Background/Objectives: The objective of this study is to evaluate the efficacy and safety of maintaining antimicrobial (AM) therapy or adjusting AM therapy during episodes of febrile neutropenia (FN) catalogued as a fever of unknown origin (FUO) in children with cancer. Methods: This is a prospective, multicenter, noninferiority, randomized study, approved by ethics committee, in children with episodes of FN in eight hospitals in Chile. Microbiological and molecular samples were drawn at admission. Patients with FUO (negative bacterial and viral study with no clinical focus suggesting infection) and favorable evolution during the first 48-72 h of AM therapy were randomized 1:1 to maintain or adjust treatment, reducing the number and spectrum of AMs. The primary endpoint was the percentage of episodes with an uneventful resolution; the secondary endpoints were the re-adjustment of AM therapy, days of fever/hospitalization/AM therapy, days of vancomycin and meropenem per 1000 days of neutropenia, number of AMs after randomization, pediatric intensive care unit (PICU) admission, sepsis, and death. Results: A total of 266 of 939 FN episodes recruited between March 2021 and January 2024 were catalogued as FUO, of which 231 had a favorable evolution at 48-72 h and were randomized, 111 to maintain and 120 to adjust AM therapy. Both groups presented the same percentage of uneventful resolution, with 106 (96%) in the group that maintain AM therapy and 114 (95%) in the adjusted group (p = 1.00); relative risk 1.01, (95%CI 0.95-1.06); absolute risk difference 0.01, (95%CI -0.05-0.06). Conclusions: The main finding of this study demonstrates that adjusting antimicrobial therapy appears safe in carefully selected FUO cases with a favorable early evolution, during episodes of FN catalogued as FUO in children with cancer. These findings open an opportunity to new AM stewardship strategies in this population, with a possible future impact on AM resistance.

BACKGROUND:Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high-risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016-2020 compared to 2004-2006 in six hospitals in Chile. METHODS:Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004-2006. The incidence rate was estimated. RESULTS:A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent-HRFN occurring in 174 patients. The median age was 7 years (IQR: 3-12 years) and 52.3% (N = 91) were male. Fifty-three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent-HRFN with an IFD incidence of 14.6% (95% CI 10.5-19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5-20.0). Compared to 2004-2006 cohort (incidence: 8.5% (95% CI 5.2-13.5)), a significant increase in incidence of 6.1% (95% CI 0.2-12.1, p = .047) was detected in cohorts between 2016 and 2020. CONCLUSION:We observed a significant increase in IFD in 2016-2020, compared to 2004-2006 period.

Objectives: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. Methods: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. Results: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI,-0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. Discussion: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance. Juan P. Torres, Clin Microbiol Infect 2024;30:1029 (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:The collection of blood cultures (BC) is key for guiding antimicrobial therapy in children with febrile neutropenia (FN), more than 90% have central venous catheters (CVC). There is no consensus on the need for peripheral BC over central BC in this population. The aim of this study was to determine the contribution of peripheral BC over central BC in the diagnosis of bloodstream infections in children with FN.METHODS:Descriptive, retrospective study, episodes of FN recorded prospectively in 6 hospitals in Santiago, Chile, from 2016 to 2021. Central and peripheral BC were drawn upon admission. All episodes with at least one (+) BC were allocated to one of these groups: consistent (+) BC, inconsistent (+) BC, only CVC (+) BC and only peripheral (+) BC. The volume of the samples was recorded.RESULTS:The analysis included 241 episodes of FN with at least one (+) BC. The median age was 7.2 years, 51% were female, 84% had hematological cancer and 98% had episodes of high-risk FN. Of a total of 241 episodes, 135 (56%) had consistent (+) BC, 13 (5%) had inconsistent (+) BC, 35 (15%) had only CVC (+) BC and 58 (24%) had only peripheral (+) BC. There were no significant differences in the volume of the samples between central and peripheral BC.CONCLUSIONS:The proportion of bloodstream infections detected only through peripheral BC was 24%, higher than previously reported, not due to sample volume. We recommend obtaining peripheral as well CVC BC in children with FN.

Introducción: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa.

Head and neck cancer is a major health problem worldwide, with most cases arising in the oral cavity. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for over 90% of all cases. Compared to other types of cancer, OSCC, has the worse prognosis, with a 5-year survival rate of 50%. Additionally, OSCC is characterized by a high rate of resistance to chemotherapy treatment, which may be partly explained by the presence of cancer stem cells (CSC) subpopulation. CSC can adapt to harmful environmental condition and are highly resistant to both chemotherapy and radiotherapy treatments, thus contributing to tumor relapse. The aim of this review is to highlight the role of mitochondria in oral CSC as a potential target for oral cancer treatment. For this purpose, we reviewed some fundamental aspects of the most validated protein markers of stemness, autophagy, the mitochondrial function and energy metabolism in oral CSC. Moreover, a discussion will be made on why energy metabolism, especially oxidative phosphorylation in CSC, may offer such a diverse source of original pharmacological target for new drugs. Finally, we will describe some drugs able to disturb mitochondrial function, with emphasis on those aimed to interrupt the electron transport chain function, as novel therapeutic strategies in multidrug-resistant oral CSC. The reutilization of old drugs approved for clinical use as new antineoplastics, in cancer treatment, is also matter of revision.

Background: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). Aim: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. Methods: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. Results: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. Conclusion: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Cationic Surfactant's quantification in aqueous solution is relevant in fundamental and applied research, as well as for quality control in processes in the chemical industry. Colloidal titration is a commonly used method for surface charge determination in colloidal systems such as polyelectrolytes, macromolecules and solid particles, but it can also be applied for the detection of ionic surfactants in aqueous solution. It is a simple technique, easy to implement in a laboratory and its principle is based on the stoichiometric neutralization between two species of opposite charge, potassium polyvinylsulfonate (standard PVSK) and a cationic polyelectrolyte or cationic surfactant. When the stoichiometric ratio is exceeded, the excess polyelectrolyte reacts with a cationic indicator (crystal violet) forming an electrically neutral pair that modifies the solutions' absorbance value which is determined by spectrophotometry at 587 nm. To assess the feasibility of this technique, the colloidal titration method was normalized by titration between two standard polyelectrolytes (PDADMAC and PVSK), also with analytical grade cationic surfactants (DDBAB, CTAB and HDBAC) and finally with some commercial ones (Praepagen WK, Dodigen 1828, Empygen BAC 50). High molecular weight surfactants showed stoichiometric proportionality between their concentration and the amount of tritant added for concentration between 10-100 mN. This proportionality was not observed for low molecular weight surfactants. Finally, it was also observed that for commercial surfactants the presence of 0.01 M sodium chloride does not affect the titration results.

Bipolar Disorder (BD) has recently been related to a process of accelerated aging, with shortened leukocyte telomere length (LTL) in this population. It has also been observed that the suicide rate in BD patients is higher than in the general population, and more recently the telomere length variation has been described as shorter in suicide completers compared with control subjects. Objectives The aim of the present study was to investigate if there is an association between LTL and BD in families where two or more members have BD including clinical symptomatology variables, along with suicide behavior. Methods Telomere length and single copy gene ratio (T/S ratio) was measured using quantitative polymerase chain reaction in a sample of 143 relatives from 22 families, of which 60 had BD. The statistical analysis was performed with a polygenic mixed model. Results LTL was associated with suicidal ideation (p = 0.02) as that there is an interaction between suicidal ideation and course of the disorder (p = 0.02). The estimated heritability for LTL in these families was 0.68. In addition, covariates that relate to severity of disease, i.e. suicidal ideation and course of the disorder, showed an association with shorter LTL in BD patients. No difference in LTL between BD patients and healthy relatives was observed. Conclusion LTL are shorter in subjects with familial BD suggesting that stress related sub-phenotypes possibly accelerate the process of cellular aging and correlate with disease severity and suicidal ideation.

This paper examines the drivers of Chinese overseas financing in renewable energy and the political economy factors in recipient countries that steer this finance towards climate-friendly projects. We examine utility-scale renewable energy projects in Argentina, Bulgaria, Chile, Ecuador, Ethiopia, Kenya, Lesotho, Pakistan, and Romania. Through in-depth interviews with policymakers and relevant stakeholders, we gathered data on the factors that led to Chinese policy bank investment in renewables. We find that where host country governments have offered strong policy incentives for renewables, the Chinese banks and developers readily provided bundled financing, technology, and construction services even in markets considered to be risky. Additional risk mitigation instruments were utilized by the Chinese policy banks in some cases. In five of the nine countries studied, political agreements preceded the investments. Developing countries are found to value the bundled nature of finance, technology, and construction services offered by China as well as the timeliness of construction. As governments move towards policies utilizing competitive price discovery mechanisms, such as reverse auctions where developers compete to submit the lowest bid, the Chinese policy bank appetite for low-carbon investments may wane. Potential future synergies between China's policy banks and other multilateral development banks are explored.

BACKGROUND:Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN. METHODS:Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation. RESULTS:A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003). CONCLUSIONS:Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation.

Extracorporeal membrane oxygenation (ECMO) support requires skills that can only be found in specialized centers. The number of patients annually supported with ECMO is positively associated with the survival rate, so transport to a specialized center is recommended.1 Some patients are too ill to be transferred under conventional transport (mechanical ventilation/vasoactive drugs), so they must be transferred on ECMO. Cannulating the patient at the referring hospital and transporting on ECMO was first described by Bartlett et al.2; since then, a large number of ECMO transports have been described. Mobile ECMO for pediatric patients combines specificities of hemodynamic management of a low-weight patient with transportation’s technical issues, and currently, there is a paucity of reported data of indications, processes, and outcomes of pediatric ECMO transport[3]. To our knowledge, in Latin America, pediatric ECMO transport is only available in Brazil, Colombia, Mexico, and Chile, and no reports have been published. Our institution implemented Mobile ECMO in March 2007, and the first pediatric ECMO transport was carried out in July 2011. We retrospectively reviewed our institutional database of all patients ≤18 years old who were transferred on mobile ECMO. The institutional review board approved the study. Requests for mobile ECMO were initiated by the referring physician calling by phone to an ECMO-team pediatric intensivist to evaluate 1) the referral indication, 2) the eligibility to ECMO support according to ELSO Guidelines,4–6 and 3) the chance to improve the local management avoiding the use of ECMO when not necessary. Patients were eligible for respiratory ECMO if they had a severe, refractory, potentially reversible hypoxemic or hypercapnic respiratory failure and met any of the following criteria: oxygenation index >30, PaO2/FiO2 ratio less than 100 despite maximal medical therapy (prone positioning, fluid restriction, NO, neuromuscular blockade, high-frequency oscillatory ventilation [HFOV]), hypercapnia, and respiratory acidosis with pH <7.15 or plateau pressure >35 mmH2O despite optimized ventilator settings. For cardiac ECMO, patients were candidates with cardiogenic shock, hypotension with more than three vasoactive drugs and elevated lactate, refractory to medical management. Patients with known ECMO contraindications or a nonreversible disease were denied support, consistent with the ELSO guidelines.3,5,6 After the ECMO eligibility was confirmed, an on-call ECMO team consisting of a cardiothoracic surgeon, anesthetist, perfusionist, and an ICU nurse, with high training in cannulation and technical management of the ECMO system, were alerted. The team was available 24 h per day, 7 days per week, all year round. The time from the decision to go until the departure was between 30 and 90 min. The equipment and devices used for the transfer on ECMO are detailed in Table 1. Table 1 - Cannulation Material Extracorporeal Circuit Material Emergency Support Material Vessel dilators 6-28 FrOpus by MC3Insertion kit by Medtronic Surgical venous cannula 8- 14 Fr, Biomedicus by Medtronic and/or percutaneous venous cannulas Biomedicus by Medtronic according to patient’s weight and two different sizes 1 Fr above and 1 Fr over. Face masks N° 1, 2 and 3, ET tubes N° 3-7.5. Introducers 4 Fr and 5 Fr, radiofocus by terumo Surgical arterial cannula 8- 14 Fr, and/or percutaneous arterial cannulas 15-23 Fr according to patient´s weight and two different sizes (Medtronic) CPR material + emergency drugs. 2× micropuncture introducer set by Cook® 2× ECMO membrane lung and circuit by Maquet or by Eurosets Vascular arterial, venous catheters, connectors by arrow or terumo. Connectors 1/4-1/4, 1/4-1/4 Luer, 3/8 × 3/8, 3/8 × 3/8 Luer, Y 1/4-1/4-1/4, Y 3/8 × 3/8-3/8 by Maquet or Eurosets or Medtronic Sterile priming solutionSaline solution, albumin 20%, ringer, could be replaced by blood to keep the hematocrit over 30%, mainly in patients ≤ 10 kg. IV fluids, saline solution, ringer, albumin 20% and one RBC pack. 2× 0.035” Flex L × 260 cm vascular guidewires Radiofocus by Terumo Three-way stopcocks by terumo. 2× 0.035” × 180 cm angle vascular guidewires, Radiofocus by Terumo US special gel for centrifugal pump flowmeter by Maquet. Gas connector for the ambulance or aircraft type Ohio. Electrical adaptors and check the power supply at ambulance and aircraft. Electrical and biomedical equipment Oxygen tanks enough for the distance × 2. ICU portable monitor by Spacelab or Lifepak 15 by Physio Control 4 Syringe Infusion pumps by Terumo. Jackson Rees ventilation circuit.Transport ventilator by Hamilton® ECMO centrifugal pump Rotaflow by Maquet or Cardiohelp. ECMO water heater by Maquet. ECMO emergency manual drive, Hand-crank by Maquet. Portable ultrasound by SonositePortable Ultrasound flowmeter by Transonic. CPR, cardiopulmonary resuscitation; ECMO, Extracorporeal membrane oxygenation; ET, endotracheal; Fr, French; RBC, red blood cells. At the referral hospital, ultrasonography was carried out by the cardiovascular anesthesiologist and surgeon and used to determine the ECMO mode and to guide cannulation. Veno-venous (VV) ECMO was implemented for respiratory indications without hemodynamic compromise, while peripheral veno-arterial (VA) ECMO was used for patients with cardiogenic shock, hemodynamic compromise, or due to technical difficulties in younger patients with respiratory failure. Before cannulation, patients received a bolus of unfractionated heparin of 5–10 IU/kg. The internal jugular vein was preferentially cannulated for double-lumen VV ECMO. For dual-site VV-ECMO, the right internal jugular and right femoral veins were the preferred access sites. The neck vessels were used for VA ECMO. The position of the cannulas was confirmed by x-ray before departure. The circuit was primed with blood if the patient’s weight was ≤10 kg or with saline solution in patients with higher weights. Once ECMO was established, patients were ventilated with rest settings: PEEP 10cmH2O, PIM 10cmH2O, Respiratory Rate 10×´. ROTAFLOW centrifugal pumps and PLS-i oxygenators (Maquet Cardiopulmonary, Hirrlingen, Germany) were used during transportation. Between July 2011 and March 2020, 30 pediatric patients fulfilled ECMO transport criteria and were cannulated by our ECMO mobile team at the referral center. One patient died during cannulation. Twenty-nine patients were safely retrieved with no severe adverse events during transfer, except for one monitoring arterial line displacement without bleeding. There were no intra transport power failures or malfunctions. The patients were retrieved by ambulance (n = 17), fixed-wing aircraft (n = 11), and by helicopter (n = 2). The median distance of transport was 123.5 km, and the furthest referral hospital from where a patient was transported was 1,708 km. Population demographic variables, ECMO characteristics, and outcomes are described in Table 2. The most common indication for ECMO was a severe refractory respiratory failure (77%), and viral pneumonia was the most frequent etiology (n = 9). Twenty-one patients were connected to HFOV as a rescue therapy before ECMO, and 10 patients used iNO. The survived ECMO was 80% (24 out of 30 patients) and survival to discharge from hospital was 73% (22 out 30 patients). All patients discharged from the hospital are alive at the time of this review. The survival of these patients was compared with pediatric ECMO patients cannulated in our center in the same period. This group consisted of 55 patients, of whom three had a cardiac failure, four were extracorporeal cardiopulmonary resuscitation, four had septic shock, and forty-four had respiratory failure. The survived ECMO of the in-house ECMO group was 60% (33 out of 55 patients), with no significant difference with the mobile ECMO group (P = 0.4). Table 2 - Raw Number and Percentage OR Median (IQR) Total 30 Age (years) 2 (0–10) Male 21 (70%) Weight (kg) 12.75 (6–26) Body mass index (BMI) 14.1 (12.3–19.5) ECMO indication *Cardiac 6 (20%) *Respiratory 24 (80%) *Severity of illness (PIM2 score) 26.01 (18.5–68.5) Diagnosis Pneumonia 13 (43%) Respiratory distress syndrome 5 (17%) Septic shock 3 (10%) Hantavirus cardiopulmonary syndrome 2 (7%) Myocarditis 2 (7%) Congenital cardiopathy 2 (7%) Meconium aspiration syndrome 1 (3%) Congenital diaphragmatic hernia 1 (3%) Atrial flutter 1 (3%) Pre ECMO (respiratory indication) *Mechanical ventilation before ECMO (days) 2.5 (1–4.5) *PaO2/FiO2 52 (39–60) *Oxygenation Index 37 (28–45) *PaCO2 67 (49–113) *CPR before ECMO 4 (*16%) *pH 7.22 (7.025–7.35) Pre ECMO (cardiac indication) *Mechanical ventilation before ECMO (days) 1.5 (1–2) *Lactate 19.8 (12–51.3) *CPR before ECMO 3 (†50%) Mode of ECMO *VV 12 (40%) *VA 18 (60%) Mode of transport: *Ambulance 17 (56.6%) *Fixed wings aircraft 11(36.6%) *Helicopter 2 (6.7%) *Time of transport (hours) 2.13 (0.95–2.4) Median run distance (km) 123.5 (24–517) Complication during transport *Patient-related 1 (3.3%) *ECMO-related 0 *Monitoring devices-related 1 (3.3%) ECMO Outcomes *Days of ECMO 10 (4–17) *All-cause mortality 8 (27%) *Survived ECMO 24 (80%) *Survival to hospital discharge 22 (73%) *16% of all patients with Respiratory indication for ECMO support.†50% of all patients with Cardiac indication for ECMO support.CPR, cardiopulmonary resuscitation; ECMO, Extracorporeal membrane oxygenation; VA, veno-arterial; VV, Veno-venous. To our knowledge, this is the first report of a pediatric mobile ECMO program in South America. Chile is a middle-income country located in the southwest region of South America characterized by geographic isolation determined by the Andes mountains and the Pacific Ocean. All the centers with pediatric ECMO are in Santiago (the biggest city). Therefore, patients from remote regions need to be transferred there. Despite these difficulties, the clinical outcomes of our mobile ECMO program, including survived ECMO, hospital discharge, and 1-year follow-up, are similar to those reported by other authors from high-income countries.3,7–9 In summary, we report that cannulation of pediatric patients at the referring center followed by transport to an experienced center on pediatric ECMO is feasible and safe when conducted by a highly skilled team, even in lower-income countries with geographic difficulties.

Mitochondrial E3 ubiquitin ligase 1 (MUL1) is a mitochondrial outer membrane-anchored protein-containing transmembrane domain in its N- and C-terminal regions, where both are exposed to the cytosol. Interestingly the C-terminal region has a RING finger domain responsible for its E3 ligase activity, as ubiquitin or in SUMOylation, interacting with proteins related to mitochondrial fusion and fission, cell survival, and tumor suppressor process, such as Akt. Therefore, MUL1 is involved in various cellular processes, such as mitochondrial dynamics, inter-organelle communication, proliferation, mitophagy, immune response, inflammation and cell apoptosis. MUL1 is expressed at a higher basal level in the heart, immune system organs, and blood. Here, we discuss the role of MUL1 in mitochondrial dynamics and its function in various pathological models, both in vitro and in vivo. In this context, we describe the role of MUL1 in: (1) the inflammatory response, by regulating NF-κB activity; (2) cancer, by promoting cell death and regulating exonuclear function of proteins, such as p53; (3) neurological diseases, by maintaining communication with other organelles and interacting with proteins to eliminate damaged organelles and; (4) cardiovascular diseases, by maintaining mitochondrial fusion/fission homeostasis. In this review, we summarize the latest advances in the physiological and pathological functions of MUL1. We also describe the different substrates of MUL1, acting as a positive or negative regulator in various pathologies associated with mitochondrial dysfunction. In conclusion, MUL1 could be a potential key target for the development of therapies that focus on ensuring the functionality of the mitochondrial network and, furthermore, the quality control of intracellular components by synchronously modulating the activity of different cellular mechanisms involved in the aforementioned pathologies. This, in turn, will guide the development of targeted therapies.

"Hectorite is a mineral of the phyllosilicate group based on layered clay, known as smectite. Among these phyllosilicates are montmorillonite, beidellite, nontronite, saponite and hectorite. Organophilic clays are obtained by exchanging sodium cations with a cationic surfactant, such as quaternary ammonium-type surfactants. The main function of hectorite, as an ingredient in cosmetics, is as gelling/thickening agent, preventing the oil’s separation in the formulation and producing the suspension of pigments and other components. The great stability of these formulations is mainly due to an increased viscosity of the oily phase and in addition, it provides the product with spreadability. Among the cosmetic products that contain it are: cosmetic bases, masks, and in general, morphologies of the water-in-oil type or suspension of solids in oily bases. In this study, the swelling capacity, the rheological behavior and the phase diagram for hectorite/polar activator/isoparaffin systems for different hectorite/polar activator ratios are presented. Through the rheological study and the construction of the activator concentration map as a function of the amount of hectorite, the areas of colloidal solution, gel and gel with solid consistency are shown, as well as the transition line from colloidal solution to gel."

Streptococcus equi subspecies zooepidemicus is a Gram-positive, P-hemolytic coccus considered part of the commensal flora in horses and an opportunistic pathogen in other animals. Infection in humans is rare, but it usually manifests as serious symptoms, it has been associated with contact with animals, especially horses, and the consumption of unpasteurized dairy products. In this report we describe a case of bacteremia of the mother-child binomial by this agent, associated with the consumption of artisan cheeses. Although penicillin is the treatment of choice, the newborn was successfully treated with ampicillin and the mother with ceftriaxone, none of them presented complications associated with bacteremia. To our knowledge, this is the first report of connatal infection by this agent.

Streptococcus equi subespecie zooepidemicus es una cocácea grampositiva, p-hemolítica, considerada parte de la microbiota de los equinos y un patógeno oportunista en otros animales. La infección en humanos es poco frecuente, pero suele manifestarse como cuadros graves. Se ha asociado al contacto con animales, especialmente caballos, y al consumo de productos lácteos no pasteurizados. Presentamos el caso de una bacteriemia en un binomio madre-hijo por este agente, asociado al consumo de quesos artesanales. Pese a que la penicilina es el tratamiento de elección, la recién nacida fue tratada en forma exitosa con ampicilina y la madre con ceftriaxona. Ninguna de ellas presentó complicaciones asociadas a la bacteriemia. A nuestro conocimiento, este es el primer reporte de infección connatal por este agente.

We investigated the association between varicocele and benign prostatic hyperplasia in men over the age of 40 years. A total of 296 outpatients were evaluated. Prostate volume was measured with transrectal ultrasound. Varicocele was diagnosed by physical examination and ultrasound. Prostatic hyperplasia was defined as prostate volume greater than or equal to 40 ml. Two groups were compared: patients with prostate volume less than 40 ml and patients with prostate volume greater than or equal to 40 ml. There was a statistically significant difference between the groups in terms of mean age, post-void residual, International Prostate Symptom Score and PSA. The percentage of patients with clinical varicocele in the group with a volume less than 40 ml and the group with a volume equal to or greater than 40 ml was 38.2% and 47.7% respectively (p = .12). There were no differences between the two groups in the percentage of patients with clinical or subclinical varicocele (43.2% vs. 52.2%, respectively, p = .12). No differences were found in the percentage of patients with varicocele when comparing men with prostates smaller than 40 ml and greater than or equal to 40 ml.

Preterm infants, especially those born with less than 32 weeks of gestational age, have a higher risk of acquiring serious infections compared to term infants due among other factors, to a decrease in several components of the immune system. Many of these infections are immunopreventable by vaccines available in our country. The current recommendation is to vaccinate all preterm or low weight born infants with few exceptions, using vaccines routinely recommended according to their chronological age just as term infants. However, on many occasions there is a delay in the immunization schedules of these infants mainly due to the apprehensions regarding the immunogenicity and safety of vaccines in this population. The aim of this article is to review the available evidence regarding the efficacy and safety of vaccines commonly used in preterm infants.

El recién nacido de pretérmino (RNPT), especialmente el menor de 32 semanas de edad gestacional, presenta un mayor riesgo de adquirir infecciones y que estas sean de curso más grave respecto a los recién nacidos de término (RNT), debido, entre otros factores a una inmadurez de varios componentes del sistema inmune. Muchas de estas infecciones son inmunoprevenibles por vacunas disponibles en nuestro medio y la recomendación actual es vacunar a los lactantes nacidos de pretérmino o bajo peso, salvo pocas excepciones, con todas las vacunas rutinariamente recomendadas según su edad cronológica al igual que un RNT. Sin embrago, en muchas oportunidades se observa un retraso en los calendarios de inmunización de estos lactantes principalmente por las aprehensiones respecto a la inmunogenicidad y seguridad de las vacunas en esta población. El objetivo de este artículo es revisar la evidencia disponible respecto a la eficacia y seguridad de las vacunas habitualmente utilizadas en lactantes, enfocados en los RNPT.

There is already a number of reports correlating the effect of parents’ ages with the risk of schizophrenia, but studies looking for an association between parental age and Bipolar Disorder (BD) are scarce and with inconsistent findings. BD has recently been related to a process of accelerated aging, with studies showing association with Leukocyte Telomere Length (LTL) in this population. However, little is known regarding the inheritance of telomere length, with some studies estimating the heritability between 36–86%. About the effect of a parent' age determining LTL, just a few studies have noted longer telomere lengths among offspring of older mothers, and none have shown an interaction or association with a psychiatric disorder. The present investigation assessed the impact of maternal and paternal age at birth as a determinant for the offspring's LTL with and without BD diagnosis within families with several members affected by this disease. Telomere length (T) was estimated in a sample of 144 individuals, including 60 BD patients from 18 Brazilian families, which was measured in relation to the single copy gene (S) – β-globin gene (HBB) – using a singleplex real time PCR, providing a ratio of number of copies of T by S (T/S). The analysis were obtained by a linear mixed model (LMM). We found a positive association between maternal age at childbirth and offspring early life telomere length (β=0.012; p=0.015), whereas there was no association of paternal age on offspring telomere length (β=0.008; p=0.232). The LMM analysis also showed a significant positive relationship on interaction between bipolarity and maternal age demonstrates a strong influence on telomere length (β=0.022; p=0.024). The same analysis showed no association on interaction between bipolarity and paternal age (β=0.009; p=0.223). An association between maternal age and offspring LTL and the interaction with BD was observed. It could be speculated that an influence of oxidative stress during first pregnancy, changes in mitochondrial DNA or even other parent-specific imprinting mechanism, such as DNA methylation, relevant to the neurodevelopment of the brain. To our knowledge, this is the first study evaluating association of maternal age and telomere length in the offspring of families with several members affected by BD. Additional studies are needed to confirm these preliminary findings.