Intravitreal methotrexate infusion for prophylaxis of proliferative vitreoretinopathy after pars plana vitrectomy for rhegmatogenous retinal detachment

Background: Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment after surgical repair of rhegmatogenous retinal detachment (RRD). Our study aimed to assess the efficacy and safety of intravitreal methotrexate infusion (IMI) for the prevention of PVR after pars plana vitrectomy (PPV) in eyes with RRD. Methods: This prospective comparative interventional study was conducted from September 2020 to November 2021 at Ain Shams University Hospitals, Egypt. We recruited a consecutive, non-randomized sample of 47 eyes of 47 patients with RRD undergoing PPV. Participants were allocated to a control group or an intervention group that received IMI during surgery. Each group was subdivided into subgroups of eyes at high-risk of developing PVR and eyes with established preoperative PVR grade C. Outcome measures at the 3-month postoperative follow-up were the rate of retinal attachment, incidence of PVR, reoperation rate to flatten the retina, and changes in the retina and/or optic nerve function as assessed by full-field electroretinogram and flash visual evoked potential. Results: Data from 47 eyes (23 and 24 eyes in the intervention and control groups, respectively) were evaluated. Subgroups IA, IB, and IIB each included 12 eyes, subgroup IIA included 11 eyes, and all subgroups had comparable sex ratios and age distributions. Postoperative PVR at 1 month and between 1 and 3 months was present in 13% and 4% of eyes in the intervention group, respectively. Reoperation to flatten the retina was required in 2 (9%) eyes in the intervention group, while 22 eyes (96%) had complete flattening of the retina at 3 months. No significant differences were found between the study groups and the corresponding subgroups regarding the outcome measures (all P > 0.05). No adverse events attributable to IMI were detected up to 3 months postoperatively. Conclusions: Although IMI was safe for intraocular use in eyes with RRD and PVR grade C or a high risk of developing PVR, it did not affect the anatomical success rate or development of PVR up to 3 months after PPV. Further multicenter randomized clinical trials with longer follow-up periods and larger sample sizes are needed to verify these preliminary outcomes

Marine brominated tyrosine alkaloids as promising inhibitors of SARS-CoV-2

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = -7.78, -7.65, -6.39, -6.28, -8.84 Kcal/mol) for the main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited

Clinical characteristics of depression among adolescent females: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Adolescents rarely seek psychiatric help; they even hesitate to disclose their feelings to their parents. However; the adolescents especially the females experience depressive symptoms more frequently than general population. Do they experience classic depressive symptoms? Are there symptoms specific to this subpopulation?</p> <p>Aim of the study</p> <p>Through this study, the authors aimed to estimate the prevalence of depressive disorders in Egyptian adolescent female students. They also expected a characteristic profile of symptoms for the adolescent females. However available literature provides no guidance in the description of this profile of symptoms.</p> <p>Methods</p> <p>A number of 602 adolescent females were interviewed, and subjected to General Health Questionnaire (GHQ); Children Depression Inventory (CDI), Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), then Hamilton Rating Scale for Depression (Ham-D). Results were analyzed by the use of SPSS-15.</p> <p>Results</p> <p>The study revealed the prevalence of depression in the sample of the study to be 15.3% (measured by CDI), and 13.3% (measured by SCID-I). Fatigue was the most common presenting depressive symptom (81.3%), in addition to other emotional, cognitive and physiological symptoms. Suicidal ideations were the most common suicidal symptoms in depressed adolescent females (20%), with 2.5% serious suicidal attempts.</p> <p>Conclusions</p> <p>The somatic symptoms were by far the most common presenting symptom for female adolescents suffering from depressive disorders. Depressive phenomena including unexplained fatigue, decreased energy, psychomotor changes, lack of concentration, weight changes and suicidal ideations may be the presenting complaints instead of the classic sad mood.</p

The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at control-ling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming

Comprehensive virtual screening of the antiviral potentialities of marine polycyclic guanidine alkaloids against SARS-CoV-2 (COVID-19)

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (∆G = −8.05 kcal/mol), nucleocapsid phosphoprotein (∆G = −6.49 kcal/mol), and nsp10 (∆G = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (∆G = −7.99 kcal/mol), spike glycoproteins (∆G = −6.95 kcal/mol), and nucleocapsid phosphoprotein (∆G = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and13 showed promising docking,ADMET,toxicity and MD results which open the door for further investigations for them against SARS-CoV-2

Identification and Characterization of Novel Proteins from Arizona Bark Scorpion Venom That Inhibit Nav1.8, a Voltage-Gated Sodium Channel Regulator of Pain Signaling

The voltage-gated sodium channel Nav1.8 is linked to neuropathic and inflammatory pain, highlighting the potential to serve as a drug target. However, the biophysical mechanisms that regulate Nav1.8 activation and inactivation gating are not completely understood. Progress has been hindered by a lack of biochemical tools for examining Nav1.8 gating mechanisms. Arizona bark scorpion (Centruroides sculpturatus) venom proteins inhibit Nav1.8 and block pain in grasshopper mice (Onychomys torridus). These proteins provide tools for examining Nav1.8 structure-activity relationships. To identify proteins that inhibit Nav1.8 activity, venom samples were fractioned using liquid chromatography (reversed-phase and ion exchange). A recombinant Nav1.8 clone expressed in ND7/23 cells was used to identify subfractions that inhibited Nav1.8 Na+ current. Mass-spectrometry-based bottom-up proteomic analyses identified unique peptides from inhibitory subfractions. A search of the peptides against the AZ bark scorpion venom gland transcriptome revealed four novel proteins between 40 and 60% conserved with venom proteins from scorpions in four genera (Centruroides, Parabuthus, Androctonus, and Tityus). Ranging from 63 to 82 amino acids, each primary structure includes eight cysteines and a "CXCE" motif, where X = an aromatic residue (tryptophan, tyrosine, or phenylalanine). Electrophysiology data demonstrated that the inhibitory effects of bioactive subfractions can be removed by hyperpolarizing the channels, suggesting that proteins may function as gating modifiers as opposed to pore blockers

The Importance of Research on the Origin of SARS-CoV-2

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational “hot spot” as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required