Pseudoachalasia as a paraneoplastic event in a patient with Hodgkin's disease.

Pseudoachalasia or secondary achalasia (5% of achalasias that are deemed primary achalasias) is an esophageal motor disorder with manometric criteria for achalasia, but it appears in the context of an underlying pathology that can be attributed to its origin. Usually appears in >60 years with rapid evolution of symptoms (<1 year). The main cause of pseudoachalasia is neoformative etiology, but there are others. Our patient started with rapid progression dysphagia and was diagnosed with type II achalasia within a Hodgkin's lymphoma. In the radiological-metabolic studies, disease involvement was ruled out as an extrinsic compression of the esophagogastric junction as well as signs of its activity at this level. Chemotherapy has not been shown to play a role in the development of this pathology. On the other hand, radiotherapy has been associated with an esophageal motor disorder, but, in our case, it was after its onset. Therefore, we propose that the mechanism of pseudoachalasia in our case is a paraneoplastic event. This hypothesis is related to other similar cases reported, and it reflects the importance of continuing to investigate this clinical condition that is indistinguishable by manometry from primary achalasia. In addition, it usually presents differential clinical characteristics whose early recognition has implications for the diagnostic, therapeutic, and prognostic management of the patient.

Descriptive observational study on the use of virtual reality in patients with inflammatory bowel disease undergoing biological treatment.

BACKGROUND: Virtual reality (VR) is a neurosensory experience in which simulated spaces a person has the sensation of being able to function within them. Some patients with inflammatory bowel disease (IBD) receive intravenous biological treatments in an Adult Day Hospital (ADH) regime. VR has been used in some fields of medicine, demonstrating its usefulness in reducing negative symptoms. However, we do not have any literature showing the applicability in real clinical practice of VR in IBD. METHODS: Descriptive observational pilot study based on an initial cohort of 87 patients that were obtained from the ADH of the IBD Unit. Satisfaction and acceptance of VR through the use of 3D glasses and the reduction of negative symptoms during intravenous biological treatment in patients with IBD in ADH have been assessed. RESULTS: 43 patients (52.4%) used VR and completed the study. In the comparative analysis of the results of the questionnaires before and after the use of VR, a statistically significant improvement was observed in the patients' view on the ability of VR to achieve a reduction in stress (65% patients improve; p: 0.0021) and pain (VAS, 54% p. improve; p<0.05) during treatment. Likewise, with the applicability of VR in other areas of medicine (53%; p: 0.05) and with the possibility of improving well-being during the stay in the ADH (56%; p: 0.0014). No side effects were reported with the use of the 3D glasses. CONCLUSIONS: VR is a useful complementary tool to improve the stay of patients with IBD on ADH during intravenous treatment.

Seasonal heat stress compromises testicular thermoregulation and semen quality of Dorper rams raised in a desert climate.

Dorper rams are widely distributed throughout the world under different climatic conditions, however, little is known about their reproductive performance in desert regions. Ten Dorper rams were individually housed and exposed to thermoneutrality for 35 d in spring (23.6 ± 5.6 °C, mean ± SD) and outdoor heat stress (HS) for 35 d in summer (33.6 ± 2.0 °C) to evaluate the effect of seasonal HS on physiological responses, testicular biometry, and seminal quality under desert climatic conditions. Rectal temperature, respiration rate and coat surface temperatures in different body regions were measured every 7 d (0600, 1200, and 1800 h); also, testicular biometry was registered at 0600 h. Semen was collected via an artificial vagina 3 d after physiological variables were measured and seminal traits were evaluated. Rectal temperature, respiration rate and coat surface temperatures were higher (P < 0.01) at each hour of measurement in summer compared to spring. Overall, scrotal length and circumference, as well as testicular volume were higher (P < 0.01) in summer than in spring. Compared to spring conditions, summer HS caused lower (P ≤ 0.05) sperm concentration and viability combined with a higher percentage of sperm abnormalities without affecting ejaculate volume. Both mass and sperm motility were similar between seasons in the first two sampling weeks, and then decreased (P ≤ 0.03) due to summer HS. In conclusion, Dorper rams developed testicle hyperthermia and, consequently, showed poor semen quality due to the high environmental temperatures prevailing in desert regions.

A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells.

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify protein expression, and the zymography technique was used to observe the secretion of metalloproteinases. Molecular docking showed interactions in regions of interest of the FAK and Src proteins. Moreover, the biological activity assays demonstrated an inhibitory effect on cell migration and invasion, an important suppression of metalloproteinase secretion, and a decrease in the expression of p-FAK and p-Src proteins in treated PC3 cells. Triazaspirane-type molecules have important inhibitory effects on the mechanisms associated with metastasis in PC3 tumor cells.

Recurrent hemobilia secondary to extrahepatic biliary tract cholangiocarcinoma. A diagnostic challenge.

The etiology of hemobilia has mainly iatrogenic (>50%), followed by traumatic causes. Others are biliopathy due to portal high pressure, or neoplastic or infective biliopathy. In the case of non-clear hemobilia, direct-vision-cholangioscopy can change the management in >34% of cases. Our patient had episodes of obstructive hemobilia with secondary cholangitis without objectifying underlying pathology. When she was referred to our center, SpyGlass®-cholangioscopy identified the suspicious lesion compatible with early-stage cholangiocarcinoma despite the diagnostic delay. In conclusion, it is important to keep in mind the neoformative etiology as a potential cause of hemobilia of unclear origin, in which case, cholangioscopy (SpyGlass®) can contribute to the recognition of the signs of malignancy of the lesion and, therefore, to the diagnosis.

Mesalazine-induced esophageal ulcers. a rare adverse effect.

31-year-old woman. Diagnosis of ulcerative proctitis in February/2022. Calprotectin 1832 µg/g. Colonoscopy: erythematous, friable and erosive mucosa up to 10 cm from the anal margin. Pathology: compatible with ulcerative colitis with moderate activity. Start of oral mesalazine (3 gr/24 h granules) and topical (1 gr/24 h suppository). After three months, she achieved clinical remission. Calprotectin 57 µg/g. Two months later, she consulted for solid dysphagia, loss of 10 kg, and low-grade fever for a month. Fifteen days before, she went to an emergency room where Prednisone 50 mg/24 h was started. On the day of the assessment, she was receiving 30 mg with no improvement. The next day, gastroscopy showed 6-12 mm esophageal ulcers with non-confluent shallow geographic borders, biopsies were taken. Viral serologies and HLA B51 were requested. Given the severity of the symptoms, empirical treatment was started with Valaciclovir 1 g/12 h. Serologies: IgG for Ebstein Barr virus, cytomegalovirus and herpes virus with negative IgM. Cytomegalovirus viral load: <30 IU/ml. Pathology: acute extensively ulcerated esophagitis, inflammatory infiltrate and some eosinophils with negative histochemical staining for fungi, cytomegalovirus and herpes virus I and II. HLA B51 was negative. Valaciclovir and mesalazine are discontinued after seven days given the known relationship of the latter with low-grade fever and, exceptionally, with esophageal pathology. Three days later, the patient reported clear improvement in dysphagia from the day the mesalazine was discontinued. After eight months, she was still asymptomatic. Upon resolution of the symptoms, control gastroscopy was not performed, and mesalazine has not been reintroduced due to its probable causal association. Mesalazine has an excellent safety profile. Adverse effects include fever, headache, diarrhea and.

Histiocytic sarcoma of the esophagus.

A 20-year-old male with no medical history of interest who goes to the emergency room because of retrosternal pain, odynophagia, dysphagia, and fever. On physical examination: 37.7ºC axillary temperature, bad general condition, and central chest pain on palpation. In the blood test: 16,200x10^6/L white blood cells, 12,800x10^6/L neutrophils, and 11.66mg/dL C reactive protein, with the rest of the complete blood count, coagulation, and biochemistry within normal values.

Matrix metalloproteinase-2 and matrix metalloproteinase-9 serum levels in patients with vertebrobasilar dolichoectasia with and without stroke: case-control study.

PURPOSE: To describe the differences in the serum levels of MMP-2 and MMP-9 of patients with vertebrobasilar dolichoectasia (VBD) with and without acute stroke. METHODS: Case-control study. From an outpatient clinic, we recruited 14 controls and 19 patients with VBD. We also recruited 33 patients with stroke from two emergency departments, 14 without VBD (S/-VBD) and 19 with VBD (S/ + VBD). All the patients underwent serum MMP-2 and MMP-9 measurements and a non-contrast CT scan. Two investigators assessed the intracranial vertebral arteries (VA) and the basilar artery (BA) at the mid-pons. Diagnosis of VBD was made if the BA diameter was ≥ 4.5 mm. RESULTS: The mean age of the 66 patients studied was 57.6 + 16.0 years, 41% female. In the 33 patients with stroke, the median NIHSS was 8 (range 15); there were no differences in the NIHSS scores between both groups with stroke. Median MMP-2 levels were lower in the S/-VBD when compared to controls. Median MMP-9 serum levels were higher in both groups with VBD when compared to controls and the S/-VDB group. Both groups with stroke exhibited higher MMP-9 serum levels than controls but were not statistically different from those found in patients with VBD. Serum levels of MMP-9 were significantly correlated with the diameters of the BA (r = 0.344, p = 0.01) and the left VA (r = 0.305, p = 0.05). CONCLUSION: This study found that high serum levels of MMP-9 are associated with VBD independently of stroke and correlated with the degree of VBD.

Progesterone supplementation in Holstein heifers subjected to cooling and timed AI during summer: physiological and reproductive variables and thyroid hormone concentrations.

Our aim was to evaluate the effects of progesterone supplementation after fixed-time artificial insemination (FTAI) on physiological and reproductive variables and serum thyroid hormone concentrations of cooled Holstein heifers during a hot summer season. Sixty-nine Holstein heifers were randomly assigned to three treatments: (1) heifers under visual estrus detection and inseminated according to AM-PM rule (n = 23; control (C)), (2) heifers subjected to FTAI after estrus synchronization using a CIDR insert (n = 24; FTAI group), and (3) heifers treated as the FTAI group plus progesterone supplementation between the day 4 and 14 post-insemination with a reused CIDR device (n = 22; FTAI+SP4 group). All heifers were cooled daily with misting and fans. Physiological variables were measured; likewise, blood samples were collected to determine serum progesterone, thyroxine, and triiodothyronine concentrations. Both respiration rate and rectal temperature were similar among treatments. Conception rate was greater (P < 0.05) in C (65.2%) and FTAI+SP4 (59.1%) heifers than in FTAI heifers (33.3%). Serum triiodothyronine and progesterone concentrations of FTAI+SP4 heifers were similar to those of C heifers but greater (P < 0.05) than those of FTAI heifers. In conclusion, progesterone supplementation post-insemination increased conception rate and serum progesterone concentrations without affecting thermoregulation capacity in Holstein heifers subjected to FTAI and cooling during a hot summer season.

Conception rate following artificial insemination with sexed semen in Holstein heifers under artificial cooling during summer compared with winter season.

The objective of this study was to compare the fertility of Holstein heifers under cooling and inseminated with sexed semen during the summer versus winter season. Eighty heifers were divided into two groups: (1) summer group (n = 40), consisted of heifers under visual heat detection and inseminated with sexed semen. These heifers were also provided with artificial cooling under shade area from 1000 to 1800 h. (2) Winter group (n = 40), heifers under shade only and with the same reproductive protocol than the summer group. The rectal temperature and respiratory rate were higher (P < 0.05) in the summer group. Vaginal temperature presented higher values in summer (P < 0.05) in most of the daylight hours except between 1100 and 1200 h (P > 0.05). Progesterone, as measured from the AI to 21 days after AI, showed higher values (P < 0.05) in days 6, 12, 18, and 21 during summer compared with winter in pregnant heifers; also, non-pregnant heifers had higher concentrations of progesterone on days 6, 9, 15, and 21 (P < 0.05) in winter. The conception rate in winter at day 35 post-AI (65%) was higher (P < 0.05) than those observed during summer (37.5%). In conclusion, although the lower fertility observed during summer with sexed semen, it can be considered as normal and comparable to the conception rate with conventional semen under hot climate.

[Breast osteosarcoma originating in a phyllodes tumor. Report of one case]. / Tumor Phyllodes con transformación a osteosarcoma.

Phyllodes tumors account for less than 1% of tumors of the mammary gland, have both epithelial and stromal components and are classified as benign, borderline and malignant. The malignant tumors are highly heterogeneous: they can differentiate to liposarcomas, fibrosarcomas, rhabdomyosarcomas, chondrosarcomas or osteosarcomas. The differentiation to osteosarcoma is extremely rare, constitutes 1.3% of cases and is very aggressive. The standard treatment of these tumors is surgical. The role of radiotherapy and chemotherapy is not clear. However, in patients in whom wide surgical margins are not achieved, adjuvant radiotherapy can be of help. We report a 63 years old female with a right breast osteosarcoma with an osteoclastic component, originating in a phyllodes tumor. The tumor was excised surgically and afterwards she was treated with 10 sessions of 50 Gy of radiotherapy in 25 fractions. She has remained free of disease for the last 10 months.

Association of high sensitivity C-reactive protein with diet composition in Mexican school children. / Asociación de la proteína C-reactiva ultrasensible con la composición de la dieta en niños escolares mexicanos.

The high-Sensitivity C-Reactive Protein (hs-CRP) is a cardiovascular risk marker. In healthy Mexican children, there islittle evidence that shows any relationship between serum levels of this marker with diet. The objective of this studywas to associate serum levels of hs-CRP with the diet composition in Mexican school children. The cross-sectional study included 300 seemingly healthy children of 10 to 12 years of age, 53.7% were girls and 46.3% boys.hs-CRP quantification was determined by nephelometry. The diet was quantified with a validated food frequency questionnaire. A descriptive statistical analysis, correlation and multivariate regression models were performed by using the SPSS v18 statistical software. The median of the hs-CRP was 0.3 mg / L (range: 0.3 to 6.8 mg / L). A significant direct correlation was found between serum hs-CRP with protein intake (rho=0.126, p=0.029), total fatty acids (rho = 0.128, p = 0.027) and saturated fatty acids (rho = 0.159, p = 0.006). hs-CRP was associated with the intake of protein (ß = 0.203, p = 0.037) by multiple regression analysis, and inversely with whole grains (ß = -0.175, p = 0,002). No significant association was found with the rest of the other variables. The serum concentration of hs-CRP was directly associated with the consumption of protein, total and saturated fatty acids and was indirectly proportional with the consumption of whole grains.

Protein Folding and Mechanisms of Proteostasis.

Highly sophisticated mechanisms that modulate protein structure and function, which involve synthesis and degradation, have evolved to maintain cellular homeostasis. Perturbations in these mechanisms can lead to protein dysfunction as well as deleterious cell processes. Therefore in recent years the etiology of a great number of diseases has been attributed to failures in mechanisms that modulate protein structure. Interconnections among metabolic and cell signaling pathways are critical for homeostasis to converge on mechanisms associated with protein folding as well as for the preservation of the native structure of proteins. For instance, imbalances in secretory protein synthesis pathways lead to a condition known as endoplasmic reticulum (ER) stress which elicits the adaptive unfolded protein response (UPR). Therefore, taking this into consideration, a key part of this paper is developed around the protein folding phenomenon, and cellular mechanisms which support this pivotal condition. We provide an overview of chaperone protein function, UPR via, spatial compartmentalization of protein folding, proteasome role, autophagy, as well as the intertwining between these processes. Several diseases are known to have a molecular etiology in the malfunction of mechanisms responsible for protein folding and in the shielding of native structure, phenomena which ultimately lead to misfolded protein accumulation. This review centers on our current knowledge about pathways that modulate protein folding, and cell responses involved in protein homeostasis.

Intensified-Fenton process for the treatment of phenol aqueous solutions.

An intensified-Fenton process for the treatment of phenol aqueous solutions has been studied as a continuous catalytic wet hydrogen peroxide oxidation system. This process consists of coupling the catalytic activity of a heterogeneous Fenton-like catalyst with the homogeneous contribution of its dissolved iron species. Agglomerated mesoporous SBA-15 silica-supported iron oxide (Fe2O3/SBA-15) material was used as heterogeneous catalyst. The influence of the reaction temperature and the initial hydrogen peroxide dosages was studied in order to minimize the operation cost of the process. The catalytic performance of the process was assessed in terms of total organic carbon (TOC) and hydrogen peroxide conversions. Likewise, the stability of the solid Fenton-like catalyst was also evaluated in terms of the dissolved iron species. The increase of the reaction temperature enhanced the TOC conversion and reduced the iron leaching from the heterogeneous catalyst. These results were related to the degradation of oxalic acid as responsible for iron extraction by formation of soluble stable iron complexes into the aqueous medium. Finally, the use of a moderate hydrogen peroxide concentration (2.6 g/L) and milder temperatures (80-120 °C) has led to remarkable results of TOC and phenol reductions as well as oxidant efficiency through the intensified-Fenton process.

Having children in cross-border contexts: late-family formation among homoparental families in Spain.

Considered until recently unfit to rear children, non-heterosexual people have been excluded from forming families in most countries. Many, worldwide, demand access to family formation, claiming the same aptitudes as heterosexual people for raising children. However, when non-heterosexual singles and couples want to become parents in Spain, they must consider transnational contexts, resorting to inter-country adoption or surrogacy abroad, processes that contribute to delay their family formation. They must consider not only Spanish sociocultural conditions, but other countries' legal restrictions regarding parents' gender, social status, and sexual identity. These families experience great difficulty in gaining access to reproductive health services. Based on multi-site ethnographic fieldwork, this text addresses how, despite legislative changes allowing homoparental family formation in Spain, these parents must overcome complex bureaucratic processes when they decide to have children, while facing homophobic attitudes and policies in their quests to become parents.

Brucella abortus triggers the differential expression of immunomodulatory lncRNAs in infected murine macrophages.

Introduction: The lncRNAs (long non-coding RNAs) are the most diverse group of non-coding RNAs and are involved in most biological processes including the immune response. While some of them have been recognized for their influence on the regulation of inflammatory activity, little is known in the context of infection by Brucella abortus, a pathogen that presents significant challenges due to its ability to manipulate and evade the host immune system. This study focuses on characterize the expression profile of LincRNA-cox2, Lethe, lincRNA-EPS, Malat1 and Gas5 during infection of macrophages by B. abortus. Methods: Using public raw RNA-seq datasets we constructed for a lncRNA expression profile in macrophages Brucella-infected. In addition, from public RNA-seq raw datasets of RAW264.7 cells infected with B. abortus we constructed a transcriptomic profile of lncRNAs in order to know the expression of the five immunomodulating lncRNAs studied here at 8 and 24 h post-infection. Finally, we performed in vitro infection assays in RAW264.7 cells and peritoneal macrophages to detect by qPCR changes in the expression of these lncRNAs at first 12 hours post infection, a key stage in the infection cycle where Brucella modulates the immune response to survive. Results: Our results demonstrate that infection of macrophages with Brucella abortus, induces significant changes in the expression of LincRNA-Cox2, Lethe, LincRNA-EPS, Gas5, and Malat1. Discussion: The change in the expression profile of these immunomodulatory lncRNAs in response to infection, suggest a potential involvement in the immune evasion strategy employed by Brucella to facilitate its intracellular survival.

Multivariate data analysis of process parameters affecting the growth and productivity of stable Chinese hamster ovary cell pools expressing SARS-CoV-2 spike protein as vaccine antigen in early process development.

The recent COVID-19 pandemic revealed an urgent need to develop robust cell culture platforms which can react rapidly to respond to this kind of global health issue. Chinese hamster ovary (CHO) stable pools can be a vital alternative to quickly provide gram amounts of recombinant proteins required for early-phase clinical assays. In this study, we analyze early process development data of recombinant trimeric spike protein Cumate-inducible manufacturing platform utilizing CHO stable pool as a preferred production host across three different stirred-tank bioreactor scales (0.75, 1, and 10 L). The impact of cell passage number as an indicator of cell age, methionine sulfoximine (MSX) concentration as a selection pressure, and cell seeding density was investigated using stable pools expressing three variants of concern. Multivariate data analysis with principal component analysis and batch-wise unfolding technique was applied to evaluate the effect of critical process parameters on production variability and a random forest (RF) model was developed to forecast protein production. In order to further improve process understanding, the RF model was analyzed with Shapley value dependency plots so as to determine what ranges of variables were most associated with increased protein production. Increasing longevity, controlling lactate build-up, and altering pH deadband are considered promising approaches to improve overall culture outcomes. The results also demonstrated that these pools are in general stable expressing similar level of spike proteins up to cell passage 11 (~31 cell generations). This enables to expand enough cells required to seed large volume of 200-2000 L bioreactor.

Auraptene Boosts the Efficacy of the Tamoxifen Metabolites Endoxifen and 4-OH-Tamoxifen in a Chemoresistant ER+ Breast Cancer Model.

Approximately 80% of breast cancer (BC) cases are estrogen receptor positive (ER+) and sensitive to hormone treatment; Tamoxifen is a prodrug, and its main plasmatic active metabolites are 4-hydroxytamoxifen (4-OH Tam) and endoxifen. Despite the effectiveness of tamoxifen therapy, resistance can be developed. An increment in eukaryotic initiation factor-4A complex (eIF4A) activity can result in tamoxifen-resistant tumor cells. For this work, we developed a cell variant resistant to 4-OH Tam and endoxifen, denominated MCF-7Var E; then, the aim of this research was to reverse the acquired resistance of this variant to tamoxifen metabolites by incorporating the natural compound auraptene. Combination treatments of tamoxifen derivatives and auraptene successfully sensitized the chemoresistant MCF-7Var E. Our data suggest a dual regulation of eIF4A and ER by auraptene. Joint treatments of 4-OH Tam and endoxifen with auraptene identified a novel focus for chemoresistance disruption. Synergy was observed using the auraptene molecule and tamoxifen-derived metabolites, which induced a sensitization in MCF-7Var E cells and ERα parental cells that was not observed in triple-negative breast cancer cells (TNBC). Our results suggest a synergistic effect between auraptene and tamoxifen metabolites in a resistant ER+ breast cancer model, which could represent the first step to achieving a pharmacologic strategy.

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.