School of cheminformatics in Latin America.

We report the major highlights of the School of Cheminformatics in Latin America, Mexico City, November 24-25, 2022. Six lectures, one workshop, and one roundtable with four editors were presented during an online public event with speakers from academia, big pharma, and public research institutions. One thousand one hundred eighty-one students and academics from seventy-nine countries registered for the meeting. As part of the meeting, advances in enumeration and visualization of chemical space, applications in natural product-based drug discovery, drug discovery for neglected diseases, toxicity prediction, and general guidelines for data analysis were discussed. Experts from ChEMBL presented a workshop on how to use the resources of this major compounds database used in cheminformatics. The school also included a round table with editors of cheminformatics journals. The full program of the meeting and the recordings of the sessions are publicly available at https://www.youtube.com/@SchoolChemInfLA/featured .

Cell-free protein synthesis: advances on production process for biopharmaceuticals and immunobiological products.

Biopharmaceutical products are of great importance in the treatment or prevention of many diseases and represent a growing share of the global pharmaceutical market. The usual technology for protein synthesis (cell-based expression) faces certain obstacles, especially with 'difficult-to-express' proteins. Cell-free protein synthesis (CFPS) can overcome the main bottlenecks of cell-based expression. This review aims to present recent advances in the production process of biologic products by CFPS. First, key aspects of CFPS systems are summarized. A description of several biologic products that have been successfully produced using the CFPS system is provided. Finally, the CFPS system's ability to scale up and scale down, its main limitations and its application for biologics production are discussed.

Sarco-Endoplasmic Reticulum Calcium Release Model Based on Changes in the Luminal Calcium Content.

The sarcoplasmic/endoplasmic reticulum (SR/ER) is the main intracellular calcium (Ca2+) pool in muscle and non-muscle eukaryotic cells, respectively. The reticulum accumulates Ca2+ against its electrochemical gradient by the action of sarco/endoplasmic reticulum calcium ATPases (SERCA pumps), and the capacity of this Ca2+ store is increased by the presence of Ca2+ binding proteins in the lumen of the reticulum. A diversity of physical and chemical signals, activate the main Ca2+ release channels, i.e. ryanodine receptors (RyRs) and inositol (1, 4, 5) trisphosphate receptors (IP3Rs), to produce transient elevations of the cytoplasmic calcium concentration ([Ca2+]i) while the reticulum is being depleted of Ca2+. This picture is incomplete because it implies that the elements involved in the Ca2+ release process are acting alone and independently of each other. However, it appears that the Ca2+ released by RyRs and IP3Rs is trapped in luminal Ca2+ binding proteins (Ca2+ lattice), which are associated with these release channels, and the activation of these channels appears to facilitate that the trapped Ca2+ ions become available for release. This situation makes the initial stage of the Ca2+ release process a highly efficient one; accordingly, there is a large increase in the [Ca2+]i with minimal reductions in the bulk of the free luminal SR/ER [Ca2+] ([Ca2+]SR/ER). Additionally, it has been shown that active SERCA pumps are required for attaining this highly efficient Ca2+ release process. All these data indicate that Ca2+ release by the SR/ER is a highly regulated event and not just Ca2+ coming down its electrochemical gradient via the open release channels. One obvious advantage of this sophisticated Ca2+ release process is to avoid depletion of the ER Ca2+ store and accordingly, to prevent the activation of ER stress during each Ca2+ release event.

Randomized comparison of prophylaxis and on-demand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors.

Factor replacement therapy for the treatment of moderate to severe haemophilia A and B can be complicated by the production of inhibitory alloantibodies to factor VIII (FVIII) or factor IX. Treatment with the nanofiltered anti-inhibitor coagulant complex, Factor Eight Inhibitor Bypassing Activity (FEIBA NF), is a key therapeutic option for controlling acute haemorrhages in patients with high-titre inhibitors or low-titre inhibitors refractory to replacement therapy. Given the high risk for morbidity and mortality in haemophilia patients with inhibitors to FVIII or FIX, we conducted this Phase 3 prospective study to evaluate whether prophylaxis with FEIBA NF is a safe and effective treatment option. Over a 1-year period, 17 subjects were treated prophylactically (85 ± 15 U kg(-1) every other day) while 19 subjects were treated on demand. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 7.9 (8.1), compared to 28.7 (32.3) during on-demand treatment, which amounts to a 72.5% reduction and a statistically significant difference in ABRs between arms (P = 0.0003). Three (17.6%) subjects (ITT) on prophylaxis experienced no bleeding episodes, whereas none treated on demand were bleeding episode-free. Total utilization of FEIBA NF for the treatment of bleeding episodes was significantly higher during on-demand therapy than prophylaxis (P = 0.0067). There were no differences in the rates of related adverse events between arms. This study demonstrates that FEIBA prophylaxis significantly reduces all types of bleeding compared with on-demand treatment, and the safety of prophylaxis is comparable to that of on-demand treatment.

Estudio de pacientes relaparotomizados en el Hospital General Docente "Dr. Enrique Cabrera". 2006-2010 / Study of relaparotomied patients at University Hospital "Dr. Enrique Cabrera". 2006 - 2010

Introducción: persisten las discrepancias sobre la reintervención quirúrgica o relaparotomías en pacientes con peritonitis. Objetivo: Caracterizar las relaparotomías en pacientes con peritonitis ingresados en la Unidad de Cuidados Intensivos del Hospital General Docente "Dr. Enrique Cabrera". Material y método: se realizó un estudio descriptivo, transversal y retrospectivo de los pacientes relaparotomizados por diagnóstico de peritonitis ingresados en la Unidad de Cuidados Intensivos del Hospital General "Enrique Cabrera" desde el 2006 al 2010. Se analizaron variables como tipo de relaparotomía, diagnóstico preoperatorio, indicaciones y complicaciones. La información se obtuvo de las historias clínicas de los pacientes. Resultados: se relaparotomizaron 44 pacientes, 27 relaparotomías a demanda (RD), 15 relaparotomías programadas (RP) y 2, por técnica abdomen abierto (AA). 45,5% de los pacientes fueron por síndromes peritoneales y de ellos los perforativos los más frecuentes. Las principales indicaciones fueron por peritonitis fecaloidea, abscesos intrabdominales y peritonitis fibrinopurulenta. Las complicaciones más frecuentes fueron shock séptico e infección del sitio quirúrgico. Las complicaciones más graves se presentaron en la RD. Conclusiones: las relaparotomías se realizan fundamentalmente por peritonitis fecaloidea o fibrinopurulenta constatándose que las complicaciones más graves fueron más frecuentes en las relaparotomías a demanda.

Introducción: discrepancies about surgical reinterventions in patients with peritonitis still persist at present. Objective: characterize the relaparatomy in a patient who entered with peritonitis in the intensive care unit at "Enrique Cabrera" Hospital. Material and Methods: it was carried out a retrospective and descriptive study in patients who were practice a second laparatomy for peritonitis from January 2006 to December 2010. Some variables were analyzed such as: type of relaparatomy performed, indications and complications. Information was taken from the clinical records of the patients. Results: from a total of 44 patients who were relaparatomied 27 of them demanded laparatomies (RD)15 programmed relaparatomies and 2 open abdomen techniques. The principal indications of relaparatomy were: fecal peritonitis, intraabdominal abscesses and fibrinopurulent peritonitis. The most frequent complications were septic shock and infection of the surgical place. Conclusions: relaparatomy is usually carried out for fecal and fibrinopurulent peritonitis. Relaparatomy was frequently demanded arising serious complications.

Cómo enfrenta el hinduismo un dilema ético-clínico / How does Hinduism analyze an ethical clinical dilemma

It is indispensable for physicians to understand and recognize the fusion of different cultures, to deliver the best possible service to patients with different cultural backgrounds, especially when ethical-medical problems are involved. The Hindu community in Chile differs in significant ways with the western culture. This is especially true for some issues such as the belief in reincarnation or gender inequality, among others. These discrepancies can be relevant for the analysis of several bioethical problems. Therefore, it is necessary to understand the different beliefs, traditions and Hindu visions. We hereby present a review of Hinduism, its relation with medical practice and, as an example, a case of abortion in a Hindu family. Reviewing the traditions, beliefs and methods will help to understand and respect the beliefs of different cultures in contemporary and globalized bioethics.