Northwest African Neolithic initiated by migrants from Iberia and Levant.

In northwestern Africa, lifestyle transitioned from foraging to food production around 7,400 years ago but what sparked that change remains unclear. Archaeological data support conflicting views: (1) that migrant European Neolithic farmers brought the new way of life to North Africa1-3 or (2) that local hunter-gatherers adopted technological innovations4,5. The latter view is also supported by archaeogenetic data6. Here we fill key chronological and archaeogenetic gaps for the Maghreb, from Epipalaeolithic to Middle Neolithic, by sequencing the genomes of nine individuals (to between 45.8- and 0.2-fold genome coverage). Notably, we trace 8,000 years of population continuity and isolation from the Upper Palaeolithic, via the Epipaleolithic, to some Maghrebi Neolithic farming groups. However, remains from the earliest Neolithic contexts showed mostly European Neolithic ancestry. We suggest that farming was introduced by European migrants and was then rapidly adopted by local groups. During the Middle Neolithic a new ancestry from the Levant appears in the Maghreb, coinciding with the arrival of pastoralism in the region, and all three ancestries blend together during the Late Neolithic. Our results show ancestry shifts in the Neolithization of northwestern Africa that probably mirrored a heterogeneous economic and cultural landscape, in a more multifaceted process than observed in other regions.

Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit.

Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency. Design: Prospective, observational, single-center study. Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021. Patients: Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included. Interventions: Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients. Measurement: Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L). Main results: Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients. Conclusion: This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.

The antimicrobial capacity of Cistus salviifolius and Punica granatum plant extracts against clinical pathogens is related to their polyphenolic composition.

Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50-80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.

Peptide Glycodendrimers as Potential Vaccines for Olive Pollen Allergy.

Olive pollen is one of the most important causes of respiratory allergy, with Ole e 1 being the most clinically relevant sensitizing allergen. Peptide-based vaccines represent promising therapeutic approaches, but the use of adjuvants is required to strengthen the weak immunogenicity of small peptides. We propose the use of dendrimeric scaffolds conjugated to the T cell immunodominant epitope of Ole e 1 (OE109-130) for the development of novel vaccines against olive pollen allergy. Four dendrimeric scaffolds containing an ester/ether with nine mannoses, an ester succinimidyl linker with nine N-acetyl-glucosamine units or nine ethylene glycol units conjugated to OE109-130 peptide were designed, and their cytotoxicity, internalization pattern, and immunomodulatory properties were analyzed in vitro. None of the dendrimers exhibited cytotoxicity in humanized rat basophil (RBL-2H3), human bronchial epithelial Calu-3, and human mast LAD2 cell lines. Confocal images indicated that mannosylated glycodendropeptides exhibited lower colocalization with a lysosomal marker. Moreover, mannosylated glycodendropeptides showed higher transport tendency through the epithelial barrier formed by Calu-3 cells cultured at the air-liquid interface. Finally, mannosylated glycodendropeptides promoted Treg and IL10+Treg proliferation and IL-10 secretion by peripheral blood mononuclear cells from allergic patients. Mannosylated dendrimers conjugated with OE109-130 peptide from Ole e 1 have been identified as suitable candidates for the development of novel vaccines of olive pollen allergy.

Chemoprotective effects of Ulva lactuca (green seaweed) aqueous-ethanolic extract against subchronic exposure to benzo(a)pyrene by CYP1A1 inhibition in mice.

The protective effect of the supplementation with an aqueous-ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene-induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL-1ß and TNF-α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene-exposed group. The benzo(a)pyrene-induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract-supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene-induced-toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.

Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia.

Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7,500-3,500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up.

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents.

Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

Frecuencia de la resistencia a fluoroquinolonas en Mycobacterium tuberculosisen Elche (Alicante) / Frequency of fluoroquinolone resistance in Mycobacterium tuberculosis in Southeast Spain

No disponible

Occular complications following dental local anesthesia

Objective: To determine the frequency of app earance and the factors most comm only associated with ocular complicationsfollowing dental local anesthesia, also establishing the location and typ e of anesthesia used.Study Design: An indexed search in the Pubmed and Comp ludoc databases was carried out with the keywords“oral anesthesia”, “ocular”, “ophthalmologic”, “damage”, “comp lications”, “injection”. We established a limitationthat the literature had to have been published after the year 1970. A total of 19 articles were obtained, forming atotal samp le of 37 patients. The patient’s sex, age, nerve anesthetized, typ e of anesthetic used, ophthalmologicalcomp lication present, recovery time, treatment and side effects were analyzed.Results: There is a higher involvement of females (77%). The average age was 34.2 years. There was no preferencefor an anesthetic technique. Diplopia was the most comm on comp lication (65%), which coincides with the datafrom other authors. Almost all of the comp lications were of a temp orary nature, with an average recovery time of68 minutes.Conclusions: This is one of the few studies of its kind in dental literature, it thus being difficult to make preciseconclusions. Ophthalmological comp lications are seldom a problem, diplopia being the most comm on amongthem. The authors app ear to indicate an intravascular injection of the anesthetic as the cause of the problem, andtherefore, it should be avoided in order to prevent accidents at the ocular level (AU)

Mutant prevention concentration: a new tool for choosing treatment in nontuberculous mycobacterial infections.

The mutant prevention concentration (MPC) of fluoroquinolones, linezolid, rifabutin, rifampicin and macrolides was determined in 16 nontuberculous Mycobacterium species in order to compare the incidence of resistant mutant occurrence for different antibiotics. Linezolid showed good activity against Mycobacterium gordonae and Mycobacterium kansasii. Rifabutin had a lower MPC values than rifampicin. The fluoroquinolones were more active against M. gordonae and Mycobacterium chelonae. Clarithromycin had better MPC values than azithromycin but its intracellular concentration was high. Mutant prevention concentration may help to establish a better clinico-microbiological correlation, the sub-populations of drug-resistant micro-organisms may be detected by that method. It is still important to administer correct drug doses, to use combined therapies and to find new drugs that are useful in the treatment of these infections.

Diagnóstico y plan de tratamiento en cirugía ortognática / Diagnosis and Treatment Planning in Orthognatic Surgery

La cirugía ortognática es una práctica cada vez más extendida y que, en el momento actual, no se aplica exclusivamente en deformidades dentofaciales extremadamente severas. Debido a sus implicaciones tanto estéticas como funcionales, los pacientes aceptan cada vez con más frecuencia someterse a este tipo de tratamientos. El objetivo de este trabajo consiste en mostrar al odontólogo general algunos de los aspectos concernientes al manejo que realiza el cirujano con respecto al diagnóstico y plan de tratamiento de este tipo de deformidades. (AU)

Coartación aórtica: a propósito de un caso clínico / Aortic coarctation: clinical case

La coartación aórtica es una de las causas de hipertensión arterial corregible quirúrgicamente. En más del 65 por ciento de los casos el diagnóstico se realiza con el examen físico y la radiografía de tórax. A pesar de ello, transcurren habitualmente de 10 a 33 años entre la pesqisa del soplo; el desarrollo de la hipertensión arterial; el establecimiento del diagnóstico y la corrección quirúrgica de la malformación. En esta circunstancia generalmente ha existido una insuficiente valoración del cuadro clínico y el examen físico