The lacustrine deposits infilling the intramontane Guadix-Baza Basin, in the Betic Range of Southern Spain, have yielded abundant well-preserved lithic artifacts. In addition, the lake beds contain a ...wide range of micromammals including Mimomys savini and Allophaiomys burgondiae and large mammals such as Mammuthus and Hippopotamus together with the African saber-toothed felid Megantereon. The association of the lithic artifacts along with the fossil assemblages, themselves of prime significance in the Eurasian mammal biochronology, is providing new insight into the controversy of the human settlement in Southern Europe. Despite the importance of the artifacts and fossil assemblage, estimates of the geological age of the site are still in conflict. Some attempts at dating the sediments have included biochronology, uranium series, amino acid racemization, and stratigraphic correlation with other well-dated sections in the basin, but so far have failed to yield unambiguous ages. Here we present paleomagnetic age dating at the relevant localities and thus provide useful age constraints for this critical paleoanthropological and mammal site. Our data provide firm evidence for human occupation in Southern Europe in the Lower Pleistocene, around 1 mega-annum ago. The current view of when and how hominids first dispersed into Europe needs to be reevaluated.
Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the ...chalcogen atom (S, Se). These compounds were evaluated towards
and
. Thiosemicarbazide
showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC
(
)=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC
(BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC
> 256 µM). Thiosemicarbazones
,
and
showed remarkable trichomonacidal effects (IC
=16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC
≥ 275 µM). Selenoisosters
and
presented a slightly enhanced activity (IC
=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.
Colour polymorphism is a widespread phenomenon in natural populations of several species. In particular, it is especially common on marine gastropod species from the genus
Littorina
. Recently, it ...has been argued that intrapopulation shell colour polymorphism in
Littorina fabalis
could be caused by negative frequency-dependent sexual selection via a mechanism of mate choice (indirectly estimated through negative assortative mating). Here we try to determine the existence of negative assortative mating in three species of the subgenus
Neritrema
(
L. fabalis
,
L. obtusata, L. saxatilis
) that share a similar shell colour polymorphism, to ascertain if this mechanism could represent an ancestral character in this subgenus that could be contributing to the maintenance of the colour polymorphism observed in each species. We collected or reanalysed from previous studies a sample of mating pairs of these three species from seven locations from NW Spain and NE Russia and estimated assortative mating using the
I
PSI
index. Our results suggest that all species and populations show a systematic tendency towards negative assortative mating when shell colour is grouped in the broad categories ‘light’ and ‘dark’. Moreover, a more detailed analysis of each colour separately suggests that shell colour may not be the main target of assortative mating, but perhaps a physically-linked trait to the real target of selection. This hypothesis opens interesting new lines of research in
Littorina
snails.
In the work environment, there are usually different pathologies that are related to Repetitive Efforts and Movements (REM) that tend to predominantly affect the upper limbs. To determine whether a ...worker is at risk of suffering some type of pathology, observation techniques are usually used by qualified technical personnel. In order to define from quantitative data if there is a risk of suffering a pathology due to movements and repetitive efforts in the upper limb, a prototype of a movement measurement system has been designed and manufactured. This system interferes minimally with the activity studied, maintaining a reduced cost of manufacture and use. The system allows the study of the movements made by the subject in the work environment by determining the origin of the Musculoskeletal Disorder (MSD) from the movements of the elbow and wrist, collecting data on the position and accelerations of the arm, forearm and hand, and taking into account the risk factors established for suffering from an MSD: high repetition of movements, the use of a high force in a repetitive manner, or the adoption of forced positions. The data obtained with this system can be analyzed by qualified personnel from tables, graphs, and 3D animations at the time of execution, or stored for later analysis.
The involvement of carbonic anhydrases (CAs) in a myriad of biological events makes the development of new inhibitors of these metalloenzymes a hot topic in current Medicinal Chemistry. In ...particular, CA IX and XII are membrane-bound enzymes, responsible for tumour survival and chemoresistance. Herein, a bicyclic carbohydrate-based hydrophilic tail (imidazolidine-2-thione) has been appended to a CA-targeting pharmacophore (arylsulfonamide, coumarin) with the aim of studying the influence of the conformational restriction of the tail on the CA inhibition. For this purpose, the coupling of sulfonamido- or coumarin-based isothiocyanates with reducing 2-aminosugars, followed by the sequential acid-promoted intramolecular cyclization of the corresponding thiourea and dehydration reactions, afforded the corresponding bicyclic imidazoline-2-thiones in good overall yield. The effects of the carbohydrate configuration, the position of the sulfonamido motif on the aryl fragment, and the tether length and substitution pattern on the coumarin were analysed in the in vitro inhibition of human CAs. Regarding sulfonamido-based inhibitors, the best template turned out to be a d-
-configured carbohydrate residue,
-substitution on the aryl moiety (
), with
against CA XII within the low nM range (5.1 nM), and remarkable selectivity indexes (1531 for CA I and 181.9 for CA II); this provided an enhanced profile in terms of potency and selectivity compared to more flexible linear thioureas
-
and the drug acetazolamide (AAZ), used herein as a reference compound. For coumarins, the strongest activities were found for substituents devoid of steric hindrance (Me, Cl), and short linkages; derivatives
and
were found to be the most potent inhibitors against CA IX and XII, respectively (
= 6.8, 10.1 nM), and also endowed with outstanding selectivity (
> 100 µM against CA I, II, as off-target enzymes). Docking simulations were conducted on
and
to gain more insight into the key inhibitor-enzyme interactions.
Background
Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that ...unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC.
Design and methods
Type of study: National multicenter longitudinal analytical observational study. Study population: Patients with FPTMC. Study groups: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). Study variables: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. Statistical analysis: Cox regression analysis and survival analysis.
Results
Ninety-four patients were included, 44% (
n
= 41) with unicentric FPTMC and 56% (
n
= 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%;
p
= 0.003), lymph node dissection (41 vs. 15%;
p
= 0.005) and therapy with radioactive iodine (96 vs. 73%;
p
= 0.002). Tumor stage was similar in both groups (
p
= 0.237), with a higher number of T3 cases in the group B (24 vs. 5%;
p
= 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%;
p
= 0.337), disease recurrence rate (21 vs. 8%;
p
= 0.159) and disease-free survival (
p
= 0.075).
Conclusions
Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.
Graphical Abstract
Purpose
Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is ...to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain.
Methods
Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence).
Results
Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210–5.473;
p
= 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638–1000;
p
< 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405–333.333;
p
< 0.001).
Conclusion
FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.
Graphical abstract
In case of significant imperfections on the cornea, data acquisition is difficult and a significant level of missing data could require the interpolation of important areas of the cornea, resulting ...in a very ambiguous model. The development of methods to define in vivo customised geometric properties of the cornea based only on real raw data is extremely useful to diagnose and assess the progression of diseases directly related to the corneal architecture. The present work tries to improve the prognostic of corneal ectasia creating a 3D customised model of the cornea and analysing different geometric variables from this model to determine which variables or combination of them could be defined as an indicator of susceptibility to develop keratoconus.
A corneal geometric reconstruction was performed using zonal functions and retrospective Scheimpflug tomography data from 187 eyes of 187 patients. Morphology of healthy and keratoconic corneas was characterized by means of geometric variables. The performance of these variables as predictors of a new geometric marker was assessed and their correlations were analysed.
The more representative variable to classify the corneal anomalies related to keratoconus was posterior apex deviation (area under receiver operating characteristic curve > 0.899; p < 0.0001). However, the strongest correlations in both healthy and pathological corneas were provided by the metrics directly related to the thickness, as deviations of the anterior/posterior minimum thickness points.
The presented morphogeometric approach based on the analysis and custom geometric modelling of the cornea demonstrates to be useful for the characterization and diagnosis of keratoconus disease, stating that geometrical deformation is an effective marker of the ectatic disease's progression.
Two in vitro and one in vivo experiments were conducted to investigate the effects of a selection of plant compounds on rumen fermentation, microbial concentration and methane emissions in goats. ...Treatments were: control (no additive), carvacrol (CAR), cinnamaldehyde (CIN), eugenol (EUG), propyl propane thiosulfinate (PTS), propyl propane thiosulfonate (PTSO), diallyl disulfide (DDS), a mixture (40 : 60) of PTS and PTSO (PTS+PTSO), and bromochloromethane (BCM) as positive control with proven antimethanogenic effectiveness. Four doses (40, 80, 160 and 320 µl/l) of the different compounds were incubated in vitro for 24 h in diluted rumen fluid from goats using two diets differing in starch and protein source within the concentrate (Experiment 1).The total gas production was linearly decreased (P<0.012) by all compounds, with the exception of EUG and PTS+PTSO (P⩾0.366). Total volatile fatty-acid (VFA) concentration decreased (P⩽0.018) only with PTS, PTSO and CAR, whereas the acetate:propionate ratio decreased (P⩽0.002) with PTS, PTSO and BCM, and a tendency (P=0.064) was observed for DDS. On the basis of results from Experiment 1, two doses of PTS, CAR, CIN, BCM (160 and 320 µl/l), PTSO (40 and 160 µl/l) and DDS (80 and 320 µl/l) were further tested in vitro for 72 h (Experiment 2). The gas production kinetics were affected (P⩽0.045) by all compounds, and digested NDF (DNDF) after 72 h of incubation was only linearly decreased (P⩽0.004) by CAR and PTS. The addition of all compounds linearly decreased (P⩽0.009) methane production, although the greatest reductions were observed for PTS (up to 96%), DDS (62%) and BCM (95%). No diet–dose interaction was observed. To further test the results obtained in vitro, two groups of 16 adult non-pregnant goats were used to study in vivo the effect of adding PTS (50, 100 and 200 mg/l rumen content per day) and BCM (50, 100 and 160 mg/l rumen content per day) during the 9 days on methane emissions (Experiment 3). The addition of PTS and BCM resulted in linear reductions (33% and 64%, respectively, P⩽0.002) of methane production per unit of dry matter intake, which were lower than the maximum inhibition observed in vitro (87% and 96%, respectively). We conclude that applying the same doses in vivo as in vitro resulted in a proportional lower extent of methane decrease, and that PTS at 200 mg/l rumen content per day has the potential to reduce methane emissions in goats. Whether the reduction in methane emission observed in vivo persists over longer periods of treatments and improves feed conversion efficiency requires further research.
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