RNF212B E3 ligase is essential for crossover designation and maturation during male and female meiosis in the mouse.

Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation of homologous chromosomes during metaphase I. This process is regulated by the interplay of RING-E3 ligases such as RNF212 and HEI10 in mammals. In this study, we functionally characterized a recently identified RING-E3 ligase, RNF212B. RNF212B colocalizes and interacts with RNF212, forming foci along chromosomes from zygonema onward in a synapsis-dependent and DSB-independent manner. These consolidate into larger foci at maturing COs, colocalizing with HEI10, CNTD1, and MLH1 by late pachynema. Genetically, RNF212B foci formation depends on Rnf212 but not on Msh4, Hei10, and Cntd1, while the unloading of RNF212B at the end of pachynema is dependent on Hei10 and Cntd1. Mice lacking RNF212B, or expressing an inactive RNF212B protein, exhibit modest synapsis defects, a reduction in the localization of pro-CO factors (MSH4, TEX11, RPA, MZIP2) and absence of late CO-intermediates (MLH1). This loss of most COs by diakinesis results in mostly univalent chromosomes. Double mutants for Rnf212b and Rnf212 exhibit an identical phenotype to that of Rnf212b single mutants, while double heterozygous demonstrate a dosage-dependent reduction in CO number, indicating a functional interplay between paralogs. SUMOylome analysis of testes from Rnf212b mutants and pull-down analysis of Sumo- and Ubiquitin-tagged HeLa cells, suggest that RNF212B is an E3-ligase with Ubiquitin activity, serving as a crucial factor for CO maturation. Thus, RNF212 and RNF212B play vital, yet overlapping roles, in ensuring CO homeostasis through their distinct E3 ligase activities.

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Influence of soil chemical composition on U, 226Ra and 210Pb uptake in leaves and fruits of Quercus ilex L.

To determine their transfer factors, activity concentrations of natural radionuclides were measured in the leaves and acorns of holm oak (Quercus ilex L.) trees collected from seven locations with different soil properties and radionuclide activity concentrations. The chemical and mineralogical compositions of the soils were also analysed to investigate the effect these had on radionuclide absorption by the trees. Soil chemistry showed significant effects on radionuclide incorporation into Quercus ilex L. tissues. A significant relationship was established between activity concentrations and soil content of Ca and P with 238U and 226Ra in the leaves and acorns of Quercus ilex L. Differentiated transfer was found for 40K, which showed greater transfer to the leaves than the other radionuclides. The activity concentration of U and 226Ra was higher in the fruits than in the leaves, with the opposite effect being observed for 40K. The risk of U and 226Ra transfer into the food chain through acorn consumption by livestock is predicted to increase in soils poor in Ca and rich in P.

Mechanotransduction in tumor dynamics modeling.

Mechanotherapy is a groundbreaking approach to impact carcinogenesis. Cells sense and respond to mechanical stimuli, translating them into biochemical signals in a process known as mechanotransduction. The impact of stress on tumor growth has been studied in the last three decades, and many papers highlight the role of mechanics as a critical self-inducer of tumor fate at the in vitro and in vivo biological levels. Meanwhile, mathematical models attempt to determine laws to reproduce tumor dynamics. This review discusses biological mechanotransduction mechanisms and mathematical-biomechanical models together. The aim is to provide a common framework for the different approaches that have emerged in the literature from the perspective of tumor avascularity and to provide insight into emerging mechanotherapies that have attracted interest in recent years.

Spatial Analysis and Lead-Risk Assessment of Philadelphia, USA.

Childhood lead poisoning is an issue that continues to plague major U.S. cities. Despite efforts by the Philadelphia Department of Public Health to curtail systemic childhood lead poisoning, children continue to be identified with elevated blood lead levels. The persistence of elevated blood lead levels in children is concerning because lead poisoning has been linked to decreases in academic achievement and IQ, with associated repercussions for entire communities. This paper reports the results of an analysis of the spatial distribution of houses with lead paint (i.e., pre-1978), demolitions, and occurrence of historic smelters, in West and North Philadelphia, relative to elevated blood lead level data, to determine which lead sources act as primary lead-risk factors. The presence of lead paint in homes and the number of demolitions of older properties were found to have the highest correlations to elevated blood lead levels for children in Philadelphia. Using lead-risk factors including lead paint, housing code violations, demolitions, and owner-occupied housing units, a lead-risk assessment was performed at the census tract level to identify future soil sampling sites and high-risk neighborhoods in Philadelphia. These sites of high risk for lead exposure, and in particular the census tracts 175 and 172, should be prioritized for lead poisoning prevention initiatives.

Association of Fusobacterium nucleatum infection and colorectal cancer: A Mexican study.

INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum (F. nucleatum) is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p < 0.05). There was no significant association between F. nucleatum and the cytokines (p > 0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.

[Pulmonary cavitations, late complication of COVID-19].

Patients who have recently suffered from SARS-CoV-2 infections may suffer serious complications, such as pneumothorax or pulmonary cavitations that increase morbi-mortality and imply a challenge for the design of the most appropriate therapeutic strategy to improve their prognosis. Pulmonary cavities are usually associated with secondary complications such as hemoptysis and pneumothorax, and so offer a poor prognosis. We present the case of two patients with COVID-19 disease confirmed by nasopharyngeal PCR who showed satisfactory evolution before readmission with pulmonary involvement compatible with pulmonary cavitation and respiratory failure. Cavitated lesions in the lungs of patients who recently suffered COVID-19 must be identified early in order to discard additional superinfections that may worsen the prognosis.

Segundas resecciones anatómicas en pacientes con resección anatómica previa / Second pulmonary anatomical lung resections in patients with previous anatomical resections

Resumen Introducción: Las segundas resecciones anatómicas son cada vez más frecuentes en el tratamiento de carcinomas pulmonares sincrónicos, metacrónicos y de metástasis pulmonares de origen extrapulmonar. Objetivo: Determinar si las segundas resecciones anatómicas pulmonares se asocian con un mayor riesgo de complicaciones posoperatorias comparadas con la primera intervención. Materiales y Método: Hemos analizado todos los pacientes sometidos a una segunda resección anatómica en nuestro centro entre octubre de 2000 y febrero de 2019. Las complicaciones fueron clasificadas en mayores y menores según la clasificación estandarizada de morbilidad posoperatoria de Clavien-Dindo. Se compararon las características clínicas y demográficas de los pacientes y la ocurrencia de complicaciones mayores tras la primera y la segunda intervención quirúrgica mediante la prueba T para muestras relacionadas y la prueba exacta de McNemar para las variables cuantitativas y categóricas, respectivamente. Resultados: Setenta y cinco pacientes fueron sometidos a una segunda resección anatómica. La prevalencia de complicaciones globales y mayores tras la primera intervención fue del 26,7% y el 4% frente al 34,7% y al 6,7% tras la segunda intervención (p = 0,362 y p = 0,727, respectivamente). Las segundas resecciones pulmonares ipsilaterales se asociaron con un 16,7% de complicaciones mayores y los procedimientos consistentes en completar la neumonectomía con un 25%. Conclusión: Las segundas resecciones anatómicas pulmonares no se asocian con un mayor riesgo de complicaciones posoperatorias comparadas con la primera intervención. Sin embargo, las segundas resecciones ipsilaterales y las resecciones que impliquen completar la neumonectomía se asocian con riesgo significativamente superior de complicaciones mayores posoperatorias.

Introduction: Second anatomical resections are becoming more frequent in the treatment of synchronous, metachronous and pulmonary metastases of extrapulmonary origin. Aim: The objective of this study is to determine whether second pulmonary anatomical resections are associated with an increased risk of postoperative complications compared to the first intervention. Materials and Method: We have analyzed all patients undergoing a second anatomical resection in our center between October 2000 and February 2019. Complications were classified in major and minor according to the standardized Clavien-Dindo postoperative morbidity classification. The clinical and demographic characteristics of the patients and the occurrence of major complications after the first and second surgical intervention were compared using the T test for related samples and the McNemar exact test for quantitative and categorical variables, respectively. Results: Seventy-five patients underwent a second anatomic resection. The prevalence of global and major complications after the first intervention was 26.7% and 4% compared to 34.7% and 6.7% after the second intervention (p = 0.362 and p = 0.727, respectively). Second ipsilateral lung resections were associated with 16.7% of major complications and procedures consisting of completing pneumonectomy with 25%. Conclusion: Second lung anatomical resections are not associated with an increased risk of postoperative complications compared to the first intervention. However, second ipsilateral resections and resections that involve completing pneumonectomy are associated with a significantly higher risk of major postoperative complications.

Association of Fusobacterium nucleatum infection and colorectal cancer: A Mexican study. / Asociación entre infección por Fusobacterium nucleatum y cáncer colorrectal: un estudio mexicano.

INTRODUCTION AND AIMS: Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Many risk factors are involved, and current evidence links the gut microbiota and colorectal carcinogenesis. Fusobacterium nucleatum is proposed as one of the risk factors at the onset and during the progression of CRC, due to immune system and inflammatory modulation. MATERIALS AND METHODS: Ninety samples from three different regions of the colon were collected through colonoscopy in patients with CRC, and qPCR TagMan® was conducted to detect F. nucleatum and cytokines (IL-17, IL-23, and IL-10) in tumor, peritumor, and normal samples. The differences between them were analyzed and correlated. RESULTS: The abundance of F. nucleatum determined through the 2-ΔΔCt method in CRC (7.750 [5.790-10.469]) was significantly higher than in the normal control (0.409 [0.251-0.817]) (p<0.05). There was no significant association between F. nucleatum and the cytokines (p>0.05). CONCLUSIONS: CRC is a heterogeneous disease that presents and progresses in a complex microenvironment, partially due to gut microbiome imbalance. F. nucleatum was enriched in CRC tissue, but whether that is a cause of the pathology or a consequence, has not yet been clearly defined.

Coexistence of idiopathic intracranial hypertension and optic disc drusen in a latin american patient: case report.

Optic nerve drusen are acellular concretions of calcium located in the parenchyma of the optical nerve head described as the most common cause of pseudo-papilloedema, which makes it difficult to differentiate from a true optical disc oedema. Despite it being rare, the drusen of the optic nerve and the papilloedema secondary to idiopathic intracranial hypertension can coexist in the same patient. The case is presented of a 34 year-old woman referred to the Ophthalmology Department with visual discomfort, headaches, and pulsatile tinnitus of two months onset. In the physical examination there was bilateral blurring of the optic disc margin with absence of spontaneous venous pulsation. The diagnosis of idiopathic intracranial hypertension was made by lumbar puncture with the measurement of the opening pressure, and due to the findings of the magnetic resonance scan of the brain and the eye sockets. The optic nerve drusen was an incidental finding in an optical coherence tomography angiography, which would later be confirmed with an eye ultrasound. To our knowledge, this the first case reported in Latin America of the coexistence of optic nerve drusen and papilloedema secondary to idiopathic intracranial hypertension.

Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility.

Meiotic reductional division depends on the synaptonemal complex (SC), a supramolecular protein assembly that mediates homologous chromosomes synapsis and promotes crossover formation. The mammalian SC has eight structural components, including SYCE1, the only central element protein with known causative mutations in human infertility. We combine mouse genetics, cellular, and biochemical studies to reveal that SYCE1 undergoes multivalent interactions with SC component SIX6OS1. The N terminus of SIX6OS1 binds and disrupts SYCE1's core dimeric structure to form a 1:1 complex, while their downstream sequences provide a distinct second interface. These interfaces are separately disrupted by SYCE1 mutations associated with nonobstructive azoospermia and premature ovarian failure (POF), respectively. Mice harboring SYCE1's POF mutation and a targeted deletion within SIX6OS1's N terminus are infertile with failure of chromosome synapsis. We conclude that both SYCE1-SIX6OS1 binding interfaces are essential for SC assembly, thus explaining how SYCE1's reported clinical mutations give rise to human infertility.

A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1.

Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility.

Complete Susac syndrome in a 22-year old male in Colombia: Case report and a review of the literature. / Síndrome de Susac completo en un hombre de 22 años en Colombia: a propósito de un caso y revisión de la literatura.

We report the case of a 22 year-old male with a clinical picture of 4 months onset of headaches, deafness, and a decrease of vision in the left eye. His mother mentioned he also had changes in behaviour and mood. The magnetic resonance scan of the brain showed multiple hyper-intense lesions in the knee of the corpus callosum. The hearing test reported a neurosensory deafness. In the ophthalmoscopy, a retinal infarction was observed in the nerve fibre layer in the left eye, which was confirmed using optical coherence tomography. The fluorescein angiography showed multiple foci of hyperfluorescence of the arteriole walls, arteriole filling defects, and regional ischaemia foci of the choroid. These findings confirmed the presumed diagnosis of a Susac syndrome. This is one of the few cases reported in the literature of a Susac syndrome in a young man with the complete diagnostic triad, and the first in Colombia.

Nutritional value and antioxidant compounds during the ripening and after domestic cooking of bananas and plantains.

Genotypes of bananas and plantains have been studied for biofortification purposes, mainly due to content of resistant starch (RS) and polyphenols. This study aims to identify banana and plantain genotypes with a high content of resistant starch, phenolic compounds and minerals, and to evaluate the impact of the ripening stage and domestic thermal processing to select superior genotypes with high levels of functional compounds. In this study, it was used bunches of bananas and plantain genotypes. The phenolic compounds profiles were determined by HPLC-DAD in pulps and peels. The resistant starch and the minerals (K, Na, Zn, Cu and Fe) were evaluated in pulps and peels of unripe fruit. The results of phenolic compounds were studied in three ripening stages, and after thermal processing (ripe stage) of two genotypes, which were most promising for biofortification studies. Resistant starch and minerals were analysed in the unripe fruits. The peel biomass showed the highest values of phenolic compounds and minerals. The total starch content in the pulp varied from 42.3% ('FC06-02') to 80.6% ('Pelipita'). Plantains and cooking bananas presented the highest contents of starch and resistant starch (stage 2 - green with yellow traces). The pulps of the dessert genotypes 'Khai' and 'Ouro da Mata', and cooking genotype 'Pacha Nadam' stood out due to their minerals high contents (P, K and Fe; Zn and Fe; Ca, Mg and Zn, respectively). The dessert bananas (e.g., 'Ney Poovan') and cooking bananas (e.g., 'Tiparot') had the highest concentrations of phenolic compounds, mainly in ripe fruit (stage 5 - yellow with green). In addition, the thermal processing of Musa spp. fruit led to increasing these secondary metabolites, mainly the cooking of fruit with peel by boiling, which should be preferred in domestic preparations.

Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2.

Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin1-3. Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin1. In the absence of securin, mammalian chromosomes still segregate on schedule, but it is unclear how separase is regulated under these conditions4,5. Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma6,7, is turned into a separase inhibitor upon association with SAC-activated MAD2. SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin8,9, SGO2 is a competitive inhibitor that uses a pseudo-substrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31comet liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.

Factors associated with sepsis development in 606 Spanish adult patients with cellulitis.

BACKGROUND: Cellulitis, a frequent cause of admission of adult patients to medical wards, occasionally evolves to sepsis. In this study we analyze the factors related to sepsis development. METHODS: Prospective and observational study of 606 adult patients with cellulitis admitted to several Spanish hospitals. Comorbidities, microbiological, clinical, lab, diagnostic, and treatment data were analyzed. Sepsis was diagnosed according to the criteria of the 2016 International Sepsis Definitions Conference. Multiple logistic regression modelling was performed to determine the variables independently associated with sepsis development. RESULTS: Mean age was 63.4 years and 51.8% were men. Overall 65 (10.7%) patients developed sepsis, 7 (10.8%) of whom died, but only 4 (6.2%) due to cellulitis. Drawing of blood (P < 0.0001) or any (P < 0.0001) culture, and identification of the agent (P = 0.005) were more likely among patients with sepsis. These patients had also a longer duration of symptoms (P = 0.04), higher temperature (P = 0.03), more extensive cellulitis (P = 0.02), higher leukocyte (P < 0.0001) and neutrophil (P < 0.0001) counts, serum creatinine (P = 0.001), and CRP (P = 0.008) than patients without sepsis. Regarding therapy, patients with sepsis were more likely to undergo changes in the initial antimicrobial regimen (P < 0.0001), received more antimicrobials (P < 0.0001), received longer intravenous treatment (P = 0.03), and underwent surgery more commonly (P = 0.01) than patients without sepsis. Leukocyte counts (P = 0.002), serum creatinine (P = 0.003), drawing of blood cultures (P = 0.004), change of the initial antimicrobial regimen (P = 0.007) and length of cellulitis (P = 0.009) were independently associated with sepsis development in the multivariate analysis. CONCLUSIONS: Increased blood leukocytes and serum creatinine, blood culture drawn, modification of the initial antimicrobial regimen, and maximum length of cellulitis were associated with sepsis in these patients.

Quasi-binomial zero-inflated regression model suitable for variables with bounded support.

In recent years, a variety of regression models, including zero-inflated and hurdle versions, have been proposed to explain the case of a dependent variable with respect to exogenous covariates. Apart from the classical Poisson, negative binomial and generalised Poisson distributions, many proposals have appeared in the statistical literature, perhaps in response to the new possibilities offered by advanced software that now enables researchers to implement numerous special functions in a relatively simple way. However, we believe that a significant research gap remains, since very little attention has been paid to the quasi-binomial distribution, which was first proposed over fifty years ago. We believe this distribution might constitute a valid alternative to existing regression models, in situations in which the variable has bounded support. Therefore, in this paper we present a zero-inflated regression model based on the quasi-binomial distribution, taking into account the moments and maximum likelihood estimators, and perform a score test to compare the zero-inflated quasi-binomial distribution with the zero-inflated binomial distribution, and the zero-inflated model with the homogeneous model (the model in which covariates are not considered). This analysis is illustrated with two data sets that are well known in the statistical literature and which contain a large number of zeros.

Dendritic Spine Density and Dynamics of Layer 5 Pyramidal Neurons of the Primary Motor Cortex Are Elevated With Aging.

It is well established that motor impairment often occurs alongside healthy aging, leading to problems with fine motor skills and coordination. Although previously thought to be caused by neuronal death accumulating across the lifespan, it is now believed that the source of this impairment instead stems from more subtle changes in neural connectivity. The dendritic spine is a prime target for exploration of this problem because it is the postsynaptic partner of most excitatory synapses received by the pyramidal neuron, a cortical cell that carries much of the information processing load in the cerebral cortex. We repeatedly imaged the same dendrites in young adult and aged mouse motor cortex over the course of 1 month to look for differences in the baseline state of the dendritic spine population. These experiments reveal increased dendritic spine density, without obvious changes in spine clustering, occurring at the aged dendrite. Additionally, aged dendrites exhibit elevated spine turnover and stabilization alongside decreased long-term spine survival. These results suggest that at baseline the aged motor cortex may exist in a perpetual state of relative instability and attempts at compensation. This phenotype of aging may provide clues for future targets of aging-related motor impairment remediation.

Clostridioides difficile-associated diarrhea in surgical service patients in Mexico. / Diarrea asociada a Clostridioides difficile en pacientes de servicios quirúrgicos en México.

INTRODUCTION: Clostridioides difficile is the first cause of healthcare-associated diarrhea in developed countries. In recent years the incidence of C. difficile infection (CDI) has increased worldwide. There is not much information on the topic in Mexico, and little is known about the risk factors for the infection in patients that are hospitalized in surgical services. MATERIALS AND METHODS: A case-control study was conducted that compared the epidemiologic findings and risk factors between surgical patients with PCR-confirmed CDI, surgical patients with diarrhea and a negative PCR test, and surgical patients with no diarrhea. The statistical analysis was carried out using the SPSS version 22.0 program. RESULTS: The majority of the surgical patients with CDI belonged to the areas of neurosurgery, cardiac surgery, orthopedics, and general surgery. A total of 53% of the CDI cases were associated with the hypervirulent CD NAP1/027 strain. The presence of mucus in stools (OR: 1.5, P=.001), fever (OR: 1.4, P=.011), leukocytes in stools (OR: 3.2, P<.001), hospitalization within the past 12weeks (OR: 2.0, P<.001), antibiotic use (OR: 1.3, P=.023), and ceftriaxone use (OR: 1.4, P=.01) were independent risk factors for the development of CDI. CONCLUSIONS: C. difficile-induced diarrhea in the surgical services is frequent at the Hospital Civil de Guadalajara "Fray Antonio Alcalde".

Multigene assays in early breast cancer: Insights from recent phase 3 studies.

Multigene assays (MGAs) guide treatment in early-stage breast cancer (ESBC) enabling selective and effective use of adjuvant chemotherapy (CT). Support for all MGAs had previously been derived from retrospectively-analyzed, prospective studies. Only 2 ESBC MGAs, the 70-gene signature (MammaPrint®) and the 21-gene Recurrence Score (RS) assay (Oncotype DX®), are now supported by entirely prospective randomized phase 3 trials. These studies varied in their primary objectives, design, and eligibility. The MINDACT study provided the first level 1 evidence for the 70-gene signature, identifying a prognostic capability irrespective of lymph node (LN) or hormone receptor (HR) status. However, the study did not support predictive value for the assay regarding adjuvant CT utility. The second prospective study, WSG-PlanB, confirmed the prognostic value of the 21-gene RS assay in HR-positive tumors with RS ≤ 11. A 5-year disease free survival (DFS) of 94% was identified in this group when treated with endocrine therapy (ET) alone regardless of N0 or N1 nodal status. The final new prospective study, TAILORx, confirmed the prognostic value of the 21-gene assay in N0 HR-positive disease, demonstrating a lack of CT benefit in patients with midrange RS. The information from these phase 3 studies confirms that MGAs are not interchangeable and that each provides different information for differing patient populations. Prognosis-only is supported for the 70-gene signature while both prognosis and the predictive value of CT are provided by the 21-gene assay. This review assesses and contrasts these phase 3 studies in the context of target populations and clinical utility.