Oxygenation Instability during Bolus versus Continuous Feeding among Very Low Birth Weight Premature Infants, Supported by Noninvasive Ventilation: A Randomized Prospective Study.

OBJECTIVE: This study aimed to compare oxygenation instability, as documented by the oxygen saturation (SpO2) histograms, during bolus (over 30 minutes) versus continuous (over 2 hours) feeding among very low birth weight (VLBW) premature infants, supported with noninvasive ventilation (NIV). STUDY DESIGN: This was a randomized prospective study. VLBW infants supported with NIV received three consecutive feeds in a random order of bolus-continuous-bolus or continuous-bolus-continuous. During each feed, 30 minutes and 2 hours histograms were documented. RESULTS: Twenty-four infants (birth weight [mean ± standard deviation, SD] 820 ± 168 g, gestational age [mean ± SD] 27.0 ± 1.6 weeks) were included in our study (12 infants started with bolus feeding and 12 with continuous feeding) and 72 histograms were obtained (36 during bolus feeding and 36 during continuous feeding). No differences in mean fraction of inspired oxygen (FiO2), and number of apnea events were observed between the two feeding modes. Oxygenation instability as assessed by time spent in different SpO2 ranges and histogram types (stable or unstable) was comparable during bolus and continuous feedings. Changing feeding mode from bolus to continuous or vice versa did not significantly change the oxygenation instability of the group, though individual infants did show a consistence response to feeding length changes. CONCLUSION: Among VLBW infants supported with NIV, oxygenation instability, as documented by SpO2 histograms, was comparable between bolus and continuous feedings. Individual infants may benefit from specific feeding length, and this can be easily demonstrated by the SpO2 histograms. KEY POINTS: · Feeding length did not affect oxygenation instability of preterm infants on noninvasive respiratory Support.. · Oxygen saturation histograms allow objective quantification of oxygenation instability at the bedside.. · Individual infants benefit from specific feeding length, as demonstrated by SpO2 histograms..

The Systemin Signaling Cascade As Derived from Time Course Analyses of the Systemin-responsive Phosphoproteome.

Systemin is a small peptide with important functions in plant wound response signaling. Although the transcriptional responses of systemin action are well described, the signaling cascades involved in systemin perception and signal transduction at the protein level are poorly understood. Here we used a tomato cell suspension culture system to profile phosphoproteomic responses induced by systemin and its inactive Thr17Ala analog, allowing us to reconstruct a systemin-specific kinase/phosphatase signaling network. Our time-course analysis revealed early phosphorylation events at the plasma membrane, such as dephosphorylation of H+-ATPase, rapid phosphorylation of NADPH-oxidase and Ca2+-ATPase. Later responses involved transient phosphorylation of small GTPases, vesicle trafficking proteins and transcription factors. Based on a correlation analysis of systemin-induced phosphorylation profiles, we predicted substrate candidates for 44 early systemin-responsive kinases, which includes receptor kinases and downstream kinases such as MAP kinases, as well as nine phosphatases. We propose a regulatory module in which H+-ATPase LHA1 is rapidly de-phosphorylated at its C-terminal regulatory residue T955 by phosphatase PLL5, resulting in the alkalization of the growth medium within 2 mins of systemin treatment. We found the MAP kinase MPK2 to have increased phosphorylation level at its activating TEY-motif at 15 min post-treatment. The predicted interaction of MPK2 with LHA1 was confirmed by in vitro kinase assays, suggesting that the H+-ATPase LHA1 is re-activated by MPK2 later in the systemin response. Our data set provides a resource of proteomic events involved in systemin signaling that will be valuable for further in-depth functional studies in elucidation of systemin signaling cascades.

The prognostic significance of lysosomal protective protein (cathepsin A) in breast ductal carcinoma in situ.

AIMS: Cathepsin A (CTSA) is a key regulatory enzyme for galactoside metabolism. Additionally, it has a distinct proteolytic activity and plays a role in tumour progression. CTSA is differentially expressed at the mRNA level between breast ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). In this study, we aimed to characterise CTSA protein expression in DCIS and evaluate its prognostic significance. METHODS AND RESULTS: A large cohort of DCIS [n = 776 for pure DCIS and n = 239 for DCIS associated with IBC (DCIS/IBC)] prepared as a tissue microarray was immunohistochemically stained for CTSA. High CTSA expression was observed in 48% of pure DCIS. High expression was associated with features of poor DCIS prognosis, including younger age at diagnosis (<50 years), higher nuclear grade, hormone receptor negativity, HER2 positivity, high proliferative index and high hypoxia inducible factor 1 alpha expression. High CTSA expression was associated with shorter recurrence-free interval (RFI) (P = 0.0001). In multivariate survival analysis for patients treated with breast conserving surgery, CTSA was an independent predictor of shorter RFI (P = 0.015). DCIS associated with IBC showed higher CTSA expression than pure DCIS (P = 0.04). In the DCIS/IBC cohort, CTSA expression was higher in the invasive component than the DCIS component (P < 0.0001). CONCLUSION: CTSA is not only associated with aggressive behaviour and poor outcome in DCIS but also a potential marker to predict co-existing invasion in DCIS.

Diversity and signature of small RNA in different bodily fluids using next generation sequencing.

BACKGROUND: Small RNAs are critical components in regulating various cellular pathways. These molecules may be tissue-associated or circulating in bodily fluids and have been shown to associate with different tumors. Next generation sequencing (NGS) on small RNAs is a powerful tool for profiling and discovery of microRNAs (miRNAs). RESULTS: In this study, we isolated total RNA from various bodily fluids: blood, leukocytes, serum, plasma, saliva, cell-free saliva, urine and cell-free urine. Next, we used Illumina's NGS platform and intensive bioinformatics analysis to investigate the distribution and signature of small RNAs in the various fluids. Successful NGS was accomplished despite the variations in RNA concentrations among the different fluids. Among the fluids studied, blood and plasma were found to be the most promising fluids for small RNA profiling as well as novel miRNA prediction. Saliva and urine yielded lower numbers of identifiable molecules and therefore were less reliable in small RNA profiling and less useful in predicting novel molecules. In addition, all fluids shared many molecules, including 139 miRNAs, the most abundant tRNAs, and the most abundant piwi-interacting RNAs (piRNAs). Fluids of similar origin (blood, urine or saliva) displayed closer clustering, while each fluid still retains its own characteristic signature based on its unique molecules and its levels of the common molecules. Donor urine samples showed sex-dependent differential clustering, which may prove useful for future studies. CONCLUSIONS: This study shows the successful clustering and unique signatures of bodily fluids based on their miRNA, tRNA and piRNA content. With this information, cohorts may be differentiated based on multiple molecules from each small RNA class by a multidimensional assessment of the overall molecular signature.

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredients (APIs) used in chemotherapy are highly cytotoxic to both cancer and normal cells. Accordingly, targeting the tumour vasculatures is essential for tumour treatment. In this context, encapsulation of anti-cancer drugs within the liposomal system offers secure platforms for the targeted delivery of anti-cancer drugs for the treatment of cancer. This, in turn, can be helpful for reducing the cytotoxic side effects of anti-cancer drugs on normal cells. This short-review focuses on the use of liposomes in anti-cancer drug delivery.

Oncolytic E1B 55KDa-deleted adenovirus replication is independent of p53 levels in cancer cells.

Oncolytic adenoviruses represent a new approach for cancer therapy due to its tumor specificity. E1B 55kDa-deleted adenovirus type 5 (Ad5dlE1B 55kDa) is a promising therapeutic agent that can selectively replicate in and lyse p53 defective cancer cells. However, the overall efficacy has shown varying degrees of success with raised doubts about the correlation between p53 status and E1B-deleted adenovirus replication ability. In this study, we investigated the relationship between the efficiency of Ad5dlE1B 55kDa replication and p53 levels in cancer cells. Five transient p53 expression vectors were engineered to expresses different p53 levels in transfected cells. Then, the effect of the variable p53 levels and cellular backgrounds on the replication efficiency of oncolytic Ad5dlE1B 55kDa was evaluated in H1299 and HeLa cell lines. We found that the replication efficiency of these oncolytic viruses is dependent on the status, but not the expression levels, of p53. Ad5dlE1B 55kDa was shown to have selective replication activity in H1299 cells (p53-null) and decreased viral replication in HeLa cells (p53-positive), relative to the wild-type adenovirus in both cell lines. Our findings suggest that there is a relation between the E1B-deleted adenovirus replication and the presence as well as the activity of p53, independent of its quantity.

Porous Inorganic Drug Delivery Systems-a Review.

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Role of Endonuclease G in Exogenous DNA Stability in HeLa Cells.

Endonuclease G (EndoG) is a well-conserved mitochondrial-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four-day time course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances, it may nonspecifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from nonviral DNA vectors in gene therapy efforts.

Influences of copolymers (Copovidone, Eudragit RL PO and Kollicoat MAE 30 DP) on stability and bioactivity of spray-dried and freeze-dried lysozyme.

Protein stability is the most crucial factor in protein pharmaceutical preparations. Various techniques were applied for producing stable protein formulations such as spray-drying and freeze-drying. However, heating and freezing stresses are disadvantages for proteins using these methods, respectively. Accordingly, excipients have been used to preserve therapeutic effects of proteins during processing and for long period of time. Therefore, influences of Copovidone, Eudragit® RL-PO and Kollicoat® MAE-30 DP (as excipients) on stability and integrity of lysozyme (as a model protein) in spray-dried and freeze-dried forms were investigated. Protein formulations in both dried forms were prepared without and with the addition of mentioned excipients at different concentrations. Protein formulations were characterized for yield determination, morphology using scanning electron microscopic (SEM), thermal analysis by Differential Scanning Calorimetry (DSC), secondary structure stability using Fourier transform infrared (FT-IR) spectroscopy and biological activity. All protein formulations were subjected to a stability study as solid protein formulations for 3 weeks at 24 °C/76% relative humidity and aqueous protein samples were stored at 50 °C for 30 min in a water bath. Results showed that Copovidone successfully preserved integrity and biological activity of lysozyme before and after storage in both spray-dried and freeze-dried forms with more advantage for using higher concentration of the same excipient. Smooth spheres of spray-dried lysozyme formulations with Copovidone were smaller than spray-dried lysozyme without and with Kollicoat® MAE-30 DP, which affected %yield produced. Copovidone has demonstrated valuable protection ability for lysozyme.

[Effect of endonuclease G depletion on plasmid DNA uptake and levels of homologous recombination in hela cells].

Endonuclease G (EndoG) is a mitochondrial apoptosis regulator that also has roles outside of programmed cell death. It has been implicated as a defence DNase involved in the degradation of exogenous DNA after transfection of mammalian cells and in homologous recombination of viral and endogenous DNA. In this study, we looked at the effect of EndoG depletion on plasmid DNA uptake and the levels of homologous recombination in HeLa cells. We show that the proposed defence role of EndoG against uptake of non-viral DNA vectors does not extend to the cervical carcinoma HeLa cells, as targeting of EndoG expression by RNA interference failed to increase intracellular plasmid DNA levels. However, reducing EndoG levels in HeLa cells resulted in a statistically significant reduction of homologous recombination between two plasmid DNA substrates. These findings suggest that non-viral DNA vectors are also substrates for EndoG in its role in homologous recombination.

Endonuclease G depletion may improve efficiency of first generation adenovirus vector DNA replication in HeLa cells.

First generation adenovirus (Ad5 ΔE1,E3) vectors are able to replicate their DNA in many tumour cells and can be used for oncotherapy. Highest rates of viral DNA replication occur in the G2/M transition of the cell cycle. In this study, we tried to increase the efficiency of Ad5 ΔE1,E3 DNA replication in the cervical carcinoma HeLa cells by using RNA interference (RNAi) to target endonuclease G (EndoG) whose depletion leads to an accumulation of cells in the G2/M transition. Targeting of EndoG by an shRNA encoded on an Ad5 ΔE1,E3 vector resulted in an early proliferation defect of cervical carcinoma HeLa cells. This effect coincided with enhanced DNA replication and encoded transgene expression of an Ad5 ΔE1,E3 vector. Applied in high concentrations, the EndoG-targeting Ad5 ΔE1,E3 vector showed enhanced HeLa cell killing ability relative to control Ad5 ΔE1,E3 vectors. These effects are most likely the result of EndoG depletion, which causes cells to accumulate in the G2/M transition of the cell cycle and extends favourable cellular conditions for Ad5 ΔE1,E3 DNA replication. Targeting of EndoG by RNAi may be a viable strategy for improving both the levels of transgene expression and the oncolytic properties of first generation adenovirus vectors.

Attitudes and Practices Regarding Helicobacter Pylori Infection Among the Public in Jordan: A Cross-Sectional Survey.

BACKGROUND: Helicobacter pylori is a major infection that can cause a variety of complications, including stomach cancer and peptic ulcers. There is a scarcity of research on the awareness of H. pylori in the general population in Jordan. Because public awareness and behavioral changes are powerful tools in curbing transmission rates, this study evaluated Jordanians' beliefs and behaviors about H. pylori infection. METHODS: The study was carried out in 2021 between May and July. Those who met the requirements for inclusion were asked to fill out a questionnaire through interviews. The questionnaire had three sections: sociodemographic data, participants' attitudes regarding H. pylori infection, and daily practices that could affect H. pylori transmission. RESULTS: Responses were collected from 767 participants, 50.7% were females, 65.8% were married, and 65.1% had a high educational level. Only 31.6% of the participants held a positive attitude. The female gender was significantly associated with better attitudes regarding H. pylori infection. One-third of the interviewed participants showed good practices. The female gender and being 50 years old and above were significantly associated with better practices. CONCLUSION: This study demonstrated that attitudes and practices regarding H. pylori infection in Jordan were unsatisfactory. Subsequently, public health efforts should be aimed at modifying those behaviors to decrease the disease burden.

Absent Meckel's cave as a possible cause of trigeminal neuralgia: A case report.

Trigeminal neuralgia (TN) is a debilitating yet potentially treatable facial pain disorder.TN is difficult to miss clinically, as patients' clinical presentation is often strikingly stereotypical: unilateral, paroxysmal, stimulus-dependent pain involving the trigeminal territory. Magnetic resonance imaging (MRI), which is used for further evaluation of an underlying etiology of TN, most commonly shows neurovascular compression of the trigeminal nerve to be the culprit. Secondary etiologies, though less common, do exist. An absent Meckel's cave with ipsilateral TN was reported in a few case reports and series, and whether an etiological relationship exists is yet to be established. We herein present a case of a 22-year-old female patient who presented with typical TN clinical manifestations. MRI was ordered to assess for the underlying cause and an ipsilateral absent Meckel's cave was the only significant finding. This case report adds to the scarcity of literature highlighting this entity, further larger clinical studies are needed to establish a causal relationship.

Serum IGF-1 to IGFBP-3 Molar Ratio: A Promising Diagnostic Tool for Growth Hormone Deficiency in Children.

BACKGROUND: The serum insulin-like growth factor-1 (IGF-1)/insulin-like growth factor binding protein-3 (IGFBP-3) ratio has various potential applications in growth hormone-related disorders. This study aimed to investigate the performance of the IGF-1/IGFBP-3 ratio, independently and in combination with serum IGF-1 and IGFBP-3, in the diagnosis of growth hormone deficiency (GHD) in children with short stature (SS). METHODS: A 7-year cross-sectional observational study was conducted on 235 children with SS. Participants with known disorders that may affect IGF-1 other than GHD were excluded. Participants were classified into GHD (n = 64) and non-GHD (n = 171) groups. GHD was defined as a slow growth rate (<25th percentile over 1 year) and suboptimal growth hormone (GH) response to 2 GH stimulation tests (peak GH < 6.25 ng/mL using the DiaSorin Liaison assay). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio, independently and in various combinations, were determined. RESULTS: GHD was diagnosed in 27.2% of participants. Among all studied variables, a low serum IGF-1/IGFBP-3 ratio demonstrated the greatest sensitivity for GHD (87.5%), with a comparable specificity (83.0%). The combination of low serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for GHD (97.7%), whereas the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of SS (100.0%). CONCLUSION: Our data suggest that the serum IGF-1/IGFBP-3 ratio is a useful marker for the diagnosis of GHD in children who do not have other disorders that may affect serum IGF-1 levels. Further large studies are needed to confirm the diagnostic utility of the serum IGF-1/IGFBP-3 ratio.

Myositis ossificans of the chest wall in an 8-year-old boy: a case report of a diagnostic pitfall.

Myositis ossificans of the chest wall is extremely unusual with fewer than a dozen reported cases. In addition, the occurrence in children younger than 10 years is extremely rare. We report a case of an 8-year-old male who presented with painful and progressively enlarging left-sided chest wall mass. The tumor showed close histo-morphological mimicry with osteosarcoma. Moreover, the characteristic radiographic findings of myositis ossificans were absent. The age of the patient and the absence of attachment to the rib helped exclude extra-skeletal and parosteal osteosarcomas, respectively. The patient was doing well 4 months after surgery.

Progressive censoring schemes for marshall-olkin pareto distribution with applications: Estimation and prediction.

In this paper two prediction methods are used to predict the non-observed (censored) units under progressive Type-II censored samples. The lifetimes of the units follow Marshall-Olkin Pareto distribution. We observe the posterior predictive density of the non-observed units and construct predictive intervals as well. Furthermore, we provide inference on the unknown parameters of the Marshall-Olkin model, so we observe point and interval estimation by using maximum likelihood and Bayesian estimation methods. Bayes estimation methods are obtained under quadratic loss function. EM algorithm is used to obtain numerical values of the Maximum likelihood method and Gibbs and the Monte Carlo Markov chain techniques are utilized for Bayesian calculations. A simulation study is performed to evaluate the performance of the estimators with respect to the mean square errors and the biases. Finally, we find the best prediction method by implementing a real data example under progressive Type-II censoring schemes.

Brain insulin resistance as a mechanistic mediator links peripheral metabolic disorders with declining cognition.

BACKGROUND AND AIMS: Studies continue to investigate the underlying mechanism of the association between the increased risk of different types of cognitive decline and metabolic dysregulation. Brain insulin resistance (BIR) has been suggested to explain this association. The vital role of insulin in the body has been examined intensively and extensively; however, its role in the brain requires further investigation. Herein, we confined our focus to summarize the role of brain insulin signaling and the negative effect of dysmetabolism on insulin functioning in the brain. METHODS: Published scientific manuscripts between 1998 and 2020 that discussed the effect of selected metabolic disorder conditions such as obesity, type 2 diabetes mellitus (T2DM), and high-fat diet (HFD) on brain functions were reviewed. The main keywords used were insulin resistance, brain insulin resistance, obesity, T2DM, and cognition. RESULTS: Various metabolic disorders were linked to the increased risk of BIR, and was suggested to increase the probability of cognition impairment occurrence. Several proposed mechanisms explain this association among which insulin resistance and hyperinsulinemia were primary factors attributed to an increased risk of BIR among various metabolic disorders. CONCLUSIONS: Understanding the trajectory of the association between metabolic disorders and alternation in cognition status could expand our vision of those overlapping conditions and pave the road to both treatment and preventative strategies for cognitive disorders.

Modeling of COVID-19 vaccination rate using odd Lomax inverted Nadarajah-Haghighi distribution.

Since the spread of COVID-19 pandemic in early 2020, modeling the related factors became mandatory, requiring new families of statistical distributions to be formulated. In the present paper we are interested in modeling the vaccination rate in some African countries. The recorded data in these countries show less vaccination rate, which will affect the spread of new active cases and will increase the mortality rate. A new extension of the inverted Nadarajah-Haghighi distribution is considered, which has four parameters and is obtained by combining the inverted Nadarajah-Haghighi distribution and the odd Lomax-G family. The proposed distribution is called the odd Lomax inverted Nadarajah-Haghighi (OLINH) distribution. This distribution owns many virtuous characteristics and attractive statistical properties, such as, the simple linear representation of density function, the flexibility of the hazard rate curve and the odd ratio of failure, in addition to other properties related to quantile, the rth-moment, moment generating function, Rényi entropy, and the function of ordered statistics. In this paper we address the problem of parameter estimation from frequentest and Bayesian approach, accordingly a comparison between the performance of the two estimation methods is implemented using simulation analysis and some numerical techniques. Finally different goodness of fit measures are used for modeling the COVID-19 vaccination rate, which proves the suitability of the OLINH distribution over other competitive distributions.

A late-diagnosed dermoid cyst complicated with a fistula in the left scapular region: a case report.

Dermoid cysts are a rare case of developmental abnormality that results in benign tumors, which are classified into three categories based on their cause and appearance. Dermoid cysts tend to present within the first year after birth and are most commonly diagnosed by the age of 5. A 15-year-old girl presented with a complaint of localized, paroxysmal pain and malodorous fluid oozing from the left shoulder for the last 2 weeks. A fistulogram showed an extension of the fistula behind the clavicle and above the scapula with a cystic formation measuring ~2 cm on the upper part of the fistula tract, which called for appropriate surgical intervention. Our case is the first reported dermoid cyst in the left shoulder area associated with a fistula at birth, which is a rare complication since the complications of dermoid cysts differ depending on their location and size.

Bayesian and non-Bayesian inference under adaptive type-II progressive censored sample with exponentiated power Lindley distribution.

This paper deals with the statistical inference of the unknown parameters of three-parameter exponentiated power Lindley distribution under adaptive progressive type-II censored samples. The maximum likelihood estimator (MLE) cannot be expressed explicitly, hence approximate MLEs are conducted using the Newton-Raphson method. Bayesian estimation is studied and the Markov Chain Monte Carlo method is used for computing the Bayes estimation. For Bayesian estimation, we consider two loss functions, namely: squared error and linear exponential (LINEX) loss functions, furthermore, we perform asymptotic confidence intervals and the credible intervals for the unknown parameters. A comparison between Bayes estimation and the MLE is observed using simulation analysis and we perform an optimally criterion for some suggested censoring schemes by minimizing bias and mean square error for the point estimation of the parameters. Finally, a real data example is used for the illustration of the goodness of fit for this model.