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Despite their ancient past and high diversity, African populations are the least represented in human population genetic studies. In this study, uniparental markers (mtDNA and Y chromosome) were used to investigate the impact of sociocultural factors on the genetic diversity and inter-ethnolinguistic gene flow in the three major Nigerian groups: Hausa (n = 89), Yoruba (n = 135) and Igbo (n = 134). The results show a distinct history from the maternal and paternal perspectives. The three Nigerian groups present a similar substrate for mtDNA, but not for the Y chromosome. The two Niger–Congo groups, Yoruba and Igbo, are paternally genetically correlated with populations from the same ethnolinguistic affiliation. Meanwhile, the Hausa is paternally closer to other Afro-Asiatic populations and presented a high diversity of lineages from across Africa. When expanding the analyses to other African populations, it is observed that language did not act as a major barrier to female-mediated gene flow and that the differentiation of paternal lineages is better correlated with linguistic than geographic distances. The results obtained demonstrate the impact of patrilocality, a common and well-established practice in populations from Central-West Africa, in the preservation of the patrilineage gene pool and in the affirmation of identity between groups. [ABSTRACT FROM AUTHOR]

Gambling risk behaviour is an emerging problem among adolescents. "Unplugged" is an effective Social Influence curriculum for preventing substance use among students. This study aims to develop and test a new component focused on gambling added to the Unplugged program. Schools of Piedmont region and Rome city were invited to participate in the study. A self-completed anonymous questionnaire including questions on socio-demographic characteristics, addictive behaviours, beliefs, attitudes and risk perceptions about gambling, normative perceptions, parental practices, school climate, refusal skills, impulsiveness, self-esteem, antisocial behaviours and sensation seeking was prepared for baseline and follow-up surveys. The protocol of the study was submitted and approved by the Novara Ethical Committee and registered in ClinicalTrials.gov (NCT05630157, Protocol ID: 080.742, 11/17/2022). Twenty-nine schools accepted to participate in the study. Sixty-three classes (1325 students) satisfied the eligibility criteria for intervention and were allocated to the intervention arm, and the other 61 (1269 students) were allocated to the control arm. Because of drop-out, absentees, refusals, and invalid questionnaires, data on 1874 students (998 in the intervention and 876 in the control arm), were available for the analysis at baseline. Data management of follow-up questionnaires is in progress. Results of the present study will be useful to clarify the effectiveness of prevention interventions in reducing gambling behaviours among adolescents. Moreover, this will be the first experience of evaluating a new component focused on a different risk behaviour, added to a curriculum previously shown as effective on other risk behaviours. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS). Methods: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients. Results: Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates. Conclusions: Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered. [ABSTRACT FROM AUTHOR]

Purpose: To compare toxicity of radiotherapy (RT) with concomitant chemotherapy (CHT) in patients (pts) with anal cancer treated with simultaneous integrated boost (SIB) versus sequential boost (SeqB). Methods: Sixty-six patients were treated from 2007 to 2021. Thirty patients underwent to SeqB concurrent to CHT and 37 to SIB-group. Toxicity assessment has been considered in acute and in late toxicities for gastrointestinal (GI), genitourinary (GU), cutaneous (CU) districts, according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. The Wexner scale among summary scoring systems has been used as a tool to measure fecal incontinence. The chi-square test for ordinal variables were used to evaluate the association between patient and treatment characteristics and acute or late severe toxicity. Univariable logistic regression models were fit to evaluate predictive factors associated with fecal incontinence. Results: Median follow-up was 61.5 months (IQR, 27.1–121.7 months) for all patients. Severe acute toxicity (≥ G2) was observed in 49 patients (74.2%). Late toxicity (≥ G2) occurred in 13 cases (19.6%). In assessment of cutaneous toxicity, there was also a significant reduction in ≥ G1 in SIB group with 29 patients (80.5%) vs SeqB group with 29 patients (96.6%) (p-value = 0.046). Of both groups 11 patients (16.6%) developed fecal incontinence, 8 (22%) in the SIB group and 3 (10%) in the SeqB. Conclusion: SIB for anal cancer treatment results in reduced acute and late cutaneous toxicity compared to SeqB. According to our results the rate of other acute and late toxicities are low and comparable between the two groups. [ABSTRACT FROM AUTHOR]

The impact produced by agrochemicals on periurban agriculture soils generates an environmental concern. The objective of this work was to evaluate the potential of native plant growth-promoting bacteria to recover the horticultural soil quality for bioinoculant design using Eisenia andrei as bioindicator. Total phosphorus determination and bioassays with E. andrei cholinesterases, carboxylesterases and glutathione S-transferases as biomarkers were performed. Glutathione S-transferase levels were significantly augmented (~ 30%) evidencing the risk of uncontrolled use of agrochemicals. Native Pseudomonas migulae S1-2, Sphingobium yanoikuyae SP-3 and Leucobacter aridicollis RP-7 exhibited plant growth-promoting properties. Indole-3-acetic acid production of 14.0 ± 0.1, 69 ± 1 and 6.4 ± 0.1 µg mL−1 and phosphorus solubilisation of 46, 133 and 158 mg P L−1 were obtained from culture supernatants. Bacterial supernatants increased the root elongation of Lactuca sativa seeds up to 10%. These selected bacteria demonstrated their potential to design a biofertiliser formulation to restore deteriorated horticultural soils. [ABSTRACT FROM AUTHOR]

Adrenal metastases occur in 15–35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion's volume was 28.5 cm3 (2.5–323.4). The median SBRT dose was 40 Gy (10–60). Median follow-up was 14.4 months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3 months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches. [ABSTRACT FROM AUTHOR]

In order to determine the population allele frequencies of autosomal STR markers of forensic interest in the Zimbabwean population, we analyzed a sample of 478 individuals from 19 different ethnic groups using the PowerPlex® Fusion 6C Kit (Promega Corp, Madison, Wisconsin). The data obtained were compared among the different Zimbabwean ethnic groups as well as with several African populations to establish whether significant differences exist among them. No significant differences were found among the ethnic groups in Zimbabwe. Statistically significant differences were observed between allele frequencies in Zimbabwe and some other African populations, although FST with neighboring Bantu populations from South and Southeast regions were low (below 0.005 in most single locus comparisons). [ABSTRACT FROM AUTHOR]

Purpose: Local neck symptoms (LNS) may be related to goiter, but are also reported by patients suffering from laryngeal–pharyngeal reflux (LPR). The aim of this study was to investigate whether LPR could play a role in the persistence of some LNS after total thyroidectomy (TT). Methods: A consecutive case series of 160 patients with multinodular goiter (MNG) candidate for TT were included in this study. Each patient was closely studied for both the thyroid pathology and reflux disease before and 6 months after surgery to assess the persistence of LNS after surgery. Results: Only throat discomfort showed a significant improvement (p = 0.031) after surgery. On the other hand, swallowing and voice disorders persisted after surgery in 82.3% and 77.3% of patients, respectively (p = 0.250 and p = 0.062), such as the correlated reflux laryngopharyngitis (p = 0.5). Conclusions: LPR can be considered a predisposing factor or an important concurrent causa to the persistence of LNS after TT, in particular for swallowing disorders and voice disorders. In patients with non-toxic MNG who complain of local neck symptoms, the investigation of a possible coexistence of a reflux disease is appropriate before surgery. Patients should be informed about the possibility that some symptoms can persist even after removal of the goiter. [ABSTRACT FROM AUTHOR]

With the advent of expanded STR (short tandem repeats) typing kits, it was necessary to determine allele frequencies and other appropriate population data parameters for El Salvador. Samples were collected from the central, east, and west regions of the country and typed for 21 forensically relevant STR loci. The data indicate that all loci are highly polymorphic, the three regions are genetically similar, and the population data are similar to those of US Hispanics. The results of this study support that the allele frequency data described herein can be used for statistical calculations for human identity testing in El Salvador. [ABSTRACT FROM AUTHOR]

In Argentina, periurban agriculture is performed by farmers with inadequate training in the use of pesticides and chemical fertilizers, developing horticulture with serious soil deterioration. The aim of this work was to monitor bacterial diversity of a horticultural soil (S) and a reference soil (R) as quality index for the design of future restoration strategies. As crops changed together with the agrochemical applications, sample collection was before harvest for strawberries, post-harvest for red peppers, pre-harvest broccoli crop and of a resting soil in treatment with poultry litter as a fertilizing amendment. Bacterial diversity was analysed by the use of high throughput sequencing of the V1–V3 region of the 16S rRNA gene. Analysis of R soils seemed relatively constant in time, enriched in Alphaproteobacteria and Acidobacteria consistent with a reference to soil health. The effect of the intensive use of S soils was proved by differences in Chloroflexi, Bacteroidetes and Proteobacteria relative abundances. The main evidence of the alteration of S soils was the increase in Bacteroidetes and Betaproteobacteria. A weak recuperation trend of S soil microbiota was registered during a post-harvest inactive period. A strong influence of the soil use routine—consisting in high crop rotation and short time-rest cycles—on microbial community structure was verified. These results indicate the microbiota perturbation, caused by the intense use of periurban agriculture soils and will contribute for further actions to improve environment quality. [ABSTRACT FROM AUTHOR]

The assessment of water quality is critical to implement preventive and emergency interventions aimed to limit/avoid environmental contamination and human exposure to toxic compounds. While established high-resolution techniques allow quantitative and qualitative determination of contaminants, their widespread application is not feasible due to cost, time, and need for trained personnel. In this context, the development of easy-to-implement approaches for preliminary detection of contaminants is of the utmost importance. Herein, a portable self-powered microbial electrochemical sensor enabling online monitoring of Cr(VI) is reported. The biosensor employs a bio-inspired redox mediating system to allow extracellular electron transfer between a bacterial isolate from chromium-contaminated environments and the electrode, providing a clear response to Cr(VI) presence. The biosensor shows good linearity (R2 = 0.983) and a limit of detection of 2.4 mg L−1 Cr(VI), with a sensitivity of 0.31 ± 0.02 μA cm−2 mgCr(VI)−1 L. The presented microbial bioanode architecture enhanced biosensor performance thanks to the improved "electrical wiring" between biological entities and the abiotic electrode surface. This approach could be easily implemented in engineered electrode surfaces, such as paper-based multi-anodes that maximize bacterial colonization, further improving biosensor response. [ABSTRACT FROM AUTHOR]

Several studies evidenced that a sedentary lifestyle is related with higher levels of systemic inflammation and highlighted that physical activity can trigger anti-inflammatory effects. To evaluate the impact of self-prescribed physical activity on fitness status, metabolism, inflammation and immune-activation in people living with HIV, an interim analysis of the results of the clinical trial PRIMO (NCT03392805) was performed. Patients enrolled were divided in 2 groups on the basis of self-prescribed physical activity: a physically active group (self-prescribed physical activity) and a sedentary group. Physical fitness was evaluated by sport medicine specialists and related to nutritional status, anthropometric variables, adipokines levels (adiponectin, leptin, resistin), peripheral immune-activation (CD38, HLA-DR on CD4 and CD8), and plasma inflammatory markers (IL-6 and TNF-α). The physically active group had a better profile in anthropometric measures and aerobic fitness but did not show lower levels of immune-activation compared to sedentary group. Also serum IL-6, TNF-α, and adipokines levels showed no statistical differences. On the basis of these data, a regular self-organized physical activity seems useful to improve cardio-respiratory fitness, but unable to control HIV-related immune-activation. [ABSTRACT FROM AUTHOR]

Background and Aim: Growing attention is being given to physical functioning measures to assess interventions for low back pain (LBP). The Quebec Back Pain Disability Questionnaire (QBPDS) has never been validated in Italian patients, and the aim of the study was culturally adapting and validating the Italian version of the QBPDS (QBPDS-I), to allow its use with Italian-speaking patients with chronic LBP.Methods: The QBPDS-I was developed by means of forward-backward translation, a final review by an expert committee and a test of the prefinal version to evaluate its comprehensibility. The psychometric testing included structural validity by exploratory factor analysis (EFA), reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation coefficient, ICC 2.1), measurement error by calculating the minimum detectable change (MDC), construct validity by assessing hypotheses of QBPDS correlations with the Roland Morris Disability Scale (RMDQ), the Oswestry Disability Questionnaire (ODI) and a pain numerical rating scale (NRS) (Spearman's correlations).Results: It took one month to develop a consensus-based version of the QBPDS-I. The questionnaire was administered to 201 subjects with chronic LBP and was well accepted. EFA suggested a one-factor 20-item solution (first factor variance explained = 54.7%). Internal consistency (α = 0.95) and test-retest reliability (ICC = 0.90) were excellent. The MDC was 12 scale points. Construct validity was good as all of the hypotheses were met; correlations: RMDQ (r = 0.40), ODI (r = 0.48) and NRS (r = 0.44).Conclusions: The QBPDS-I is unidimensional, reliable and valid in patients with chronic LBP. Its use is recommended for clinical and research purposes. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment. Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software. Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4+CD38+HLA–DR+ T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS. Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level. [ABSTRACT FROM AUTHOR]

The new QuantiFERON-TB Gold Plus employs modified peptides optimized to elicit an IFNγ response from CD8+ cytotoxic T lymphocytes in addition to CD4+ T cells. With a view to improve the difficult identification of TB cases, we assessed the combination of two specific immunological markers comprising IFNγ secretion and T cells co-expression of CD25 and CD134 in response to Mycobacterium tuberculosis-specific antigens. A total of 34 subjects with suspected TB and 10 age-matched HD were prospectively enrolled. Assessing the performance of QFT-Plus in terms of the TB1 and TB2 results, we found that in TB patients, the quantitative IFNγ value in TB2 was similar to that in TB1, and we did not find any differences irrespective of the disease (pulmonary or extra-pulmonary). The flow cytometric CD25/CD134 assay, allowed a more accurate differentiation between M. tuberculosis-infected and uninfected patients, with a better combination of sensitivity and specificity, especially by evaluation of CD4+ T-cell subset. All individuals with negative QFT-Plus results displayed a positive CD25/CD134 response. Overall, a positive correlation was found between T cells co-expressing CD25/CD134 and IFNγ levels in response to both QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes. We demonstrated that both TB1 and TB2 induce a higher expression of CD25+CD134+ markers on CD4+ T cells among infected TB subjects, compared to the lower degree of CD8+ T cells, mainly induced to TB2 stimulation. We suggest that a combined use of classic QFT-Plus and specific CD25/CD134 response may be a useful means in the diagnostic workup for active TB. [ABSTRACT FROM AUTHOR]

Dihydroartemisinin-piperaquine (DHA-PPQ) is the artemisinin combination therapy that was recently introduced for the treatment of Plasmodium falciparum uncomplicated malaria, but emerging resistance in South-East Asia is threatening its use. This report describes a case of DHA-PPQ treatment failure in uncomplicated malaria occurring in an immigrant living in Italy, after a travel to Ethiopia. Thirty days after malaria recovery following DHA-PPQ therapy, the patient had malaria recrudescence. According to the genotyping analysis, the same P. falciparum was responsible for both episodes. Thus, it seems important to consider possible malaria recrudescence occurring after DHA-PPQ therapy in patients from African countries [ABSTRACT FROM AUTHOR]

The aim of the present study is to offer our experience concerning post-mortem magnetic resonance (PMMR) in foetal death cases and an evaluation of the differences between the findings acquired by PMMR and by forensic autopsy. Fifteen foetuses were recruited from July 2014 to December 2015. These had suffered intrauterine death in women in the 21st to 38th week of gestation who were treated in the emergency department for non-perception of foetal movements. We performed a PMMR on foetuses, 3 ± 1 days on average from the time of death, and then a complete forensic autopsy was performed. All 15 foetuses were examined with a whole-body study protocol, starting from the skull, down to and including the lower limbs. The total time of examination ranged from 20 to 30 min in each case. The external evaluation and description of post-mortem phenomena (maceration), record of the weight and detection and the various measurements of foetal diameters were evaluated before performing autopsy. A complete histopathological study was performed in each case. Out of 15 cases examined, eight were negative for structural anatomical abnormalities and/or diseases, both in the preliminary radiological examination and the traditional autopsy. In the remaining seven cases, pathological findings were detected by PMMR with corresponding results at autopsy. PMMR can provide useful information on foetal medical conditions and result in improved diagnostic classification. It may enable the planning of a more suitable technique before proceeding to autopsy, including focusing on certain aspects of organ pathology otherwise not detectable. The association between PMMR, post-mortem examination and related histological study of the foetus-placenta unit could help reduce the percentage of cases in which the cause of foetal death remains unexplained. Lastly, it may allow a selective sampling of the organ in order to target histological investigations. [ABSTRACT FROM AUTHOR]

Human carbonic anhydrase IX (hCA IX) is a tumour-associated enzyme present in a limited number of normal tissues, but overexpressed in several malignant human tumours. It is a transmembrane protein, where the extracellular region consists of a greatly investigated catalytic CA domain and a much less investigated proteoglycan-like (PG) domain. Considering its important role in tumour biology, here, we report for the first time the full characterization of the PG domain, providing insights into its structural and functional features. In particular, this domain has been produced at high yields in bacterial cells and characterized by means of biochemical, biophysical and molecular dynamics studies. Results show that it belongs to the family of intrinsically disordered proteins, being globally unfolded with only some local residual polyproline II secondary structure. The observed conformational flexibility may have several important roles in tumour progression, facilitating interactions of hCA IX with partner proteins assisting tumour spreading and progression. [ABSTRACT FROM AUTHOR]

The paleontological heritage of the fossil site of Las Hoyas (Early Cretaceous of Cuenca, Spain) is becoming a relevant part of the sociocultural identity of Castilla-La Mancha autonomous community in general, and of Cuenca province in particular. The most recent scientific advances, including several fossil findings that have had high scientific impact, have made Las Hoyas to regularly be the center of attention in the local, national, and international media, especially since the reinterpretation of the paleoecosystem represented by the locality published in 2010. These results have led to a renaissance of the interest of the society for this unique site. As a consequence, Las Hoyas has been declared Site of Cultural Interest by the regional government, in the form of paleontological zone. This recognition, which grants the locality with the highest level of protection, sets a legal framework for the educative initiatives developed at this locality, which can be categorized as non-formal education, formal education, and Social Paleontology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to validate the role of MR/Ultrasound Fusion-Guided Targeted Biopsy as a first diagnostic modality in subjects with clinical suspicion of prostate cancer (PCa).Materials and methods: 108 men (age range 46–78 years) with clinical suspicion for PCa (PSA > 4 ng/mL) underwent multiparametric MRI of the prostate (mpMRI) and, when suspicious lesion were found (according to the PIRADSv2 scoring system), targeted biopsy was performed. All patients without significant alteration patterns at mpMRI have been referred for follow-up at 1 year.Results: 91/108 patients showed on the mpMRI highly suspicious lesions (PIRADS 4 and 5); the remaining 17/108 patients revealed no significant alteration consistent with PCa (PIRADS 3). Among the first group of patients, 58/91 proved to be positive for PCa on the pathology report: 24 patients had a Gleason Score (GS) 6 (3 + 3); 18 patients GS 7 of which 7 (3 + 4) and 11 (4 + 3); 14 patients GS 8 (4 + 4); two patients GS 9 (5 + 4); 33 proved to be negative. Overall cancer detection rate (CDR) was 63%. However, the CDR rises significantly, up to 77%, after the 53 initial consecutive biopsies that were performed (p < 0,05) and thus identified as part of the learning curve. Patients of the second group (17/108) have been followed with serial PSA assessments, clinical reevaluation, and follow-up mpMRI.Conclusion: Performing exclusively targeted MR/Ultrasound Fusion-Guided biopsies for the diagnosis of PCa in patients with suspicious PSA levels (> 4 ng/mL) increases the detection rate of clinically significant cancer, changing both the therapeutic options and the prognosis. [ABSTRACT FROM AUTHOR]

A new dinosaur tracksite was recently discovered in the Upper Jurassic deposits from the Oléron Island (Atlantic Ocean, western France). Tracks are located along the coastline in the tidal area of La Morelière near 'Pointe de Chassiron'. They were observed in situ in an evaporitic interval from the 'Purbeck beds' Unit. Sediments consist of calcite recrystallised after gypsum dissolution within limestone layers which are composed of thin laminites. The track-bearing surface shows abundant mud cracks and some ripple marks. Ichnofossils consist of medium-sized tridactyl footprints of theropods forming a narrow trackway. In order to obtain 3D reconstructions of the track-bearing surface, the trackway was scanned with a resolution of 0.5 mm using an Artec Eva 3D white-light scanner. As indicated by the track dimensions, the probable trackmaker is assigned to a medium-sized non-coelurosaur tetanuran, such as a megalosauroid or an allosauroid theropod. The palaeoenvironmental context is interpreted as a tidal flat in an evaporitic basin. In addition to the tridactyl tracks, we report sauropod- and thyreophoran-like tracks on two other surfaces from Chassiron-La Morelière. [ABSTRACT FROM AUTHOR]

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe, rare, and life-threatening adverse reactions to medications. Their incidence is approximately two patients per million population per year. Several cases have been reported in the literature in which SJS and TEN have occurred in patients with a neoplasm undergoing radiation therapy and who are taking an anticonvulsant. We report a case of SJS-TEN that developed in a 51-year-old woman with nonresectable non-small-cell lung cancer during treatment with phenobarbital plus radiation therapy for bone metastases but in whom the irradiated areas did not exhibit the SJS skin reaction. To our knowledge, no similar cases have been reported in the literature. [ABSTRACT FROM AUTHOR]

Background: Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2) to bicarbonate and a proton, and alpha-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpalphaCA). The purpose of this study was to characterize the beta-class CA of H. pylori (hpbetaCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy.Methods: We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpalphaCA and hpbetaCA, was studied with an in vitro killing assay.Results: DNA sequences of all 37 hpbetaCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 microg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin.Conclusions: Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of alpha-and beta-class CAs could be applied as alternative therapy for eradication of H. pylori. [ABSTRACT FROM AUTHOR]

Conversions and reversions of interferon-gamma (IFN-γ) release assays (IGRAs) were observed when these tests were repeated over time in the same individuals, including those treated with biological agents. In most studies, the variability of IFN-γ plasma levels was not paralleled by clinical change, but a few exceptions exist, in which IGRA conversion predicted the emergence of active tuberculosis (TB). We report the case of a Peruvian patient with rheumatoid arthritis (RA) and Crohn's disease scheduled for treatment with adalimumab. TB screening demonstrated latent TB infection (LTBI), and the patient was started on isoniazid (INH) for 9 months. Adalimumab was initiated after 1 month since INH. QuantiFERON-TB Gold In-Tube, one of the IGRAs currently available, was serially repeated to monitor the status of TB infection during treatment with the biological agent. The patient developed active TB preceded by progressively rising levels of released IFN-γ. We came to know that she had withdrawn INH after 2 months on her own initiative. Considering the low rate of INH completion, serial IGRAs may help in the clinical vigilance during prophylaxis as well as anti-TNF treatment, at least in patients presenting other risk factors aside from the state of immunosuppression. [ABSTRACT FROM AUTHOR]

To ascertain whether multiparametric flow cytometry assessment of multifunctional Mycobacterium tuberculosis ( Mtb)-specific CD4 and CD8 T cells can distinguish between untreated and treated patients with latent tuberculosis infection (LTBI), we enrolled 14 LTBI subjects treated with isoniazid (INH) therapy, 16 untreated LTBI patients, and 25 healthy controls. The analysis of mono-functional CD4 and CD8 T cells producing single cytokines showed significant differences only between uninfected and infected LTBI subjects (both treated and untreated). Conversely, the analysis of multifunctional CD4 T cells revealed a significant reduction in the frequency of two CD4 T cells subsets, those producing IFN-γ, IL-2, and TNF-α simultaneously (triple positive; p = 0.005) and those producing IL-2 alone ( p = 0.0359), as well as a shift towards T cells producing only one cytokine in treated as compared to untreated LTBI subjects. Assigning a triple-positive CD4 T cells a cut-off >0.082 %, 94 % of untreated LTBI patients were scored as positive, as compared to only 28 % of treated LTBI patients and none of the healthy controls. No significant differences between untreated and treated LTBI subjects in terms of Mtb-specific CD8 T cell cytokine profiles ( p > 0.05) were identified. The significant changes in the cytokine profiles of Mtb-specific T cells after INH therapy suggest that analysis of multifunctional T cells may be a promising means for the monitoring of LTBI treatment success. [ABSTRACT FROM AUTHOR]

In the last years, the treatment of multiple sclerosis (MS) patients with natalizumab has been associated with the occurrence of progressive multifocal leukoencephalopathy (PML) caused by human polyomavirus JC (JCV). Here, we have shown a significant correlation between patients with JC viruria and positive JC-specific antibody response and patients without JCV-specific antibodies after 1 year of natalizumab ( p = 0.0006). Furthermore, JCV-specific quantitative PCR on urine and plasma samples, collected at the enrollment (t0) and every 4 months (t1, t2, t3) in the first year and at two time points (t4 and t5) in the second year of natalizumab treatment, indicated the prevalence of JC viremia rather than JC viruria only in the second year of treatment ( p = 0.04). Moreover, the analysis of JCV non-coding control region (NCCR) sequences in peripheral blood mononuclear cells of patients with JC-specific antibodies after 12 natalizumab infusions (t3) revealed the presence of rearranged sequences, whereas the prevalence of genotypes 1A, 1B, and 4 was detected in these patients by VP1 sequence analysis. In summary, JC viruria evaluation seems to be useful to identify early those patients who do not already develop a humoral immune response against JCV. It may also be interesting to study the JCV NCCR rearrangements since they could give us new insights on the onset of neuro-invasive viral variants. [ABSTRACT FROM AUTHOR]

The Mesozoic era (252-66 million years ago), known as the domain of dinosaurs, witnessed a remarkable ecomorphological diversity of early mammals. The key mammalian characteristics originated during this period and were prerequisite for their evolutionary success after extinction of the non-avian dinosaurs 66 million years ago. Many ecomorphotypes familiar to modern mammal fauna evolved independently early in mammalian evolutionary history. Here we report a 125-million-year-old eutriconodontan mammal from Spain with extraordinary preservation of skin and pelage that extends the record of key mammalian integumentary features into the Mesozoic era. The new mammalian specimen exhibits such typical mammalian features as pelage, mane, pinna, and a variety of skin structures: keratinous dermal scutes, protospines composed of hair-like tubules, and compound follicles with primary and secondary hairs. The skin structures of this new Mesozoic mammal encompass the same combination of integumentary features as those evolved independently in other crown Mammalia, with similarly broad structural variations as in extant mammals. Soft tissues in the thorax and abdomen (alveolar lungs and liver) suggest the presence of a muscular diaphragm. The eutriconodont has molariform tooth replacement, ossified Meckel's cartilage of the middle ear, and specialized xenarthrous articulations of posterior dorsal vertebrae, convergent with extant xenarthran mammals, which strengthened the vertebral column for locomotion. [ABSTRACT FROM AUTHOR]

Purpose: [(18)F]VM4-037 was recently developed as a positron emission tomography (PET) tracer for the detection of carbonic anhydrase IX (CAIX), a tumor-specific protein upregulated under hypoxic conditions. In this study, the accumulation of [(18)F]VM4-037 was determined in two CAIX-expressing preclinical human tumor models.Procedures: U373 and HT29 tumor-bearing animals were injected with [(18)F]VM4-037 and underwent microPET imaging up to 4 h post-injection (p.i.). Biodistribution throughout the different organs was assessed at 2 and 4 h p.i. using gamma counting.Results: MicroPET imaging showed high [(18)F]VM4-037 uptake in the abdominal region, and biodistribution revealed high radioactivity in the kidney, ileum, colon, liver, stomach, and bladder. Although high CAIX expression was confirmed in both tumor models, tumor uptake assessed with microPET and biodistribution experiments was comparable to background tissues.Conclusions: In this study, [(18)F]VM4-037 does not specifically accumulate in CAIX-expressing tumors, indicating that the tracer is not suitable for the detection of CAIX. [ABSTRACT FROM AUTHOR]

For the correct evaluation of the weight of genetic evidence in a forensic context, databases must reflect the structure of the population, with all possible groups being represented. Countries with a recent history of admixture between strongly differentiated populations are usually highly heterogeneous and sub-structured. Bolivia is one of these countries, with a high diversity of ethnic groups and different levels of admixture (among Native Americans, Europeans and Africans) across the territory. For a better characterization of the male lineages in Bolivia, 17 Y-STR and 42 Y-SNP loci were genotyped in samples from La Paz and Chuquisaca. Only European and Native American Y-haplogroups were detected, and no sub-Saharan African chromosomes were found. Significant differences were observed between the two samples, with a higher frequency of European lineages in Chuquisaca than in La Paz. A sample belonging to haplogroup Q1a3a1a1-M19 was detected in La Paz, in a haplotype background different from those previously found in Argentina. This result supports an old M19 North-south dispersion in South America, possibly via two routes. When comparing the ancestry of each individual assessed through his Y chromosome with the one estimated using autosomal AIMs, (a) increased European ancestry in individuals with European Y chromosomes and (b) higher Native American ancestry in the carriers of Native American Y-haplogroups were observed, revealing an association between autosomal and Y-chromosomal markers. The results of this study demonstrate that a sub-structure does exist in Bolivia at both inter- and intrapopulation levels, a fact which must be taken into account in the evaluation of forensic genetic evidence. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) has been reported with nearly all forms of the inherited as well as the acquired hemolytic anemias. Although screening studies suggested that PAH has emerged as major complication of thalassemia patients, its impact on survival is unknown; the pathophysiology of the PAH in these patients is multifactorial, and a thorough diagnostic evaluation is essential. Understanding the PAH pathogenesis, diagnostic options, prevention is critical for clinicians who care for the thalassemic patients; there are virtually no high-quality data on the safety/efficacy of PAH treatment strategy in this patient population. We are reporting the case of a thalassemic patient suffering from progressive severe PAH, not responding to medical treatment and related to chronic thromboembolic disease. After carefully considering all the options, we decided to proceed with vascular disobliteration by pulmonary endarterectomy (PEA), the first line choice in these cases. This intervention led to a significant improvement in the clinical status and in the functional parameters. Therefore, even if haemolytic anemia-associated-PAH is included in the group I of the Dana-point classification, an individualized approach is recommended as well as a particular management with disease-specific measures and a comprehensive evaluation of other causes of PAH; this current report supports the feasibility and effectiveness of PEA also in the thalassemic patients with surgically accessible chronic thromboembolic pulmonary hypertension. [ABSTRACT FROM AUTHOR]