Mutational landscape of HSP family on human breast cancer.

Breast cancer (BRCA) is a prevalent malignancy with the highest incidence among females. BRCA can be categorized into five intrinsic molecular subtypes (LumA, LumB, HER2, Basal, and Normal), each characterized by varying molecular and clinical features determined by the expression of intrinsic genes (PAM50). The Heat Shock Protein (HSP) family is composed of 95 genes evolutionary conservated, they have critical roles in proteostasis in both normal and cancerous processes. Many studies have linked HSP to the development and spread of cancer. They modulate the activity of multiple proteins expressed by oncogenes and anti-oncogenes through a range of interactions. In this study, we evaluate the mutational changes that HSP undergoes in BRCA mainly from the TCGA database. We observe that Copy Number Variations (CNV) are the more frequent events analyzed surpassing the occurrence of point mutations, indels, and translation start site mutations. The Basal subtype showcased the highest count of amplified CNV, including subtype-specific changes, whereas the Luminals tumors accumulated the greatest number of deletion CNV. Meanwhile, the HER2 subtype exhibited a comparatively lower frequency of CNV alterations when compared to the other subtypes. This study integrates CNV and expression data, finding associations between these two variables and the influence of CNV on the deregulation of HSP expression. To enhance the role of HSP as a risk predictor in BRCA, we succeeded in identifying CNV profiles as a prognostic marker. We included Artificial Intelligence to improve the clustering of patients, and we achieved a molecular CNV signature as a significant risk factor independent of known classic markers, including molecular subtypes PAM50. This research enhances the comprehension of HSP DNA alterations in BRCA and its relation with predicting the risk of affected individuals providing insights to develop guide personalized treatment strategies.

Inpatient and outpatient treatment by specialist infant nutrition centres in Argentina effectively reduced child malnourishment.

AIM: We evaluated the impact of inpatient and outpatient treatment provided by an infant nutrition foundation in Las Heras, Mendoza, Argentina and identified the factors that influenced nutritional recovery. METHODS: This 2010-2018 retrospective study was based on 300 children up to 5 years of age with primary malnutrition, who were treated by an inpatient recovery centre, then an outpatient prevention centre. We analysed the children's height, weight, psychomotor development and living conditions when they were admitted, discharged and had received 1 year of outpatient treatment. There were full data on 241 children and just admission and discharge data for 59. RESULTS: The children's mean age on admission and weight were 14.8 ± 12.4 months and 6.9 ± 2.3 kg and they stayed in hospital for a mean of 59.5 ± 49.7 days. We observed a significant increase in the weight-for-age, height-for-age and weight-for-height z-scores when all three time points were compared (p < 0.001). Psychomotor development improved considerably in all patients after treatment. The factors that negatively influenced nutritional recovery were higher age at admission, suboptimal breastfeeding practices, low birth weight, longer hospital stays, younger maternal age and overcrowded housing. CONCLUSION: Combining inpatient recovery and outpatient preventive treatment was effective for undernourished children in Argentina.

Omicron Waves in Argentina: Dynamics of SARS-CoV-2 Lineages BA.1, BA.2 and the Emerging BA.2.12.1 and BA.4/BA.5.

The COVID-19 pandemic has lately been driven by Omicron. This work aimed to study the dynamics of SARS-CoV-2 Omicron lineages during the third and fourth waves of COVID-19 in Argentina. Molecular surveillance was performed on 3431 samples from Argentina, between EW44/2021 and EW31/2022. Sequencing, phylogenetic and phylodynamic analyses were performed. A differential dynamic between the Omicron waves was found. The third wave was associated with lineage BA.1, characterized by a high number of cases, very fast displacement of Delta, doubling times of 3.3 days and a low level of lineage diversity and clustering. In contrast, the fourth wave was longer but associated with a lower number of cases, initially caused by BA.2, and later by BA.4/BA.5, with doubling times of about 10 days. Several BA.2 and BA.4/BA.5 sublineages and introductions were detected, although very few clusters with a constrained geographical distribution were observed, suggesting limited transmission chains. The differential dynamic could be due to waning immunity and an increase in population gatherings in the BA.1 wave, and a boosted population (for vaccination or recent prior immunity for BA.1 infection) in the wave caused by BA2/BA.4/BA.5, which may have limited the establishment of the new lineages.

Rare earth elements as statistical sentinels of pollution and paleoenvironments?: Application to a highly polluted estuary in southwestern Spain.

Multivariate analyses have been applied to the REE contents of three cores collected in the Tinto estuary, SW Spain, an extremely polluted area. Results indicate an extremely correlation between all REE, which behave as a single variable. A slight natural pollution peak and three anthropogenic pollution peaks are identified, related with the first mining activities, the Roman period and a recent intensive mining accompanied by a heavy industrial pollution. In all these peaks, the increase of Cu is parallel to that of MREE, which are configured as the best indicators of pollution among REE. Statistical analyses clearly differentiate four groups, each consisting of samples from different environments. Although grain size and this strong pollution alter the study of REE as environmental indicators, it is possible to recognise groups of samples with a common origin or to identify the surface extent of a given pollution peak.

Ovarian Response and Fertility after Short-Term Progestagen/eCG Treatments Are Compromised in Nulliparous Sheep during Non-Breeding Season.

The objective of this investigation was to determine the ovarian response, fertility, and prolificacy of nulliparous sheep when compared to multiparous sheep after a short-term (7 days) CIDR/eCG treatment which was administered during the non-breeding season. All the multiparous sheep, whereas only 54% of the nulliparous ewes, showed signs of estrus. However, 81.8% of the multiparous sheep and 100% of the nulliparous ewes ovulated. Fertility was also low after short-term progesterone treatments during the anestrous season in maiden sheep (30.8 vs. 72.7% in multiparous ewes). Such results indicate significant differences in the response to CIDR/eCG protocols for induction and synchronization of estrus and ovulation between nulliparous and multiparous sheep during the non-breeding season.

Combination Treatment of Retinoic Acid Plus Focal Adhesion Kinase Inhibitor Prevents Tumor Growth and Breast Cancer Cell Metastasis.

All-trans retinoic acid (RA), the primary metabolite of vitamin A, controls the development and homeostasis of organisms and tissues. RA and its natural and synthetic derivatives, both known as retinoids, are promising agents in treating and chemopreventing different neoplasias, including breast cancer (BC). Focal adhesion kinase (FAK) is a crucial regulator of cell migration, and its overexpression is associated with tumor metastatic behavior. Thus, pharmaceutical FAK inhibitors (FAKi) have been developed to counter its action. In this work, we hypothesize that the RA plus FAKi (RA + FAKi) approach could improve the inhibition of tumor progression. By in silico analysis and its subsequent validation by qPCR, we confirmed RARA, SRC, and PTK2 (encoding RARα, Src, and FAK, respectively) overexpression in all breast cells tested. We also showed a different pattern of genes up/down-regulated between RA-resistant and RA-sensitive BC cells. In addition, we demonstrated that both RA-resistant BC cells (MDA-MB-231 and MDA-MB-468) display the same behavior after RA treatment, modulating the expression of genes involved in Src-FAK signaling. Furthermore, we demonstrated that although RA and FAKi administered separately decrease viability, adhesion, and migration in mammary adenocarcinoma LM3 cells, their combination exerts a higher effect. Additionally, we show that both drugs individually, as well as in combination, induce the expression of apoptosis markers such as active-caspase-3 and cleaved-PARP1. We also provided evidence that RA effects are extrapolated to other cancer cells, including T-47D BC and the human cervical carcinoma HeLa cells. In an orthotopic assay of LM3 tumor growth, whereas RA and FAKi administered separately reduced tumor growth, the combined treatment induced a more potent inhibition increasing mice survival. Moreover, in an experimental metastatic assay, RA significantly reduced metastatic lung dissemination of LM3 cells. Overall, these results indicate that RA resistance could reflect deregulation of most RA-target genes, including genes encoding components of the Src-FAK pathway. Our study demonstrates that RA plays an essential role in disrupting BC tumor growth and metastatic dissemination in vitro and in vivo by controlling FAK expression and localization. RA plus FAKi exacerbate these effects, thus suggesting that the sensitivity to RA therapies could be increased with FAKi coadministration in BC tumors.

Desmoglein-4 Deficiency Exacerbates Psoriasiform Dermatitis in Rats While Psoriasis Patients Displayed a Decreased Gene Expression of DSG4.

Desmogleins are involved in cell adhesion conferring structural skin integrity. However, their role in inflammation has been barely studied, and whether desmoglein-4 modulates psoriasis lesions is completely unknown. In this study, we assessed the impact of desmoglein-4 deficiency on the severity of imiquimod (IMQ)-induced skin inflammation and psoriasiform lesions. To this end, desmoglein-4-/- Oncins France Colony A (OFA) with Sprague-Dawley (SD) genetic background were used. Additionally, human RNA-Seq datasets from psoriasis (PSO), atopic dermatitis (AD), and a healthy cohort were analyzed to obtain a desmosome gene expression overview. OFA rats displayed an intense skin inflammation while SD showed only mild inflammatory changes after IMQ treatment. We found that IMQ treatment increased CD3+ T cells in skin from both OFA and SD, being higher in desmoglein-4-deficient rats. In-depth transcriptomic analysis determined that PSO displayed twofold less DSG4 expression than healthy samples while both, PSO and AD showed more than three-fold change expression of DSG3 and DSC2 genes. Although underlying mechanisms are still unknown, these results suggest that the lack of desmoglein-4 may contribute to immune-mediated skin disease progression, promoting leukocyte recruitment to skin. Although further research is needed, targeting desmoglein-4 could have a potential impact on designing new biomarkers for skin diseases.

Changes in prolactin receptor location in prostate tumors. / Cambios en la localización del receptor prolactina en tumores prostáticos.

INTRODUCTION: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. OBJECTIVE: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. METHODS: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. RESULTS: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p< 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process.In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles.The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. CONCLUSION: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.

INTRODUCCIÓN: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT.OBJETIVO: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopio confocal.RESULTADOS: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentaje de células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino.CONCLUSIÓN: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con la proliferación celular y la supervivencia.

Changes in prolactin receptor location in prostate tumors / Cambios en la ubicación del receptor de prolactina en tumores de próstata

Introduction: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. Objetive: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. Methos: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. Results: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process. In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles. The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. Conclusion: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.(AU)

Introducción: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT. Objetivo: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopioconfocal. Resultados: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentajede células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino. Conclusión: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con laproliferación celular y la supervivencia.(AU)

SPECT/CT Correlation in the Diagnosis of Unilateral Condilar Hyperplasia.

OBJECTIVE: To evaluate the correlation between metabolic bone activity measured by single photon emission computed tomography (SPECT) and the anatomic condylar characteristics acquired by computed tomography (CT), in patients with unilateral condylar hyperplasia (UCH). Method and Materials/Patients: Observational, descriptive study in a group of 71 patients with clinical diagnosis of UCH and indication of SPECT/CT. Bone SPECT images obtained in a gamma-camera GE Infina and processed in a station Xeleris 3 with the program Volumetrix MI Evolution for bone. CT images acquired in a PET/CT Biograph mcT20 equipment (Siemens) processed in a station Osirix V 7.5.1 (Pixmeo, Bomex, Switzerland). RESULTS: The sample included 24 men (33.8%) and 47 women (66.2%). Active state UCH was detected in 40 (56.3%) cases (over 55% uptake in the affected condyle) and 38 (53.5%) presented mandibular deviation to the right side. No significant differences related to sex, age, or mandibular deviation side were found. Mandibular deviation was the only morphologic feature related to active/inactive UCH (p = 0.003). The likelihood of active CH was significantly higher in patients with mandibular deviation higher than 6 mm compared with <6 mm (odds ratio (OR): 3.51, confidence interval (CI) 95%: 1.27-9.72). CONCLUSION: There is a significant correlation between the magnitude of mandibular deviation quantified on CT and metabolic findings obtained by SPECT in patients with UCH. The risk of active UCH is 3.5 times higher in patients with a mandibular deviation ≥6 mm.

SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular level.

The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.

Reference values of mandibular condyles metabolic activity: A study using 99m Tc-MDP single-photon emission computed tomography.

OBJECTIVE: To assess the condylar bone metabolic activity in patients with temporomandibular joint health by measuring 99m Tc-MDP uptake using a single-photon emission computed tomography (SPECT) to establish reference values of the uptake difference between condyles and the ratio with respect to the clivus. SETTING AND SAMPLE POPULATION: Eighty consecutive patients of both sexes who were admitted to a Nuclear Medicine Centre between 2017 and 2019 were included in the study. METHOD: This was an observational cross-sectional study in patients with SPECT indications to evaluate pathologies other than those of the temporomandibular joint. The values of the total and normalized counts in a fixed region of interest of five trans-axial slides were obtained to assess the percentage difference between the sides and the uptake ratio. The reference values are expressed as median and 5th and 95th percentiles. RESULTS: The sample included 53 women (66.25%) and 27 men (33.75%) aged 15-55 years. The percentage of uptake difference between condyles was 5.04% (0.46-14.78) for men and 5.17% (0.27-13.21) for women (difference not significant, P = .9). The uptake difference was below 10% in 85% of the subjects (n = 68). The ratio values for total counts in women (0.87, 0.46-1.33) were significantly different (P = .0030) from those in men (1.08, 0.61-2.09). No significant correlation with age was found. CONCLUSIONS: These new reference ranges are applicable to the diagnosis of unilateral and bilateral condylar hyperplasia.

HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity.

Heat shock factor 1 (HSF1) is the primary component for initiation of the powerful heat shock response (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism for responding to proteotoxic stress and involves the rapid expression of heat shock protein (HSP) molecular chaperones that promote cell viability by facilitating proteostasis. HSF1 activity is amplified in many tumor contexts in a manner that resembles a chronic state of stress, characterized by high levels of HSP gene expression as well as HSF1-mediated non-HSP gene regulation. HSF1 and its gene targets are essential for tumorigenesis across several experimental tumor models, and facilitate metastatic and resistant properties within cancer cells. Recent studies have suggested the significant potential of HSF1 as a therapeutic target and have motivated research efforts to understand the mechanisms of HSF1 regulation and develop methods for pharmacological intervention. We review what is currently known regarding the contribution of HSF1 activity to cancer pathology, its regulation and expression across human cancers, and strategies to target HSF1 for cancer therapy.

Are There Mandibular Morphological Differences in the Various Facial Asymmetry Etiologies? A Tomographic Three-Dimensional Reconstruction Study.

PURPOSE: Facial asymmetries (FAs) have been classified according to the mandibular morphological differences to obtain better diagnostic and treatment decisions. The purpose of the present study was to establish diagnostic differentiation among FAs using computed tomography (CT) and 3-dimensional (3D) reconstruction. MATERIALS AND METHODS: We performed a cross-sectional study of patients with a diagnosis of FA, who had been evaluated by CT and 3D reconstruction in the same clinical center from 2015 to 2018. The following mandibular anatomic characteristics were compared between the 2 sides (deviated side vs contralateral side) and type of FA: condylar length, mandibular ramus length and width, mandibular body length, and symphysis deviation. RESULTS: The 53 patients included 23 men and 30 women (age range, 16 to 25 years). Six categories of FA were identified: hemimandibular elongation (n = 25), hemimandibular hyperplasia (n = 2), hybrid hyperplasia (n = 3), asymmetric mandibular prognathism (n = 14), asymmetry of the glenoid fossa (n = 2), and functional laterognathism (n = 7). The condylar length and mandibular ramus width were greater in the displaced side than in the contralateral side, with differences of -2.0 ± 2.8 mm (P < .001) and -0.5 ± 1.7 mm (P = .009), respectively. The mandibular body length was greater on the contralateral side (mean difference, 2.1 ± 3.5 mm; P < .001). The symphysis deviation was 5.0 ± 3.4 mm, and those with a hybrid form presented with a greater deviation, with values greater than 10 mm, followed by those with hemimandibular elongation. CONCLUSIONS: The evaluation of the CT images and 3D reconstructions in patients with FA provided detailed information of the mandibular structure that is useful to compare the differences between sides and to classify the entities associated with FA.

Acanthocytosis and brain damage in area postrema and choroid plexus: Description of novel signs of Loxosceles apachea envenomation in rats.

Loxocelism is a neglected medical problem that depends on its severity, can cause a cutaneous or viscero-cutaneous syndrome. This syndrome is characterized by hemostatic effects and necrosis, and the severity of the loxoscelism depends on the amount of venom injected, the zone of inoculation, and the species. In the Chihuahuan desert, the most abundant species is L. apachea. Its venom and biological effects are understudied, including neurological effects. Thus, our aim is to explore the effect of this regional species of medical interest in the United States-Mexico border community, using rat blood and central nervous system (CNS), particularly, two brain structures involved in brain homeostasis, Area postrema (AP) and Choroid plexus (PC). L. apachea specimens were collected and venom was obtained. Different venom concentrations (0, 0.178 and 0.87 µg/g) were inoculated into Sprague-Dawley rats (intraperitoneal injection). Subsequently, blood was extracted and stained with Wright staining; coronal sections of AP were obtained and stained with Hematoxylin-Eosin (HE) staining and laminin γ immunolabelling, the same was done with CP sections. Blood, AP and CP were observed under the microscope and abnormalities in erythrocytes and fluctuation in leukocyte types were described and quantified in blood. Capillaries were also quantified in AP and damage was described in CP. L. apachea venom produced a segmented neutrophil increment (neutrophilia), lymphocyte diminishment (leukopenia) and erythrocytes presented membrane abnormalities (acanthocytosis). Extravasated erythrocytes were observed in HE stained sections from both, AP and CP, which suggest that near to this section a hemorrhage is present; through immunohistofluorescence, a diminishment of laminin γ was observed in AP endothelial cells and in CP ependymal cells when these structures were exposed to L. apachea venom. In conclusion, L. apachea venom produced leukopenia, netrophilia and acanthocytosis in rat peripheral blood, and also generated hemorrhages on AP and CP through degradation of laminin γ.

Reemplazo de cadera en pacientes jóvenes: Experiencia con vástago corto preservador de cuello femoral / Hip replacement in young patients: Experience with a femoral neck preserving short stem

Introduccion La tendencia creciente de uso de implantes no cementados y el desarrollo de tecnologías que buscan restablecer la anatomía y función articular con una mayor preservación ósea, ha incrementado el uso de vástagos cortos en el remplazo total de cadera (RTC). El objetivo de este estudio es describir resultados funcionales, restauración radiológica de la anatomía, tasa de complicaciones y reintervención de pacientes sometidos a RTC usando vástagos femorales cortos de fijación cervico metafisiaria con apoyo en cortical lateral. Materiales y Métodos Estudio descriptivo prospectivo, donde se incluyeron 45 caderas en pacientes con artrosis de cadera de cualquier etiología. El seguimiento fue de 18 meses. Las variables de desenlace evaluadas fueron: 1. Integración del implante, 2. Complicaciones dependientes del implante femoral, 3. Subsidencia y 4. Reintervención. Se evaluó adicionalmente el resultado funcional con escala WOMAC. Resultados Durante el periodo comprendido entre diciembre de 2011 a julio 2017, encontramos una mejoría en estado funcional en el 97% (n:44) de los pacientes, no hubo reintervenciones. Discusión En el 100% de los casos se encontró osteointegración del implante y los resultados son comparables con los reportes de la literatura. Consideramos que el uso de vástagos cortos en el Reemplazo total de Cadera es un procedimiento seguro, con buenos resultados, teniendo la ventaja de una adecuada integración ósea del implante y garantizar un mejor stock óseo en una próxima cirugía.

Background The growing trend in the use of non-cemented implants and the development of technologies that attempt to restore the anatomy and joint function with greater bone preservation has increased the use of short stems in the total hip replacement (THR). The objective of this study is to describe functional results, radiological restoration of the anatomy, complication and revision rate of patients undergoing THR using short femoral stems with metaphyseal cervical fixation with lateral cortical support. Materials and Methods A prospective descriptive study was performed that included 45 hips of patients with hip osteoarthritis of any origin. The follow-up was 18 months. The outcome variables evaluated were: 1. Integration of the implant, 2. Complications dependent on the femoral implant, 3. Subsidence, and 4. Re-intervention. The functional result was additionally evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Results During the period from December 2011 to July 2017, an improvement was observed in functional status in 97% (n: 44) of patients, with no reoperations. Discussion Bone integration of the implant was observed in 100% of the cases, making the results comparable with the reports in the literature. It is believed that the use of short stems in total hip replacement is a safe procedure, with good outcomes. It also has the advantage of an adequate bone integration of the implant, and guaranteeing a better bone stock in the next surgery.

Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes.

BACKGROUND: Globally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules. Currently, the effects of the overproduction of methemoglobin derived from snake venom are not extensively recorded. Therefore, the present study aims to describe the oxidative stress induced by Crotalus molossus nigrescens venom using erythrocytes. METHODS: Human erythrocytes were washed and incubated with different Crotalus molossus nigrescens venom concentrations (0-640 µg/mL). After 24 h, the hemolytic activity was measured followed by attenuated total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE, conjugated diene and thiobarbituric acid reactive substances determination. RESULTS: Low concentrations of venom (<10 µg/mL) generates oxyhemoglobin release by hemolysis, whereas higher concentrations produced a hemoglobin shift of valence, producing methemoglobin (>40 µg/mL). This substance is not degraded by proteases present in the venom. By infrared spectroscopy, starting in 80 µg/mL, we observed changes in bands that are associated with protein damage (1660 and 1540 cm-1) and lipid peroxidation (2960, 2920 and 1740 cm-1). Lipid peroxidation was confirmed by conjugated diene and thiobarbituric acid reactive substance determination, in which differences were observed between the control and erythrocytes treated with venom. CONCLUSIONS: Crotalus molossus nigrescens venom provokes hemolysis and oxidative stress, which induces methemoglobin formation, loss of protein structure and lipid peroxidation.

One-domain approach for studying multiphase transport phenomena in biofilm growing systems.

The one-domain approach (ODA) was used as an alternative to solve fluid-biofilm interfacial behavior in a 2-D model for diffusion-reaction-convection coupled with prediction of irregular growth of biofilms via a cellular automaton strategy. The simulations exhibited errors of <7% compared with the porosity of a previously reported capillary experimental system. Additionally, biofilm surface geometrical aspects were satisfactorily compared with reports of experimental and similar rigorously simulated benchmark systems. The method developed was applied to simulate typical biofilm systems predicting recirculation flow patterns, interface concentration profiles, and clogging of the inlet section of the capillary tube, which are phenomena that affect the efficiency of diverse biotechnological applications, including membrane bioreactors and biofilters. The ODA method applied to the governing equations of momentum and mass transfer combined with a cellular automaton algorithm is a suitable and straightforward approach for modeling solid-state fermentation at different sophistication levels.

Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes

Abstract Background Globally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules. Currently, the effects of the overproduction of methemoglobin derived from snake venom are not extensively recorded. Therefore, the present study aims to describe the oxidative stress induced by Crotalus molossus nigrescens venom using erythrocytes. Methods Human erythrocytes were washed and incubated with different Crotalus molossus nigrescens venom concentrations (0640 g/mL). After 24 h, the hemolytic activity was measured followed by attenuated total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE, conjugated diene and thiobarbituric acid reactive substances determination. Results Low concentrations of venom ( 10 g/mL) generates oxyhemoglobin release by hemolysis, whereas higher concentrations produced a hemoglobin shift of valence, producing methemoglobin (>40 g/mL). This substance is not degraded by proteases present in the venom. By infrared spectroscopy, starting in 80 g/mL, we observed changes in bands that are associated with protein damage (1660 and 1540 cm1) and lipid peroxidation (2960, 2920 and 1740 cm1). Lipid peroxidation was confirmed by conjugated diene and thiobarbituric acid reactive substance determination, in which differences were observed between the control and erythrocytes treated with venom. Conclusions Crotalus molossus nigrescens venom provokes hemolysis and oxidative stress, which induces methemoglobin formation, loss of protein structure and lipid peroxidation.