Thoracolumbar fracture-dislocation in a two-year-old female child following child abuse: A case report and literature review.

Child abuse is a matter of serious concern that can often result in devastating injuries. Incidence of spinal injuries from child abuse has been reported in <1-3 % of spinal injury cases. In the present study, a case of thoracolumbar translational injury (AO type C) is presented following an incidence of child abuse in a 2-year-old female. After successful management with operative fixation, the child showed a remarkable recovery in her neurological function with ambulatory power.

Treatment of Failed Proximal Femoral Nail Anti-rotation Asia (PFNA2) in a Severely Osteoporotic Patient With a Revision Stem.

An intertrochanteric fracture is a prevalent and perilous kind of fracture that often affects older persons. A customized implant, proximal femoral nail anti-rotation Asia (PFNA2) is being used expressly in unstable intertrochanteric fractures in people with osteoporosis. In this case report, we examined a female osteoporosis patient, age 74, who underwent a failed PFNA2 procedure. Subsequently, the patient had bipolar hemiarthroplasty as a treatment. To prevent mechanical failure, it is crucial to strive for a high level of reduction quality and precise alignment of the central blade throughout hip X-ray procedures. Improved surgical proficiency and skill are crucial for managing patients with severe osteoporosis and prolonged weight-bearing requirements, hence reducing the occurrence of postoperative problems. Depending on the cause of the failure and the individual circumstances of the patient when internal fixation fails, it is recommended to either replace the joint with a prosthetic or reapply fixation. These interventions may facilitate the production of beneficial healing outcomes.

Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

Design, optimization, and evaluation of topical gel of Cardiospermum halicacabum and Ricinus communis L. leaves extract for the treatment of rheumatoid arthritis.

This research aims to develop and assess the anti-arthritic properties of a topically herbal gel including leaf extracts from Cardiospermum halicacabum and Ricinus communis L. in rats. Utilizing gelling agents carbopol 940 (2.5, 5, 7.5 g), nine herbal gel compositions were created. Prepared formulations were then assessed for physical appearance, spreadability, viscosity, net content, pH, extrudability, in vitro diffusion profile, and main skin irritant tests. According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations, the stability research for the topical herbal gel composition was completed, and Freund's Complete Adjuvant (FCA) induced arthritis technique was used to assess the anti-arthritic efficacy. Additional procedures included measuring the body weight, paw volume, biochemical and hematological variables, histological analysis, and in vitro serum biomarker detection. The prepared gels followed the instructions and were uniform and stable. F5 performed better than the other compositions in terms of release kinetics (97.20%). The gel proved safe and non-toxic since no erythema or edema was seen during the skin irritation test. Comparing the herbal gel F5 comprising carbopol 940 to rats with arthritis, the topical treatment showed considerable (p < .001) anti-arthritic effect. The anti-arthritic action of the gel formulations was confirmed by decreased paw volume, absence of agglutination in reacting protein and rheumatic factor, a decline in TNFα level, restoration to baseline biochemical and hematological characteristics, decrease in thymus and spleen weight, and histopathological study.

CryoEM structures reveal how the bacterial flagellum rotates and switches direction.

Bacterial chemotaxis requires bidirectional flagellar rotation at different rates. Rotation is driven by a flagellar motor, which is a supercomplex containing multiple rings. Architectural uncertainty regarding the cytoplasmic C-ring, or 'switch', limits our understanding of how the motor transmits torque and direction to the flagellar rod. Here we report cryogenic electron microscopy structures for Salmonella enterica serovar typhimurium inner membrane MS-ring and C-ring in a counterclockwise pose (4.0 Å) and isolated C-ring in a clockwise pose alone (4.6 Å) and bound to a regulator (5.9 Å). Conformational differences between rotational poses include a 180° shift in FliF/FliG domains that rotates the outward-facing MotA/B binding site to inward facing. The regulator has specificity for the clockwise pose by bridging elements unique to this conformation. We used these structures to propose how the switch reverses rotation and transmits torque to the flagellum, which advances the understanding of bacterial chemotaxis and bidirectional motor rotation.

Emerging drugs for the treatment of herpetic keratitis.

INTRODUCTION: Herpes simplex keratitis stands as a prominent factor contributing to infectious blindness among developed nations. On a global scale, over 60% of the population tests positive for herpes simplex virus type-1 (HSV-1). Despite these statistics, there is currently no vaccine available for the virus. Moreover, the conventional nucleoside drugs prescribed to patients are proving ineffective in addressing issues related to drug resistance, recurrence, latency, and the escalating risk of vision loss. Hence, it is imperative to continually explore all potential avenues to restrict the virus. This review article centers on the present treatment methods for HSV-1 keratitis (HSK), highlighting the ongoing clinical trials. It delves into the emerging drugs, their mode-of-action and future therapeutics. AREAS COVERED: The review focuses on the significance of a variety of small molecules targeting HSV-1 lifecycle at multiple steps. Peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and clinical trial websites. EXPERT OPINION: The exploration of small molecules that target specific pathways within the herpes lifecycle holds the potential for substantial impact on the antiviral pharmaceutical market. Simultaneously, the pursuit of disease-specific biomarkers has the capacity to usher in a transformative era in diagnostics within the field.

Integrated analysis of transcriptome and genome variations in pediatric T cell acute lymphoblastic leukemia: data from north Indian tertiary care center.

INTRODUCTION: T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with poor prognosis and inferior outcome. Although multiple studies have been perform on genomics of T-ALL, data from Indian sub-continent is scarce. METHODS: In the current study we aimed to identify the genetic variability of T-ALL in an Indian cohort of pediatric (age ≤ 12 years) T-ALL patients (n = 25) by whole transcriptome sequencing along with whole exome sequencing and correlated the findings with clinical characteristics and disease outcome. RESULTS: The median age was 7 years (range 3 -12 years). RNA sequencing revealed a definitive fusion event in 14 cases (56%) (including a novel fusions) with STIL::TAL1 in 4 (16%), followed by NUP21::ABL1, TCF7::SPI1, ETV6::HDAC8, LMO1::RIC3, DIAPH1::JAK2, SETD2::CCDC12 and RCBTB2::LPAR6 in 1 (4%) case each. Significant aberrant expression was noted in RAG1 (64%), RAG2 (80%), MYCN (52%), NKX3-1 (52%), NKX3-2 (32%), TLX3 (28%), LMO1 (20%) and MYB (16%) genes. WES data showed frequent mutations in NOTCH1 (35%) followed by WT1 (23%), FBXW7 (12%), KRAS (12%), PHF6 (12%) and JAK3 (12%). Nearly 88.2% of cases showed a deletion of CDKN2A/CDKN2B/MTAP genes. Clinically significant association of a better EFS and OS (p=0.01) was noted with RAG2 over-expression at a median follow up of 22 months, while a poor EFS (p=0.041) and high relapse rate (p=0.045) was observed with MYB over-expression. CONCLUSION: Overall, the present study demonstrates the frequencies of transcriptomic and genetic alterations from Indian cohort of pediatric T-ALL and is a salient addition to current genomics data sets available in T-ALL.

Exploring Heparanase Levels in Tears: Insights From Herpes Simplex Virus-1 Keratitis Patients and Animal Studies.

Purpose: Heparanase (HPSE) cleaves heparan sulfate proteoglycans during herpes simplex virus-1 (HSV-1) infection, aiding in viral egress and disease progression. Its action has been well established in in vitro and in vivo models, but its relevance in human patients remains unclear. This study aimed to specifically evaluate tear HPSE levels of patients with herpes simplex keratitis (HSK) and to correlate these findings with a commonly used murine model. Methods: Tear samples from patient and mice samples were collected at LV Prasad Eye Institute, Hyderabad, India, and at the University of Illinois, Chicago, IL, respectively. Tears were collected from HSV-1 patients, bacterial/fungal keratitis cases, and healthy individuals. For in vivo study, C57BL/6 mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Results: The HSV-1, bacterial keratitis, fungal keratitis, and healthy control groups each had 30 patients. There was a significant difference in HPSE expression in the HSV-1 infected eyes (1.55 ± 0.19 units/mL) compared to HSV-1 contralateral eyes (1.23 ± 0.13 units/mL; P = 0.82), bacterial keratitis eyes (0.87 ± 0.15 units/mL; P = 0.0078), fungal keratitis eyes (0.64 ± 0.09 units/mL; P < 0.00001), and normal controls (0.53 ± 0.06 units/mL; P < 0.00001). C57BL/6 mice tear HPSE expression in infected eyes was 0.66 to 5.57 ng heparan sulfate (HS) removed per minute when compared to non-infected eye (range, 0.70-3.67 ng HS removed per minute). Conclusions: To the best of our knowledge, this study is the first to report elevated HPSE levels in the tears of patients with different forms of HSV-1 keratitis, and it confirms similar findings in a murine model, providing a valuable basis for future in vivo and clinical research on HSV-1 ocular infection.

Sex-specific independent risk factors of urinary incontinence in acute stroke patients: A multicentre registry-based cohort study.

BACKGROUND: The presence of urinary incontinence (UI) in acute stroke patients indicates poor outcomes in men and women. However, there is a paucity and inconsistency of data on UI risk factors in this group and hence we conducted a sex-specific analysis to identify risk factors. METHODS: Data were collected prospectively (2014-2016) from the Sentinel Stroke National Audit Program for patients admitted to four UK hyperacute stroke units. Relevant risk factors for UI were determined by stepwise multivariable logistic regression, presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The mean (±SD) age of UI onset in men (73.9 year ± 13.1; n = 1593) was significantly earlier than for women (79.8 year ± 12.9; n = 1591: p < 0.001). Older age between 70 and 79 year in men (OR = 1.61: CI = 1.24-2.10) and women (OR = 1.55: CI = 1.12-2.15), or ≥80 year in men (OR = 2.19: CI = 1.71-2.81), and women (OR = 2.07: CI = 1.57-2.74)-reference: <70 year-both predicted UI. In addition, intracranial hemorrhage (reference: acute ischemic stroke) in men (OR = 1.64: CI = 1.22-2.20) and women (OR = 1.75: CI = 1.30-2.34); and prestroke disability (mRS scores ≥ 4) in men (OR = 1.90: CI = 1.02-3.5) and women (OR = 1.62: CI = 1.05-2.49) (reference: mRS scores < 4); and stroke severity at admission: NIHSS scores = 5-15 in men (OR = 1.50: CI = 1.20-1.88) and women (OR = 1.72: CI = 1.37-2.16), and NIHSS scores = 16-42 in men (OR = 4.68: CI = 3.20-6.85) and women (OR = 3.89: CI = 2.82-5.37) (reference: NIHSS scores = 0-4) were also significant. Factors not selected were: a history of congestive heart failure, hypertension, atrial fibrillation, diabetes and previous stroke. CONCLUSIONS: We have identified similar risk factors for UI after stroke in men and women including age >70 year, intracranial hemorrhage, prestroke disability and stroke severity.

Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

Impact of healthcare-associated infections within 7-days of acute stroke on health outcomes and risk of care-dependency: a multi-centre registry-based cohort study.

Healthcare-associated infections (HCAIs) in patients admitted with acute conditions remain a major challenge to healthcare services. Here, we assessed the impact of HCAIs acquired within 7-days of acute stroke on indicators of care-quality outcomes and dependency. Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme for 3309 patients (mean age = 76.2 yr, SD = 13.5) admitted to four UK hyperacute stroke units (HASU). Associations between variables were assessed by multivariable logistic regression (odds ratios, 95% confidence intervals), adjusted for age, sex, co-morbidities, pre-stroke disability, swallow screening, stroke type and severity. Within 7-days of admission, urinary tract infection (UTI) and pneumonia occurred in 7.6% and 11.3% of patients. Female (UTI only), older age, underlying hypertension, atrial fibrillation, previous stroke, pre-stroke disability, intracranial haemorrhage, severe stroke, and delay in swallow screening (pneumonia only) were independent risk factors of UTI and pneumonia. Compared to patients without UTI or pneumonia, those with either or both of these HCAIs were more likely to have prolonged stay (> 14-days) on HASU: 5.1 (3.8-6.8); high risk of malnutrition: 3.6 (2.9-4.5); palliative care: 4.5 (3.4-6.1); in-hospital mortality: 4.8 (3.8-6.2); disability at discharge: 7.5 (5.9-9.7); activity of daily living support: 1.6 (1.2-2.2); and discharge to care-home: 2.3 (1.6-3.3). In conclusion, HCAIs acquired within 7-days of an acute stroke led to prolonged hospitalisation, adverse health consequences and risk of care-dependency. These findings provide valuable information for timely intervention to reduce HCAIs, and minimising subsequent adverse outcomes.

Molecular size distribution in pentavalent (A, C, Y, W, X) meningococcal polysaccharide conjugate vaccine by HPSEC-UV-MALS-RI method- a conceivable stability indicating parameter.

Molecular size distribution (MSD) of polysaccharides serves as a key parameter that directly correlates to the immunogenicity of vaccine. MSD at meningococcal polysaccharide (A, C, Y and W) or conjugate bulk level is well established under detailed pharmacopeial and WHO guidelines. We report here, a newly developed method for determination of molecular size distribution of pentavalent Meningococcal conjugate vaccine comprising of A, C, Y, W and X (MenFive). Although serogroup specific molecular size could not be estimated here; lot to lot consistency monitoring, molecular aggregates distribution in final lot, are key takeaways of this method. Determination of MSD in pentavalent fill finished product was quite challenging. Various columns/detectors combination, buffers, physico-chemical conditions (temperature, 2-8 °C, 25 °C, 40 °C and 60 °C; flow rate, 0.3 mL to 0.8 mL), liquid/lyophilized formulations, were explored. Polymer-based packed columns were explored for estimation for MSD by aqueous size exclusion chromatography, using combinations of- Shodex OHPAK SB 807 HQ, Shodex OHPAK SB 806 HQ, G6000 PWXL, coupled with guard Shodex OHPAK SB-G-6B. MenFive showed heterogenous distribution of molecules ranging from 200 to 19000 kDa, indicating its complex nature. However, 1000-8000 kDa was dominant range, comprising of ≥ 50 % distribution of molecules, in both liquid as well as lyophilized formulations, with average molecular weight around 6000-6500 kDa. The molar mass distribution after slicing would provide an insight to the conformation of molecules through its presentation as HMW, LMW, aggregates and subsequently, the presence of dominant population of molecules of a particular molecular weight and its total contribution in the sample.

Engineering Domain Variants in 0.7Pb(Mg1/3Nb2/3)-0.3PbTiO3 Single Crystals Using High-Frequency AC Poling.

Single crystals of (001)-oriented 0.7Pb(Mg1/3Nb2/3)-0.3PbTiO3 (PMN-30PT) with a composition near the morphotropic phase boundary have attracted considerable attention due to their superior dielectric and electromechanical performance. Recently, a new alternating current (electric field) poling approach used for the enhancement of dielectric and piezoelectric properties. However, the microscopic domain variants that govern the performance, especially under high-frequency alternating current (AC) voltages, remain largely unexplored. In this work, the domain microstructure under AC poling reveals the presence of four monoclinic (MA) domain variants using a suite of scanning probe microscopy methods, and X-ray diffraction (XRD) reciprocal space mapping is tuned. It is reported on the emergence of hierarchical fine domains - needle-shaped, and 109° domain walls under applied high-frequency AC poling. Time-resolved Kelvin probe force microscopy (KPFM) reveals the charge dynamics and relaxation behavior of these needle domains and walls. The findings provide new insight and guidance to the domain engineering by high-frequency AC poling for the development of advanced transducer technology.

Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting.

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.

Direct oral anticoagulants compared to warfarin in long-term management of cerebral venous thrombosis: A comprehensive meta-analysis.

Objectives: We compared the safety and efficacy of direct oral anticoagulants (DOACs) with those of warfarin in the long-term (≥6 months) treatment of cerebral venous thrombosis (CVT). Methods: We searched electronic databases up to November 2023 to compare the use of DOACs and warfarin in CVT management. Modified Rankin scores (mRS), new intracranial hemorrhage, all-cause mortality, recurrence and nonrecanalisation events were used to assess outcome. RevMan v5.4 software and the Cochran-Mantel-Haenszel method were utilized to analyse data. Results: A total of 25 studies involving 2301 patients were identified as having treated CVT with either DOACs or warfarin. Good long-term mRS scores 0-2 (risk ratio [RR] = 1.01, 95% CI = 0.98-1.03; p = 0.61), new intracranial hemorrhage (RR = 1.00, 95% CI = 0.48-2.08; p = 0.99), all-cause mortality (RR = 1.00, 95% CI = 0.50-1.98; p = 0.99), nonrecanalisation (RR = 0.95, 95% CI = 0.77-1.18; p = 0.65) and recurrence venous thrombosis events (RR = 0.63, 95% CI = 0.33-1.22; p = 0.17) were similar between the two treatment arms. Subgroup analysis found recurrence of venous thrombosis was lower in the rivaroxaban group compared to warfarin (2.2% vs. 8.5%, RR = 0.33, 95% CI = 0.11-0.98; p = 0.05). Conclusion: DOACs and warfarin provide comparable long-term safety and efficacy profiles. DOACs may be preferred over warfarin due to their ease of clinical management.

Urinary incontinence indicates mortality, disability, and infections in hospitalised stroke patients.

OBJECTIVES: To assess the impact of urinary incontinence (UI) on health outcomes over the entire spectrum of acute stroke severity (National Institutes of Health Stroke Scale [NIHSS] scores: 0-42), due to a paucity of data on patients with milder strokes. PATIENTS AND METHODS: Data were prospectively collected (2014-2016) from the Sentinel Stroke National Audit Programme (1593 men, 1591 women; mean [SD] age 76.8 [13.3] years) admitted to four UK hyperacute stroke units (HASUs). Relationships between variables were assessed by multivariable logistic regression. Data were adjusted for age, sex, comorbidities, pre-stroke disability and intra-cranial haemorrhage, and presented as odds ratios with 95% confidence intervals. RESULTS: Amongst patients with no symptoms or a minor stroke (NIHSS scores of 0-4), compared to patients without UI, patients with UI had significantly greater risks of poor outcomes including: in-hospital mortality; disability at discharge; in-hospital pneumonia; urinary tract infection within 7 days of admission; prolonged length of stay on the HASU; palliative care by discharge; activity of daily living (ADL) support, and new discharge to care home. In patients with more moderate stroke (NIHSS score of 5-15) the same outcomes were identified; being at greater risk for patients with UI, except for palliative care by discharge and ADL support. With the highest stroke severity group (NIHSS score of 16-48) all outcomes were identified except in-patient mortality, pneumonia, and ADL support. However, odds ratios diminished as NIHSS scores increased. CONCLUSIONS: Urinary incontinence is a useful indicator of poor short-term outcomes in older patients with an acute stroke, but irrespective of stroke severity. This provides valuable information to healthcare professionals to identify at-risk individuals.

trans-Di-chlorido-bis-[(S)-(-)-1-(4-methyl-phen-yl)ethyl-amine-κN]palladium(II).

The title complex, [PdCl2(C9H13N)2], comprises a single mol-ecule in the asymmetric unit. The PdII atom is tetra-coordinated by two N atoms from two trans-aligned organic ligands and two Cl ligands, forming a square-planar metal coordination environment. The distances from the ortho-H atoms on the phenyl ring to the central PdII atom fall within the range 4.70-5.30 Å, precluding any significant intra-molecular Pd⋯H inter-actions.

Novel lncRNAs LINC01221, RP11-472G21.2 and CRNDE are markers of differential expression in pediatric patients with T cell acute lymphoblastic leukemia.

INTRODUCTION: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) poses significant challenges due to its aggressive nature and resistance to standard treatments. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers and therapeutic targets in leukemia. This study aims to characterize the lncRNA landscape in pediatric T-ALL, identify specific lncRNAs signatures, and assess their clinical relevance. METHODS: RNA sequencing was performed on T-ALL patient and control samples. Differential expression analysis identified dysregulated lncRNAs and mRNAs. Functional enrichment analysis revealed potential roles of these lncRNAs in cancer pathogenesis. Validation of candidate lncRNAs was conducted using real-time PCR. Clinical correlations were assessed, including associations with patients' clinical characteristics and survival outcomes. RESULTS: Analysis identified 674 dysregulated lncRNAs in pediatric T-ALL, with LINC01221 and CRNDE showing the most interactions in cancer progression pathways. Functional enrichment indicated involvement in apoptosis, survival, proliferation, and metastasis. Top 10 lncRNAs based on adjusted p value < 0.05 and Fold Change > 2 were selected for validation. Seven lncRNAs LINC01221, PCAT18, LINC00977, RP11-620J15.3, RP11-472G21.2, CTD-2291D10.4, and CRNDE showed correlation with RNA sequencing data. RP11-472G21.2 and CTD-2291D10.4 were highly expressed in T-ALL patients, with RP11-620J15.3 correlating significantly with better overall survival (p = 0.0007) at a median follow up of 32 months. The identified lncRNAs were further analysed in B-ALL patients. Distinct lncRNAs signatures were noted, distinguishing T-ALL from B-ALL and healthy controls, with lineage-specific overexpression of LINC01221 (p < 0.0001), RP11-472G21.2 (p < 0.001) and CRNDE (p = 0.04) in T-ALL. CONCLUSION: This study provides insights into the lncRNA landscape of pediatric T-ALL, offering potential diagnostic and prognostic markers. RP11-620J15.3 emerges as a promising prognostic marker, and distinct lncRNAs signatures may aid in the differentiation of T-ALL subtypes. Further research with larger cohorts is warranted to validate these findings and advance personalized treatment strategies for pediatric T-ALL patients.

Blockchain technology: A potential tool for the management of pharma supply chain.

BACKGROUND: The pharma supply chain comprises various parties including distributors, manufacturers, raw material suppliers, regulators, pharmacies, hospitals, and patients. Due to the product's complexity and transaction flows, an efficient traceability system is needed in the pharma supply chain to identify the current and all previous product owners. Digitizing the track and trace process significantly improves regulatory oversight and guarantees product quality. A distributed platform for shared data that is immutable, trustworthy, accountable, and transparent in the pharmaceutical supply chain could be built using blockchain-based drug traceability. OBJECTIVE: This review aims to shed light on blockchain technology's significance and necessity for pharmaceutical supply chain management systems. METHOD: A comprehensive literature review was performed between January 2017 and September 2023. The search was conducted to elaborate on blockchain technology. Blockchain is a software-based technology that logs and records transactions using a block structure arranged chronologically. Cryptography technology links and secures these blocks on a peer-to-peer network. Blockchain is anticipated to transform the pharmaceutical supply chain by giving all participants access to a single, straightforward system that provides transparency, security, and oversight of the end-to-end delivery of goods. RESULT: In all, various literature data were included in this review. Using a supply chain powered by blockchain has many benefits. To begin with, it gives a thorough account of the entire procedure from start to finish. A single piece of software can manage the entire supply chain. Additionally, it increases communication between parties with permission. The enhanced security and traceability that blockchain offers is another important benefit. A blockchain system can track, trace, and recall products. CONCLUSION: Blockchain-based pharmaceutical supply chain management enables the tracking of medicinal drug transactions from raw materials suppliers to end consumers. The pharma blockchain has the potential to enhance the security, integrity, data provenance, and functionality of the supply chain due to its transparency, immutability, and auditability.

The lipid globotriaosylceramide promotes germinal center B cell responses and antiviral immunity.

Influenza viruses escape immunity owing to rapid antigenic evolution, which requires vaccination strategies that allow for broadly protective antibody responses. We found that the lipid globotriaosylceramide (Gb3) expressed on germinal center (GC) B cells is essential for the production of high-affinity antibodies. Mechanistically, Gb3 bound and disengaged CD19 from its chaperone CD81, permitting CD19 to translocate to the B cell receptor complex to trigger signaling. Moreover, Gb3 regulated major histocompatibility complex class II expression to increase diversity of T follicular helper and GC B cells reactive with subdominant epitopes. In influenza infection, elevating Gb3, either endogenously or exogenously, promoted broadly reactive antibody responses and cross-protection. These data demonstrate that Gb3 determines the affinity and breadth of B cell immunity and has potential as a vaccine adjuvant.