Prospective Evaluation of Risk Factors Responsible for Infection Following Retrograde Intrarenal Surgery.

OBJECTIVE: The study aimed to identify the various risk factors for infective complications following retrograde intrarenal surgery (RIRS). MATERIALS AND METHODS: The study was conducted over one year, and the incidence of infectious complications after RIRS was calculated. Patients were divided into two groups based on the presence and absence of infective complications and were compared in terms of preoperative and operative characteristics. The complications were assessed and graded according to the Modified Clavien classification system (MCCS). The Fisher's exact test, Student's t-test, and Mann-Whitney U test were used for univariate analysis. Multivariate logistic regression analysis was used to identify independent risk factors for postoperative urinary tract infection (UTI). RESULTS: Out of 165 patients in the study, 27 (16.7%) patients developed UTI within one month of undergoing RIRS. The most frequent complication was fever, which occurred in 13 (7.8%) patients. When stratified by MCCS, 13 were grade I, nine were grade II, four were grade III, and one was a grade IV complication. High stone burden, concomitant diabetes mellitus, and multiple renal stones were identified as substantial risk factors for postoperative UTI in univariate analysis. On multivariate analysis, preoperative UTI and prolonged operative time were found to have a significant association with postoperative UTI. CONCLUSION: The present study demonstrated that preoperative UTI and prolonged operative time are independent factors responsible for postoperative UTI. Large stone burden, stone multiplicity, and diabetes mellitus contribute to a higher risk for UTI following RIRS.

Artificial Intelligence and Healthcare: A Journey through History, Present Innovations, and Future Possibilities.

Artificial intelligence (AI) has emerged as a powerful tool in healthcare significantly impacting practices from diagnostics to treatment delivery and patient management. This article examines the progress of AI in healthcare, starting from the field's inception in the 1960s to present-day innovative applications in areas such as precision medicine, robotic surgery, and drug development. In addition, the impact of the COVID-19 pandemic on the acceleration of the use of AI in technologies such as telemedicine and chatbots to enhance accessibility and improve medical education is also explored. Looking forward, the paper speculates on the promising future of AI in healthcare while critically addressing the ethical and societal considerations that accompany the integration of AI technologies. Furthermore, the potential to mitigate health disparities and the ethical implications surrounding data usage and patient privacy are discussed, emphasizing the need for evolving guidelines to govern AI's application in healthcare.

Navigating Post-Traumatic Osteoporosis: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis, Treatment, and Future Directions.

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies' efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes.

Long Non-Coding RNAs as Determinants of Thyroid Cancer Phenotypes: Investigating Differential Gene Expression Patterns and Novel Biomarker Discovery.

Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations.

The Patient Population at Homeopathic Outpatient Clinics across India: A Clinical Data Collection Study.

BACKGROUND: Even though several initiatives have been undertaken in different locations worldwide to collect clinical data in homeopathy, it is important to further investigate these aspects in the context of health care in India. OBJECTIVE: The study aimed to gather and analyze patients' clinical data and to derive insights into homeopathic treatment using an internet-based software program for data storage, retrieval and repertorization. METHODS: A multi-center observational study was conducted across 14 homeopathy outpatient clinics in India that are affiliated with the Central Council for Research in Homoeopathy (CCRH). Patient symptoms and demographic details were documented anonymously, and prescriptions were guided by repertorial suggestions from the Vithoulkas Compass software. During follow-up visits, treatment outcome was also recorded using an online assessment form. A retrospective analysis of data on patients' demographics, follow-up visits, morbidity (International Classification of Diseases 11th Revision), rubrics used, prescribed medicines and the level of improvement was achieved using Microsoft Excel-generated pivot tables. RESULTS: Throughout the study duration of one year a total of 2,811 patients attended the 14 outpatient clinics, of whom 2,468 were new patients with a total of 2,172 initial homeopathic prescription entries. Across the study, there were 3,491 prescriptions and 1,628 follow-up consultations for 868 follow-up patients, all of which data were thoroughly analyzed. The highest frequency of patients was in the 20-49 age group, and a higher proportion of the patients overall was female. Musculoskeletal, dermatological and respiratory complaints were the most frequently reported. The rubrics "Desire for sweets" and "Desire for spices" emerged as the most commonly used in the repertorizations. Further, Sulphur stood out as the most commonly prescribed medicine overall. With homeopathic treatment, some degree of clinical improvement was reported in 86% of the follow-up cases. CONCLUSION: Homeopathy is prescribed in CCRH outpatient clinics for a wide range of ailments in people across India, with at least some clinical improvement noted in a high proportion of those patients. The large-scale systematic data collection in these clinics has provided clear insights into the use and clinical value of homeopathy in India, with the potential to build a substantive nationwide data inventory over time.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Dynamic Nuclear Polarization Using Electron Spin Cluster.

Dynamic nuclear polarization (DNP) utilizing narrow-line electron spin clusters (ESCs) to achieve nuclear spin resonance matching (ESC-DNP) by microwave irradiation is a promising way to achieve NMR signal enhancements with a wide design scope requiring low microwave power at high magnetic field. Here we present the design for a trityl-based tetra-radical (TetraTrityl) to achieve DNP for 1H NMR at 7 T, supported by experimental data and quantum mechanical simulations. A slow-relaxing (T1e ≈ 1 ms) 4-ESC is found to require at least two electron spin pairs at <8 Å e-e spin distance to yield 1H ESC-DNP enhancement, while squeezing the rest of the e-e spin distances to <12 Å results in optimal 1H ESC-DNP enhancements. Fast-relaxing ESCs (T1e ≈ 10 µs) are found to require a weakly coupled narrow-line radical (sensitizer) to extract polarization from the ESC. These results provide design principles for achieving a power-efficient DNP at high field via ESC-DNP.

Beneficiary's Satisfaction with Primary Palliative Care Services in Kerala - A Cross-Sectional Survey.

Objectives: Kerala was the first state to implement a community-based, sustainable primary palliative care (PC) home care (HC) model. Beneficiary satisfaction, an important indicator to assess the quality of service provision with the HC program, has not been assessed since the programme was launched 14 years ago. This study tried to assess the satisfaction of beneficiaries receiving primary PC services through the Kerala State PC programme and the factors associated with the same. Materials and Methods: The cross-sectional survey was conducted among 450 patients registered under the Kerala State Primary PC Programme. Data were collected using a semi-structured questionnaire from October 2022 to January 2023. We summarised the data as proportions and performed Chi-square tests to make comparisons wherever applicable. Results: Most of the beneficiaries (69.1%) were satisfied with HC services. The mean age of the beneficiaries was 65.51 ± 17 years. More than 80% of the participants (88.4%) were married, and the primary caregivers were wives (31.8%) and daughters/daughters-in-law (35.3%). The primary diagnosis of the beneficiaries was a cerebrovascular accident (27.4%), cancer (18.8%), and spinal cord injury (13.2%). The study examined the needs of beneficiaries and found that the top three requirements reported by the patients were the inclusion of doctor visits in HC (71.8%), medicine distribution at home (67.4%), and physical rehabilitation services at home with a minimum of three sessions per month (52.3%). The study found a statistically significant association (P < 0.05) between the Beneficiary's satisfaction and behaviour of PC nurses and certain services, including physiotherapy, procedural care specifically catheterisation and wound dressing, and health check-ups received through the HC program. Satisfaction was reported more in Thiruvananthapuram district, followed by Malappuram. Conclusion: The overall satisfaction with the Kerala State Primary PC Programme was found to be high at about 69%. Despite the fact that the study identified significant relationships between nurses' behaviour, services provided (physical therapy, procedures, and health checks), and satisfaction, the findings suggested expanding the scope of the HC programme by including doctor visits and medicine delivery at patient's home.

Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones.

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.

Identification and characterisation of novel CAR-T cells to target IL13Rα2 positive human glioma in vitro and in vivo.

BACKGROUND: Previously, we discovered that human solid tumours, but not normal human tissues, preferentially overexpress interleukin-13Receptor alpha2, a high binding receptor for IL-13. To develop novel anti-cancer approaches, we constructed a chimeric antigen receptor construct using a high binding and codon optimised scFv-IL-13Rα2 fragment fused with CD3ζ and co-stimulatory cytoplasmic domains of CD28 and 4-1BB. METHODS: We developed a scFv clone, designated 14-1, by biopanning the bound scFv phages using huIL-13Rα2Fc chimeric protein and compared its binding with our previously published clone 4-1. We performed bioinformatic analyses for complementary determining regions (CDR) framework and residue analyses of the light and heavy chains. This construct was packaged with helper plasmids to produce CAR-lentivirus and transduced human Jurkat T or activated T cells from peripheral blood mononuclear cells (PBMCs) to produce CAR-T cells and tested for their quality attributes in vitro and in vivo. Serum enzymes including body weight from non-tumour bearing mice were tested for assessing general toxicity of CAR-T cells. RESULTS: The binding of 14-1 clone is to IL-13Rα2Fc-chimeric protein is ∼5 times higher than our previous clone 4-1. The 14-1-CAR-T cells grew exponentially in the presence of cytokines and maintained phenotype and biological attributes such as cell viability, potency, migration and T cell activation. Clone 14-1 migrated to IL-13Rα2Fc and cell free supernatants only from IL-13Rα2+ve confluent glioma tumour cells in a chemotaxis assay. scFv-IL-13Rα2-CAR-T cells specifically killed IL-13Rα2+ve but not IL-13Rα2-ve tumour cells in vitro and selectively caused significant release of IFN-γ only from IL-13Rα2+ve co-cultures. These CAR-T cells regressed IL-13Rα2+ve glioma xenografts in vivo without any general toxicity. In contrast, the IL-13Rα2 gene knocked-down U251 and U87 xenografts failed to respond to the CAR-T therapy. CONCLUSION: Taken together, we conclude that the novel scFv-IL-13Rα2 CAR-T cell therapy may offer an effective therapeutic option after designing a careful pre-clinical and clinical study.

The Impact of Paediatric Obesity on Drug Pharmacokinetics: A Virtual Clinical Trials Case Study with Amlodipine.

The incidence of paediatric obesity continues to rise worldwide and contributes to a range of diseases including cardiovascular disease. Obesity in children has been shown to impact upon the plasma concentrations of various compounds, including amlodipine. Nonetheless, information on the influence of obesity on amlodipine pharmacokinetics and the need for dose adjustment has not been studied previously. This study applied the physiologically based pharmacokinetic modelling and established a paediatric obesity population to assess the impact of obesity on amlodipine pharmacokinetics in children and explore the possible dose adjustments required to reach the same plasma concentration as non-obese paediatrics. The difference in predicted maximum concentration (Cmax) and area under the curve (AUC) were significant between children with and without obesity across the age group 2 to 18 years old when a fixed-dose regimen was used. On the contrary, a weight-based dose regimen showed no difference in Cmax between obese and non-obese from 2 to 9 years old. Thus, when a fixed-dose regimen is to be administered, a 1.25- to 1.5-fold increase in dose is required in obese children to achieve the same Cmax concentration as non-obese children, specifically for children aged 5 years and above.

Ambient Temperature Metal-Free Thiomethylation of Chloroheteroarenes and Chloropurines.

Herein, we report an in-situ mild and metal-free protocol for thiomethylation of heteroarenes in high yields. The thiomethylation of various chloropurines, nucleosides, and chloroheteroarenes has been accomplished offering easy access to agrochemicals and synthetic molecules useful for drug discovery.

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential.

Circular RNAs (circRNAs) are stable, enclosed, non-coding RNA molecules with dynamic regulatory propensity. Their biogenesis involves a back-splicing process, forming a highly stable and operational RNA molecule. Dysregulated circRNA expression can drive carcinogenic and tumorigenic transformation through the orchestration of epigenetic modifications via extensive RNA and protein-binding domains. These multi-ranged functional capabilities have unveiled extensive identification of previously unknown molecular and cellular patterns of cancer cells. Reliable circRNA expression patterns can aid in early disease detection and provide criteria for genome-specific personalized medicine. Studies described in this review have revealed the novelty of circRNAs and their biological ss as prognostic and diagnostic biomarkers.

Assessment of G10 Intraoperative Scoring System for Conversion in Patients Undergoing Laparoscopic Cholecystectomy: A Cross-Sectional Study From Nepal.

INTRODUCTION: Various preoperative risk factors for conversion in laparoscopic cholecystectomy (LC) have been well studied. However, the assessment of intraoperative factors for conversion in patients with cholecystitis is unclear. The G10 scoring system, which incorporates 10 parameters, has tried to fill this void by developing a scoring system for the most commonly encountered surgical illnesses. So, we aimed to assess the utility of the G10 scoring system among patients presenting for LC for symptomatic cholelithiasis (both acute and chronic cholecystitis) in the clinical setting of a low- and middle-income country. METHODS: All the patients undergoing LC were assigned a G10 value. Gallbladder surgery was considered easy if the G10 score was <2, moderate (2 ≦ 4), difficult (5 ≦ 7), and extreme (8 ≦ 10). All 10 risk factors were analyzed into a binary logistics model, and statistically significant risk factors were assessed. RESULTS: Among 177 patients, there were 36 males and 141 females. The median age of the patient was 42 years (range 11-79). There were 70 easy, 89 moderate, and 18 difficult cases. The overall mean G10 score was 2.32±1.5, which significantly increased as the severity progressed, with a mean value of 5.5±0.51 for difficult cases (P=0.0001). The mean G10 score for surgeries completed laparoscopically was 2.1±1.4, while it was 3.71±1.4 for open conversions [P=0.0001, AUC=0.79, CI=0.70-0.87]. There were 18 patients with G10 ≥5 with a conversion rate of 27.7%, while the overall conversion rate was 13.6%. Multivariate analysis showed free bile or pus outside the gallbladder [P=0.02, OR=5.1, CI=1.2-21.1] and fistula [P=0.01, OR=15.8, CI=1.9-129.8] as significant risk factors for conversion. CONCLUSION: Intraoperative risk factors for the prediction of conversion included the presence of free bile or pus outside the gallbladder and cholecystoenteric fistula. Based on the F1 score analysis, complemented with the Youden Index, the optimal cutoff value for conversion, based on the G10 score, lies around 4. Broader application and validation of the G10 scoring system are mandated to assess the utilization of this novel intraoperative scoring system.

Five million years of Antarctic Circumpolar Current strength variability.

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit.

End-of-life care (EOLC) exemplifies the joint mission of intensive and palliative care (PC) in their human-centeredness. The explosion of technological advances in medicine must be balanced with the culture of holistic care. Inevitably, it brings together the science and the art of medicine in their full expression. High-quality EOLC in the ICU is grounded in evidence, ethical principles, and professionalism within the framework of the Law. Expert professional statements over the last two decades in India were developed while the law was evolving. Recent landmark Supreme Court judgments have necessitated a review of the clinical pathway for EOLC outlined in the previous statements. Much empirical and interventional evidence has accumulated since the position statement in 2014. This iteration of the joint Indian Society of Critical Care Medicine-Indian Association of Palliative Care (ISCCM-IAPC) Position Statement for EOLC combines contemporary evidence, ethics, and law for decision support by the bedside in Indian ICUs. How to cite this article: Mani RK, Bhatnagar S, Butola S, Gursahani R, Mehta D, Simha S, et al. Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit. Indian J Crit Care Med 2024;28(3):200-250.

Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell.

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. Methods: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. Results: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. Conclusions: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.

The Duration and Intensity of High Frequency Alternating Current Influences the Degree and Recovery of Nerve Conduction Block.

OBJECTIVE: The purpose of this paper is to investigate the persistence of nerve blockade beyond the duration of applying high frequency alternating current (HFAC) to thinly myelinated and non-myelinated fibers, also termed a "carry-over effect". METHODS: In this study, we used electrically-evoked compound action potentials from isolated rat vagus nerves to assess the influence of 5 kHz HFAC amplitude and duration on the degree of the carry-over effect. Current amplitudes from 1-10 mA and 5 kHz durations from 10-120 seconds were tested. RESULTS: By testing 20 different combinations of 5 kHz amplitude and duration, we found a significant interaction between 5 kHz amplitude and duration on influencing the carry-over effect. CONCLUSION: The degree of carry-over effect was dependent on 5 kHz amplitude, as well as duration. SIGNIFICANCE: Utilizing the carry-over effect may be useful in designing energy efficient nerve blocking algorithms for the treatment of diseases influenced by nerve activity.

Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity of < 20/40.

PURPOSE: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network protocol AC. DESIGN: Post hoc analysis of data from a randomized clinical trial. PARTICIPANTS: Two hundred seventy participants with one or both eyes harboring CI-DME with visual acuity (VA) letter score of 69 to 24 (Snellen equivalent, 20/50-20/320). METHODS: Eligible eyes were assigned to receive intravitreal aflibercept monotherapy (n = 158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (n = 154). MAIN OUTCOME MEASURES: Meeting switching criteria: (1) at any time, (2) at 12 weeks, and (3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. RESULTS: In the group receiving bevacizumab first, older participants showed a higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age of 1.32 (95% confidence interval [CI], 1.11-1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (for male vs. female: odds ratio [OR], 4.84 [95% CI, 1.32-17.81]; 5-letter lower baseline VA: OR, 1.30 [95% CI, 1.03-1.63]). Worse 12-week central subfield thickness (CST; 10-µm greater: HR, 1.06 [95% CI, 1.04-1.07]) was associated with increased risk of switching after 12 weeks. The mean ± standard deviation improvement in visual acuity after completing the switch to aflibercept was 3.7 ± 4.9 letters compared with the day of switching. CONCLUSIONS: The identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At 12 weeks, thicker CST was predictive of eyes most likely to be switched in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.