POS-1 Regulation of Endo-mesoderm Identity in C. elegans: A Dissertation

How do embryos develop with such poise from a single zygote to multiple cells with different identities, and yet survive? At the four-cell stage of the C. elegans embryo, only the blastomere EMS adopts the endo-mesoderm identity. This fate requires SKN-1, the master regulator of endoderm and mesoderm differentiation. However, in the absence of the RNA binding protein POS-1, EMS fails to fulfill its fate despite the presence of SKN-1. pos-1(-) embryos die gutless. Conversely, the RNA binding protein MEX-5 prevents ectoderm blastomeres from adopting the endo-mesoderm identity by repressing SKN-1. mex-5(-) embryos die with excess muscle at the expense of skin and neurons. Through forward and reverse genetics, I found that genes gld-3/Bicaudal C, cytoplasmic adenylase gld-2, cye-1/Cyclin E, glp-1/Notch and the novel gene neg-1 are suppressors that restore gut development despite the absence of pos-1. Both POS-1 and MEX-5 bind the 3’UTR of neg-1 mRNA and its poly(A) tail requires GLD-3/2 for elongation. Moreover, neg-1 requires MEX-5 for its expression in anterior ectoderm blastomeres and is repressed in EMS by POS-1. Most neg-1(-) embryos die with defects in anterior ectoderm development where the mesoderm transcription factor pha-4 becomes ectopically expressed. This lethality is reduced by the concomitant loss of med- 1, a key mesoderm-promoting transcription factor. Thus the endo-mesoderm identity of EMS is determined by the presence of SKN- 1 and the POS-1 repression of neg-1, whose expression is promoted by MEX-5. Together they promote the anterior ectoderm identity by repressing mesoderm differentiation. Such checks and balances ensure the vital plurality of cellular identity without the lethal tyranny of a single fate

Diosgenin alleviates D-galactose-induced oxidative stress in rats’ brain and liver targeting aging and apoptotic marker genes

The theory of aging is primarily concerned with oxidative stress caused by an imbalance in reactive oxygen species generation and cellular antioxidants. To alleviate the oxidative stress, we investigated the protective effect of diosgenin (DSG) for D-galactose (D-gal) using 20 and 40 mg of DSG/kg/day/orally for 42 days. The findings showed that D-gal caused brain and liver oxidative injuries by upregulating aging and oxidative markers. To counteract the oxidative stress caused by D-gal, DSG upregulated glutathione peroxidase-1, superoxide dismutase-1, and glutathione S-transferase-α. DSG also diminished the expression of p53, p21, Bcl-2-associated X protein, caspase-3, and mammalian target of rapamycin in brain and liver, as well as the build-up of β-galactosidase. DSG, in a dose-dependent manner, decreased the oxidative aging effects of D-gal in brain and liver tissues through targeting of aging and apoptotic marker genes. Finally, it should be noted that consuming DSG supplements is a suggesting natural preventative agent that may counteract aging and preserve health through improvement of body antioxidant status and control aging associated inflammation and cellular apoptosis

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The early warning application role in facing the environmental crisis and disasters: "Preliminarily risk management strategy for the greater city of Cairo"

Natural disasters are inevitable and it is almost impossible to fully recoup the damage caused by the disasters. But it is possible to minimize the potential risk by developing disaster early warning strategies, methods using the new technology applications which play a crucial role in efficient mitigation and management of disasters. This paper describes the importance of the remote sensing and Geographical Information System (GIS) in evolving a suitable strategy for disaster, crises and risk management using these technologies. The main objective of this paper is to make a Preliminary risk management plan (it is a logical and systematic method of identifying, analyzing, treating and monitoring the risks involved in any activity or process. This process helps Administrations to focus on priorities and in decisions on deploying limited resources to deal with the highest risks) using the Environmental risk map of the greater city of Cairo demonstrating the most high-risk administrative areas in the city, supported by field evidence and different sources of information. to reduce the loss of life and property and protect the Nation from all hazards, including natural disasters and other man-made disasters, by leading and supporting the Nation in a risk-based, comprehensive emergency management system of preparedness, protection, response, recovery, and mitigation. This study has shown that how can the early warning Applications can be useful in analyzing, Integrating and managing different datasets for predicting the environmental crises and disasters that may affect the urbanism inside the city and help in the preparation of the Risk management plan

Erector spinae plane block versus paravertebral block in analgesic outcomes following breast surgery

Abstract This article represents the response to the inquiries adopted by Dr. Raghuraman M Sethuraman, M.D., regarding our recently published study which compared the erector spinae plane block (ESPB) versus paravertebral block (PVB) regarding postoperative analgesic consumption following breast surgeries (Elewa et al, BMC Anesthesiol 22: 1-9, 2022). We would like to introduce our appreciation and gratitude to the author for his interest in our work, despite being inaccurate in some of his comments

Comparison between erector spinae plane block and paravertebral block regarding postoperative analgesic consumption following breast surgery : a randomized controlled study

Background: Pain control following breast surgery is of utmost importance in order to reduce the chance of chronic pain development, and facilitate early rehabilitation. The erector spinae plane block (ESPB) is a recently developed regional anaesthesia procedure successfully used for different types of surgical procedures including thoracic and abdominal surgeries. Methods: A double-blind, randomized, controlled trial was conducted on 90 patients who were scheduled for modified radical mastectomy (MRM). Patients were randomly categorized into groups I (women who underwent ESPB), II (women who underwent paravertebral block (PVB), and III (women who underwent general anaesthesia). Results: The ESPB (4.9 +/- 1.2 mg) and PVB (5.8 +/- 1.3 mg) groups had significantly lower total morphine consumption than the control group had (16.4 +/- 3.1 mg; p &lt; 0.001). Notably, patients in the ESPB group had insignificantly lower morphine consumption than those in the PVB group had (p= 0.076). Moreover, patients in the ESPB and PVB groups had a significantly longer time to first required anaesthesia than those in the control group (7.9 +/- 1.2 versus 7.5 +/- 0.9 versus 2 +/- 1.2 h, respectively; p&lt;0.001).The postoperative visual analog scale scores were lower in the ESPB and PVB groups than in the control group on the first 24 h after the procedure (p&lt; 0.001). Conclusion: ESPB and PVB provide effective postoperative analgesia for women undergoing MRM. The ESPB appears to be as effective as the PVB.Funding Agencies|Science, Technology &amp; Innovation Funding Authority (STDF); Egyptian Knowledge Bank (EKB)</p

Divide and differentiate: CDK/Cyclins and the art of development

The elegant choreography of metazoan development demands exquisite regulation of cell-division timing, orientation, and asymmetry. In this review, we discuss studies in Drosophila and C. elegans that reveal how the cell cycle machinery, comprised of cyclin-dependent kinase (CDK) and cyclins functions as a master regulator of development. We provide examples of how CDK/cyclins: (1) regulate the asymmetric localization and timely destruction of cell fate determinants; (2) couple signaling to the control of cell division orientation; and (3) maintain mitotic zones for stem cell proliferation. These studies illustrate how the core cell cycle machinery should be viewed not merely as an engine that drives the cell cycle forward, but rather as a dynamic regulator that integrates the cell-division cycle with cellular differentiation, ensuring the coherent and faithful execution of developmental programs

Osteoblast-activating peptide exhibits a specific distribution pattern in mouse ovary and may regulate ovarian steroids and local calcium levels

Osteoblast-activating peptide (OBAP) is a novel protein affecting osteoblast proliferation and differentiation, but its ovarian expression is yet to be reported. Osteoporosis is a common disease, caused mainly by low estrogen levels in females. We investigated whether OBAP regulates estrogen synthesis and osteoporosis. Using immunohistochemical analyses, we studied the distribution of OBAP in different parts of the mouse ovary. We also attempted to clarify the correlation of OBAP with ovarian steroids and calcium-regulating factors in the same ovarian tissues, including aromatase (CYP19), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), estrogen receptor (ER), progesterone receptor (PR), receptor activator of nuclear factor-kappa B (RANK), calmodulin, calbindin, and calcium-sensing receptor. The ovarian interstitial endocrine cells (IC) showed the greatest localization of OBAP, followed by the mature corpus luteum and the oocytes of mature Graafian follicles (MGF), while there were strong negative correlations of OBAP with CYP19. Strong positive correlations with 3 beta-HSD (except MGF), RANK (except IC), and calmodulin (except MGF and IC) were demonstrated. OBAP also showed partially positive correlations with ER and PR in the corpus luteum and with IC and calbindin in the MGF. We conclude that OBAP might be related to estrogen synthesis and calcium homeostasis