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Summary: Lamin A/C is a well-established key contributor to nuclear stiffness and its role in nucleus mechanical properties has been extensively studied. However, its impact on whole-cell mechanics has been poorly addressed, particularly concerning measurable physical parameters. In this study, we combined microfluidic experiments with theoretical analyses to quantitatively estimate the whole-cell mechanical properties. This allowed us to characterize the mechanical changes induced in cells by lamin A/C alterations and prelamin A accumulation resulting from atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant. Our results reveal a distinctive increase in long-time viscosity as a signature of cells affected by lamin A/C alterations. Furthermore, they show that the whole-cell response to mechanical stress is driven not only by the nucleus but also by the nucleo-cytoskeleton links and the microtubule network. The enhanced cell viscosity assessed with our microfluidic assay could serve as a valuable diagnosis marker for lamin-related diseases.

Monkeypox is the latest reemerging zoonosis worldwide. Anyone is susceptible to contracting this infection; however, the clinical presentation may be atypical in a particularly vulnerable group that identifies as men who have sex with men. Herein, we present two cases of patients diagnosed with monkeypox infection, both of whom were also co-infected with human immunodeficiency virus (HIV) and exhibited different degrees of immunosuppression. Notably, the clinical presentations differed significantly. Patients co-infected with HIV are prone to develop clinical features ranging from barely visible lesions to severe or even fatal disease.

Objectives: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors., Methods: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors., Results: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32)., Conclusion: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare the cost-effectiveness of a universal mass vaccination (UMV) program with a 2 + 1 schedule of a 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) against two strategies: 1) a no-vaccination strategy and 2) a pneumococcal 13-valent conjugate vaccine (PCV13) 2 + 1 strategy in the Philippines., Methods: A published Markov cohort model was adapted to simulate the epidemiological and economic burden of pneumococcal diseases (meningitis, bacteremia, pneumonia, and acute otitis media) within a projected birth cohort in 2012 of 1,812,137 newborns over lifetime. Analyses were conducted at an annual discount rate of 5% from the perspective of the Philippine government. The current evaluation was updated with the best available local/regional clinical epidemiological data and published efficacy evidence., Results: Compared with the no-vaccination strategy, the PHiD-CV 2 + 1 UMV program was projected to prevent 3,343 deaths due to invasive pneumococcal diseases and pneumonia and 326,862 cases of pneumococcal diseases, resulting in an incremental cost-effectiveness ratio of 50,913 pesos/quality-adjusted life-year gained, which was considered to be highly cost-effective according to the threshold recommended by the World Health Organization. In comparison with the PCV13 2 + 1 strategy, the PHiD-CV 2 + 1 strategy was estimated to have a substantial reduction in acute otitis media (127,680 cases) and therefore a cost saving of potential 92.5 million pesos assuming price parity between PHiD-CV and PCV13 (US $1 = 42.13 pesos in 2012)., Conclusions: The PHiD-CV 2 + 1 UMV program is projected to be cost-effective, compared with no vaccination, and would provide substantial savings with higher quality-adjusted life-year gains as compared with the PCV13 2 + 1 strategy in the context of the Philippines., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: There is no short screening tool for perpetrators of intimate partner violence (IPV), although one is needed., Objective: To retrospectively derive and prospectively validate a brief screening tool for perpetrators of IPV: the PErpetration RaPid Scale (PERPS)., Methods: In the derivation phase of the study, we developed the PERPS based on historical data. The PERPS consists of three Yes/No questions about physical abuse of a partner. In the validation phase, we prospectively screened subjects during randomized 4-h shifts in a busy emergency department (ED). Subjects were asked to complete the newly derived three-question PERPS as well as the Physical Abuse of Partner Scale (PAPS), a 25-question Likert scale that is the gold standard for detection of physical abuse of a partner. The main outcome measures were sensitivity, specificity, predictive values, accuracy, and Cronbach alpha of the PERPS for internal consistency., Results: The PERP Scale derivation was based on a 207-subject historical database, and resulted in a three-question PERPS. Validation was completed on a new set of 214 patients presenting to the ED during 52 randomized 4-h shifts. The prevalence of IPV perpetration using the PERPS was 47/207 (22.7%; 95% confidence interval [CI] 16-27). For the PAPS, prevalence was 56/207 (27%; 95% CI 20-32). Compared with the PAPS, the sensitivity of the PERPS was 66%, specificity 93%, negative predictive value 87%, positive predictive value 78%, with an accuracy of 85%. Cronbach alpha of the PERPS was 0.68. Age, gender, and race were not predictive of positive results on either scale., Conclusion: We successfully derived and validated a three-question perpetrator of IPV scale that can be used in a busy ED or office setting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years., Methods: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality., Findings: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting., Interpretation: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available., Funding: WHO; Bill & Melinda Gates Foundation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A matrix solid-phase dispersion (MSPD) procedure for the isolation and HPLC determination of a new antiallergic agent, bilastine, in rat faeces is presented. The effect on recovery of empirical variables such as nature, pH and volume of the washing and elution liquids and nature of the adsorbent has been tested. The best recoveries were attained using an octadecylsilyl sorbent, 10 ml of a 0.1 M NaHCO3-Na2CO3 aqueous buffer of pH 10.0 as washing solvent and 10 ml of methanol as elution solvent. The extracts were evaporated to dryness and reconstituted in mobile phase before their injection into a HPLC system, equipped with a Discovery RP-amide C16 column and a fluorescence detector. The method allows one to reach recoveries of 95.0% within the concentration range 0.05-10 microg/g, with within-day repeatabilities of less than 5% and between-day repeatabilities of less than 9% within this range. This method has been successfully applied to the excretion studies of bilastine in the rat.

We have previously identified multipotent neuroepithelial (NEP) stem cells and lineage-restricted, self-renewing precursor cells termed NRPs (neuron-restricted precursors) and GRPs (glial-restricted precursors) present in the developing rat spinal cord (A. Kalyani, K. Hobson, and M. S. Rao, 1997, Dev. Biol. 186, 202-223; M. S. Rao and M. Mayer-Proschel, 1997, Dev. Biol. 188, 48-63; M. Mayer-Proschel, A. J. Kalyani, T. Mujtaba, and M. S. Rao, 1997, Neuron 19, 773-785). We now show that cells identical to rat NEPs, NRPs, and GRPs are present in mouse neural tubes and that immunoselection against cell surface markers E-NCAM and A2B5 can be used to isolate NRPs and GRPs, respectively. Restricted precursors similar to NRPs and GRPs can also be isolated from mouse embryonic stem cells (ES cells). ES cell-derived NRPs are E-NCAM immunoreactive, undergo self-renewal in defined medium, and differentiate into multiple neuronal phenotypes in mass culture. ES cells also generate A2B5-immunoreactive cells that are similar to E9 NEP-cell-derived GRPs and can differentiate into oligodendrocytes and astrocytes. Thus, lineage restricted precursors can be generated in vitro from cultured ES cells and these restricted precursors resemble those derived from mouse neural tubes. These results demonstrate the utility of using ES cells as a source of late embryonic precursor cells., (Copyright 1999 Academic Press.)

A solid-phase extraction (SPE) method for sample clean-up followed by a reversed-phase HPLC procedure for the assay of alinastina (pINN) in biological fluids is reported. The effects of the sample pH, composition of the washing and elution solvents and the nature of the SPE cartridge on recovery were evaluated. The selectivity of SPE was examined using spiked rat urine and plasma samples and the CH and PH cartridges gave rise to the cleanest extracts. The recoveries obtained in spiked rat urine and plasma samples were 91.2+/-2.7 and 99.9+/-2.8%, respectively. The proposed SPE method coupled off-line with a reserved-phase HPLC system with fluorimetric detection was applied to the quantitation of alinastine in real rat urine samples. The analytical method was also applied and validated for the determination of alinastine in dog plasma. The recovery from spiked dog plasma samples using the PH cartridge was around 65%. The within-day and between-day precisions were 7 and 12%, respectively. The detection and quantitation limits in dog plasma were 0.024 and 0.078 microg/ml, respectively.

A simple, accurate and rapid method for the determination of ipriflavone and its synthetic impurities has been developed. It consists in RP-HPLC separation and identification of the impurities from their UV spectra using photodiode-array detection. The method has been validated and shows good specificity, accuracy, precision and sensitivity.