMMA groups was significantly less than that of the other two groups. Conclusion: The flexural strength of PMMA is unaffected by the inclusion of AgNP at a concentration of 1%, and its incorporation would allow the benefit from its antibacterial qualities. It is not advised to add fluconazole or siwak because doing so reduces the flexural strength.

Sports-associated orofacial trauma causes negative sequelae in an athlete. To prevent this, we must closely assess the mechanism as well as the available literature regarding the prevalence. It is easier to apply knowledge of sports dentistry if the injury mechanism, types of injury, and management are known. Every single game is accompanied by its own set of injuries. Basketball is a dynamic game. Athletes involved in this game are at high risk of orofacial injuries. The preventive aspect is often a blind spot, especially in Indian Sports. This review gives a bird's-eye view of the type of orofacial trauma and prevention in athletes playing basketball game.

Abstract Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment.

Abstract The Archean Superior craton was formed by the assemblage of continental and oceanic terranes at ∼2.6 Ga. The craton is surrounded by multiple Proterozoic mobile belts, including the Paleoproterozoic Trans‐Hudson Orogen which brought together the Superior and Rae/Hearne cratons at ∼1.9–1.8 Ga. Despite numerous studies on Precambrian lithospheric formation and evolution, the deep thermochemical structure of the Superior craton and its surroundings remains poorly understood. Here we investigate the upper mantle beneath the region from the surface to 400 km depth by jointly inverting Rayleigh wave phase velocity dispersion data, elevation, geoid height and surface heat flow, using a probabilistic inversion to obtain a (pseudo‐)3D model of composition, density and temperature. The lithospheric structure is dominated by thick cratonic roots (>300 km) beneath the eastern and western arms of the Superior craton, with a chemically depleted signature (Mg# > 92.5), consistent with independent results from mantle xenoliths. Beneath the surrounding Proterozoic and Phanerozoic orogens, the Mid‐continent Rift and Hudson Strait, we observe a relatively thinner lithosphere and more fertile composition, indicating that these regions have undergone lithospheric modification and erosion. Our model supports the hypothesis that the core of the Superior craton is well‐preserved and has evaded lithospheric destruction and refertilization. We propose three factors playing a critical role in the craton's stability: (a) the presence of a mid‐lithospheric discontinuity, (b) the correct isopycnic conditions to sustain a strength contrast between the craton and the surrounding mantle, and (c) the presence of weaker mobile belts around the craton.

Flow has been described as a state of optimal performance, experienced universally across a broad range of domains: from art to athletics, gaming to writing. However, its phenomenal characteristics can, at first glance, be puzzling. Firstly, individuals in flow supposedly report a loss of self-awareness, even though they perform in a manner which seems to evince their agency and skill. Secondly, flow states are felt to be effortless, despite the prerequisite complexity of the tasks that engender them. In this paper, we unpick these features of flow, as well as others, through the active inference framework, which posits that action and perception are forms of active Bayesian inference directed at sustained self-organisation; i.e., the minimisation of variational free energy. We propose that the phenomenology of flow is rooted in the deployment of high precision weight over (i) the expected sensory consequences of action and (ii) beliefs about how action will sequentially unfold. This computational mechanism thus draws the embodied cognitive system to minimise the ensuing (i.e., expected) free energy through the exploitation of the pragmatic affordances at hand. Furthermore, given the challenging dynamics the flow-inducing situation presents, attention must be wholly focussed on the unfolding task whilst counterfactual planning is restricted, leading to the attested loss of the sense of self-as-object. This involves the inhibition of both the sense of self as a temporally extended object and higher–order, meta-cognitive forms of self-conceptualisation. Nevertheless, we stress that self-awareness is not entirely lost in flow. Rather, it is pre-reflective and bodily. Our approach to bodily-action-centred phenomenology can be applied to similar facets of seemingly agentive experience beyond canonical flow states, providing insights into the mechanisms of so-called selfless experiences, embodied expertise and wellbeing.

Immune thrombocytopenic purpura (ITP) is a condition where the body's immune system mistakenly attacks and destroys platelets, resulting in a decreased platelet count. This leads to the development of purpura on the skin and may cause bleeding episodes due to the presence of antibodies that target and damage platelets. Excluding the usual suspects helps in identifying the underlying causes of thrombocytopenia. The diagnosis of immune thrombocytopenia (ITP) relies on clinical suspicion and the presence of thrombocytopenia, as indicated on a normal peripheral smear. Bone marrow examination is performed in order to eliminate the possibility of leukemia, myelodysplastic syndrome or aplastic anemia. Circulating platelets become sensitized due to the presence of IgG autoantibodies. As a result, these cells are swiftly eliminated by antigen-presenting cells, such as macrophages, which are primarily found in the spleen, and occasionally in the liver or other parts of the monocyte-macrophage system. In response, the bone marrow increases the production of platelets. ITP frequently occurs in healthy individuals, including children and young adults, following a viral infection. Certain medications can also lead to immune thrombocytopenia, which is practically indistinguishable from idiopathic thrombocytopenic purpura. Children usually recover spontaneously within a few weeks or months, and splenectomy is rarely required. However, spontaneous remissions necessitating splenectomy in young adults are uncommon in the first several months following diagnosis. This article discusses the most frequent causes of ITP and outline an interdisciplinary diagnostic and therapeutic approach based on current research.

Abstract We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson’s correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r − 0.23, p = 0.01), McAuley index (r − 0.65, p

The purpose of this in vitro study was to develop calcium sulfate (CS)-based disks infused with an antimicrobial drug, which can be used as a post-surgical treatment modality for osteomyelitis. CS powder was embedded with 10% antibiotic, amoxicillin (AMX) or moxifloxacin (MFX), to form composite disks 11 mm in diameter that were tested for their degradation and antibiotic release profiles. For the disk degradation study portion, the single drug-loaded disks were placed in individual meshes, subsequently submerged in phosphate-buffered saline (PBS), and incubated at 37 °C. The disks were weighed once every seven days and analyzed via Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and scanning electron microscopy. During the antibiotic release analysis, composite disks were placed in PBS solution, which was changed every 3 days, and analyzed for antibiotic activity and efficacy. The antibacterial effects of these sustained-release composites were tested by agar diffusion assay using Streptococcus mutans (S. mutans) UA 159 as an indicator strain. The degradation data showed significant increases in the degradation of all disks with the addition of antibiotics. Following PBS incubation, there were significant increases in the amount of phosphate and decreases in the amount of sulfate. The agar diffusion assay demonstrated that the released concentrations of the respective antibiotics from the disks were significantly higher than the minimum inhibitory concentration exhibited against S. mutans over a 2–3-week period. In conclusion, CS-antibiotic composite disks can potentially serve as a resorbable, osteoconductive, and antibacterial therapy in the treatment of bone defects and osteomyelitis.

The heterogenization of molecular catalysts within a porous solid acting as macroligand can advantageously open access to enhanced stability and productivity, and thus to more sustainable catalytic process. Herein, a porous organic polymer (POP) made through metal‐free polymerization using bipyridine repeating units is reported. This N‐rich POP is an efficient macroligand for the heterogenization of molecular rhodium complexes. The intrinsic catalytic activity of the heterogenized catalyst is slightly higher than that of its homogeneous molecular counterpart for formic acid production as a unique carbon‐containing product. The heterogenization of the rhodium catalysts enables recycling for a total productivity of up to 8.3 g of formic acid per gram of catalyst after 7 reuses using visible light as the sole energy source.

Objective: To determine whether a postdischarge video visit with patients, conducted by hospital medicine advanced practice providers, improves adherence to hospital discharge recommendations. Patients and Methods: We conducted a single-institution 2-site randomized clinical trial with 1:1 assignment to intervention vs control, with enrollment from August 10, 2020, to June 23, 2022. Hospital medicine patients discharged home or to an assisted living facility were randomized to a video visit 2-5 days postdischarge in addition to usual care (intervention) vs usual care (control). During the video visit, advanced practice providers reviewed discharge recommendations. Both intervention and control groups received telephone follow-up 3-6 days postdischarge to ascertain the primary outcome of adherence to all discharge recommendations for new and chronic medication management, self-management and action plan, and home support. Results: Among 1190 participants (594 intervention; 596 control), the primary outcome was ascertained in 768 participants (314 intervention; 454 control). In intervention vs control, there was no difference in the proportion of participants with the primary outcome (76.7% vs 72.5%; P=.19) or in the individual domains of the primary outcome: new and chronic medication management (94.1% vs 92.8%; P=.50), self-management and action plan (76.5% vs 71.5%; P=.18), and home support (94.1% vs 94.3%; P=.94). Women receiving intervention vs control had higher adherence to recommendations (odds ratio, 1.77; 95% CI, 1.08-2.91). Conclusion: In hospital medicine patients, a postdischarge video visit did not improve adherence to discharge recommendations. Potential gender differences in adherence require further investigation.Clinicaltrials.gov number, NCT04547803.

Abstract Activated macrophages play a critical role in the orchestration of inflammation and inflammatory pain in several chronic diseases. We present here the first perfluorocarbon nanoemulsion (PFC NE) that is designed to preferentially target activated macrophages and can deliver up to three payloads (two fluorescent dyes and a COX-2 inhibitor). Folate receptors are overexpressed on activated macrophages. Therefore, we introduced a folate-PEG-cholesterol conjugate into the formulation. The incorporation of folate conjugate did not require changes in processing parameters and did not change the droplet size or fluorescent properties of the PFC NE. The uptake of folate-conjugated PFC NE was higher in activated macrophages than in resting macrophages. Flow cytometry showed that the uptake of folate-conjugated PFC NE occurred by both phagocytosis and receptor-mediated endocytosis. Furthermore, folate-conjugated PFC NE inhibited the release of proinflammatory cytokines (TNF-α and IL-6) more effectively than nonmodified PFC NE, while drug loading and COX-2 inhibition were comparable. The PFC NEs reported here were successfully produced on multiple scales, from 25 to 200 mL, and by using two distinct processors (microfluidizers: M110S and LM20). Therefore, folate-conjugated PFC NEs are viable anti-inflammatory theranostic nanosystems for macrophage drug delivery and imaging.

Abstract Sleep restriction is associated with increased cardiovascular risk, which is more pronounced in female than male persons. We reported recently first causal evidence that mild, prolonged sleep restriction mimicking “real-life” conditions impairs endothelial function, a key step in the development and progression of cardiovascular disease, in healthy female persons. However, the underlying mechanisms are unclear. In model organisms, sleep restriction increases oxidative stress and upregulates antioxidant response via induction of the antioxidant regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Here, we assessed directly endothelial cell oxidative stress and antioxidant responses in healthy female persons (n = 35) after 6 weeks of mild sleep restriction (1.5 h less than habitual sleep) using randomized crossover design. Sleep restriction markedly increased endothelial oxidative stress without upregulating antioxidant response. Using RNA-seq and a predicted protein–protein interaction database, we identified reduced expression of endothelial Defective in Cullin Neddylation-1 Domain Containing 3 (DCUN1D3), a protein that licenses Nrf2 antioxidant responses, as a mediator of impaired endothelial antioxidant response in sleep restriction. Thus, sleep restriction impairs clearance of endothelial oxidative stress that over time increases cardiovascular risk. Trial Registration: NCT02835261

Abstract The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. The transcription changes triggered by DDR depend on the nature of DNA damage, activation of checkpoint kinases, and the stage of cell cycle. The transcription changes can be localized and affect only damaged DNA, but they can be also global and affect genes that are not damaged. While the purpose of localized transcription inhibition is to avoid transcription of damaged genes and make DNA accessible for repair, the purpose and mechanisms of global transcription inhibition of undamaged genes are less well understood. We show here that a brief cell treatment with hydroxyurea (HU) globally inhibits RNA synthesis and transcription by RNA polymerase I, II, and III (RNAPI, RNAPII, and RNAPIII). HU reduces efficiency of transcription termination and inhibits pre-mRNA cleavage at the polyadenylation (pA) sites, destabilizes mRNAs, and shortens poly(A) tails of mRNAs, indicating defects in pre-mRNA 3′ end processing. Inactivation of the checkpoint kinase Mec1p downregulates the efficiency of transcription termination and reduces the efficiency of pre-mRNAs clevage at the pA sites, suggesting the involvement of DNA damage checkpoint in transcription termination and pre-mRNA 3′ end processing.

Abstract While there have been numerous sequential algorithms developed to estimate community structure in networks, there is little available guidance and study of what significance level or stopping parameter to use in these sequential testing procedures. Most algorithms rely on prespecifiying the number of communities or use an arbitrary stopping rule. We provide a principled approach to selecting a nominal significance level for sequential community detection procedures by controlling the tolerance ratio, defined as the ratio of underfitting and overfitting probability of estimating the number of clusters in fitting a network. We introduce an algorithm for specifying this significance level from a user-specified tolerance ratio, and demonstrate its utility with a sequential modularity maximization approach in a stochastic block model framework. We evaluate the performance of the proposed algorithm through extensive simulations and demonstrate its utility in controlling the tolerance ratio in single-cell RNA sequencing clustering by cell type and by clustering a congressional voting network.

Abstract Water quality can be affected due to organic or inorganic salts present in water depending upon different regions. An increase in salts has deteriorated the quality of the water, harming both human health and aquatic life. Various technologies are developed to extract salts, bioadsorption being the most preferred, eco-friendly, and economical method for desalination. To remove salts from aqueous solutions, an array of adsorbents, including natural, low-cost materials, or wastes, called bioadsorbents are studied. The review aims at studying different bioadsorbents used for reducing salinity and the effect of pH, contact time, bioadsorbent dosage, initial concentration, temperature, and size of particulate matter on the removal efficacy of salts from saline water. The pseudo-second-order kinetics and Freundlich isotherm are the governing models that described salinity ions equilibrium and isotherm data. Prospects of the study including the potential for commercialization, scaling up, extensive applications of adsorbents, and their functional utility are discussed.

Secretory Carcinoma (SC) or Mammary Analogue Secretory Carcinoma (MASC) is a recently described tumour of the salivary gland that shares morphological and genetic characteristics with secretory carcinoma of the breast. Due to their complex and heterogeneous presentations, majority of these tumors were previously histologically diagnosed as acinic cell carcinoma or mucoepidermoid carcinoma. Here, we present a case of secretory carcinoma of the parotid gland in a 29-year-old female and discuss the cytological, histological and immunohistochemical characteristics that can be used to diagnose the condition and distinguish it from its histologic mimics.

Abstract Metachromatic leukodystrophy (MLD) due to Sap‐B deficiency is a rare autosomal recessive disorder caused due to biallelic variants in the PSAP gene. The PSAP gene encodes a precursor protein prosaposin, which is subsequently cleaved to form four active glycoproteins: Sap‐A, Sap‐B, Sap‐C, and Sap‐D. In case of deficiency of the sphingolipid activator protein Sap‐B, there is a gradual accumulation of cerebroside‐3‐sulfate in the myelin of the nervous system resulting in progressive demyelination. Only 12 variants have been reported in the PSAP gene causing Sap‐B deficiency to date. Here, we report two cases of MLD due to Sap‐B deficiency (late‐infantile and adult‐onset form) harboring two novel missense variants c.688T > G and c.593G > A in the PSAP gene respectively. This study reports the third case of adult‐onset MLD due to Sap‐B deficiency in the world. The proband, a 3‐year‐old male child presented with complaints of hypotonia, lower limb tremors and global developmental delay. His MRI showed hyperintense signals in the bilateral cerebellar white matter. Overall, the findings were suggestive of metachromatic leukodystrophy. The second case was a 19‐year‐old male child with clinical features of regression of speech, gait ataxia and bilateral tremors referred to our clinic. MRI data suggested metachromatic leukodystrophy. Normal enzyme activity of arylsulfatase‐A led to a suspicion of saposin B deficiency. For both cases, targeted sequencing was performed. This identified homozygous variant c.688T > G (p.Cys230Gly) and c.593G > A (p.Cys198Tyr) in exon 6 of the PSAP gene, respectively.

Background: Oral anticoagulants (OACs), such as apixaban and warfarin, are indicated for reducing the risk of recurrent venous thromboembolism (VTE) and are often initiated in the hospital. The aim of this study was to evaluate OAC continuity from inpatient to outpatient settings and the risk of recurrent VTE among patients with an initial event. Methods: This retrospective cohort study utilized hospital charge data and medical and prescription claims from 1 July 2016 to 31 December 2022 to identify adults treated with apixaban or warfarin while hospitalized for VTE. Patients were followed to assess switching or discontinuation post-discharge and the risk of recurrent VTE. The index date was the date of the first apixaban or warfarin claim within 30 days post-discharge. Results: Of the 19,303 eligible patients hospitalized with VTE, 85% (n = 16,401) were treated with apixaban and 15% (n = 2902) received warfarin. After discharge, approximately 70% had ≥1 fill for their respective apixaban or warfarin therapy. The cumulative incidence of discontinuation over the 6 months following index was 50.5% and 52.2% for the apixaban and warfarin cohorts, respectively; the cumulative incidence of switching was 6.0% and 20.9%, respectively. The incidence rates of recurrent VTE were 1.2 and 2.5 per 100 person-years for the apixaban and warfarin cohorts, respectively. Conclusions: The majority of patients continued their apixaban or warfarin therapy following hospital discharge; however, a considerable proportion either switched or discontinued OAC upon transitioning from inpatient care. Among those who continued therapy, discontinuation, switch, and recurrent VTE occurred less often with apixaban vs. warfarin.

In this paper, we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the free energy principle, we can emphasize the role of fostering resource renewal, harmonious system–entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability both as an agent and as a part of a collective. We start by connecting active inference with well-being, building on existing work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

The cultural context of an organisation may significantly shape the nature of transgressions and consequent forgiveness relevant to understanding the workplace outcomes. This study explored the nature of transgressions and the dynamics of forgiveness in the workplace of a heterogeneous Indian sample which have not been well addressed in previous studies. Qualitative research design was employed. Using a purposive sampling method, 48 participants from the government (n = 30) and private organisations (n = 18) were selected to form the final sample. The transcriptions from semi-structured interviews were analyzed by the Thematic Analysis Method. Two themes related to the nature of transgressions emerged: multiplicity of the sources of workplace transgressions (such as anger, discrimination, and work overload) and communications of workplace transgressions (e.g., through criticism, altered relationships, warnings). Concerning the dynamics of forgiveness in the workplace, three broad themes emerged: facilitators of workplace forgiveness (such as positive treatment, direct communication, scolding), barriers to workplace forgiveness (like, the intention behind wrongdoing, repetition of wrongdoing, decreased trust), and benefits of workplace forgiveness (such as positive emotions, good relations, healthy work environment). Management should develop an in-depth understanding of the nature of transgressions and the dynamics of forgiveness embedded in a specific cultural context which may help enhance a variety of positive organisational outcomes. Workplace transgressions and concomitant forgiveness are interwoven with the nature of organisations, individual level factors and socio-cultural contexts. Findings also provide some support that the coexistence of individualistic and collectivistic cultural values among Indians may have shaped workplace transgressions and consequent forgiveness.

Abstract Two-dimensional (2D) materials have attracted attention for quantum information science due to their ability to host single-photon emitters (SPEs). Although the properties of atomically thin materials are highly sensitive to surface modification, chemical functionalization remains unexplored in the design and control of 2D material SPEs. Here, we report a chemomechanical approach to modify SPEs in monolayer WSe2 through the synergistic combination of localized mechanical strain and noncovalent surface functionalization with aryl diazonium chemistry. Following the deposition of an aryl oligomer adlayer, the spectrally complex defect-related emission of strained monolayer WSe2 is simplified into spectrally isolated SPEs with high single-photon purity. Density functional theory calculations reveal energetic alignment between WSe2 defect states and adsorbed aryl oligomer energy levels, thus providing insight into the observed chemomechanically modified quantum emission. By revealing conditions under which chemical functionalization tunes SPEs, this work broadens the parameter space for controlling quantum emission in 2D materials.

Background: Hepatitis B virus (HBV), hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) infections are prevalent throughout the world. HIV infection increases the risk of HBV and HCV liver disease especially when HIV-associated immunodeficiency progresses. Aims and Objectives: This study was carried out with the objectives as follows: Estimation of the prevalence of HIV- Hepatitis co-infection, determine CD4+T lymphocyte count in co-infected patients, identify most common opportunistic infections in HIV – Hepatitis co- infection. Materials and Methods: A hospital-based, prospective, cross-sectional, and observational study was carried among people with confirmed HIV infection. HIV antibody, hepatitis B surface antigen (HBsAg), and HCV antibody tests were done in all patients visiting to integrated counseling and testing center. HIV, HBV, and HCV viral load were done in all serologically confirmed patients. In HBsAg positive patients various markers for hepatitis such as hepatitis B envelop antigen (HBeAg), anti-hepatitis B core antibody (HBcAb), and anti-hepatitis B envelop antibody were also done. Results: Out of 357 people living with HIV/AIDS (PLHA) patients 15/357 (4.20%) were co-infected with HBV, 03/357 (0.84%) were co-infected with HCV. The overall seroprevalence of Hepatitis virus (HBV+HCV) in PLHA patients was found to be 5.04% (18/357). CD4+T lymphocyte count 2000 IU/mL. All hepatitis B co-infected patients were positive for HBcAb test; HBeAg was positive in 40% (n=06). All HBeAg positive were having viral load >2000 IU/mL. Conclusion: HIV-infected patients are more prone to hepatitis associated liver diseases and exposure to the HBV infection than the general population.

Category: Trauma; Hindfoot Introduction/Purpose: Malunion is a disabling complication of talar neck fractures and is prevalent in approximately 17% of cases. The impact of talar neck malunions (TNM) on foot biomechanics and functional outcomes is not well established. The available evidence is primarily derived from cadaveric studies which have demonstrated that TNMs result in reduced motion and significant alterations in contact characteristics of the subtalar joint. Owing to the paucity of literature on this subject, we conducted this study to evaluate the kinematic and pedobarographic changes and functional outcomes associated with TNMs. Methods: In this study, adult patients with talar neck malunions (TNM) without ankle arthrosis were prospectively enrolled over a 5-year period. The Rammelt and Zwipp classification was utilized to categorize the deformities. Demographic data and ankle and subtalar range of motion were assessed. Weight-bearing anteroposterior (AP), lateral, and long axial radiographs, as well as CT scans of both feet, were obtained. Dynamic pedobarography was performed to evaluate gait kinematics and plantar pressure distribution. Functional outcomes were evaluated using the Manchester Oxford Foot Questionnaire (MOxFQ), Visual Analog Score, and the EQ5D questionnaire. The t-test was utilized to compare the range of motion, pedobarographic and kinematic parameters between the normal and pathologic foot. Furthermore, correlation coefficients were calculated to determine the strength of the association between changes in talar neck geometry, plantar pressures, kinematics, and functional outcomes. Results: A total of 10 patients, 6 males, and 4 females, with a mean age of 32.4 years were enrolled. On the TNM side, significant increases were observed in step length and step time, while significant decreases were noted in the single limb support time and single limb support center of pressure line. Moreover, midfoot forces were significantly increased, whereas the forefoot and hindfoot forces were significantly decreased on the TNM side. A strong positive correlation was found between midfoot force and the talar torsion angle, and a moderate negative correlation was observed between hindfoot and midfoot forces and the inclination angle. A strong positive correlation was also noted between high midfoot pressures and VAS Scores, MOxFQ scores, and the EQ5D walking and usual activities domains. Conclusion: This study demonstrates that TNMs are associated with decreased single limb support time, increased step length and time, increased midfoot pressures, and decreased forefoot and hindfoot pressures. Additionally, an increase in talar neck torsion after TNM is linked with higher midfoot pressures, which can lead to higher levels of pain and poorer function. Our findings provide valuable insights into the altered foot biomechanics after TNMs, which can assist surgeons in offering optimal management strategies for these patients.

In situ cryo-electron tomography (cryo-ET) is the most current, state-of-the-art technique to study cell machinery in its hydrated near-native state. The method provides ultrastructural details at sub-nanometer resolution for many components within the cellular context. Making use of recent advances in sample preparation techniques and combining this method with correlative light and electron microscopy (CLEM) approaches have enabled targeted molecular visualization. Nevertheless, the implementation has also added to the complexity of the workflow and introduced new obstacles in the way of streamlining and achieving high throughput, sample yield, and sample quality. Here, we report a detailed protocol by combining multiple newly available technologies to establish an integrated, high-throughput, optimized, and streamlined cryo-CLEM workflow for improved sample yield.Key features• PRIMO micropatterning allows precise cell positioning and maximum number of cell targets amenable to thinning with cryo focused-ion-beam–scanning electron microscopy.• CERES ice shield ensures that the lamellae remain free of ice contamination during the batch milling process.• METEOR in-chamber fluorescence microscope facilitates the targeted cryo focused-ion-beam (cryo FIB) milling of these targets.• Combining the three technologies into one cryo-CLEM workflow maximizes sample yield, throughput, and efficiency.Graphical overview

The oyster mushroom (Pleurotus ostreatus) was cultivated on diverse substrates, encompassing wheat straw (T1), paddy straw (T2), groundnut leaves and straw (T3), sugarcane bagasses (T4), cotton stalk (T5), coconut husk (T6), pigeon pea straw (T7), and banana pseudostem (T8). The study comprised of the estimation of proximate composition, antioxidants, and mineral content of the sun-dried mushrooms during the initial two harvests. The average values of nutritional parameters were as follows: moisture (90.93 to 85.18 %), ash (7.62 to 4.86%), carbohydrates (37.57 to 20.10%), crude protein (45.45 to 23.10%), crude fiber (29.08 to 19.29%), crude fat (2.68 to 1.63%), total phenol (14.23 to 9.12 mg/g) and ascorbic acid (11.58 to 8.72 mg/100g). The average mineral content exhibited the trend K>P>Mg>Ca>Zn>Fe>Cu. Upon consideration of average values from both harvests, the groundnut leaves and straw had the highest crude protein (45.45 %), total phenol (14.23 mg/g), ascorbic acid (11.58 mg/100g), phosphorous (0.43 %), iron (7.12 mg/100g) and zinc (12.43 mg/100g). The paddy straw resulted in the highest crude fiber (29.08 %) and crude fat (2.68 %), while the wheat straw resulted in the highest potassium (1.52 %) and calcium (179.65 mg/100g). The various substrates had an impact on nutritional parameters as seen by either an increase or decrease in various parameters which can be reflected in turn by the composition of the substrates itself. In conclusion, groundnut leaves and straw (T3) along with paddy straw (T2) and wheat straw (T1) resulted in significant improvement of nutritional composition compared to other treatments. This study underscores the environmentally friendly utilization of nutrients from agricultural waste for mushroom production.

Category: Midfoot/Forefoot; Other Introduction/Purpose: Plantar fibromatosis (PF) is a rare disease affecting the plantar aponeurosis, characterized by disordered fibrous tissue and subsequent formation of subcutaneous nodules on the foot/feet. There are no established clinical guidelines for management of PF symptoms, and real-world evidence on treatment patterns among PF patients in the United States (US) is scarce. This retrospective observational study used a comprehensive approach to identify newly diagnosed PF patients and describe subsequent conservative (non-surgical) and surgical treatment patterns. Methods: Patients with evidence of PF from ICD-9/10 diagnosis codes in IQVIA’s PharMetrics ® Plus were identified between January 2015-March 2020 and linked to IQVIA’s Ambulatory Electronic Medical Records (AEMR) to confirm diagnosis, using PF- specific SNOMED diagnosis codes or problem name; the earliest evidence of PF was the diagnosis date. Further, eligible patients were required to have continuous enrollment (CE) in a health plan for 12 months before diagnosis (baseline), 24 months of CE after diagnosis (follow-up), evidence of PF ≥30 days after first diagnosis, and age ≥18 years on diagnosis date. Patients with prior diagnosis of PF (through 2014) or other select lower limb conditions during baseline were excluded. Baseline demographic/clinical characteristics and conservative treatment utilization prior to PF diagnosis were assessed. Proportion of patients receiving PF- related conservative and surgical treatment, frequency of use, and time from diagnosis to initiation of first treatment were reported during follow-up. Results: The incident PF cohort (N=620) had mean (SD) age of 52.2(9.9) years and 63.2% were women. Most common baseline comorbidities were thyroid diseases (14.2%), diabetes without complications (12.3%), and smoking (12.3%); 19.0% had evidence of foot or ankle pain/stiffness. During baseline, 53.5% of patients received prescribed analgesic medications (30.6% received opioids). Most patients (91.1%) received conservative treatment after PF diagnosis, including analgesics and physical/occupational therapy (Figure 1A). Among all treatment modalities, time to initiation (months) was shortest for orthotics (median:0.5; IQR:5.5), injectable corticosteroids (median:2.0; IQR:9.2) and prescribed NSAID (median:2.5; IQR:9.1; Figure 1B). Among 42 patients (6.8%) receiving PF-related surgery, conservative treatments were common both before surgery (83.3%; median time from diagnosis to surgery:6.0 months) and after surgery (92.9%). Conclusion: Most newly diagnosed PF patients received conservative treatments within the first 3 months after diagnosis. Analgesic use was high during baseline as well as follow-up. During the 24 months after diagnosis, few patients received surgery and conservative treatment modalities often continued after surgery. Overall, continued and widespread conservative management among PF patients indicates lack of treatment options for PF. Further studies on treatment patterns in US patients aged ≥65 years are needed.

This study explored the value of Adaptive Learning Technologies (ALTs) in K-12 education by examining the advantages and challenges these tools create for teaching and learning from the perspectives of stakeholders involved in the use (Teachers), implementation (Teacher Support professionals), and development (EdTech professionals) of ALTs. We conducted qualitative thematic analysis on 25 stakeholder interviews using the Teacher Response Model as a guide for examining stakeholders’ perceptions of the advantages and challenges of ALTs. Analysis resulted in three overarching concepts (i.e., learning management, student agency and engagement, and implementation challenges), under which themes regarding stakeholder perspectives on the advantages and challenges of ALTs could be organized and contrasted with one another. Learning management themes suggest that stakeholders perceive features such as real-time student data and tailored learning content as creating value for teachers by supporting efficiency in their learning management, however that value is impacted by stakeholders’ concerns with ALT grading and data collection processes. Student agency and engagement themes highlight how certain user interaction features can create value or challenges for learners depending on whether the features were designed with students’ developmental and competence needs in mind. Finally, the implementation challenges themes suggest that for ALTs to create value in K-12 settings, stakeholders need better alignment around their ALT implementation goals and expectations. We leverage these data to make recommendations for future research and development so stakeholders can maximize the affordances of ALTs for K-12 students and teachers.

Synchronous Tumours (ST) are defined as two or more neoplasms originating within six months of diagnosing the first neoplasm. Due to the rarity of synchronous cervical Squamous Cell Carcinoma (SCC) and ovarian Brenner tumours, their pathology has been poorly understood. These patients usually present with symptoms related to cervical cancer and are often diagnosed early. Since many synchronous tumours are incidentally discovered postoperatively, it is important to conduct thorough grossing and histopathological examinations. The primary differential diagnosis for synchronous tumours is multiple metastases from a single primary tumour. The management of multiple tumours is not well-defined and depends on various factors. In the present case, authors present a rare occurrence of synchronous neoplasms: cervical SCC and preoperatively undiagnosed benign Brenner tumour of the left ovary in a 52-year-old postmenopausal female. Immunohistochemistry helped rule out metastasis from a single primary and metastasis from cervical cancer to the ovary. The ovarian tumour showed immunoreactivity for GATA Binding Protein 3 (GATA) but was negative for Carcinoembryonic Antigen (CEA). The cervical SCC was immunopositive for CEA and p40, while no immunoreactivity was observed with GATA 3.

Phaeohyphomycosis is an infection due to dematiaceous fungi which usually involve the skin and subcutaneous tissue. Phaeohyphomycosis in subcutaneous location has presentation in the form of nodules, papules ulcerated plaques, verruca-like hyperkeratotic plaques, cystic lesions, abscess formation, pyo-granuloma, discharging sinuses, non-healing ulcers. Brown-walled hyphae in the epidermis and dermis are its hallmark. Aspergillosis is ubiquitous, invasive fungal infection in diabetics and immunocompromised hosts. Here, we are reporting a mixed fungal infection of right maxillary sinus in a newly diagnosed case of diabetes mellitus.

Diabetic nephropathy (DN) is characterized by an increase in urinary albumin excretion, diabetic glomerular lesions, and a decline in glomerular filtration rate (GFR). We assessed the expression of phosphatase and tensin homolog (PTEN), nuclear factor kappa-β (NF-κB), matrix metalloproteinase-2 (MMP2), and microRNA-181 in healthy controls (HC), individuals with type 2 diabetes mellitus (T2DM) without nephropathy, and those with DN. Our study investigated the association between these genes, insulin resistance (IR), and eGFR to gain insight into their roles in the pathogenesis and progression of DN. Anthropometric measurements and biochemical tests were conducted on HC (N = 36), T2DM (N = 38) patients, and DN (N = 35) patients. We used real-time polymerase chain reaction (RT-PCR) for whole blood gene expression analysis and performed bioinformatics analyses, including protein–protein interaction, gene ontology, and co-expression networks. We compared our expression data with other GEO-Microarray datasets. Our study highlights the role of IR in the progression of nephropathy in T2DM via the PTEN-Akt-mTOR signalling pathway. We also observed a decreasing trend in the expression of MMP2 and PTEN and an increasing trend in the expression of NF-κB and miR-181b-5p with the progression of nephropathy to the severe stage. The dysregulated expression of MMP2, PTEN, NF-κB, and miR-181b-5p in patients with T2DM contributes to the progression of T2DM to DN by aggravating IR, inflammation, accelerating basement membrane thickening, mesangial matrix expansion, and renal fibrosis.

Background and Aims: The 25°back-up position is proposed to increase the efficacy of preoxygenation and provide better tracheal intubating conditions when using a direct laryngoscope. This study aimed to compare the ease of tracheal intubation between supine and 25° back-up positions when using two video laryngoscopes (VLS). Methods: One hundred adults with normal airways and belonging to the American Society of Anesthesiologists physical status classes I and II, requiring general anaesthesia, were randomised in groups K and M. The trachea was intubated using King Vision and McGrath VLS in either supine (groups K1 and M1) or 25° back-up (groups K2 and M2) positions. The 25° backup position was given by raising the operating table from the horizontal position by flexing the torso at the hips so that an imaginary line connected the patient's external auditory meatus to the sternal notch. Modified Intubation Difficulty Scale (mIDS) was the primary outcome, and intubation time, the number of intubation attempts, vital parameters, and complications were compared secondarily. Statistical analysis was done using MedCalc software by applying an independent t-test for parametric data and a Chi-square test for categorical data and finding the risk ratio. Result: Mean (Standard deviation) mIDS was significantly reduced using both VLS in the 25° back-up position [0.92 (0.75) versus 0.48 (0.58), P = 0.025, degree of freedom (DF): 48, mean difference (95% confidence interval [CI]):−0.44 (−0.821 to − 0.059) in group K1 versus group K2 and 0.76 (0.59) versus 0.36 (0.48), P = 0.012, DF: 48, mean difference (95% CI): −0.40(−0.706 to − 0.094) in group M1 versus group M2, respectively]. The risk ratio comparing both the positions for the total number of patients requiring manoeuvres during intubation using both the VLS was 0.48 with P = 0.0004 and 95% CI = 0.305 − 0.765. Intubation time was shorter in the 25° backup position by using King Vision (P = 0.005) and McGrath (P = 0.042) VLS. Conclusion: The 25° backup position helps provide ease of intubation using both the channelled (King Vision) and non-channelled (McGrath) VLS.

Paratesticular embryonal rhabdomyosarcoma (RMS) is a very rare and aggressive mesenchymal tumor. It is usually seen in children and adolescents presenting as a painless intrascrotal mass, localized in the paratesticular region. Hereby, we report two cases of paratesticular embryonal RMS in adults. One case was clinically suspected to be a testicular abscess, whereas the other presented with testicular swelling and lung metastasis. Localized forms have a good prognosis, whereas tumors presenting with metastases show a poor outcome. A treatment based on surgery and chemotherapy yields good results. Sperm cryopreservation and endocrine follow-up improve the overall survival and quality of life of these patients.

Background: Pre-conception care (PCC) is a set of interventions that aim to identify and modify biomedical, behavioural and social risks to women's health and pregnancy outcomes. Materials and Methods: It was an observational descriptive cross-sectional study conducted in the obstetrics and gynaecology (OBGY) outpatient department (OPD) of a tertiary care teaching institute in a rural set-up. Two hundred women in the first trimester of pregnancy were interviewed using a pre-designed and pretested questionnaire following informed verbal consent. The study was conducted between May and September 2019. The study excluded women in the 2nd or 3rd trimester of pregnancy, inpatient department (IPD) patients and those unwilling to participate. Results: The study revealed that 25.5% of the women had conceived between 14 and 19 years of age. Fifty-four percent of the pregnancies were unplanned. Merely 14.5% had consulted and 15% had their laboratory investigations performed before pregnancy. Only 11% had received pre-conception folic acid supplementation. Pregnancies with birth spacing

Context: Human growth shows considerable variation. In addition to constitutional differences in the timing of maturation, there are diseases, systemic disorders and environmental factors that may affect a child's physiologic maturity. Interrelationships among skeletal, somatic and sexual maturity have been shown to be consistently strong. The study was conducted to evaluate the relationship between dental calcification stages and skeletal maturity indicators. Materials and Methods: The hand wrist radiographs, the lateral cephalogram and the orthopantomogram (OPG) of 120 patients (60 males and 60 females, age group 8–14 years) were taken. The hand wrist radiographs were analyzed using Fishman's skeletal maturity index (SMI), and the cephalograms analyzed by cervical vertebrae maturation (CVM) by Baccetti. OPG was analyzed according to the Demirjian's system. Result: On assessment, cervical vertebrae maturation indicator (CVMI) staging showed significant results with a correlation coefficient of 0.716 being the highest in canines in males while assessment of dental calcification stages and its comparison with skeletal maturity indicator showed insignificant results. The correlation coefficient values were 0.11, 0.09, 0.09 and 0.13 for canine, first premolar, second premolar and second molar respectively. Conclusion: There is a strong correlation between the maturation stage of cervical vertebrae and calcification stages of canine, first premolar, second premolar and second molar as determined by Demirjian's method.

Background: Restoration of caries having multisurface involvement in primary teeth is a challenge to dentists. The success of the restoration often depends on its longevity. Hence, it is important to systematically review the longevity of stainless steel crowns (SSCs) on primary molars. Objectives: To determine the longevity of SSC and to determine the reasons of failure for the same. Data Sources: A systematic search was conducted in three databases: PubMed, Embase, and Google Scholar for the studies published from January 1, 2009 to September 25, 2019. Cross references of the selected articles were also searched and hand searching was done for the studies whose full texts were not available through the electronic search. Gray literature was also searched for the studies according to the relevance of this review. Study Eligibility: Studies were included if they were published between January 1, 2009 and September 25, 2019, which included comparative assessment of SSCs and other multisurface restorations in primary teeth. The study setting should be clinical based. The study designs included in the review were prospective, retrospective, and randomized control clinical trials. Studies written in the English language and studies written in any other language but are possible to get translated into English were included. Reviews, letters to the editor, and short communications were not included in the review. Studies conducted in permanent dentition were not included. For meta-analysis, randomized control trials and retrospective studies were included. Results: 1398 records were identified through data search using search strategy in PubMed, Google Scholar, and through Gray literature. After further exclusion, the total number of articles came out to be 41. Finally, six articles were included in the systematic review. These articles were also subjected to meta-analysis. The pooled success rate for SSC over 12 months was shown to be 96.096%. This was seen to be significantly higher. Conclusion: SSCs showed good longevity than the other restorative materials on primary molars.

Background: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has emerged as one of the biggest health threats of our generation. Since its outbreak, COVID-19 has been showing many typical and some atypical manifestations. One of the common complications in COVID-19 is delirium. Delirium should be detected at the earliest to reduce mortality in COVID-19. Methods: We prospectively studied hospitalized adult (age ≥ 18 years) patients with confirmed COVID-19 from May 1 to May 31, 2021, at GMERS Medical College and Civil Hospital, Sola, Ahmedabad, India. We included all patients suffering from COVID-19 and diagnosed with delirium in the study. Delirium was assessed using the Confusion Assessment Method and Richmond Agitation Sedation Scale. Follow-up was done for delirium patients on days 0, 5, 10, and 30. Results: We included 1,233 patients in the analysis. The incidence of delirium was found 2.43% in which 63.3% were hypoactive delirium while 36.7% were hypoactive delirium presentation. The mean age ± standard deviation of delirium patients was 68.33 ± 14.67 years (range = 46-92) years, and 20 (66.7%) were male and 10 (33.3%) were female. The result of the study also showed statistical significance between deaths in patients of confirmed cases of COVID-19 with delirium (93.33%) than patients of confirmed cases of COVID-19 without delirium (12.38%, p < 0.001). Conclusion: The presence of delirium was associated with increased risk of mortality in hospitalized adults with COVID-19.