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Ultrasound tomography is an emerging imaging modality that uses the transmission of ultrasound through tissue to reconstruct images of its mechanical properties. Initially, ray-based methods were used to reconstruct these images, but their inability to account for diffraction often resulted in poor resolution. Waveform inversion overcame this limitation, providing high-resolution images of the tissue. Most clinical implementations, often directed at breast cancer imaging, currently rely on a frequency-domain waveform inversion to reduce computation time. For ring arrays, ray tomography was long considered a necessary step prior to waveform inversion in order to avoid cycle skipping. However, in this paper, we demonstrate that frequency-domain waveform inversion can reliably reconstruct high-resolution images of sound speed and attenuation without relying on ray tomography to provide an initial model. We provide a detailed description of our frequency-domain waveform inversion algorithm with open-source code and data that we make publicly available.

Purpose To demonstrate that intense pulsed light therapy (IPL) of the upper and lower eyelids with meibomian gland expression (MGX) is effective in improving dry eye disease due to meibomian gland dysfunction (MGD).Methods Patients with ocular discomfort (Ocular Surface Disease Index -OSDI- above 13) and signs of MGD were recruited. All patients underwent OSDI, visual acuity (VA), intraocular pressure, Schirmer test, meibography, non-invasive tear breakup time (NITBUT), slit-lamp examination (corneal and conjunctival staining, hyperemia, gland expressibility, and meibum quality), tear osmolarity and lipid layer thickness. IPL was performed with Optima IPL (Lumenis Ltd.) following a standardized protocol on upper and lower eyelids of both eyes, with inferior eyelid MGX. Patients received four sessions separated by two weeks each. Four weeks after, examinations were repeated.Results 160 patients (320 eyes) were included, of which 108 (67.5%) were women and mean age was 59.2 ± 15.08 (range 20–89). After four sessions, VA, OSDI, tear osmolarity, lipid layer thickness, NITBUT, hyperemia, corneal and conjunctival staining, gland expressibility, meibum quality, inferior eyelid Meiboscore and Schirmer test improved (all, p < 0.027). Changes in OSDI, initial and average NITBUT increased with dry eye disease severity (according to OSDI). Increased pre-treatment OSDI, hyperemia, corneal and conjunctival staining and Schirmer test were associated with an improvement in OSDI (all, p < 0.040). No adverse events were noted.Conclusions The combination of IPL on upper and lower eyelids with MGX is safe and effective for the treatment of MGD. Patients with severe dry eye disease present greater improvements.

Byline: Cristina. Casanova-Martinez, Elena. Romero-Ventosa, Sonia. González-Costas, Cecilia. Arroyo-Conde, Guadalupe. Piñeiro-Corrales Context: Pancreatic cancer in a common tumor in our country for which there are various treatment alternatives. Objective: Evaluate [...]

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce.Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups.Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic.Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI.Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51–13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17–4.36); others vs TNFi: 3.21 (1.59–6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine.Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy.

During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n= 11) and a Control group (<10, n= 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8α & β ILR7α, and CCR4among others, were found in the Index group (P< 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named “Primary immunodeficiency” was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.Mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy.Graphical Abstract

BackgroundMonitoring tobacco control policy implementation is one of the keys for tobacco consumption reduction in Latin America (LA). This study reports on the adaptation of the Tobacco Control Scale (TCS) for use in LA countries and the level of tobacco control policy implementation in this region according to the scale.MethodsEcological cross-sectional survey. The questionnaire to measure tobacco control policies was a translated (into Spanish and Portuguese) and adapted version of the last TCS as used in Europe. The resulting TCS-LA maintains the same structure as the original TCS, with eight policy domains and 100 points (pts) as maximum score; however, four policy domains were adapted because the exact same rationale could not be applied. At least two non-governmental tobacco control experts were contacted per country to answer the TCS-LA.ResultsInformants from 17 out of 18 countries completed the questionnaire. Using the TCS-LA, Panama (70 pts), Uruguay (68 pts) and Ecuador (61 pts) exhibited the strongest tobacco control policies, while Guatemala (32 pts), Bolivia (30 pts) and Dominican Republic (29 pts) have implemented a lower number of tobacco control policies. Eight countries reached 50% of the TCS-LA total possible score, indicating a relatively good implementation level of tobacco control policies.ConclusionsPanama, Uruguay and Ecuador are the tobacco control policy leaders in LA; however, tobacco control in the region has room for improvement since nine countries have a total score under 50 pts. The TCS is a feasible and adaptable tool to monitor tobacco control in other WHO regions beyond Europe.

Background Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration.Purpose To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months.Methods Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months.Results In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months (P> 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed (P> 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point (P= 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed (P> 0.05).Conclusion Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds (P> 0.05).

Diabetes in Mexian populations was shown to be higher in men than women and in older and single adults living in urban communities. This group was also associated with an increased prevalence of coronary risk factors. Diabetes was assoicated with higher fat, low carbohydrate and low fat diets and an increase of central distribution of adiposity.

AbstractTransrectal palpation (TP) is a basic skill in equine practice. Traditional TP learning methods include instructor-assisted TP in live animals, but this approach presents animal welfare concerns, especially when it needs to be used with large numbers of students. The main objective of this study is to compare two learning methods of TP: traditional methodology with live horses (LH) and alternative methodology using a cadaver with its flanks dissected (CDV). Twenty students with no previous equine TP experience were randomly assigned to two groups: LH (n= 10) and CDV (n= 10). Both groups received initial theoretical training before the LH or CDV session. Learning outcomes of both groups were assessed in a new TP session with live horses. All students were asked about their success in palpating seven intra-abdominal structures and objective ultrasound confirmation (UC) was also performed. Successful perception in palpation and by UC was similar in both LH and CDV students’ groups, without significant differences. Anonymous surveys answered by these 20 volunteers and by 126 students enrolled in the regulated course who also received this CDV training showed very positive feedback on the CDV methodology. As a limitation of the study, there were few students in each group and most of the results are based on subjective criteria. Nevertheless, we can conclude that CDV is a useful tool for teaching TP, with good learning results, allowing the instructor to see what the student is touching and avoiding the LH disadvantages.

Aim:To investigate the impact of various feeding strategies on the growth and productivity of a GS-CHO cell line. Methods:Feed additions were conducted at fixed volumes or linked to a marker such as cell growth or metabolism and added as bolus or near-continuously using the automated feeding module of the micro-Matrix (Applikon). Results:The selected feeding regimens supported maximum viable cell densities of up to 1.9 × 107cells ml−1and final titers of up to 1.13 g l−1. Differences in growth and titer between feeding strategies were insignificant, with the exception of one feeding strategy. Conclusion:As the more complex feeding strategies did not create an advantage, the selection of a simple feeding strategy such as bolus or continuous addition of feed medium is preferred.

Introduction

Combined pituitary hormone deficiency (CPHD) is characterized by a malformed or underdeveloped pituitary gland resulting in an impaired pituitary hormone secretion. Several transcription factors have been described in its etiology, but defects in known genes account for only a small proportion of cases.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a non-Hodgkin Lymphoma (NHL) localized all along the aerodigestive tract. The aim of this report is to present the case of a patient with MALT lymphoma in soft palate treated in our department.

The combination of estrus synchronization and superovulation treatments introduces molecular modifications whose effects are yet to be disclosed. Here, reproductive parameters and gene expression changes in ovaries and endometrium were explored on day 6 after artificial insemination (AI), when synthetic progestin altrenogest (ALT) was combined with gonadotropins. Sows were administered ALT for 7 d beginning on the day of weaning and superovulated with equine chorionic gonadotropin (eCG) 24 h later and human chorionic gonadotropins (hCG) at the onset of estrus (SS-7 group; n= 6). The controls were either superovulated sows with eCG 24 h postweaning and hCG at the onset of estrus (SCgroup; n= 6) or sows with postweaning spontaneous estrus (NCgroup; n= 6). Ovary examination and embryo and tissue collection were performed in all sows via laparotomy on day 6 post-AI. RNA-Seq was conducted to analyze differentially expressed genes (DEGs) between groups. Statistical analysis of the reproductive parameters was conducted with ANOVA and Tukey post hoc tests. DEGs were analyzed with an ANOVA (fold changes ≥2 or ≤2, Pvalue <0.05). Hormonal treatments almost doubled (P< 0.03) the number of corpora lutea (39.8 ± 10.2 and 38.3 ± 11.1 in SS-7 and SC sows, respectively) compared with that in the NC group (23.1 ± 3.8). In contrast, embryo viability significantly decreased (P< 0.003) in response to SS-7 treatment (75.1% ± 15.2%) compared to SC and NC groups (93.8 ± 7.6% and 91.8 ± 6.9%, respectively). RNA-Seq analyses revealed 675 and 1,583 DEGs in the SS-7 group compared to both SC and NC groups in endometrial and ovarian samples, respectively. Interestingly, many genes with key roles in the Wnt/β-catenin and Notch signaling pathways were differentially expressed in SS-7 sows relative to SC and NC groups (e.g., Ctnnb1, Myc, Gli3, Scyl2, Ccny, Daam1, Ppm1n, Rbpj,and Usp8). A key finding in this study was the downregulation of β-catenin (Ctnnb1) gene expression in the SS-7 endometrium, suggesting that this treatment influences embryo–uterine dialogue by triggering a cascade of events leading to embryo maldevelopment. These data explain the proliferative defects in SS-7 embryos and suggest a novel mechanism of a porcine embryo–maternal crosstalk.Genes with key roles in the Wnt/β-catenin and Notch signaling pathways were differentially expressed in the endometrium of sows subjected to synchronization and superovulation treatments, suggesting that these treatments influence embryo–uterine dialogue by triggering a cascade of events leading to embryo maldevelopment.Methods for porcine superovulation (increasing the number of ovulated oocytes per cycle) and estrus synchronization (grouping estrus sows on the same day) are available for assisted reproductive technologies, using hormonal treatments. The main goal of the present study was to understand how hormones used for these purposes influence gene expression patterns in the female reproductive tract (ovaries and endometrium). We observed that hormonal treatments (synchronization combined with superovulation) have the potential to alter ovarian and endometrial gene expression patterns, triggering improper follicle development and oocyte growth, and leading to abnormal embryonic development before implantation. Genes involved in two key metabolic pathways for embryo development (Wnt/β-catenin and Notch signaling pathways) were dysregulated in reproductive tissues.

Different environmental factors can have an effect on the development of asthma, as well as on its clinical expression. The main sources of environmental pollution are the burning of fossil fuels in the combustion engines of different means of transport, in industry and in heating, as well as the biomass used for cooking and heating. Also contributing to this complex mixture is the dust generated by traffic on road surfaces, or substances arising from the degradation of vehicle parts, such as brakes or tires. Among the most abundant components of air pollution in urban areas are particulate matter, nitrogen dioxide, ozone and volatile organic compounds. Sulphur dioxide is particularly abundant in industrial areas. Various mechanisms on how environmental contaminants could cause asthma have been considered. One possibility could be the direct irritation of the airway mucosa. Another possible mechanism could be the combination of the contaminants with various allergens, increasing the allergenic activity. It has also been observed that some environmental contaminants trigger cell inflammation processes. Epigenetic mechanisms, such as hypermethylation of DNA or acetylation of histones, were also described. It has been observed in animal models that a pre-existing mitochondrial dysfunction increases bronchial inflammation after exposure to ragweed pollen extract. In conclusion, it appears that there probably is a harmful effect by environmental contaminants on asthma, increasing both the severity and the prevalence of the disease. But the persistence of some contradictions in the data seems to support the need to continue research in this field, clarifying the magnitude of this effect, as well as the underlying mechanisms, which could help to identify measures to reduce the harmful effects of this exposure.

Lung cancer (LC) is a highly prevalent malignancy mainly caused by long-term exposure to tobacco smoke, although other substances in the workplace can also cause LC. This paper reviews carcinogens in the workplace linked with occupational LC, including asbestos, radon, silica, nickel, beryllium, chromium and polycyclic aromatic hydrocarbons (PAH). In LC of occupational origin, diagnosis can be difficult due to co-exposure to various carcinogens. The present review is intended to provide additional information that may help in the diagnostic approach and discusses controversial issues on certain substances like silica, beryllium or PAH as etiological factors of LC. Finally, occupational LC preventive measures are discussed.

Extracellular factors control the angiogenic switch in endothelial cells (ECs) via competing survival and apoptotic pathways. Previously, we showed that proangiogenic and antiangiogenic factors target the same signaling molecules, which thereby become pivots of angiogenic balance. Here we show that in remodeling endothelium (ECs and EC precursors) natural angiogenic inhibitors enhance nuclear factor-κB (NF-κB) DNA binding, which is critical for antiangiogenesis, and that blocking the NF-κB pathway abolishes multiple antiangiogenic events in vitro and in vivo. NF-κB induction by antiangiogenic molecules has a dual effect on transcription. NF-κB acts as an activator of proapoptotic FasL and as a repressor of prosurvival cFLIP. On the FasL promoter, NF-κB increases the recruitment of HAT p300 and acetylated histones H3 and H4. Conversely, on cFLIP promoter, NF-κB increases histone deacetylase 1 (HDAC1), decreases p300 and histone acetylation, and reduces the recruitment of NFAT, a transcription factor critical for cFLIP expression. Finally, we found a biphasic effect, when HDAC inhibitors (HDACi) were used to test the dependence of pigment epithelial-derived factor activity on histone acetylation. The cooperative effect seen at low doses switches to antagonistic as the concentrations increase. Our study defines an interactive transcriptional network underlying angiogenic balance and points to HDACi as tools to manipulate the angiogenic switch.

The Msx1 gene in mice has been proven to be induced by BMP (bone morphogenetic protein) proteins, and three binding sites for SMAD, an intracellular BMP signalling transducer, have already been identified in its promoter. Gel shift analyses were performed and they demonstrated that the consensus found very near the transcription start site, a region designed BP (basal promoter), is functional for binding nuclear proteins from 10.5, 11.5 and 13.5 dpc (days post-coitum) embryos. Notably, this binding occurs only when the SMAD-binding consensus sequence is maintained, suggesting that it is required for the formation of a protein complex over BP. Binding of purified SMAD 1 and SMAD 4 as well as supershift assay with SMAD 1/SMAD 5/SMAD 8 antibody proved that a SMAD protein is present in this complex. Transfection assays in cell cultures with fragments from BP driving the expression of luciferase confirmed that only in the presence of the SMAD consensus site is Msx1 expression activated. A proteomic analysis of the complex components after immunoprecipitation identified several proteins necessary to activate transcription including SMAD 8. Our results suggest that BMP2/BMP4 signalling through SMAD 8 is required for transcriptional activation of the mouse Msx1 gene.

Abstract Rationale. We performed this study with the intention of describing the clinical-etiological characteristics and therapeutic responses in a group of epileptic children seen at the Instituto Nacional de Pediatría (INP), a tertiary facility in Mexico City. Methods. All patients who attended the Epileptic Clinic between March and June 1998 and fulfilled the selection criteria were enrolled in the study. Clinical and therapeutic response data were recorded. Three groups were formed by etiology. Statistical tests were two-tailed, with α=0.05. Results. In all, 719 patients were studied. The distribution by etiology was as follows: group I, idiopathic (123 patients); group II, cryptogenic (132); and group III, symptomatic (464). In group I, 56% of the patients were female. Mean age at onset was 5 years 2 months (SD: 3 years 8 months) in group I; 1 year 11 months (SD: 2 years 5 months) in group II; and 2 years 10 months (SD: 3 years 1 month) in group III. The mean evolution time was 5 years 4 months (SD: 4 years) in all groups. The most frequent variety of epilepsy in the three groups was generalized epilepsy, followed by partial epilepsy. The following epileptic syndromes were identified: in group I, 28 patients had epilepsy with generalized tonic-clonic seizures, 15, absence epilepsy, and 6, benign rolandic seizures; in group II, all 32 patients had focal cryptogenic epilepsy; in group III, 235 had generalized symptomatic and 192, focal symptomatic epilepsy. The main etiologies were hypoxic ischemic encephalopathy (24%) and neural infections (22%). Appropriate seizure control was achieved in 108 (87%) patients in group I; 84 (64%) in group II; and 315 (68%) in group III. In group I, no patient needed more than two antiepileptic drugs and 90% had normal psychomotor development. Conclusion. When the three groups were compared in terms of appropriate epileptic control and normal psychomotor development, group I differed from the other groups and the difference was statistically significant.

LERMAN‐GARBER, ISRAEL, ANTONIO R. VILLA, CRISTINA LLACA MARTINEZ, LETICIA CERVANTES TURRUBIATEZ, CARLOS A. AGUILAR SALINAS, VILLAGRA LUCY, BELIA WONG, JUAN C. LÓPEZ ALVARENGA, FRANCISCO GÓMEZ PÉREZ, AND LUIS MIGUEL GUTIERREZ ROBLEDO. The prevalence of obesity and its determinants in urban and rural older mexican populations. Obes Res. Objective: To determine the prevalence of obesity and its association to different variables in urban and rural older Mexican populations. Methods and Procedures: A cross‐sectional study of three different Mexican communities. A total of 121 men and 223 women 60 years and older and 93 men and 180 women aged 35 to 59 years old were selected randomly for inclusion in the survey. A personal interview assessed demographic information, personal medical history and functional status and a 24‐hour diet recall was obtained. The physical examination included anthropometric and blood pressure measurements. A fasting blood sample was obtained for measurements of lipids, insulin and glucose. Results: Obesity was highly prevalent in women, in individuals from the urban communities and diminished with advancing age. A BMI ≥30 kg/m2was observed in 23. 6% younger vs. 15. 6% older adult men (p= 0. 21) and 28. 4% younger vs. 19. 7% older adult women (p= 0. 06). Conclusions: The present survey confirms the high prevalence of obesity in the Mexican urban population that declines with advanced age. Studies in elderly population must consider the bias produced by increased early mortality in those individuals with a more unfavorable risk profile. The association of obesity with other variables was estimated using a stepwise multivariate logistic regression, increased insulin levels [Odds Ratio (OR) 1. 68, p= 0. 006] and living in an urban area (OR 5. 90, p<0. 007) were variables independently associated to obesity in adult older individuals. In the younger adults, obesity was associated with hypertension (OR 2. 74, p<0. 0009), higher insulin levels (OR 1. 31, p<0. 03) and central adiposity (OR 2. 97, p= 0. 05), these relationship were not observed with gender, distribution of food or alcohol intake or other coronary risk factors.

Changes of energy inctaholism in maternal leukocytes were studied longitudinally in 33 normal term pregnancies at 12, 20 and 36 weeks of gestation and 40 days post partum. Nutrient intakes were calculated from 3-day weighed food records at the same periods. Women tended to decrease their mean dietary intakes of energy and of most nutrients from early to late pregnancy. Glucose-6-P dehydrogenase (G6P-DH), pyruvic kinase (PK) and adenylate kinase (AK) activities rose significantly after the 12th week of pregnancy, reaching maximal values at week 20. The following period up to week 36 showed a significant decrease that continued in the puerperium, when their values were lowest. Adenine nucleotidc contents and protein/DNA ratio followed a different pattern. A significant increase was also observed from weeks 12 to 20, remaining without changes during the second half of gestation, and falling at puerperium. The PK and AK activities showed a positive correlation with energy intake at 36 weeks of gestation and AK activity was negatively correlated with folic acid intake in the middle of pregnancy. At week 20, PK activity showed a positive correlation with both head circumference and body mass index of the newborn. There was also a correlation between protein/DNA ratio and head circumference at the 36th week of gestation. These findings may suggest a relationship between the metabolism of maternal leukocytes, and fetal development in utero.

The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlcohas not been explored.

HOME & AWAY Contributing Wr i t e r PRIYA KRISHNA On The Plates With an Attitude As I was devouring the crispy kanji wada at Besharam, a Gujarati restaurant in San Francisco, I noticed something written on the plate: "Hot chai, cold revenge!" Aarke produces 60 liters of perfect bubbly water from one CO2 canister. $219, CO2 canister not included; aarke-usa.com PHOTO (COLOR) PHOTO (COLOR) PHOTO (COLOR). [Extracted from the article]

The majority of patients with classical Hodgkinxs Lymphoma (cHL) are cured with primary treatment. However, a significant proportion of patients will not achieve a complete response (CR) or relapse after completion of initial therapy and need to be rescued with high-dose chemotherapy and stem cell transplantation (SCT): autologous (aSCT) and/or alogeneic (Alo-SCT). The identification of clinical and biological characteristics of these patients at diagnosis is still a challenge and the most prognostic systems used to date fail to identify a proportion of patients with worse prognosis. The best understanding of the biology of cHL could help to identify these patients and different groups works in the use of biological marker as determinants of clinical outcome. Bcl2 over-expression has been described in cHL and seems to be an independent marker associated to bad prognosis in probably relation with alterations in apoptosis regulatory molecules.To retrospectively analyze the frequency of Bcl2 protein over-expression in tissue biopsies of patients diagnosed with cHL, which required intensive treatment in our centre.We revised clinical data and samples at diagnosis of patients with cHL who received SCT (aSCT or/and Allo-SCT) due to partial remission, relapse or progression and we determined Bcl2 expression protein by immunohistochemistry. All patients received at least 2 lines of treatment previous to intensive treatment with SCT. We analyzed the expression of Bcl2 according to each patient histology: Nodular Sclerosis (NE), Mixed cellularity (MC), Lymphocyte-rich (LR), and Lymphocyte-depleted (LD).Between September 1997 and May 2010, 39 patients with cHL required intensive treatment in our center: 32 aSCT and 7 Allo-SCT due to partial remission, refractory, relapse or progression after first line of treatment. Average age was 32 years (range: 18–64), males: 25/females 14. The characteristics of patients and remission status at transplant are described in table 1. We had available samples at diagnosis from 31 out of 39 patients (80%): 20 NE, 5 MC, 6 LR and we found over-expression of Bcl2 in 17/20 (85%) NE; 5/5(100%) MC and 2/6 LR (33%).Our results suggest that over-expression of Bcl2 is frequent in patients with cHL which needed intensive treatment after failure of the first line of therapy (particularly with NE and MC). Further studies are needed to confirm the worse prognosis of Bcl2 expression in cHL and if may be useful at diagnosis in association with other clinical parameters to identify patients with poor prognosis.Alo-SCT: Alogeneic stem cell transplant; aSCT: autologous stem cell transplant; CR: Complete Remission; F: female; LD: Lymphocyte-deplete; LR: Lymphocyte rich; M: male; MC: mixed cellularity Md: median; n: number; NE: nodular sclerosis; Nv: negative; P: positive; PR: Parcial remision R: range; RF: refractoryNo relevant conflicts of interest to declare.

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