Pediatric Anesthesiology Milestones 2.0: An Update, Rationale, and Plan Forward.

Formal training in the subspecialty of pediatric anesthesiology began >60 years ago. Over the years, the duration and clinical work has varied, but what has stayed constant is a mission to develop clinically competent and professionally responsible pediatric anesthesiologists. Since accreditation in 1997, there has been additional guidance by the Accreditation Council on Graduate Medical Education (ACGME) and greater accountability to the public that we, indeed, are producing competent and professional pediatric anesthesiologists. This has been influenced by the slow evolution from time-based educational curriculum to a competency-based paradigm. As with all ACGME-accredited specialties, education leaders in pediatric anesthesiology first convened in 2014 to design specialty-specific developmental trajectories within the framework of the 6 core competencies, known as milestones, on which fellows were to be tracked during the 1-year fellowship. With 5 years of implementation, and substantial data and feedback, it has become clear that an iterative improvement was necessary to mirror the evolution of the profession. It was evident that the community required brevity and clarity in the next version of the milestones and required additional resources for assessment and faculty development. We describe here the methodology and considerations of our working group, guided by ACGME, in the rewriting of the milestones. We also provide suggestions for implementation and collaboration to support the education and assessment of pediatric anesthesiology fellows across the country.

Immuno-mediated colitis induced by nivolumab that mimics endoscopically and histologically an ulcerative colitis.

Immunotherapy has revolutionized the management of oncological pathology, demonstrating effectiveness in treating various cancers by stimulating the immune system against tumor cells. Among the immunotherapy drugs are programmed cell death protein 1 (PD-1) inhibitors, such as Nivolumab, which, by blocking this receptor on the surface of T lymphocytes, enhance the immune response. Despite their significant benefits, these agents present specific adverse effects on healthy tissues that need to be understood. One of these effects is immune-mediated colitis, a potentially serious gastrointestinal disorder that may require the permanent discontinuation of the drug. Although it can occur with various immunotherapy regimens, it occurs more frequently with anti-CTLA4 agents like Ipilimumab, with its incidence much lower with anti-PD1 agents. We present the case of a 62-year-old male diagnosed with metastatic clear cell renal carcinoma treated with radical nephrectomy and subsequent palliative systemic treatment with Nivolumab. After the third cycle of immunotherapy, he developed abdominal pain and diarrhea. Colonoscopy revealed continuous mucosal inflammation up to the cecum, erosions, exudates, and loss of the vascular pattern. Biopsies showed signs of active colitis, cryptic abscesses, and focal cryptitis, all consistent with a case of immuno-mediated colitis induced by Nivolumab that mimics, both endoscopically and histologically, the findings found in ulcerative colitis.

Immunometabolic Profile Associated with Progressive Damage of the Intestinal Mucosa in Adults Screened for Colorectal Cancer: Association with Diet.

Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.

Gastric lymphangioma. Diagnosis by endoscopic resection of a foreign entity.

The lymphangioma is a rare and very uncommon benign tumor at the gastric level. Its diagnosis typically involves imaging tests and endoscopy, and its treatment usually involves surgery. We present a case of an 82-year-old patient who presented with chronic anemia, with a large gastric polyp detected during the initial gastroscopy. Subsequently, an endoscopic resection was performed, confirming histologically that it was a lymphangioma.

First-attempt success rate of video laryngoscopy in small infants (VISI): a multicentre, randomised controlled trial.

BACKGROUND: Orotracheal intubation of infants using direct laryngoscopy can be challenging. We aimed to investigate whether video laryngoscopy with a standard blade done by anaesthesia clinicians improves the first-attempt success rate of orotracheal intubation and reduces the risk of complications when compared with direct laryngoscopy. We hypothesised that the first-attempt success rate would be higher with video laryngoscopy than with direct laryngoscopy. METHODS: In this multicentre, parallel group, randomised controlled trial, we recruited infants without difficult airways abnormalities requiring orotracheal intubation in operating theatres at four quaternary children's hospitals in the USA and one in Australia. We randomly assigned patients (1:1) to video laryngoscopy or direct laryngoscopy using random permuted blocks of size 2, 4, and 6, and stratified by site and clinician role. Guardians were masked to group assignment. The primary outcome was the proportion of infants with a successful first attempt at orotracheal intubation. Analysis (modified intention-to-treat [mITT] and per-protocol) used a generalised estimating equation model to account for clustering of patients treated by the same clinician and institution, and adjusted for gestational age, American Society of Anesthesiologists physical status, weight, clinician role, and institution. The trial is registered at ClinicalTrials.gov, NCT03396432. FINDINGS: Between June 4, 2018, and Aug 19, 2019, 564 infants were randomly assigned: 282 (50%) to video laryngoscopy and 282 (50%) to direct laryngoscopy. The mean age of infants was 5·5 months (SD 3·3). 274 infants in the video laryngoscopy group and 278 infants in the direct laryngoscopy group were included in the mITT analysis. In the video laryngoscopy group, 254 (93%) infants were successfully intubated on the first attempt compared with 244 (88%) in the direct laryngoscopy group (adjusted absolute risk difference 5·5% [95% CI 0·7 to 10·3]; p=0·024). Severe complications occurred in four (2%) infants in the video laryngoscopy group compared with 15 (5%) in the direct laryngoscopy group (-3·7% [-6·5 to -0·9]; p=0·0087). Fewer oesophageal intubations occurred in the video laryngoscopy group (n=1 [<1%]) compared with in the direct laryngoscopy group (n=7 [3%]; -2·3 [-4·3 to -0·3]; p=0·028). INTERPRETATION: Among anaesthetised infants, using video laryngoscopy with a standard blade improves the first-attempt success rate and reduces complications. FUNDING: Anaesthesia Patient Safety Foundation, Society for Airway Management, and Karl Storz Endoscopy.

Chest Trauma Outcomes: Public Versus Private Level I Trauma Centers.

BACKGROUND: The goal of our study was to evaluate the differences in care and clinical outcomes of patients with chest trauma between two hospitals, including one public trauma center (Pu-TC) and one private trauma center (Pri-TC). METHODS: Patients with thoracic trauma admitted from January 2012 to December 2018 at two level I trauma centers (Pu-TC: Hospital Universitario del Valle, Pri-TC: Fundación Valle del Lili) in Cali, Colombia, were included. Multivariable logistic regression was used to assess for differences in in-hospital mortality, adjusting for relevant demographic and clinical characteristics. RESULTS: A total of 482 patients were identified; 300 (62.2%) at the Pri-TC and 182 (37.8%) at the Pu-TC. Median age was 27 years (IQR 21-36) and median Injury Severity Score was 25 (IQR 16-26). 456 patients (94.6%) were male, and the majority had penetrating trauma [total 465 (96.5%); Pri-TC 287 (95.7%), Pu-TC 179 (98.4%), p 0.08]. All patients arrived at the emergency room with unstable hemodynamics. There were no statistically significant differences in post-operative complications, including retained hemothorax [Pri-TC 19 vs. Pu-TC 18], pneumonia [Pri-TC 14 vs. Pu-TC 14], empyema [Pri-TC 13 vs. Pu-TC 13] and mediastinitis [Pri-TC 6 vs. Pu-TC 2]. Logistic regression did, however, show a higher odds of mortality when patients were treated at the Pu-TC [OR 2.27 (95% CI 1.34-3.87, p < 0.001]. CONCLUSIONS: Our study found significant statistical differences in clinical outcomes between patients treated at a Pu-TC and Pri-TC. The results are intended to stimulate discussions to better understand reasons for outcome variability and ways to reduce it.

Chemical Modification of Polyhydroxyalkanoates (PHAs) for the Preparation of Hybrid Biomaterials.

Polyhydroxyalkanoates (PHAs) are biopolyesters produced by bacteria as intracellular granules under metabolic stress conditions. Many carbon sources such as alkanes, alkenes, alcohols, sugars, fatty acids can be used as feedstock and thus a wide variety of polyesters and monomer units can be potentially synthetized. The work presented here describes the process to chemically modify such biopolymers in order to render them readily available for the preparation of bio-molecular conjugates as promising new classes of biocompatible biomaterials. Such hybrid biomaterials belong to the rapidly growing class of biocompatible polymers, which are of great interest for medical and therapeutic applications. In this work, the biosynthesis of a new PHA homopolymer and the chemical modification, an epoxidation reaction, are described.

Oxidative stress in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is an autoimmune disease of unknown etiology, characterized by articular inflammation. Oxidative damage induced by reactive oxygen species has been related to the pathophysiology of rheumatoid arthritis in several studies, although results have been inconsistent and contradictory. OBJECTIVE: To determine oxidative stress markers in patients with rheumatoid arthritis. METHODS: Descriptive cross-sectional study in rheumatoid arthritis patients and healthy controls. In peripheral blood samples from all study subjects, lipid peroxide (thiobarbituric acid reactive substances) and protein carbonyl levels were quantified as oxidative damage markers; superoxide dismutase and glutathione peroxidase activities, glutathione concentration, and the reduced glutathione/oxidized glutathione ratio were analyzed as antioxidant defense indicators. Mann-Whitney U tests were run. Statistical significance (a) was 0.05%. RESULTS: We included 29 rheumatoid arthritis patients, 10 with active disease, and 41 healthy controls. Age was higher in the rheumatoid arthritis group; there were no differences in female:male ratio between groups. Oxidative damage was higher in rheumatoid arthritis patients; however, there was no difference between patients with active or inactive rheumatoid arthritis. Antioxidant enzyme activities, glutathione concentration, and reduced glutathione/oxidized glutathione ratio were higher in rheumatoid arthritis patients than in controls. CONCLUSIONS: Antioxidant levels were higher in rheumatoid arthritis patients than in healthy controls; however, they were insufficient to prevent oxidative damage. This suggests an active oxidative process in rheumatoid arthritis patients.

High Diversity of Bradyrhizobial Species Fix Nitrogen with Woody Legume Spartocytisus supranubius in a High Mountain Ecosystem.

The symbiosis between rhizobia and legumes is of pivotal importance in nitrogen-poor ecosystems. Furthermore, as it is a specific process (most legumes only establish a symbiosis with certain rhizobia), it is of great interest to know which rhizobia are able to nodulate key legumes in a specific habitat. This study describes the diversity of the rhizobia that are able to nodulate the shrub legume Spartocytisus supranubius in the harsh environmental conditions of the high mountain ecosystem of Teide National Park (Tenerife). The diversity of microsymbionts nodulating S. supranubius was estimated from a phylogenetic analysis of root nodule bacteria isolated from soils at three selected locations in the park. The results showed that a high diversity of species of Bradyrhizobium and two symbiovars can nodulate this legume. Phylogenies of ribosomal and housekeeping genes showed these strains distributed into three main clusters and a few isolates on separate branches. These clusters consist of strains representing three new phylogenetic lineages of the genus Bradyrhizobium. Two of these lineages belong to the B. japonicum superclade, which we refer to as B. canariense-like and B. hipponense-like, as the type strains of these species are the closest species to our isolates. The third main group was clustered within the B. elkanii superclade and is referred to as B. algeriense-like as B. algeriense is its closest species. This is the first time that bradyrhizobia of the B. elkanii superclade have been reported for the canarian genista. Furthermore, our results suggest that these three main groups might belong to potential new species of the genus Bradyrhizobium. Analysis of the soil physicochemical properties of the three study sites showed some significant differences in several parameters, which, however, did not have a major influence on the distribution of bradyrhizobial genotypes at the different locations. The B. algeriense-like group had a more restrictive distribution pattern, while the other two lineages were detected in all of the soils. This suggests that the microsymbionts are well adapted to the harsh environmental conditions of Teide National Park.

How harmful are exotic plantations for soils and its microbiome? A case study in an arid island.

The plantation of exotic species has been a common practice in (semi-) arid areas worldwide aiming to restore highly degraded habitats. The effects of these plantations on plant cover or soil erosion have been widely studied, while little attention has been paid to the consequences on soil quality and belowground biological communities. This study evaluates the long-term (>60 years) effects of the exotic species Acacia cyclops and Pinus halepensis revegetation on soil properties, including microbiome, in an arid island. Soils under exotic plantation were compared to both degraded soils with a very low cover of native species and soils with well-preserved native plant communities. Seven scenarios were selected in a small area (~25 ha) with similar soil type but differing in the plant cover. Topsoils (0-15 cm) were analyzed for physical, chemical and biochemical properties, and amplicon sequencing of bacterial and fungal communities. Microbial diversity was similar among soils with exotic plants and native vegetation (Shannon's index = 5.26 and 5.34, respectively), while the most eroded soils exhibited significantly lower diversity levels (Shannon's index = 4.72). Bacterial and fungal communities' composition in degraded soils greatly differed from those in vegetated soils (Canberra index = 0.85 and 0.92, respectively) likely due to high soil sodicity, fine textures and compaction. Microbial communities' composition also differed in soils covered with exotic and native species, to a greater extent for fungi than for bacteria (Canberra index = 0.94 and 0.89, respectively), due to higher levels of nutrients, microbial biomass and activity in soils with native species. Results suggest that reforestation succeeded in avoiding further soil degradation but still leading to relevant changes in soil microbial community that may have negative effects on ecosystem stability. Information gained in this research could be useful for environmental agencies and decision makers about the controversial replacement of exotic plants in insular territories.

Low rate of vaccination and risk of incident hepatitis A among HIV-infected men who have sex with men in Seville, Southern Spain.

BACKGROUND: Periodic outbreaks of hepatitis A (HAV) infection in men who have sex with men (MSM) have been reported. Low vaccination uptake in HIV-infected individuals could drive new outbreaks. We aimed at evaluating the incidence of and risk factors for HAV infection in people living with HIV (PLWH) in our area. We also assessed the rates of HAV vaccination. METHODS: This was a prospective cohort study. 915 patients were included, 272 (30%) of them were anti-HAV seronegative at baseline. RESULTS: Twenty-six (9.6%) susceptible individuals became infected. Incident cases peaked in 2009-2010 and 2017-2018. Incident HAV infection was independently associated with MSM [adjusted odds ratio (95% confidence ratio): 4.39 (1.35-14.27), p=0.014]. One hundred and five (38.6%) HAV seronegative patients were vaccinated, 21 (20%) of them did not respond, and one (1%) patient lost immunity against HAV. Four (29%) non-responders to vaccination showed incident HAV 5-9 years afterwards. CONCLUSIONS: The incidence of HAV infection in a cohort of well-controlled PLWH remains low and stable, with intermittent outbreaks involving mainly non-immunized MSM. A significant proportion of PLWH remain susceptible to HAV infection due to insufficient vaccine uptake and limited response to vaccination. Importantly, patients not responding to HAV vaccination continue at risk of infection.

Mpox Infection and Sexually Transmitted Infections: A Cross-Sectional Study from a Secondary Hospital in the May-September 2022 International Outbreak.

The aims of this study were to describe the characteristics of patients infected by mpox in our setting, to determine the prevalence of mpox in samples that are classically used for diagnosing sexually transmitted infections (STIs) such as anal, urethral, pharyngeal, and urine, and to assess the prevalence of coinfection with STIs in the same samples. A cross-sectional study was conducted, collecting all confirmed cases of mpox between June and July 2022 using polymerase chain reaction. Sociodemographic data, HIV and other STI status, and prevalence of mpox and STIs in urethral, anal, pharyngeal, or urine samples were collected. Data from 22 patients were extracted, all of whom were men who have sex with men (MSM) and 54.5% were previously HIV positive. The median age was 43 years. All the skin samples were positive for mpox, followed by anal samples (n = 10, 45.5%). Mpox was isolated in 2 or more samples simultaneously in 12 (54%) cases. Nine (41%) patients were positive for an STI and four of them had more than one STIs (18.2%). Human mpox has been epidemiologically significant among MSM. Mpox should be investigated not only in skin lesions but also in samples classically used for STIs. Mpox, such as other STIs, shares ways of transmission and coinfection may be underdiagnosed.

Meckel's diverticulum with small bowel obstruction presenting as appendicitis in a pediatric patient.

BACKGROUND: Meckel's diverticulum is a congenital anomaly resulting from incomplete obliteration of the omphalomesenteric duct. The incidence ranges from 0.3% to 2.5% with most patients being asymptomatic. In some cases, complications involving a Meckel's diverticulum may mimic other disease processes and obscure the clinical picture. METHODS: This case presents an 8-year-old male with abdominal pain, nausea, and vomiting and an examination resembling appendicitis. RESULTS: A CT scan revealed findings consistent with appendicitis with dilated loops of small bowel. During laparoscopic appendectomy, the appendix appeared unimpressive, and an inflamed Meckel's diverticulum was found with an adhesive band creating an internal hernia with small bowel obstruction. The diverticulum was resected after the appendix was removed. CONCLUSION: The incidence of an internal hernia with a Meckel's diverticulum is rare. A diseased Meckel's diverticulum can be overlooked in many cases, especially in those resembling appendicitis. It is recommended that the small bowel be assessed in all appendectomy cases for a pathological Meckel's diverticulum.

Natural-synthetic hybrid polymers developed via electrospinning: the effect of PET in chitosan/starch system.

Chitosan is an amino polysaccharide found in nature, which is biodegradable, nontoxic and biocompatible. It has versatile features and can be used in a variety of applications including films, packaging, and also in medical surgery. Recently a possibility to diversify chitosan properties has emerged by combining it with synthetic materials to produce novel natural-synthetic hybrid polymers. We have studied structural and thermophysical properties of chitosan + starch + poly(ethylene terephthalate) (Ch + S + PET) fibers developed via electrospinning. Properties of these hybrids polymers are compared with extant chitosan containing hybrids synthesized by electrospinning. Molecular interactions and orientation in the fibers are analyzed by infrared and Raman spectroscopies respectively, morphology by scanning electron microscopy and thermophysical properties by thermogravimetric analysis and differential scanning calorimetry. Addition of PET to Ch + S systems results in improved thermal stability at elevated temperatures.

Assessment of the genotoxicity of atenolol in human peripheral blood lymphocytes: correlation between chromosomal fragility and content of micronuclei.

The antihypertensive drug atenolol was found to induce chromosome loss, detected as micronuclei in the peripheral lymphocytes of treated patients. The fundamental question which chromosomes the micronuclei were derived from remains to be answered. Analysis of structural chromosomal aberrations (CAs) and expression of fragile sites (FS) were pursued in this study. They revealed a significantly higher incidence of chromosomal aberrations (chromatid and chromosome breaks) in patients compared with controls, where 10 FS emerged as specific. Also, the band 17q12-21, where known fragile sites have not been reported, was only expressed in atenolol-treated patients. Fluorescence in situ hybridization using chromosome-specific probes revealed the preferential involvement of chromosomes 7, 11, 17 and X in the micronuclei (MN) of patients. The results also suggest a correlation between chromosomal fragility and content of MN, and support the findings for a linkage between hypertension and a locus on chromosome 17.

Anti-inflammatory activity of superoxide dismutase obtained from Debaryomyces hansenii on type II collagen induced arthritis in rats.

INTRODUCTION: Rheumatoid arthritis is an autoimmune inflammatory disease of unknown etiology, free radicals have been implicated in the genesis and perpetuation of damage in this pathology. OBJECTIVE: To evaluate the anti-inflammatory effect of Cu,Zn-superoxide dismutase (SOD) obtained from two different sources (bovine erythrocytes, Be-SOD, and Debaryomyces hansenii, Dh-SOD) with Type II Collagen-induced Arthritis model in rats. MATERIAL AND METHODS: Arthritis was induced by repeated injection of a porcine type II collagen-incomplete Freund adjuvant suspension on the back of Dark Augui (DA) rats. Arthritis was clinically evaluated throughout the study. Body weight was determined at three different times. Two different doses for each treatment (Be-SOD, Dh-SOD) were tested: 100 and 1,000 U/kg. At the end of the trial (day 28), histological analyses of the most inflamed ankle joint, as well as serum anti-collagen antibodies, were determined. RESULTS: Both sources of SOD decreased, although to a different extent, the incidence and severity of the disease. Arthritis score was lower in all treatments, except for the low dose of Be-SOD. Groups receiving either source of SOD showed a significant weight increase compared to the placebo group. Histological damage was similar in all groups. Only the group that received the highest dose of Dh-SOD showed a significant lower antibody titer; nevertheless, no correlation appears to derive from arthritis score and antibody titer. CONCLUSION: Our findings suggest that, although unable to counteract the arthritis syndrome, SOD may still be beneficial due to its anti-inflammatory activity. In the case of Dh-SOD, the best effect was observed at the highest dose tested.

[Civil status and suicide]. / El estado civil y el suicidio en Baja California Sur.

OBJECTIVE: To determine if civil status acts as a risk factor in suicide and how it modifies according to gender, age and population size. METHODS: A retrospective study which analyzes information from the mortality data from the National Institute of Statistics, Geography and Information, from 1998 to 2002. Variables like suicides age, sex, cause of death, federal entity, population size and civil status were registered. RESULTS: Single men showed twofold risk for committing suicide. Women did not show any associated risk for suicide according to civil status. The risk of married men for committing suicide increased gradually with age. Medium-sized communities with less than 19,999 habitants presented the highest risk for habitants to commit suicide. CONCLUSIONS: Suicide is associated to gender especially to men who are not married and living in small and medium-sized communities. One explanation could be the lack of integrated behavior as defined by Emile Durkheim, where the physical density of society will determine behavior and ideas. This social structure phenomenon is called the "moral cocoon." This works around the individual being less individualistic and granting him/her the feeling of belonging to a group.

La Von Economo's encephalitis lethargica and the Spanish flu pandemic in Bogotá and Medellín (Colombia): An historic review one hundred years after / La encefalitis letárgica de von Economo y la pandemia de la gripe española en Bogotá y Medellín: reseña histórica cien años después.

Von Economo's encephalitis is a neuropsychiatric disorder of possible autoimmune origin, which affects basal ganglia. This reaction may occur secondary to infection by different viral or bacterial agents. Given that it appears after the acute episode has disappeared, molecular mimetism has been proposed to explain the autoimmune lesion. Several cases have been reported through time, but it was with the 1918 flu pandemic, known as the Spanish flu, that lethargic encephalitis reached epidemic levels with cases reported until 1923 in various countries. The Spanish flu pandemic appeared in Colombia at the end of 1918 in several cities but it affected especially Bogotá where the highest number of patients and deaths was reported. Our purpose with the present work was to commemorate the arrival of the Spanish flu to our country after one hundred years, as well as to reflect on its main complications, which included some lethargic encepahilitis cases.

La encefalitis letárgica de von Economo es un trastorno neuropsiquiátrico de posible origen autoinmunitario, en el cual se afectan los ganglios basales. Esta reacción puede ocurrir luego de una infección aguda por diversos agentes virales o bacterianos. Dado que aparece cuando ya se ha resuelto el cuadro agudo, se ha propuesto el mecanismo del mimetismo molecular para explicar la lesión autoinmunitaria. Se han reportado diversos casos a lo largo del tiempo, pero fue con la pandemia de influenza de 1918, conocida como la gripe española, que la encefalitis letárgica alcanzó niveles de epidemia, con casos reportados hasta 1923 en diversos países. La pandemia de la gripe española se extendió a Colombia durante los últimos meses de 1918 y afectó varias ciudades, principalmente Bogotá, donde se reportó el mayor número de enfermos y muertos. Con este trabajo se busca rememorar, cien años después, el ingreso de la gripe española a nuestro país y sus principales complicaciones, entre las que se describieron algunos casos de encefalitis letárgica.

An early Aurignacian arrival in southwestern Europe.

Westernmost Europe constitutes a key location in determining the timing of the replacement of Neanderthals by anatomically modern humans (AMHs). In this study, the replacement of late Mousterian industries by Aurignacian ones at the site of Bajondillo Cave (Málaga, southern Spain) is reported. On the basis of Bayesian analyses, a total of 26 radiocarbon dates, including 17 new ones, show that replacement at Bajondillo took place in the millennia centring on ~45-43 calibrated thousand years before the present (cal ka BP)-well before the onset of Heinrich event 4 (~40.2-38.3 cal ka BP). These dates indicate that the arrival of AMHs at the southernmost tip of Iberia was essentially synchronous with that recorded in other regions of Europe, and significantly increases the areal expansion reached by early AMHs at that time. In agreement with human dispersal scenarios on other continents, such rapid expansion points to coastal corridors as favoured routes for early AMH. The new radiocarbon dates align Iberian chronologies with AMH dispersal patterns in Eurasia.

Micronutrient content and antioxidant enzyme activities in human breast milk.

Breast milk contains micronutrients that function as cofactors of antioxidant enzymes. High concentrations of iron (Fe) and copper (Cu) can increase the production of reactive oxygen species (ROS). This study aimed to assess the relationship between the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST)) and the concentration of the micronutrients Fe, Cu and zinc (Zn) in breast milk. Breast milk samples were collected from 108 mothers (7-10 days postpartum, transitional milk). The samples were grouped into three groups according to the number of pregnancies (one, two and three or more pregnancies), also grouped according to the body mass index (BMI) suggested by the World Health Organization (WHO) in underweight, normal weight, overweight and obese. Breast milk Fe, Cu and Zn concentrations were determined by atomic absorption spectrophotometry and the activity of the antioxidant enzymes was determined by spectrophotometry. An increase in GPx, SOD and GST activities in relation to the number of pregnancies was found (p = 0.05, p = 0.04 and p < 0.01, respectively). An inverse relationship between GST activity and BMI was found (p = 0.05). A positive correlation was observed between Cu and Zn concentrations (r = 0.52, p < 0.05). A negative correlation was found between Cu concentration and catalase activity (r = -0.22, p < 0.05); Fe content was negatively correlated with GPx and GST activities (r = -0.32, r = -0.22, respectively, p < 0.05). The activities of antioxidant enzymes (GPx, SOD and GST) may be affected by the number of pregnancies and contribute to prevent oxidation of nutritional molecules in breast milk.