Search

The morphological and optical properties of noble metal nanoparticles prepared by picosecond laser generated plasmas in water were investigated. First, the ablation efficiency was maximized searching the optimal focusing conditions. The nanoparticle size, measured by Scanning Transmission Electron Microscopy, strongly depends on the laser fluence, keeping fixed the other deposition parameters such as the target to scanner objective distance and laser repetition frequency. STEM images indicate narrow gradients of NP sizes. Hence the optimization of ablation parameters favours a fine tuning of nanoparticles. UV-Visible spectroscopy helped to determine the appropriate laser wavelength to resonantly excite the localized surface plasmon to carry out Surface Enhanced Raman Scattering (SERS) measurements. The SERS activity of Ag and Au substrates, obtained spraying the colloids synthesized in water, was tested using crystal violet as a probe molecule. The good SERS performance, observed at excitation wavelength 785 nm, is attributed to aggregation phenomena of nanoparticles sprayed on the support.

Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted., Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population., Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Carbone, Bencivenga, Santoro, De Lucia, Palaia, Ercolano, Scognamiglio, Edison, Ferrara, Vitale, Rengo and Femminella.)

Background: Sepsis and acute kidney injury (AKI) are associated with mortality in the newborn intensive care unit (NICU). There is a paucity of studies that describe AKI and fluid overload in neonatal sepsis and their association with mortality., Methods: Retrospective study of neonates with culture positive sepsis admitted to the NICU between June 2020 and June 2021 was conducted. Primary outcome was in-hospital mortality according to AKI as defined by the neonatal modified Kidney Diseases Improving Outcomes criteria. Secondary outcomes were early fluid overload and vasopressor use., Results: Thirty-three percent of neonates had AKI with sepsis, and 57% of cases were severe AKI. AKI was associated with mortality after adjusting for variables that were different between survivors and non-survivors (aOR 5.7 [95% CI 1.1-36], p = 0.04). Early fluid overload occurred in 27% of neonates who were at higher risk of having AKI with sepsis (OR 7.4 [95% CI 1.6-26.0], p = 0.01) and higher risk of mortality (aOR 17.8 [95% CI 2-7545], p = 0.02)., Conclusions: AKI and early fluid overload are associated with mortality in sepsis in our retrospective cohort. Mitigating AKI and early fluid overload in sepsis might be a fruitful strategy in reducing mortality with sepsis. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

An Artificial Intelligence algorithm trained on data that reflect racial biases may yield racially biased outputs, even if the algorithm on its own is unbiased. For example, algorithms used to schedule medical appointments in the USA predict that Black patients are at a higher risk of no-show than non-Black patients, though technically accurate given existing data that prediction results in Black patients being overwhelmingly scheduled in appointment slots that cause longer wait times than non-Black patients. This perpetuates racial inequity, in this case lesser access to medical care. This gives rise to one type of Accuracy-Fairness trade-off: preserve the efficiency offered by using AI to schedule appointments or discard that efficiency in order to avoid perpetuating ethno-racial disparities. Similar trade-offs arise in a range of AI applications including others in medicine, as well as in education, judicial systems, and public security, among others. This article presents a framework for addressing such trade-offs where Machine Learning and Optimization components of the algorithm are decoupled. Applied to medical appointment scheduling, our framework articulates four approaches intervening in different ways on different components of the algorithm. Each yields specific results, in one case preserving accuracy comparable to the current state-of-the-art while eliminating the disparity., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

Background: We report the case of a patient presenting with orofacial tardive dyskinesia (TD), following administration of a first-generation antipsychotic (Loxapine)., Intervention: Four weeks of repeated sessions of mindfulness-based cognitive therapy (MBCT) and mindfulness-based stress reduction (MBSR) protocols were administered, with TD hetero-quantified before and during each session via the Abnormal Involuntary Movement Scale (AIMS)., Results: The dyskinesia ameliorated quantitatively and qualitatively (1) during each session, and (2) at resting conditions in the long term. During some sessions, after which patients' compliance was auto-evaluated as maximal, complete arrest of the TD was observed. Hypothesis and Conclusion: We suggest mindfulness meditation as a novel adjunctive therapeutic approach for tardive dyskinesia, and invite for further clinical and neurological investigations.

Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP Low ), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP High ), Sox9-EGFP Sublow progenitors, and Sox9-EGFP Negative differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology. IESC function was assessed by crypt culture, and proliferation by flow cytometry and histology. Main findings were confirmed in Lgr5-EGFP and Lgr5-LacZ mice. Aging-associated gene expression changes were analyzed by Fluidigm mRNA profiling. Crypts culture from old mice yielded fewer and less complex enteroids. Histology revealed increased villus height and Paneth cells per crypt in old mice. Old mice showed increased numbers and hyperproliferation of Sox9-EGFP Low IESC and Sox9-EGFP High cells. Cleaved caspase-3 staining demonstrated increased apoptotic cells in crypts and villi of old mice. Gene expression profiling revealed aging-associated changes in mRNAs associated with cell cycle, oxidative stress and apoptosis specifically in IESC. These findings provide new, direct evidence for aging associated IESC dysfunction, and define potential biomarkers and targets for translational studies to assess and maintain IESC function during aging.

Background: Humans are able to compensate for significant blood loss with little change in traditional vital signs, limiting early detection and intervention. We hypothesized that the Compensatory Reserve Index (CRI), a new hemodynamic parameter that trends changes in intravascular volume relative to the individual patient's response to hypovolemia, would accurately trend each subject's progression from normovolemia to decompensation (systolic blood pressure < 80) and back to normovolemia in humans., Methods: Men and women, ages 19 years to 36 years, underwent stepwise (~333 mL aliquot) removal and replacement of 20% blood volume (men, 15 mL/kg; women, 13 mL/kg) via a large bore intravenous (i.v.) line. During each experiment, subjects were monitored with four CipherOx CRI Tablets. Withdrawn blood was reinfused at the end of each experiment., Results: Forty-two subjects (24 men; 18 women) were enrolled in the study, of which 32 completed the protocol. Seven subjects became symptomatic and collapsed (systolic blood pressure < 80), six never achieving maximum blood loss; each was rescued with a saline infusion followed by reinfusion of their stored blood. The mean CRI at baseline for all 42 subjects was 0.9 ± 0.04. The mean CRI for the 32 subjects while asymptomatic at maximum blood loss was 0.611 ± 0.028. For the asymptomatic subjects, the average blood loss volume was 1018 mL ± 286 mL. In comparison, the mean CRI at maximum blood loss for the seven subjects who collapsed was 0.15 ± 0.007 and their average blood loss volume was 860 ± 183 mL. Mean CRI after reinfusion of blood was 0.89 ± 0.02. In addition symptomatic subjects demonstrated three times larger average decrease in CRI per liter of blood removed, 0.85 versus 0.28 for asymptomatic subjects., Conclusion: CRI trends change in intravascular volume relative to an individual's response to hypovolemia and is sensitive to the differing risks associated with individuals' differing tolerance to volume loss., Level of Evidence: Prognostic study, level II.

Bailey, Damian M., Christopher K. Willie, Ryan L. Hoiland, Anthony R. Bain, David B. MacLeod, Maria A. Santoro, Daniel K. DeMasi, Andrea Andrijanic, Tanja Mijacika, Otto F. Barak, Zeljko Dujic, and Philip N. Ainslie. Surviving without oxygen: how low can the human brain go? High Alt Med Biol 18:73-79, 2017.-Hypoxic cerebral vasodilation is a highly conserved physiological response coupling cerebral O 2 delivery (CDO 2 ) to metabolic demand with increasingly important roles identified for the red blood cell (sensor) and nitric oxide (effector). In the current article, we reexamine previously published cerebral blood flow (CBF) and arterial blood gas data obtained in freedivers and mountaineers, extreme athletes in whom the lowest arterial partial pressures of O 2 (19-23 mmHg) and greatest extremes of carbon dioxide (16-61 mmHg) were recorded during (acute) maximal static dry apnea or (chronic) exposure to terrestrial high altitude. Data highlight compensatory increases in CBF (+96% in freedivers to +209% in mountaineers relative to normoxic baseline controls) that were sufficient to sustain CDO 2 (+24% in freedivers to +183% in mountaineers) even in the face of the most severe reductions in arterial O 2 content (-61% in freedivers to -9% in mountaineers) reported in the literature, consistent with the conservation of mass principle. These unique findings highlight to what extent cerebral vasodilation likely contributes toward these athletes' extraordinary abilities to survive in such harsh environments characterized by physiological extremes of hypoxemia, alkalosis, and acidosis helping define the human brain's remarkable limits of tolerance.

Purpose: Lipofilling technique is significantly increasing and the need of a non-invasive method to assess the success of the procedure is becoming mandatory. In particular, US can be considered an alternative method to MRI for evaluation of tissue lipofilling due to the simplicity and easy access of the technique and can be also used for monitoring the efficacy of the surgical procedure. The goal of this study was to demonstrate, the utility of the high-resolution ultrasound technique in the evaluation of autologous adipose tissue lipofilling, used for the correction of post-surgical, post-traumatic and post-burn scars., Materials and Methods: Twenty-five patients (21 females), aged between 14 and 62 years, underwent surgical correction of scars with ''lipofilling'' technique. To evaluate the effectiveness of such treatment serial ultrasound examinations were performed at both the region affected from skin dimorphism through the adjacent skin region, using a high frequency transducer. Furthermore, it was assessed the presence of complications ranging from oedema or hematoma to necrosis or adipocyte migration of the graft. Finally, was calculated the average percentage of one-year survival of autologous fat transplant., Results: Quantitative evaluations obtained with time series of ultrasound showed that the greatest benefits of autologous adipose tissue lipofilling, are found at the level of the hypodermis, but that also all the other layers of the skin can benefit from this procedure., Conclusion: The data acquired demonstrate that the eco color Doppler with high resolution can be considered a valid non-invasive tool for the assessment of morphological and quantitative degree of engraftment of autologous adipose tissue transplanted. Lipofilling is an accurate and effective choice for the correction of congenital or acquired skin disorders for its filler effect and consequent benefit for all tissue layers.

Current views suggest that apoptosis eliminates genetically damaged cells that may otherwise form tumors. Prior human studies link elevated insulin and reduced apoptosis to risk of colorectal adenomas. We hypothesized that hyperinsulinemia associated with obesity would lead to reduced colon epithelial cell (CEC) apoptosis after radiation and that this effect would be altered by deletion of the insulin-like growth factor (IGF) 1 receptor (IGF1R) or the insulin receptor (IR). Mice with villin-Cre-mediated IGF1R or IR deletion in CECs and floxed littermates were fed a high-fat diet to induce obesity and hyperinsulinemia or control low-fat chow. Mice were exposed to 5-Gy abdominal radiation to induce DNA damage and euthanized 4 h later for evaluation of apoptosis by localization of cleaved caspase-3. Obese mice exhibited decreased apoptosis of genetically damaged CECs. IGF1R deletion did not affect CEC apoptosis in lean or obese animals. In contrast, IR loss increased CEC apoptosis in both diet groups but did not prevent antiapoptotic effects of obesity. Levels of p53 protein were significantly reduced in CECs of obese mice with intact IR but increased in both lean and obese mice without IR. Levels of mRNAs encoding proapoptotic Perp and the cell cycle inhibitor Cdkn1b/p27 were reduced in CECs of obese mice and increased in lean mice lacking IR. Together, our studies provide novel evidence for antiapoptotic roles of obesity and IR, but not IGF1R, in colonic epithelium after DNA damage. However, neither IR nor IGF1R deletion prevented a reduction in radiation-induced CEC apoptosis during obesity and hyperinsulinemia., (Copyright © 2015 the American Physiological Society.)

Insulin-like growth factor 1 (IGF1) has potent trophic effects on normal or injured intestinal epithelium, but specific effects on intestinal stem cells (ISCs) are undefined. We used Sox9-enhanced green fluorescent protein (EGFP) reporter mice that permit analyses of both actively cycling ISCs (Sox9-EGFP(Low)) and reserve/facultative ISCs (Sox9-EGFP(High)) to study IGF1 action on ISCs in normal intestine or during crypt regeneration after high-dose radiation-induced injury. We hypothesized that IGF1 differentially regulates proliferation and gene expression in actively cycling and reserve/facultative ISCs. IGF1 was delivered for 5 days using subcutaneously implanted mini-pumps in uninjured mice or after 14 Gy abdominal radiation. ISC numbers, proliferation, and transcriptome were assessed. IGF1 increased epithelial growth in nonirradiated mice and enhanced crypt regeneration after radiation. In uninjured and regenerating intestines, IGF1 increased total numbers of Sox9-EGFP(Low) ISCs and percentage of these cells in M-phase. IGF1 increased percentages of Sox9-EGFP(High) ISCs in S-phase but did not expand this population. Microarray revealed that IGF1 activated distinct gene expression signatures in the 2 Sox9-EGFP ISC populations. In vitro IGF1 enhanced enteroid formation by Sox9-EGFP(High) facultative ISCs but not Sox9-EGFP(Low) actively cycling ISCs. Our data provide new evidence that IGF1 activates 2 ISC populations via distinct regulatory pathways to promote growth of normal intestinal epithelium and crypt regeneration after irradiation., (© FASEB.)

The insulin receptor (IR) regulates nutrient uptake and utilization in multiple organs, but its role in the intestinal epithelium is not defined. This study developed a mouse model with villin-Cre (VC) recombinase-mediated intestinal epithelial cell (IEC)-specific IR deletion (VC-IR(Δ/Δ)) and littermate controls with floxed, but intact, IR (IR(fl/fl)) to define in vivo roles of IEC-IR in mice fed chow or high-fat diet (HFD). We hypothesized that loss of IEC-IR would alter intestinal growth, biomarkers of intestinal epithelial stem cells (IESC) or other lineages, body weight, adiposity, and glucose or lipid handling. In lean, chow-fed mice, IEC-IR deletion did not affect body or fat mass, plasma glucose, or IEC proliferation. In chow-fed VC-IR(Δ/Δ) mice, mRNA levels of the Paneth cell marker lysozyme (Lyz) were decreased, but markers of other differentiated lineages were unchanged. During HFD-induced obesity, IR(fl/fl) and VC-IR(Δ/Δ) mice exhibited similar increases in body and fat mass, plasma insulin, mRNAs encoding several lipid-handling proteins, a decrease in Paneth cell number, and impaired glucose tolerance. In IR(fl/fl) mice, HFD-induced obesity increased circulating cholesterol; numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC); and mRNAs encoding Chga, glucose-dependent insulinotrophic peptide (Gip), glucagon (Gcg), Lyz, IESC biomarkers, and the enterocyte cholesterol transporter Scarb1. All these effects were attenuated or lost in VC-IR(Δ/Δ) mice. These results demonstrate that IEC-IR is not required for normal growth of the intestinal epithelium in lean adult mice. However, our findings provide novel evidence that, during HFD-induced obesity, IEC-IR contributes to increases in EEC, plasma cholesterol, and increased expression of Scarb1 or IESC-, EEC-, and Paneth cell-derived mRNAs., (Copyright © 2015 the American Physiological Society.)

Background: Hyperinsulinemia resulting from obesity and insulin resistance is associated with increased risk of many cancers, but the biology underlying this risk is unclear. We hypothesized that increased mRNA levels of the insulin-like growth factor I receptor (IGFIR) versus the insulin receptor (IR) or elevated ratio of IR-A:IR-B isoforms in normal rectal mucosa would predict adenoma risk, particularly in individuals with high body mass index (BMI) or plasma insulin., Methods: Biopsies from normal rectal mucosa were obtained from consenting patients undergoing routine colonoscopy at University of North Carolina Hospitals (Chapel Hill, NC). Subjects with colorectal adenomas were classified as cases (n = 100) and were matched to adenoma-free controls (n = 98) based on age, sex, and BMI. IGFIR and IR mRNA levels were assessed by qRT-PCR, and IR-A:IR-B mRNA ratios by standard PCR. Plasma insulin and crypt apoptosis were measured by ELISA and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), respectively. Logistic regression models examined relationships between receptor mRNAs, BMI, plasma insulin, and adenoma risk., Results: Unexpectedly, cases were significantly more likely to have lower IGFIR mRNA levels than controls. No overall differences in total IR mRNA or IR-A:IR-B ratios were observed between cases and controls. Interestingly, in patients with high plasma insulin, increased IR-A:IR-B ratio was associated with increased likelihood of having adenomas., Conclusions: Our work shows novel findings that reduced IGFIR mRNA and, during high plasma insulin, increased IR-A:IR-B ratios in normal rectal mucosa are associated with colorectal adenoma risk., Impact: Our work provides evidence supporting a link between IGFIR and IR isoform expression levels and colorectal adenoma risk., (©2014 American Association for Cancer Research.)

Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells.

Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and 9 postradiation. Radiation-induced changes in number, growth, and transcriptome of the different Sox9-EGFP cell populations were determined by histology, flow cytometry, in vitro culture assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs. Irradiation caused complete crypt loss, followed by expansion and hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in culture, whereas during regeneration both Sox9-EGFP Low and High cells formed organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells exhibited transcriptomic changes linked to p53-signaling and ISC-like functions including DNA repair and reduced oxidative metabolism. These findings support a model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells contain radiation-activatable cells with ISC characteristics, and both participate in crypt regeneration.

Contradictory goals plague China's pharmaceutical policy. The government wants to develop the domestic pharmaceutical industry and has used drug pricing to cross-subsidize public hospitals. Yet the government also aims to control drug spending through price caps and profit-margin regulations to guarantee access even for poor patients. The resulting system has distorted market incentives, increased consumers' costs, and financially rewarded inappropriate prescribing, thus undermining public health. Pharmaceuticals account for about half of total health spending in China, representing 43 percent of spending per inpatient episode and 51 percent of spending per outpatient visit. Yet some essential medicines are unavailable or of questionable quality.

A newborn girl with multiple anomalies had an interstitial deletion of the long arm of chromosome 7 (46, XX,der(7)mat). The patient's mother and maternal grandmother were carriers of a balanced translocation, 46,XX, inv ins(5;7)(q14;q3200q2200). Both cytogenetic and clinical findings were similar to those in the two cases already described.

A child with cleft palate is described who was born to a mother who received corticosteroid therapy early in pregnancy. The relationship between the cleft palate and the dose and timing of the corticosteroid therapy is discussed.

This paper discusses the present hazardous waste program of 3M Company (Minnesota Mining and Manufacturing Company). 3M's definition of hazardous waste and the company's position on hazardous waste disposal are first considered. The company position is that wherever and whenever the disposal of a waste material threatens the environment or public safety, then that waste should be considered a hazardous waste and treated accordingly in terms of its handling and ultimate disposal. The generation of hazardous wastes and the differentiation of "hazardous" and "nonhazardous" wastes are described next. Handling of hazardous wastes from their generation to their disposal is then covered. This includes a definition of internal 3M terminology and a description of the hazard rating system used by the company. Finally, 3M disposal practices are presented. It is 3M's position that thermal destruction of hazardous wastes, where appropriate, is the best method for their disposal. With this in mind, 3M has constructed incineration facilities throughout the country. The rotary kiln incinerator at the 3M Chemolite plant in Cottage Grove, Minnesota is briefly described. Disposal of certain hazardous wastes in controlled secure land disposal sites is then briefly discussed.