Search

Background and Aim: Heat shock proteins are highly conserved proteins that work as molecular chaperones expressed in response to thermal stress. This study aimed to determine the expression profile of genes related to the heat stress response in whole blood obtained from the Romosinuano creole breed. Materials and Methods: Real-time polymerase chain reaction was performed to analyze the transcript of hsp90, hsp70, hsp60, and hsf1 in the whole blood of Romosinuano under different temperature-humidity indices (THIs). Results: The expression levels of the hsp70 and hsf1 genes at the high-THI level were higher (p = 0.0011 and p = 0.0003, respectively) than those at the low-THI level. In addition, no differences in the expression levels of the hsp60 and hsP90 genes were detected between the two THIs. Conclusion: The overexpression of hsf1 and hsp70 genes play an important role in protecting cells from damage induced by heat stress. Keywords: climate change, external environment, heat shock proteins, heat stress, mRNA, temperature-humidity index.

Background Factors associated with interindividual variability in the pharmacokinetics of micafungin have been identified. This variability can cause underexposure and loss of drug efficacy. For this reason, a simple, fast, cost-effective and sensitive ultra-performance liquid chromatography ultraviolet detector (UPLC-UV) method was developed and validated for the quantification of micafungin. Methods The method involves simple plasma precipitation by UPLC with a reversed phase C18 column at 40°C coupled with ultraviolet detection set at a wavelength of 264 nm. The mobile phase consisted of a mixture 42/58 of potassium phosphate 20 mm and acetonitrile. Results The method was validated over the concentration range of 0.25–15.0 mg/L and proved to be reliable and reproducible with an average percentage of recoveries of 101.59 ± 3.93% and inter and intraday variation coefficients lower than 15% in all cases. The method was successfully applied in determining 30 samples from 10 patients being treated with micafungin. Conclusions The method proposed could be useful to facilitate the implementation of therapeutic drug monitoring for personalizing micafungin treatment in invasive fungal infections.

Chemotherapy remains a mainstay in the treatment of many types of cancer even though it is associated with debilitating behavioral side effects referred to as "chemobrain," including difficulty concentrating and memory impairment. The predominant hypothesis in the field is that systemic inflammation drives these cognitive impairments, although the brain mechanisms by which this occurs remain poorly understood. Here, we hypothesized that microglia are activated by chemotherapy and drive chemotherapy-associated cognitive impairments. To test this hypothesis, we treated female C57BL/6 mice with a clinically-relevant regimen of a common chemotherapeutic, paclitaxel (6 i.p. doses at 30 mg/kg), which impairs memory of an aversive stimulus as assessed via a contextual fear conditioning (CFC) paradigm. Paclitaxel increased the percent area of IBA1 staining in the dentate gyrus of the hippocampus. Moreover, using a machine learning random forest classifier we identified immunohistochemical features of reactive microglia in multiple hippocampal subregions that were distinct between vehicle- and paclitaxel-treated mice. Paclitaxel treatment also increased gene expression of inflammatory cytokines in a microglia-enriched population of cells from mice. Lastly, a selective inhibitor of colony stimulating factor 1 receptor, PLX5622, was employed to deplete microglia and then assess CFC performance following paclitaxel treatment. PLX5622 significantly reduced hippocampal gene expression of paclitaxel-induced proinflammatory cytokines and restored memory, suggesting that microglia play a critical role in the development of chemotherapy-associated neuroinflammation and cognitive impairments. This work provides critical evidence that microglia drive paclitaxel-associated cognitive impairments, a key mechanistic detail for determining preventative and intervention strategies for these burdensome side effects.

To assess the level of implementation of medication safety practices in Intensive Care Units (ICUs) and to identify opportunities for improvement.A descriptive multicenter study was carried out.Intensive Care Units.A total of 40 ICUs voluntarily completed the "Medication use-system safety self-assessment for Intensive Care Units" between March and September 2020. The survey comprised 147 items for evaluation grouped into 10 key elements.Calculation was made of the mean scores and mean percentages based on the maximum possible values for the overall survey, for the key elements and for each individual item for evaluation.The mean score of the overall questionnaire among the participating ICUs was 436.8 (49.2% of the maximum possible score). No differences were found according to functional dependence, size of the hospital or type of ICU. The key elements referred to the incorporation of clinical pharmacists in these units, as well as the competence and training of the professionals in safety practices yielded the lowest values (31.2% and 33.2%, respectively). Three other key elements related to accessibility to information about patients and medicines; to the standardization, storage and distribution of medicines; and to the quality and risk management programs, yielded percentages below 50%.Numerous effective safety medication practices have been identified with a low level of implementation in ICUs. This situation must be addressed in order to reduce medication errors in critically ill patients.

We present the results of a long-term periodicity search in a sample of $\gamma$-ray blazars within a multiwavelength context. These blazars have been selected from the Steward Observatory sample as part of its optical monitoring program between 2008 and 2018. We study 15 sources with a temporal coverage in their optical total and polarized emission sufficiently large ($>9$ years) to perform a reliable long-term periodicity analysis. We collect data from several observatories to extend the coverage, enabling the search of longer periods. In addition, data are also gathered in the high-energy ($E>100$ MeV) $\gamma$-ray band from the $\textit{Fermi}$ Large Area Telescope; and in the 15-GHz radio band from the Owens Valley Radio Observatory. We identify 5 promising candidates to host quasi-periodic emission, AO 0235+164, PKS 1222+216, Mrk 501, BL Lacertae and 1ES 2344+514 with periods in one or more bands and statistical significances $\sim$3$\sigma$ after trial factor correction. AO 0235+164 shows a period of $\sim$8.2 years in the R band; PKS 1222+216 has a quasi-periodic modulation in its total and polarized optical emission of $\sim$1.6 years; Mrk 501 displays a $\sim$5-year quasi-periodicity in optical and radio wavelengths; BL Lacertae presents a period of $\sim$1.8 years in its polarized emission; and 1ES 2344+514 shows a hint of a $\sim$5.5-year period in its optical R band. We interpret these results in the framework of the most common models and scenarios, namely the presence of a binary supermassive black hole system; or geometrical effects like helical or precessing jets., Comment: Accepted for publication in MNRAS

To describe quantitative CT parameters of children with a typical pattern for NEHI and compare them to controls.Eleven patients (7 boys) with NEHI and an available chest CT concordant NEHI were identified. Eleven age-, sex-, height-matched, with CT technique-matching were identified for comparison. An open-source software was used to segment the lung parenchyma into lobes using the fissures. Quantitative parameters such as low attenuation areas, mean lung density, kurtosis, skewness, ventilation heterogeneity, lung mass, and volume were calculated for both controls and cases.Analysis of the lung parenchyma showed that patients with NEHI had a lower mean lung density (-615 HU vs -556 HU, p = 0.03) with higher ventilation heterogeneity (0.23 vs 0.19, p = 0.04), lung mass (232 g vs 146 g, p = 0.01) and volume (595 mL vs 339 mL, p = 0.008) compared to controls. Most lobes followed this trend, except the middle lobe that showed only a higher lung mass (32.9 g vs 19.6 g, p = 0.02) and volume (77.4 vs 46.9, p = 0.005) in patients with NEHI compared to controls.Quantitative CT is a feasible technique in children with a typical pattern for NEHI and is associated with differences in attenuation, ventilation heterogeneity, and lung volume.

Parkinson's disease (PD) patients often experience impairment of autonomic and respiratory functions. These include conditions such as orthostatic hypotension and sleep apnea, which are highly correlated with dysfunctional central chemoreception. Blood flow is a fundamental determinant of tissue CO

Both congestive (patients post-Fontan hepatopathy) and congenital (patients with ARPKD) disease can lead to hepatic fibrosis and portal hypertension with eventual development of splenomegaly. We investigated liver and spleen stiffness as measured by MRE between post-Fontan, ARPKD patients and controls independent of organ volume.Our study included 122 subjects (70 Fontan patients, 14 ARPKD patients, and 38 controls). The mean MRE liver and spleen stiffness values of Fontan patients and patients with ARPKD were compared to controls. Similarly, the liver and spleen volumes of the Fontan patients and patients with ARPKD were then compared to the volumes of controls.Post-Fontan and ARPKD patients, mean liver stiffness, mean liver volume as well as mean spleen stiffness and mean spleen volume were higher than mean liver stiffness, mean liver volume, mean spleen stiffness, and mean spleen volume of controls. While liver stiffness correlated to liver volume in controls, we found no correlation between stiffness and volume in either Fontan or ARPKD patients, which indicates MRE's ability to act as an independent biomarker. However, these findings are not true in the spleen, where there is significant association between volume and stiffness in patients with ARPKD, but not in Fontan patients or controls.Liver and spleen stiffness and volumes are significantly different among Fontan patients, ARPKD patients, and controls. Our findings suggest that beyond diagnosing fibrosis, MRE cut-off values could be disease-specific since not only the severity but the underlying pathology causing organ congestion or fibrosis influences MRE results.

Endoscopic submucosal dissection (ESD) and endoscopic submucosal resection (EMR) are non-invasive endoscopic techniques. They allow an early excised gastrointestinal (GI) mucosal precancerous lessions. For their application is necessary to use a submucosal injection that lifts the area to excise. The main objective of this study was the preparation of a microparticulate-based fluid for injection in the GI submucosa. Alginate microparticles (MPs) were developed by the solvent displacement technique and characterized by particle size, surface electrical properties, swelling, degradation, rheology, adhesion, leakage, syringeablity and stability. Furthermore, their potential to form a submucosal cushion was assayed in porcine stomach mucosa and porcine colon mucosa. Results showed MPs sizes below 160 μm, negative surface charge around -50 mV at pH = 6, high rates of swelling and good adhesion. The microparticulate-based fluid exhibited pseudoplastic behavior following the Ostwald-de Waele rheological model. A brief force is sufficient for its injection through a syringe. Finally, formulations were able to provide a submucosa elevation of 1.70 cm for more than 90 min and 120 min in the porcine stomach and colon, respectively.

With a disproportionately high burden of global morbidity and mortality caused by chronic respiratory diseases (CRDs) in low and middle-income countries (LMICs), access to radiological services is of critical importance for screening, diagnosis, and treatment guidance.

There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. The rigidity of the cortical ECM limits expansion of the follicle and consequently oocyte maturation, maintaining the follicle in its quiescent state. Quiescent primordial, primary, and secondary follicles still exist in primary ovarian insufficiency (POI) patients, and techniques as in vitro activation (IVA) and drug-free IVA have recently been developed aiming to activate these follicles based on the Hippo signaling disruption that is essential in mechanotransduction. In this context, we analyze the effect of drug-free IVA in POI patients, comparing the relationship between possible resumption ovarian function and biomechanical properties of ovarian tissue.Nineteen POI patients according to ESHRE criteria who underwent drug-free IVA by laparoscopy between January 2018 and December 2019 and were followed up for a year after the intervention. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure tissue stiffness (Young's elastic modulus, E) at the micrometer scale. Functional outcomes after drug-free were analyzed.Resumption of ovarian function was observed in 10 patients (52.6%) and two of them became pregnant with live births. There were no differences in clinical characteristics (age and duration of amenorrhea) and basal hormone parameters (FSH and AMH) depending on whether or not there was activation after surgery. However, ovarian cortex stiffness was significantly greater in patients with ovarian activity after drug-free IVA: median E = 5519 Pa (2260-11,296) vs 1501 (999-3474); p-value 0.001.Biomechanical properties of ovarian cortex in POI patients have a great variability, and higher ovarian tissue stiffness entails a more favorable status when drug-free IVA is applied in their treatment. This status is probably related to an ovary with more residual follicles, which would explain a greater possibility of ovarian follicular reactivations after treatment.

Small pelagic fish (SPF) are fundamental components of marine food webs and are subject to boom and bust periods ascribed to the interactive effects of fishing and climate, which vary depending on species’ demography and life-history traits and determine the signal that we observe in fisheries time series. However, it is poorly understood how the biology of SPFs and habitat structure shape their population demography and responses to fishing and climate. This study evaluates the influence of life-history traits and the environment on the demography and the response to exploitation and climate for 14 populations of SPFs occurring in the European Atlantic Seas. Using age-structured population matrix models we calculated elasticities to characterize the contribution of recruitment to population growth rate. We then evaluated the association between biological traits and environmental conditions (mean, seasonality, and predictability) with average recruitment elasticity and demography. Finally, we quantified the effects of biological traits and geography in shaping the temporal responses of each population’s recruitment elasticities to demography, exploitation, and climate. For all species, population growth rate correlated positively with the elasticity to the recruitment, implying that long-term persistence is driven by the contribution of recruitment. Greater elasticity was found for populations with younger spawners, earlier maturation, and higher somatic growth rate inhabiting less predictable thermal ecosystems but with more temporally similar wind conditions. Among populations, fast growers had a stronger negative relationship between demographic structure and the importance of recruitment. At high fishing pressure, populations became increasingly dependent on recruitment though this relationship was less important for fast growers which, on average, sustained higher levels of exploitation. In turn, fast-maturing populations responded more strongly to the mean, seasonality, and predictability of the environmental conditions, especially towards eastern and southern geographically extremes. The results highlight the importance of recruitment for the population growth of SPFs and illustrate how the contribution of recruitment varies among and within populations as a function of environmental conditions and life-history traits defining an ordination of SPFs along a slow-fast continuum with implications for population dynamics and the responses to endogenous and exogenous factors.

BACKGROUND: Previous studies have challenged the concept of contrast material–induced acute kidney injury (AKI) in adults; however, limited data exist for children and adolescents. PURPOSE: To calculate the incidence and determine the risks of AKI in patients who received intravenous iodinated contrast media for CT. MATERIALS AND METHODS: This retrospective study was performed at a children’s hospital from January 2008 to January 2018 and included patients aged 0–17 years in whom serum creatinine levels were measured within 48 hours before and after CT with or without contrast media. The incidence of AKI was measured according to the AKI Network guidelines. A subgroup analysis with propensity score matching of cases with control patients was performed. Differences before and after stratification based on estimated glomerular filtration rate (eGFR) were explored. Adjusted risk models were developed using log-binomial generalized estimating equations to estimate relative risk (RR). RESULTS: From a total of 54 000 CT scans, 19 377 scans from 10 407 patients (median age, 8.5 years; IQR, 3–14; 5869 boys, 4538 girls) were included in the analysis. Incidence rate of AKI for the entire sample was 1.5%; it was 1.4% (123 of 8844) in the group that underwent contrast-enhanced CT and 1.6% (171 of 10 533) in the group that did not (P = .18). In the contrast-enhanced CT group, AKI incidence was higher in the group with eGFR of at least 60 mL/min/1.73 m(2) and in the group with eGFR lower than 60 mL/min/1.73 m(2) (1.3% and 8.5%, respectively; P < .001) compared with the noncontrast group (0.1% and 2.7%, respectively; P < .001). Age was found to be a protective factor against AKI, with an RR of 0.96 (95% CI: 0.94, 0.99; P = .01), and contrast media increased risk in the subgroup analysis, with an RR of 2.19 (95% CI: 1.11, 4.35; P = .02). CONCLUSION: The overall incidence of acute kidney injury after contrast-enhanced CT in children and adolescents was very low, and exposure to contrast media did not increase the risk consistently for acute kidney injury among different groups and analyses.

BACKGROUND፡ The thyroid, along with the breast, lung, and bone marrow, is among the most radiosensitive organs. This study aims to assess the rate of unnecessary radiation exposure to the thyroid gland in patients who had chest Computed Tomography (CT) at a large teaching hospital. METHOD: Hospital-based retrospective cross-sectional study on 1,306 patients who underwent chest CT from July 2018 to January 2019. Thyroid gland inclusion along with the CT dose of the studies was evaluated. Data was collected by evaluating chest CT scans from Picture Archive and Communication System (MedWeb). RESULT: Out of 1306 patients, who had Chest CT scans intravenous iodinated contrast media was used in 95.4% of the CT scans. The thyroid was included in 99.8% of the scans, out of which 76.9% included the whole thyroid gland. Among the patients who had previous CT scans, 75.3% had one previous scan and 24.7% had two previous scans. DLP (Dose Length Product) in mGycm was lower in females (360.33±32) compared to males (426.45±378.4). The lowest DLP value was observed in the pediatric patients in the age range of 1-5 years which was 146.83, while the highest was observed among those above 18 years of age with mean DLP of 418.31. CONCLUSION: The majority of chest CT scans unnecessarily include the whole thyroid gland, which is one of the most sensitive organs for radiation-induced effects. Authors recommend optimized technique for chest scans to avoid future impacts.

Diabetes mellitus is a major health problem with increasing prevalence at a global level. The discovery of insulin in the early 1900s represented a major breakthrough in diabetes management, with further milestones being subsequently achieved with the identification of glucagon-like peptide-1 (GLP-1) and the introduction of GLP-1 receptor agonists (GLP-1 RAs) in clinical practice. Moreover, the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption. However, current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation. In this review, we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.

Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.

Background Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). Methods Participants completed US, BIS, and anthropometry immediately before and 1–2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. Results Eight participants aged 3.4–18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). Conclusion BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

Glioblastoma cells co-cultured with astrocytes in col-HA hydrogels exhibit changes in migration patterns. 3D in vitro models using ECM mimetic materials can be used to analyze glioma-astrocyte crosstalk.

In 2021 BL Lacertae underwent an extraordinary activity phase, which was intensively followed by the Whole Earth Blazar Telescope (WEBT) Collaboration. We present the WEBT optical data in the BVRI bands acquired at 36 observatories around the world. In mid 2021 the source showed its historical maximum, with R = 11.14. The light curves display many episodes of intraday variability, whose amplitude increases with source brightness, in agreement with a geometrical interpretation of the long-term flux behaviour. This is also supported by the long-term spectral variability, with an almost achromatic trend with brightness. In contrast, short-term variations are found to be strongly chromatic and are ascribed to energetic processes in the jet. We also analyse the optical polarimetric behaviour, finding evidence of a strong correlation between the intrinsic fast variations in flux density and those in polarisation degree, with a time delay of about 13 h. This suggests a common physical origin. The overall behaviour of the source can be interpreted as the result of two mechanisms: variability on time scales greater than several days is likely produced by orientation effects, while either shock waves propagating in the jet, or magnetic reconnection, possibly induced by kink instabilities in the jet, can explain variability on shorter time scales. The latter scenario could also account for the appearance of quasi-periodic oscillations, with periods from a few days to a few hours, during outbursts, when the jet is more closely aligned with our line of sight and the time scales are shortened by relativistic effects., Comment: 15 pages, 16 figures, submitted to MNRAS

Top: Schematic of DNA-caged nanoparticle composite formation. Bottom: U87 cells labeled with fluorescent DNA-caged nanoparticles before and after erasing with single stranded DNA. Scale bar = 10 μm.

Aquaporins (AQPs) are proteins with various functions related to proper cell function and early development in mammals. The aim of this study was to evaluate the presence of AQPs and determine their mRNA levels in the cumulus oocyte complex (COC) of four bovine breeds and in blastocysts of five bovine crosses. Grade I, II and III COCs were collected by ovum pick up from non-lactating heifers of the Brahaman, Holstein, Gir and Romosinuano breeds. Embryos were produced in vitro up to the blastocyst stage of the bovine ♀Gir × ♂Holstein, ♀Holstein × ♂Gir, ♀Brahman × ♂Holstein, ♀Holstein × ♂Brahman, and ♀Romosinuano × ♂Holstein crosses. mRNA expression of AQP1-AQP12b was estimated in COC and embryos by real-time-PCR. The presence of the twelve AQPs in the COCs and bovine embryos was established. Additionally, significant differences were determined in the expression of AQP6 and AQP12b in COCs, as well as in transcripts levels of AQP4, AQP8 and AQP9 from bovine embryos. Gene expression of AQPs in COCs and bovine embryos is consistent with the previously described biological functions. This is the first report of AQPs in COC of Gir, Brahman, Holstein and Romosinuano and embryos of five crossbreeds between Bos indicus and B. taurus.

Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to reformulate intravenous drug preparations with unknown ocular bioavailability and toxicity. In the present study, natamycin/voriconazole formulations were developed and characterized to improve natamycin solubility, permanence, and safety. The solubility of natamycin was studied in the presence of two cyclodextrins: HPβCD and HPγCD. The HPβCD was chosen based on the solubility results. Natamycin/cyclodextrin (HPβCD) inclusion complexes characterization and a competition study between natamycin and voriconazole were conducted by NMR (Nuclear Magnetic Resonance). Based on these results, several eye drops with different polymer compositions were developed and subsequently characterized. Permeability studies suggested that the formulations improved the passage of natamycin through the cornea compared to the commercial formulation Natacyn®. The ocular safety of the formulations was determined by BCOP and HET-CAM. The antifungal activity assay demonstrated the ability of our formulations to inhibit the in vitro growth of different fungal species. All these results concluded that the formulations developed in the present study could significantly improve the treatment of FK.

DNA-modified nanoparticles enable DNA sensing and therapeutics in nanomedicine and are also crucial for nanoparticle self-assembly with DNA-based materials. However, methods to conjugate DNA to nanoparticle surfaces are limited, inefficient, and lack control. Inspired by DNA tile nanotechnology, we demonstrate a new approach to nanoparticle modification based on electrostatic attraction between negatively charged DNA tiles and positively charged nanoparticles. This approach does not disrupt nanoparticle surfaces and leverages the programmability of DNA nanotechnology to control DNA presentation. We demonstrated this approach using a variety of nanoparticles, including polymeric micelles, polystyrene beads, gold nanoparticles, and superparamagnetic iron oxide nanoparticles with sizes ranging from 5-20 nm in diameter. DNA cage formation was confirmed through transmission electron microscopy (TEM), neutralization of zeta potential, and a series of fluorescence experiments. DNA cages present “handle” sequences that can be used for reversible target attachment or self-assembly. Handle functionality was verified in solution, at the solid-liquid interface, and inside fixed cells, corresponding to applications in biosensing, DNA microarrays, and erasable immunocytochemistry. These experiments demonstrate the versatility of the electrostatic DNA caging approach and provide a new pathway to nanoparticle modification with DNA that will empower further applications of these materials in medicine and materials science.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at −20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at −20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops.

BACKGROUND: Typhlitis, (neutropenic enterocolitis), is a necrotizing enteropathy of the right colon, and is characterized by the clinical triad of fever, abdominal pain, neutropenia and imaging findings of right-side colonic inflammation. It is seen in the setting of severe neutropenia in immune suppressed patients who undergo treatment for malignancies, in those who have organ transplant(s) or congenital or other acquired immunosuppression. We report the clinical and imaging findings of typhlitis in pediatric cancer patients who had received chemotherapy in the largest tertiary center in Addis Ababa, Ethiopia over a period of 20 months. METHODS: The medical records of hospitalized cancer patients on treatment and with suspected typhlitis and with ultrasound reports were screened (November 2018- July 2020). Retrospective analysis of the clinical and sonographic data of those with typhlitis was done. RESULTS: Typhlitis was identified in 4.2% (12/286) of the patients on chemotherapy. 11 (91.7%) had hematologic malignancies (leukemia, lymphoma), one had a solid tumor (Head and neck embryonal RMS). Most (83.3%) had abdominal pain, diarrhea and neutropenia. Fever was identified in 67.7%. All had ultrasound evidence of typhlitis. and treated with IV antibiotics. Neither complications requiring surgical intervention nor death were seen. CONCLUSION: The magnitude of disease was comparable to what had previously been reported in other studies. While the presence of clinical a triad should prompt suspicion for the diagnosis, sonography can be used for confirmation and follow up obviating radiation, with good access in a resource limited setting.

Background Advances in statistical modelling and machine learning approaches, which can be deployed locally using open source programming languages, represent a unique opportunity to improve workflows and lower costs in health care across the globe through the creation of in silico biomarkers. The goal of this study was to extract meaningful data from the publicly available Prematurity and Respiratory Outcomes Program (PROP) trial data that could help generate useful clinical diagnostic aids with minimal cost for deployment in global healthcare settings. Methods A cluster analysis of the PROP dataset was conducted. We generated a simple model using an open-source software platform that generates a growth prediction of patients born less than 30 weeks. We then obtained validation data from a Uruguayan hospital to test the capacity for deployment of the models. Results Analysis revealed two main clusters of patients in the trial, with differentiation mainly based on the clinical and anthropomorphic measurements of birth gestational age, birth weight, and head circumference. The anthropometric measurements of daily weight, birth weight, head circumference, and birth gestational age were highly correlated with respiratory dysfunction and co-morbidities We note that deviation from this predicted growth curve in PROP patients was associated with culture-proven sepsis, and may represent a more sensitive anthropomorphic biomarker than the weight percentile systems routinely used globally such as Fenton curves. We found that early deviation from our projected growth model was highly associated with patient fatality. However, over long-term predictions, models trained on PROP clinical trial patients showed significantly more error in the Uruguayan patients. Conclusions Although these prediction models built upon PROP data were not generalizable to Uruguayan patients, our data suggest that prediction models using simple anthropomorphic measurements, if trained on local patients, may be able to provide value as a low-cost in silico biomarker. We concluded that local investment in clinical informatics infrastructure is needed to train models based on locally extracted clinical data.