Overall manifestations and survival of pediatric patients with Langerhans cell histiocytosis. A middle-income country (mic) national multicenter study.

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by clonal proliferation of den-dritic cells. It is Mexico's ninth most frequent malignancy in patients under 18 years of age. The aim of the study was to determine the clinical characteristics, treatment, and survival of Mexican pediatric patients diagnosed with LCH treated from January 2010 to December 2018.

Incorporation of CF-pseudoprolines into polyproline type II foldamers confers promising biophysical features.

The development and the use of fluorinated polyproline-type II (PPII) foldamers are still underexplored. Herein, trifluoromethyl pseudoprolines have been incorporated into polyproline backbones without affecting their PPII helicity. The ability of the trifluoromethyl groups to increase hydrophobicity and to act as F NMR probes is demonstrated.

Allosteric nanobodies to study the interactions between SOS1 and RAS.

Protein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse nanobodies that either stabilize or disrupt PPIs in a single experiment. We apply ChILL and DisCO to identify competitive, connective, or fully allosteric nanobodies that inhibit or facilitate the formation of the SOS1•RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro as well as RAS signalling in cellulo.

Impact of treatment and clinical characteristics on the survival of children with medulloblastoma in Mexico.

Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting.

Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico.

Multitarget μ-Opioid Receptor Agonists─Neuropeptide FF Receptor Antagonists Induce Potent Antinociception with Reduced Adverse Side Effects.

The design of bifunctional compounds is a promising approach toward the development of strong analgesics with reduced side effects. We here report the optimization of the previously published lead peptide , which contains opioid receptor agonist and neuropeptide FF receptor antagonist pharmacophores and is shown to induce potent antinociception and reduced side effects. We evaluated the novel hybrid peptides for their activity at MOP, NPFFR1, and NPFFR2 and selected four of them () for assessment of their acute antinociceptive activity in mice.

Introduction of constrained Trp analogs in RW9 modulates structure and partition in membrane models.

Over the past decades, many cell-penetrating peptides (CPP) have been studied for their capacity to cross cellular membranes, mostly in order to improve cellular uptake of therapeutic agents. Even though hydrophobic and anionic CPPs have been described, many of them are polycationic, due to the presence of several arginine (Arg) residues. Noteworthy, however, the presence of aromatic amino acids such as tryptophan (Trp) within CPPs seems to play an important role to reach high membranotropic activity.

Nanobody Loop Mimetics Enhance Son of Sevenless 1-Catalyzed Nucleotide Exchange on RAS.

RAS proteins control various intracellular signaling networks. Mutations at specific locations were shown to stabilize their active guanosine triphosphate (GTP)-bound state, which is associated with the development of multiple cancers. An attractive approach to modulate RAS signaling is through its regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1).

Unit Collective Medical Training in the 75th Ranger Regiment.

The 75th Ranger Regiment's success with eliminating preventable death on the battlefield is innate to the execution of a continuous operational readiness training cycle that integrates individual and unit collective medical training. This is a tactical solution to a tactical problem that is solved by the entire unit, not just by medics. When a casualty occurs, the unit must immediately respond as a team to extract, treat, and evacuate the casualty while simultaneously completing the tactical mission.

Anti-HCV and Zika activities of ribavirin C-nucleosides analogues.

Ribavirin is an unnatural nucleoside exhibiting broad spectrum of antiviral and antitumor activities, still very widely studied particularly in a repositioning approach. C-triazolyl nucleoside analogues of ribavirin have been synthesized, as well as prodrugs and glycosylated or peptide conjugates to allow a better activity by vectorization into the liver or by facilitating uptake into the cells. The antiviral properties of all synthesized compounds have been evaluated in vitro against two important human viral pathogens belonging to the Flaviviridae family: hepatitis C virus (HCV) and Zika virus (ZIKV).

Identification and Characteristics of Fusion Peptides Derived From Enveloped Viruses.

Membrane fusion events allow enveloped viruses to enter and infect cells. The study of these processes has led to the identification of a number of proteins that mediate this process. These proteins are classified according to their structure, which vary according to the viral genealogy.

Case Series on 2g Tranexamic Acid Flush From the 75th Ranger Regiment Casualty Database.

Early tranexamic acid (TXA) administration for resuscitation of critically injured warfighters provides a mortality benefit. The 2019 Tactical Combat Casualty Care (TCCC) recommendations of a 1g drip over 10 minutes, followed by 1g drip over 8 hours, is intended to limit potential TXA side effects, including hypotension, seizures, and anaphylaxis. However, this slow and cumbersome TXA infusion protocol is difficult to execute in the tactical care environment.

Structure-Based Design of Melanocortin 4 Receptor Ligands Based on the SHU-9119-hMC4R Cocrystal Structure†.

The melanocortin receptors (MC1R-MC5R) belong to class A G-protein-coupled receptors (GPCRs) and are known to have receptor-specific roles in normal and diseased states. Selectivity for MC4R is of particular interest due to its involvement in various metabolic disorders, including obesity, feeding regulation, and sexual dysfunctions. To further improve the potency and selectivity of MC4R (ant)agonist peptide ligands, we designed and synthesized a series of cyclic peptides based on the recent crystal structure of MC4R in complex with the well-characterized antagonist (Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH).

Optimized Opioid-Neurotensin Multitarget Peptides: From Design to Structure-Activity Relationship Studies.

Fusion of nonopioid pharmacophores, such as neurotensin, with opioid ligands represents an attractive approach for pain treatment. Herein, the μ-/δ-opioid agonist tetrapeptide H-Dmt-d-Arg-Aba-β-Ala-NH () was fused to analogues. Since the NTS1 receptor has been linked to adverse effects, selective MOR-NTS2 ligands are preferred.

Neurotensin Analogues Containing Cyclic Surrogates of Tyrosine at Position 11 Improve NTS2 Selectivity Leading to Analgesia without Hypotension and Hypothermia.

Neurotensin (NT) exerts its analgesic effects through activation of the G protein-coupled receptors NTS1 and NTS2. This opioid-independent antinociception represents a potential alternative for pain management. While activation of NTS1 also induces a drop in blood pressure and body temperature, NTS2 appears to be an analgesic target free of these adverse effects.

Studies of membranotropic and fusogenic activity of two putative HCV fusion peptides.

Over the past decades, membranotropic peptides such as positively charged cell-penetrating peptides (CPPs) or amphipathic antimicrobial peptides (AMPs) have received increasing interest in order to improve therapeutic agent cellular uptake. As far as we are concerned, we were interested in studying HCV fusion peptides as putative anchors. Two peptides, HCV6 and HCV7, were identified and conjugated to a fluorescent tag NBD and tested for their interaction with liposomes as model membranes.

Missed Connections at the Junction of Sociolinguistics and Speech Processing.

In recent years, significant momentum has built up in efforts to integrate the social with the cognitive in theoretical models of speech production/processing and phonological representation. While acknowledging these advances, we argue that what limits our ability to elaborate models of processing and representation in which social-indexical properties of speech are effectively integrated is that we remain some way from fully understanding how these properties are manifested within spoken interaction in the first place. We explore some of these limitations, drawing on data from a study of sociophonetic variability in a population of speakers of Australian English.

[Ten years of renal transplantation in children].

One hundred and fourteen kidney transplants (87 first and 27 second and thirds) were performed in 90 children aged 1 to 15 years during the period 1979-1988; 44% were under 10 years, 14% under 5 and 8% under 3 years of age. The renal grafts were from living related donor (LD) in 30 cases and from cadaveric donor (CD) in 84; 91 were from adult donors and 23 from pediatric ones. The actuarial survival rate of the patients at one and two years was 100% in the LD and 92 and 90% respectively in the CD group.

[The direct isotopic cystography in the study of the vesico-ureteral reflux (author's transl)].

A technique of direct isotopic cystography is presented. It uses 99mTc-DTPA and scintillation camera connected to a computer. The study included a group of children affected of vesico-ureteral reflux; the results are discussed and compared to those of the classical radiological method of voiding cystography.