Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Systematic mapping review of interventions to prevent blood loss, infection and relapse in orthognathic surgery.

BACKGROUND: This systematic mapping review aims to identify, describe, and organize the currently available evidence in systematic reviews (SR) and primary studies regarding orthognathic surgery (OS) co-interventions and surgical modalities, focusing on the outcomes blood loss, infection and relapse. MATERIAL AND METHODS: A comprehensive search strategy was performed to identify all SRs, randomized controlled trials and observational studies that evaluate surgical modalities and perioperative co-interventions in OS that evaluate the outcomes blood loss, infection and relapse, regardless of language or publication date. Searches were conducted in MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. In addition, grey literature was screened. RESULTS: 27 SRs and 150 primary studies fulfilled the inclusion criteria, 91 from SRs, and 59 from our search strategy. Overall, the quality of the SRs was graded as "Critically low," and only two SRs were rated as "High" quality. 11 PICO questions were extracted from SRs and 31 from primary studies, which focused on osteosynthesis methods, surgical cutting devices, use of antibiotics, and induced hypotension. In addition, evidence bubble maps for each outcome were created to analyze in a visual manner the existing evidence. CONCLUSIONS: Future primary and secondary high-quality research should be addressed focused on the eight knowledge gaps identified in this mapping review. We concluded that the evidence mapping approach is a practical methodology for organizing the current evidence and identifying knowledge gaps in OS, helping to reduce research waste and canalize future efforts in developing studies for unsolved questions.

High chromosomal mobility of rDNA clusters in holocentric chromosomes of Triatominae, vectors of Chagas disease (Hemiptera-Reduviidae).

The subfamily Triatominae (Hemiptera-Reduviidae) includes more than 150 blood-sucking species, potential vectors of the protozoan Trypanosoma cruzi, causative agent of Chagas disease. A distinctive cytogenetic characteristic of this group is the presence of extremely stable chromosome numbers. Unexpectedly, the analyses of the chromosomal location of ribosomal gene clusters and other repetitive sequences place Triatominae as a significantly diverse hemipteran subfamily. Here, we advance the understanding of Triatominae chromosomal evolution through the analysis of the 45S rDNA cluster chromosomal location in 92 Triatominae species. We found the 45S rDNA clusters in one to four loci per haploid genome with different chromosomal patterns: On one or two autosomes, on one, two or three sex chromosomes, on the X chromosome plus one to three autosomes. The movement of 45S rDNA clusters is discussed in an evolutionary context. Our results illustrate that rDNA mobility has been relatively common in the past and in recent evolutionary history of the group. The high frequency of rDNA patterns involving autosomes and sex chromosomes among closely related species could affect genetic recombination and the viability of hybrid populations, which suggests that the mobility of rDNA clusters could be a driver of species diversification.

Flexible Synthetic Carbohydrate Receptors as Inhibitors of Viral Attachment.

Carbohydrate-receptor interactions are often involved in the docking of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered "undruggable", meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs), small molecules that bind carbohydrates, could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of SCRs, and recent results demonstrating their ability to prevent viral infections in vitro. Common SCR design strategies based on boronic ester formation, metal chelation, and noncovalent interactions are discussed. The benefits of incorporating the idiosyncrasies of natural glycan-binding proteins-including flexibility, cooperativity, and multivalency-into SCR design to achieve nonglucosidic specificity are shown. These studies into SCR design and binding could lead to new strategies for mitigating the grave threat to human health posed by enveloped viruses, which are heavily glycosylated viroids that are the cause of some of the most pressing and untreatable diseases, including HIV, Dengue, Zika, influenza, and SARS-CoV-2.

Bacteria cultured from the gut of Meccus pallidipennis (Hemiptera: Reduviidae), a triatomine species endemic to Mexico.

The study of intestinal microbiota in vector insects like triatomines is paramount in parasitology because many parasitic species inhabit the vector's gut. Although knowledge on the gut microbiota in various vectors of the parasitic flagellate Trypanosoma cruzi has grown, research efforts have focused on South American triatomines. This study reports the isolation of bacterial microbiota in the anterior and posterior gut of Meccus pallidipennis (a triatomine species endemic to Mexico) by culture, as well as its identification by phenotypic and biochemical tests and its quantification by counting colony-forming units. The study was performed on fifth-instar nymph and adult specimens of M. pallidipennis, either laboratory-bred or collected in the field and either infected or not with T. cruzi. Overall, 17 bacterial species were identified, with the genera Bacillus and Staphylococcus being the most prevalent regardless of the origin of the insects. No differences were observed in the number of bacterial species in the gut of laboratory-bred and field-collected insects, neither with respect to life stage or infection status. In general, the Shannon-Weaver diversity index was higher in non-infected insects than in infected ones. Further studies using non-culture methods are required to determine whether bacterial species diversity is modified by laboratory breeding.

Immunization with a novel recombinant protein (YidR) reduced the risk of clinical mastitis caused by Klebsiella spp. and decreased milk losses and culling risk after Escherichia coli infections.

The primary objective of this study was to evaluate the protective efficacy of a novel recombinant subunit vaccine containing the protein YidR (rYidR) against clinical mastitis (CM) caused by Klebsiella spp. and Escherichia coli. Given that E. coli infection is known to cause metritis, we also evaluated the effect of rYidR vaccination on the incidence of metritis and conception at the first artificial insemination. Retained placenta and abortion incidence, milk production and composition, and serological responses to specific antigens were also evaluated. In total, 3,107 cows were blocked by parity and randomly allocated into 1 of 3 treatment groups: experimental recombinant subunit vaccine containing the YidR protein (rYidR); commercial vaccine composed of Klebsiella pneumoniae siderophore receptors and porin protein (Kleb-SRP; KlebVax, Epitopix, Willmar, MN); and sterile water adjuvanted with aluminum hydroxide (20%; placebo). Vaccinations were performed at the dry-off for cows, and at 223 ± 3 d of pregnancy for pre-fresh heifers. A second administration was given at 21 ± 3 d after the first injection. Vaccination with rYidR significantly reduced the incidence of CM caused by Klebsiella spp. (3.2%) when compared with the placebo (5.1%) group. No difference was observed on risk of Klebsiella CM between Kleb-SRP (5.9%) and placebo groups. Cows in the rYidR group that experienced E. coli CM had a lower risk of death or culling (12.5%) compared with the Kleb-SRP (27.6%) and placebo groups (27.8%). Furthermore, among cows that developed E. coli CM, rYidR-immunized cows produced more milk than did cows in the placebo and Kleb-SRP groups. Regardless of CM occurrence, rYidR-immunized cows tended to have higher milk production up to the eighth month of lactation than cows in the other groups. No significant effect of treatment was observed on the overall incidence of abortion and metritis; however, the risk of retained placenta tended to be lower for the rYidR group (4.7%) compared with the placebo group (6.7%). In addition, primiparous cows in the rYidR group had the highest conception risk at the first artificial insemination (48.3%) compared with the placebo (39.5%) group, and no significant difference was observed when the Kleb-SRP (40.1%) group was compared with the placebo group. Generally, higher antibody serum titers (IgM and IgG) were observed for the immunized groups compared with the placebo. In conclusion, the rYidR vaccine reduced the risk of CM caused by Klebsiella spp. and the mortality or culling of cows with E. coli infections. Other benefits of the novel vaccine include maintenance of milk production after CM caused by E. coli, and higher conception risk at the first service in primiparous cows compared with cows in the placebo and Kleb-SRP groups.

Effect of treatment of pneumonia and otitis media with tildipirosin or florfenicol + flunixin meglumine on health and upper respiratory tract microbiota of preweaned Holstein dairy heifers.

The objective of this randomized clinical study was to compare the effect of 2 antimicrobial interventions, tildipirosin or florfenicol + flunixin meglumine, used for treatment of pneumonia and extralabel treatment for otitis on health parameters and upper respiratory tract (URT) microbiota of preweaned Holstein calves. Housed preweaned Holstein heifers diagnosed with either otitis or pneumonia were assigned into 1 of 2 treatment groups, receiving a single subcutaneous injection of either 4 mg/kg of tildipirosin (TLD; n = 444) or 40 mg/kg of florfenicol combined with 2.2 mg/kg of a nonsteroidal anti-inflammatory, flunixin meglumine (FLF; n = 442). Calves were enrolled and treated on the day of diagnosis of the first case of pneumonia or otitis. If a calf had a recurrent case, the opposite drug was administered, respecting an interval of 5 d between drug injections. Blood samples for leukocyte counts were collected at 0, 2, 4, and 6 d after treatment, and rectal temperature was measured daily during the 5 d after treatment. Ear scores were observed from calves with otitis. Additionally, swabs of the URT were collected from a subset of 20 calves in each treatment group at d 0, 3, 6, 9, and 11 following enrollment for analysis of URT microbiota through next-generation sequencing of the 16S rRNA gene and quantitative PCR. Swabs were also collected from a comparative group of 20 healthy calves that did not receive any drug. No differences were observed between groups for recurrence risk of either pneumonia (TLD = 32.4%; FLF = 29.7%) or otitis (TLD = 72.7%; FLF = 73.6%). Similarly, no differences were observed for the total number of treatments for pneumonia (TLD = 1.45; FLF = 1.42) or otitis (TLD = 2.96; FLF = 3.07). On the other hand, both drugs reduced rectal temperature, ear scores, and leukocyte counts, with FLF calves having a greater reduction in rectal temperature within 4 d after treatment. Both TLD and FLF reduced the total bacterial load when compared with healthy untreated calves, but no differences were observed between treatment groups. Furthermore, compared with the untreated group, treated calves had lower mean relative abundances (MRA) of the genera Mannheimia, Moraxella, and Pasteurella within 11, 9, and 3 d after treatment, respectively; however, no significant differences were observed between TLD and FLF. On the other hand, MRA of Mycoplasma was not decreased by both treatments compared to untreated animals, and a higher MRA was observed in the TLD group during 11 d after treatment in comparison to FLF and untreated calves. Based on this data, we concluded that both drugs used in the study were effective in reducing rectal temperature, ear scores, leukocyte counts, and MRA of the genera Mannheimia, Pasteurella, and Moraxella in the URT, and calves treated with FLF had a greater reduction in rectal temperature.

A laboratory study of root canal and isthmus disinfection in extracted teeth using various activation methods with a mixture of sodium hypochlorite and etidronic acid.

AIM: To evaluate in a laboratory setting the antibiofilm activity of several irrigating protocols including conventional irrigation, ultrasonic activation and XP-endo Finisher, with a mixture of sodium hypochlorite and etidronic acid in infected isthmuses and root canals of extracted human mandibular molar teeth. METHODOLOGY: Fifty-six mesial roots of mandibular molars, half of them with a continuous isthmus from the cervical to the apical third between the two root canals (type 1), and the other half with a continuous isthmus from the cervical to the middle third and one canal in the apical third (type 2), were included. The root canals were contaminated for 7 days with an Enterococcus faecalis suspension. There were three experimental groups plus a control group (n = 7 per type of root canal anatomy). All the root canals, except for the control group that was not treated, were chemomechanically prepared and then assigned to one of the experimental groups according to the final adjunctive procedure: conventional irrigation, ultrasonic activation or XP-endo Finisher activation. The irrigating solution used was a combination of 2.5% sodium hypochlorite and 9% etidronic acid, and the final protocols were applied for three cycles of 30 s with a 3 mL volume. The antibiofilm activity was evaluated at each location (root canal and isthmus) and third (cervical, middle and apical) using confocal laser scanning microscopy and the live/dead technique. Statistical analysis was performed using SPSS (descriptive statistics) and SUDAAN (P-value calculations). RESULTS: Root canals had significantly lower biovolume values than the isthmuses (P < 0.05). The biovolume in the root canals was significantly reduced in all the experimental groups in all the thirds except for conventional irrigation in the apical third (P > 0.05). In the cervical and middle thirds, ultrasonic activation was associated with the lowest biovolumes (P < 0.05), followed by XP-endo Finisher. In the isthmus, disinfection was similar in all the thirds for all the protocols. Conventional irrigation was associated with intermediate values with no significant differences from the control group or from the activated protocols (P > 0.05), although the latter were significantly different from the control group (P < 0.05). No differences were found between ultrasonic activation and XP-endo Finisher in the middle and apical thirds (P > 0.05) in the isthmuses. CONCLUSIONS: In this laboratory study on extracted teeth, the isthmus was more difficult to disinfect than root canals. In the root canals, ultrasonic activation and XP-endo Finisher had a greater effectiveness than conventional irrigation. In the isthmuses, no differences were observed between the two activation techniques and conventional irrigation.

Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors.

Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C1 -O-octyloxy glycans, α/ß-glucoside (α/ß-Glc), α/ß-mannoside (α/ß-Man), and ß-galactoside (ß-Gal), was studied by mass spectrometry, 1 H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to ß-Glc. SCR019 (3-indole) binds only to ß-Man. SCR020 (2-pyridine) binds ß-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and ß-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center-perpendicular, and off-center. Many host-guest combinations formed higher stoichiometry complexes, 2:1 glycan⋅SCR or 1:2 glycan⋅SCR, where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts.

A minimal coarse-grained model for the low-frequency normal mode analysis of icosahedral viral capsids.

The main goal of this work is the design of a coarse-grained theoretical model of minimal resolution for the study of the physical properties of icosahedral virus capsids within the linear-response regime. In this model the capsid is represented as an interacting many-body system whose composing elements are capsid subunits (capsomers), which are treated as three-dimensional rigid bodies. The total interaction potential energy is written as a sum of pairwise capsomer-capsomer interactions. Based on previous work [Gomez Llorente et al., Soft Matter, 2014, 10, 3560], a minimal and complete anisotropic binary interaction that includes a full Hessian matrix of independent force constants is proposed. In this interaction model, capsomers have rotational symmetry around an axis of order n > 2. The full coarse-grained model is applied to analyse the low-frequency normal-mode spectrum of icosahedral T = 1 capsids. The model performance is evaluated by fitting its predicted spectrum to the full-atom results for the Satellite Tobacco Necrosis Virus (STNV) capsid [Dykeman and Sankey, Phys. Rev. Lett., 2008, 100, 028101]. Two capsomer choices that are compatible with the capsid icosahedral symmetry are checked, namely pentamers (n = 5) and trimers (n = 3). Both subunit types provide fair fits, from which the magnitude of the coarse-grained force constants for a real virus is obtained. The model is able to uncover latent instabilities whose analysis is fully consistent with the current knowledge about the STNV capsid, which does not self-assemble in the absence of RNA and is thermally unstable. The straightforward generalisability of the model beyond the linear regime and its completeness make it a promising tool to theoretically interpret many experimental data such as those provided by the atomic force microscopy or even to better understand processes far from equilibrium such as the capsid self-assembly.

Fatal consequences of decreased sensitivity to pain and temperature in a frontotemporal dementia patient.

Frontotemporal dementia (FTD) is a heterogeneous syndrome characterized by the progressive damage of frontal and temporal brain regions. These networks largely overlap with those involved in pain and temperature processing. Although the impaired perception of pain and temperature has been previously described to be relatively common in patients with FTD, these symptoms are often not consistently assessed by Neurologists. We present the case of a patient with a probable behavioral variant FTD who died due to scalding with hot water in the shower. Impairments in the perception of pain and temperature might have played a fundamental role in this accident.

Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study.

INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNEN) are rare tumours and well differentiated PNEN are associated with relatively indolent physiological behaviour. For this reason, only few studies have investigated those factors associated with recurrence in this group of patients. The aim of this study is to analyse whether it is possible to predict tumour recurrence in World Health Organization (WHO) 2017 G1-G2 PNEN patients. METHODS: This is a retrospective multi-institutional study. Patients submitted to pancreatic resection from 7 Spanish centres were reviewed. Only patients with WHO G1-G2 PNEN were included. Demographic and clinicopathological variables were analysed. RESULTS: Data from 137 patients were reviewed. Median age was 59.2 (25-84) years. Recurrence of disease occurred in 19 (13.9%) patients. Median DFS was 55 months. At multivariate analysis, tumour size >20 mm, lymphnode metastasis and a new tumour grade 2 incorporating Ki-67 labelling index (LI) > 5% and mitotic index (MI) > 2 were independently associated with recurrence. We developed a risk score model with these three factors. High-risk patients had a significantly lower 5-year disease-specific survival compared to low-risk patients (70% vs 100%). CONCLUSION: We propose a novel risk score for recurrence based on lymphnode metastasis, tumour size > 20 mm and a new grade 2 based on Ki-67 LI >5% and MI > 2. If 2 factors are present, patients have a higher risk for recurrence and a significantly poorer DSS, and therefore they should be closely monitored during follow-up. The role of adjuvant chemotherapy in these patients needs to be evaluated in clinical trials.

Phytopathogenic and antagonistic potentialities of fungi associated with pistachio bark beetle, Chaetoptelius vestitus (Coleoptera, Curculionidae), infesting pistachio (Pistacia vera) in Tunisia.

AIM: This study investigated the biodiversity of fungi associated with the pistachio bark beetle, Chaetoptelius vestitus, in Tunisia. We evaluated the phytopathogenic activities and tested antagonistic potentialities with respect to phytopathogens. METHODS AND RESULTS: A total of 41 fungal isolates were randomly isolated from C. vestitus adults and galleries. We identified 28 species belonging to 13 genera using ITS sequences of the ribosomal RNA operons. Pathogenicity assays performed using the excised shoot method revealed that isolates Aal_io_1 (Alternaria alternata), Feq_io_1 (Fusarium equiseti), Fgra_io_1 (Fusarium graminearum), Fve_io_1 (Fusarium verticilloides), Tro_io_1 (Trichothecium roseum) and Nqu_io_1 (Nothophoma quercina) displayed a high pathogenic activity on pistachio stems. Estimation of the antagonistic potentialities of isolated fungi against several phytopathogenic isolates as tested using a dual-culture method showed that isolates Tpi_io_1 (Talaromyces pinophilus), Pbi_io_2 (Penicillium bilaiae), Asc_io_1 (Aspergillus sclerotiorum) and Gla_io_1 (Geosmithia lavendula) displayed a broad range of antagonistic activities. CONCLUSION: Fungi associated with C. vestitus had a variable range of pathogenic activity on pistachio stem. Phytopathogenic fungi were antagonized by different fungal isolates which could be promising in pistachio protection against phytopathogenic fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first that investigated the diversity of fungi associated with C. vestitus and evaluated both their phytopathogenic activity and antagonistic potential against fungal phytopathogens.

Psoriasis, metabolic syndrome and cardiovascular risk factors. A population-based study.

BACKGROUND: Psoriasis is a very prevalent systemic chronic inflammatory disease. Major cardiovascular events are the main cause of mortality in these patients which suggests an association between psoriasis and traditional cardiovascular risk factors. OBJECTIVE: To identify classic cardiovascular risk factors and metabolic syndrome (MS) in patients with psoriasis, their possible association with its severity and compare it with the non-psoriatic population. METHODS: This is an observational and cross-sectional population study in Lleida (Spain) from a joint hospital/primary care database. RESULTS: The database comprised 398 701 individuals. There were 6868 cases registered as psoriasis (1.7%), and 499 of them (7.3%) were classified as moderate-severe psoriasis. Patients with psoriasis had a higher prevalence of traditional cardiovascular risk factors than non-psoriatic population: diabetes mellitus 2 (13.9% vs 7.4%, OR 2.01), dyslipidaemia (28.8% vs 17.4%, OR 1.92), arterial hypertension (31.2% vs 19.0%, OR 1.93), obesity (33.7% vs 28.1%, OR 1.30), altered fasting basal glycaemia (21.4% vs 15.1%, OR 1.54), low cholesterol HDL (38.1% vs 32.3%, OR 1.29), hypertriglyceridaemia (45.7% vs 35.2%, OR 1.55) and high waist circumference (75.7% vs 72.3%, OR 1.19). MS was more prevalent in psoriatic patients (28.3% vs 15.1%, OR 2.21), and cardiovascular risk factors were similar between psoriasis severity groups. Psoriatic patients had a higher prevalence of ischaemic heart disease (3.3% vs 1.8%, OR 1.87) and vascular cerebral accidents (1.8% vs 1.2%, OR 1.55). A model for MS showed a significant nonlinear relationship with age and sex and significant differences between patients with and without psoriasis. CONCLUSION: We found statistically significant differences in relation to the prevalence of cardiovascular risk factors, MS and major cardiovascular events in psoriatic patients. However, differences were not seen between psoriasis severity groups. Our work reinforces the need for a multidisciplinary approach and close monitoring of cardiovascular risk factors in these patients to prevent a cardiovascular event.

Pharmacokinetic variations of nimesulide in mongrel dogs according to age.

The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6 months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but, the dosing regimens in humans should be different when administered at early age.

Associated factors with health-compromising behaviors among patients treated for oral cancer.

BACKGROUND: To improve eradication strategies of health-compromising behaviors between oral cancer survivors, this study aimed to explore the extent of clustering of risk behaviors and to assess possible factors associated. MATERIAL AND METHODS: A cross-sectional study was carried out among oral cancer patients at least 6 months after treatment. They completed a questionnaire about smoking, alcohol consumption, oral hygiene habits and dental visits. Presence of clusters was evaluated through pairwise Pearson correlations and principal component analysis. Factors associated with each identified cluster were analyzed with multivariate models. RESULTS: Among 142 patients, 14.8% smoked, 51.7% consumed alcohol, 52.1% performed oral hygiene less than twice a day, and 74.6% visited to dentist when there was a problem or never. There were two distinct clusters: smoking-alcohol consumption (general risk behaviors cluster) and oral hygiene-dental attendance (oral risk behaviors cluster). Multivariate analysis showed significant associations between males and both clustering patterns of health compromising behaviors, patients with clinical stage I or with longer follow-up and the presence of general risk behaviors cluster and worse social class and the presence of oral risk behaviors cluster. CONCLUSIONS: A high proportion of patients treated for oral cancer presented health-compromising behaviors occurring in clusters which reinforce the need for health promotion strategies to target multiple behaviors. Factors analyzed suggest that chances of having detrimental behavioral clustering are higher in male, patients with clinical stage I, with lower social class and those with longer follow-up after treatment.

Migration of Latin American nurses to Spain 2006-2016: a case study.

AIM: To examine the migration of nurses from Latin America to Spain over the period from 2006 to 2016. BACKGROUND: This study examines the impact of the 2008 global economic crisis on migration flows of nurses to Spain from its major source countries of Latin America. METHODS: Using an exploratory case study, we present original data provided by the Ministry of Education, Culture and Sport of the Government of Spain upon request on applications and success rates for credential recognition of nurses intending to immigrate to Spain, with an extended analysis of Latin American applications which account for the 70% of skilled worker migration to Spain. RESULTS: Successful applications for credential recognition of overseas nursing qualifications plummeted from a peak of 1384 in 2007 to 55 in 2016. Migration intentionality also decreased but has undergone a slight increase in recent years. DISCUSSION/CONCLUSION: We found that the economic crisis effectively closed the door to internationally educated nurses to work as nurses in Spain. Moreover, the denial of official recognition of nursing credentials appears to be unaffected by the existence of bilateral trade and mobility agreements between Spain and source countries. We conclude that the level of nursing migration to Spain is a sensitive indicator of domestic labour market conditions. IMPLICATIONS FOR HEALTH POLICY: Despite the lack of any transparent policy on the credential approvals, in practice the government is limiting access to the nursing labour market by overseas education nurses. We urge that attention be paid by health human resource planners on the intersection between labour market and migration trends to support a transparent and data-informed discussion by all stakeholders on the current state of the nursing labour market in Spain and its future needs.