Enhancing Gluten-Free Bread Production: Impact of Hydroxypropyl Methylcellulose, Psyllium Husk Fiber, and Xanthan Gum on Dough Characteristics and Bread Quality.

The demand for gluten-free products has increased due to improved diagnoses and awareness of gluten-related issues. This study investigated the effect of HPMC, psyllium, and xanthan gum in gluten-free bread formulations. Three tests were conducted, varying the amount of these ingredients: in the first formulation, the amount of HPMC was increased to 4.4 g/100 g of flour and starch; in the second, psyllium husk fiber was increased to 13.2 g/100 g of flour and starch; and in the third formulation, xanthan gum was removed. Differences were observed among the formulations: increasing HPMC reduced extrusion force without affecting bread quality; adding psyllium increased dough elasticity but also crumb gumminess and crust hardness. Eliminating xanthan gum altered dough rheology, resulting in a softer and less gummy crumb, and a less reddish color in the final bread.

Thermodynamics of Li+-Crown Ether Interactions in Aqueous Solvent.

Lithium ion-based batteries are ubiquitous in modern technology due to applications in personal electronics and high-capacity storage for electric vehicles. Concerns about lithium supply and battery waste have prompted interest in lithium recycling methods. The crown ether 12-crown-4 has been studied for its abilities to form stable complexes with lithium ions (Li+). In this paper, molecular dynamics simulations are applied to examine the binding properties of a 12-crown-4-Li+ system in aqueous solution. It was found that 12-crown-4 did not form stable complexes with Li+ in aqueous solution due to the binding geometry which was prone to interference by surrounding water molecules. In addition, the binding properties of sodium ions (Na+) to 12-crown-4 are examined for comparison. Subsequently, calculations were performed with the crown ethers 15-crown-5 and 18-crown-6 to study their complexation with Li+ as well as Na+. It was determined that binding was unfavorable for both types of ions for all three crown ethers tested, though 15-crown-5 and 18-crown-6 showed a marginally greater affinity for Li+ than 12-crown-4. Metastable minima present in the potential of mean force for Na+ render binding marginally more likely there. We discuss these results in the context of membrane-based applications of crown ethers for Li+ separations.

Tumor treating fields as novel combination partner in the multimodal treatment of head and neck cancer.

BACKGROUND: We aimed to demonstrate the effects of tumor treating fields (TTFields) in head and neck squamous cell carcinoma (HNSCC) cells when combined with radiotherapy (RT) and chemotherapy. METHODS: Two human HNSCC cell lines (Cal27, FaDu) received five different treatments: TTFields, RT +/- TTFields and RT + simultaneous cisplatin +/- TTFields. Effects were quantified using clonogenic assays and flow cytometric analyses of DAPI, caspase-3 activation and γH2AX foci. RESULTS: Treatment with RT + TTFields decreased the clonogenic survival as strong as treatment with RT + simultaneous cisplatin. The triple combination of RT + simultaneous cisplatin + TTFields even further decreased the clonogenic survival. Accordingly, combination of TTFields with RT or RT + simultaneous cisplatin increased cellular apoptosis and DNA double-strand breaks. CONCLUSION: TTFields therapy seems a promising combination partner in the multimodal treatment of locally advanced HNSCC. It could be used to intensify chemoradiotherapy or as alternative to chemotherapy.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients.

OBJECTIVE: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. METHODS: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. RESULTS: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). CONCLUSION: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Dermatosis más frecuentes en pacientes con trasplante renal.

OBJECTIVE: To determine the most frequent dermatoses in patients with kidney transplant in the dermatology consultation, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, in Mexico City, in the period from March 2016 to March 2020. METHOD: Descriptive, cross-sectional study that included 153 patients with a complete medical history with prior informed consent and authorization from the hospital ethics committee. RESULTS: All patients presented one or more dermatoses. The most frequent were infectious (mycosis, viral) and, in decreasing order, other dermatoses (keratosis pilaris, melasma), tumorous (benign), inflammatory (seborrheic dermatitis, eczema), probably secondary to drugs and autoimmune (alopecia areata). CONCLUSIONS: All kidney transplant patients presented at least one dermatosis, predominantly those of infectious origin. We recommend dermatological evaluation prior to transplantation for timely diagnosis and treatment of dermatoses that could increase the morbi-mortality of patients.

OBJETIVO: Determinar las dermatosis más frecuentes en pacientes con trasplante renal en la consulta de dermatología del Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, en Ciudad de México, en el período de marzo de 2016 a marzo de 2020. MÉTODO: Estudio descriptivo, transversal que incluyó 153 pacientes con historia clínica completa, previo consentimiento informado y autorización del comité de ética del hospital. RESULTADOS: Todos los pacientes presentaron una o más dermatosis. Las más frecuentes fueron las infecciosas (micosis, virales) y, en orden decreciente, otras dermatosis (queratosis pilar, melasma), tumorales (benignas), inflamatorias (dermatitis seborreica, eccemas), probablemente secundarias a fármacos y autoinmunitarias (alopecia areata). CONCLUSIONES: Todos los pacientes receptores de trasplante renal presentaron al menos una dermatosis, predominando las de origen infeccioso. Recomendamos una valoración dermatológica previa al trasplante para el diagnóstico y el tratamiento oportuno de las dermatosis que podrían aumentar la morbimortalidad de los pacientes.

Chlorine Concentration Modelling and Supervision in Water Distribution Systems.

The quality of the drinking water distributed through the networks has become the main concern of most operators. This work focuses on one of the most important variables of the drinking water distribution networks (WDN) that use disinfection, chlorine. This powerful disinfectant must be dosed carefully in order to reduce disinfection byproducts (DBPs). The literature demonstrates researchers' interest in modelling chlorine decay and using several different approaches. Nevertheless, the full-scale application of these models is far from being a reality in the supervision of water distribution networks. This paper combines the use of validated chlorine prediction models with an intensive study of a large amount of data and its influence on the model's parameters. These parameters are estimated and validated using data coming from the Supervisory Control and Data Acquisition (SCADA) software, a full-scale water distribution system, and using off-line analytics. The result is a powerful methodology for calibrating a chlorine decay model on-line which coherently evolves over time along with the significant variables that influence it.

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma.

Radiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs' apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.

[Transplant patient and kidney graft survival in a retrospective cohort in Mexico]. / Supervivencia del paciente trasplantado y del injerto renal en una cohorte retrospectiva en México.

Background: Knowledge of the functionality of the graft and patient survival is essential to assess the success of kidney transplantation. Objective: To determine the survival of transplanted patients by type of donor and the functionality of kidney grafts in a cohort in Mexico. Material and methods: Kidney transplant cohort from 2013 to 2017 in Mexico. 790 patients followed up for one year were analyzed to assess the survival of transplanted patients by type of donor and the functionality of kidney grafts. For this, measures of central tendency and dispersion were used, as well as Kaplan-Meier survival tables with SPSS, version 25. Results: Out of the 790 patients, 518 were from living donors (65.56%) with patient survival of 97.88% and graft function of 93.24% at 12 months of follow-up; 272 patients received the graft from a deceased donor with patient survival of 91.18% and renal graft function of 84.19%. Conclusions: There is still a difference of almost 5% in the survival of the recipient patient from a living donor compared to a deceased donor. For the functionality of the kidney graft, this difference is > 7%. Cadaveric donation has increased; however, even at low figures is of approximately 35% in Mexico.

Introducción: el conocimiento de la funcionalidad del injerto y la supervivencia del paciente es fundamental para valorar el éxito del trasplante renal. Objetivo: determinar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales en una cohorte en México. Material y métodos: cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 790 pacientes seguidos por un año para valorar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales. Para ello se usaron medidas de tendencia central y dispersión, así como tablas de supervivencia de Kaplan-Meier con SPSS, versión 25. Resultados: de los 790 pacientes, 518 fueron de donante vivo (65.56%) con supervivencia del paciente de 97.88% y de funcionalidad del injerto de 93.24% a 12 meses de seguimiento; 272 pacientes recibieron el injerto de donante fallecido con supervivencia del paciente de 91.18% y funcionalidad del injerto renal de 84.19%. Conclusiones: aún existe una diferencia de casi 5% en la supervivencia del paciente receptor de un donante vivo en referencia con un donante fallecido. Para la funcionalidad del injerto renal esta diferencia es > 7%. La donación cadavérica ha aumentado; sin embargo, incluso en cifras bajas es de aproximadamente el 35% en México.

Radiotherapy orchestrates natural killer cell dependent antitumor immune responses through CXCL8.

Radiotherapy is a mainstay cancer therapy whose antitumor effects partially depend on T cell responses. However, the role of Natural Killer (NK) cells in radiotherapy remains unclear. Here, using a reverse translational approach, we show a central role of NK cells in the radiation-induced immune response involving a CXCL8/IL-8-dependent mechanism. In a randomized controlled pancreatic cancer trial, CXCL8 increased under radiotherapy, and NK cell positively correlated with prolonged overall survival. Accordingly, NK cells preferentially infiltrated irradiated pancreatic tumors and exhibited CD56dim-like cytotoxic transcriptomic states. In experimental models, NF-κB and mTOR orchestrated radiation-induced CXCL8 secretion from tumor cells with senescence features causing directional migration of CD56dim NK cells, thus linking senescence-associated CXCL8 release to innate immune surveillance of human tumors. Moreover, combined high-dose radiotherapy and adoptive NK cell transfer improved tumor control over monotherapies in xenografted mice, suggesting NK cells combined with radiotherapy as a rational cancer treatment strategy.

Kidney graft functionality 1 year after kidney transplantation.

OBJECTIVE: To determine the evolution, associated factors and the outcomes of transplanted people one year after the evolution of a cohort in Mexico. METHOD: Kidney transplant cohort from 2013 to 2017 in Mexico. 1118 patients were analyzed. Five outcomes were studied: overall survival, kidney graft, patient survival, delayed function, and acute dysfunction. Kaplan-Meier was used for kidney graft survival. For risk, bivariate and multivariate analyzes were performed with a significant value of p < 0.05. RESULTS: Of the 1118 kidney transplant patients, 57 (5.09%) had kidney graft loss, 52 (4.65%) died during the one-year follow-up; survival of the patient of 95.35% and of the graft 90.25%. CONCLUSIONS: The risk factors for the outcomes were transplantation from a deceased donor, recipient over 50 years of age and use of polyclonal agents. Infections and age are related to the death of the patient.

OBJETIVO: Determinar la funcionalidad del injerto renal a 1 año en una cohorte retrospectiva en México. MÉTODO: Cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 1118 pacientes. Se estudiaron cinco desenlaces: supervivencia global, supervivencia del injerto renal, supervivencia del paciente, función retardada y disfunción aguda. Para la supervivencia del injerto renal se usó Kaplan-Meier. Para el riesgo se realizó análisis bivariado y multivariado con valor significativo p < 0.05. RESULTADOS: De los 1118 pacientes con trasplante renal, 57 (5.09%) tuvieron pérdida del injerto, 52 (4.65 %) fallecieron durante el año de seguimiento; la supervivencia del paciente fue del 95.35% y la supervivencia del injerto fue del 90.25%. CONCLUSIONES: Los factores de riesgo para los desenlaces fueron trasplante de donante fallecido, receptor mayor de 50 años y uso de agentes policlonales. Las infecciones y la edad están relacionadas con la muerte del paciente.

Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case-control study.

BACKGROUND: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk. This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. METHODS: A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were non-smokers diagnosed with LC, and controls were composed of never-smoking individuals undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. RESULTS: The study included 457 cases (42%) and 631 controls (58%), with a predominance of women (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. CONCLUSIONS: No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk.

Human mesenchymal stromal cells maintain their stem cell traits after high-LET particle irradiation - Potential implications for particle radiotherapy and manned space missions.

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton (1H), helium (4He), carbon (12C) and oxygen (16O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using γH2AX immunofluorescence and Western blots. Relative biological effectiveness values of MSCs amounted to 1.0-1.1 for 1H, 1.7-2.3 for 4He, 2.9-3.4 for 12C and 2.6-3.3 for 16O. Particle radiation did not alter the MSCs' characteristic surface marker pattern, and MSCs maintained their multi-lineage differentiation capabilities. Apoptosis rates ranged low for all radiation modalities. At 24 h after irradiation, particle radiation-induced ATM and CHK2 phosphorylation as well as γH2AX foci numbers returned to baseline levels. The resistance of human MSCs to high-LET irradiation suggests that MSCs remain functional after exposure to moderate doses of particle radiation as seen in normal tissues after particle radiotherapy or during manned space flights. In the future, in vivo models focusing on long-term consequences of particle irradiation on the bone marrow niche and MSCs are needed.

Supervivencia del paciente trasplantado y del injerto renal en una cohorte retrospectiva en México / Transplant patient and kidney graft survival in a retrospective cohort in Mexico

Introducción: el conocimiento de la funcionalidad del injerto y la supervivencia del paciente es fundamental para valorar el éxito del trasplante renal. Objetivo: determinar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales en una cohorte en México. Material y métodos: cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 790 pacientes seguidos por un año para valorar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales. Para ello se usaron medidas de tendencia central y dispersión, así como tablas de supervivencia de Kaplan-Meier con SPSS, versión 25. Resultados: de los 790 pacientes, 518 fueron de donante vivo (65.56%) con supervivencia del paciente de 97.88% y de funcionalidad del injerto de 93.24% a 12 meses de seguimiento; 272 pacientes recibieron el injerto de donante fallecido con supervivencia del paciente de 91.18% y funcionalidad del injerto renal de 84.19%. Conclusiones: aún existe una diferencia de casi 5% en la supervivencia del paciente receptor de un donante vivo en referencia con un donante fallecido. Para la funcionalidad del injerto renal esta diferencia es > 7%. La donación cadavérica ha aumentado; sin embargo, incluso en cifras bajas es de aproximadamente el 35% en México

Background: Knowledge of the functionality of the graft and patient survival is essential to assess the success of kidney transplantation. Objective: To determine the survival of transplanted patients by type of donor and the functionality of kidney grafts in a cohort in Mexico. Material and methods: Kidney transplant cohort from 2013 to 2017 in Mexico. 790 patients followed up for one year were analyzed to assess the survival of transplanted patients by type of donor and the functionality of kidney grafts. For this, measures of central tendency and dispersion were used, as well as Kaplan-Meier survival tables with SPSS, version 25. Results: Out of the 790 patients, 518 were from living donors (65.56%) with patient survival of 97.88% and graft function of 93.24% at 12 months of follow-up; 272 patients received the graft from a deceased donor with patient survival of 91.18% and renal graft function of 84.19%. Conclusions: There is still a difference of almost 5% in the survival of the recipient patient from a living donor compared to a deceased donor. For the functionality of the kidney graft, this difference is > 7%. Cadaveric donation has increased; however, even at low figures is of approximately 35% in Mexico

Novel infection of pericytes by Andes virus enhances endothelial cell permeability.

Andes Virus (ANDV) non-lytically infects pulmonary microvascular endothelial cells (PMECs) causing a severe capillary leak syndrome termed Hantavirus Pulmonary Syndrome (HPS). Basolaterally, PMECs are in contact with pericytes which play critical roles in regulating PMEC permeability and immune cell recruitment. We discovered that ANDV persistently infects primary human vascular pericytes for up to 9 days, and that PMEC monolayer permeability was increased by supernatants from ANDV-infected pericytes. Pericyte-directed PMEC permeability was consistent with the high-level secretion of the permeability factor VEGF (vascular endothelial growth factor) elicited by ANDV-infected pericytes. These findings suggest that ANDV infection of pericytes augments PMEC permeability and reveal a novel mechanism of pericyte-directed vascular barrier dysfunction that contributes to HPS and provides new therapeutic targets.

Risk factors for mortality of adult patients with COVID-19 hospitalised in an emerging country: a cohort study.

OBJECTIVE: To describe mortality of in-hospital patients with COVID-19 and compare risk factors between survivors and non-survivors. DESIGN: Prospective cohort of adult inpatients. SETTING: Tertiary healthcare teaching hospital in Guadalajara, Mexico. PARTICIPANTS: All patients with confirmed COVID-19 hospitalised from 25 March to 7 September 2020 were included. End of study: 7 November 2020. PRIMARY OUTCOME MEASURES: Patient survival analysed by the Kaplan-Meier method and comparison of factors by the log-rank test. Mortality risk factors analysed by multivariate Cox's proportional-hazard model. RESULTS: One thousand ten patients included: 386 (38%) died, 618 (61%) alive at discharge and six (0.6%) remained hospitalised. There was predominance of men (63%) and high frequency of overweight-obesity (71%); hypertension (54%); diabetes (40%); and lung (9%), cardiovascular (8%) and kidney diseases (11%); all of them significantly more frequent in non-survivors. Overweight-obesity was not different between groups, but severity of disease (Manchester Triage System and quick Sequential Organ Failure Assessment) was significantly worse in non-survivors, who were also significantly older (65 vs 45 years, respectively) and had haematological, biochemical, coagulation and inflammatory biomarkers more altered than survivors. Mortality predictors were invasive mechanical ventilation (IMV; OR 3.31, p<0.0001), admission to intensive care unit (ICU; OR 2.18, p<0.0001), age (OR 1.02, p<0.0001), Manchester Triage System (urgent OR 1.44, p=0.02; immediate/very urgent OR 2.02, p=0.004), baseline C reactive protein (CRP; OR 1.002, p=0.009) and antecedent of kidney disease (OR 1.58, p=0.04) CONCLUSIONS: Mortality in hospitalised patients with COVID-19 in this emerging country centre seemed to be higher than in developed countries. Patients displayed a high frequency of risk factors for poor outcome, but the need for IMV, ICU admission, older age, more severe disease at admission, antecedent of kidney disease and higher CRP levels significantly predicted mortality.

Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency.

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.

Alpha-1 antitrypsin deficiency and risk of lung cancer: A systematic review.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is an inherited genetic disorder associated with a risk of developing lung and liver disease. Several studies have examined its possible association with an increased risk of lung cancer. MATERIALS AND METHODS: Systematic review of the scientific literature on studies analyzing the risk of LC associated with AATD, as well as its impact on the histological type and survival. The information was located in the Medline (PubMed), Cochrane, and EMBASE databases. RESULTS: Six studies including a total of 4 038 patients with LC met the inclusion criteria. Most studies included seem to indicate that AATD increases the risk of developing LC, particularly of the squamous and adenocarcinoma types. This risk increases with exposure to tobacco smoke and the diagnosis of chronic obstructive pulmonary disease (COPD). Only one study analyzed the survival of LC patients without finding differences between AATD and non-AATD patients. CONCLUSIONS: These results suggest that AATD may increase the risk of developing LC, particularly of the squamous and adenocarcinoma histological types, but no impact on patient survival has been demonstrated. However, the low quality of the included studies makes it necessary to carry out more studies with a larger sample size and preferably of a prospective nature to confirm these results.

Lung emphysema and lung cancer: what do we know about it?

Emphysema and lung cancer (LC) are two diseases which share common risk factors, e.g., smoking. In recent years, many studies have sought to analyse this association. By way of illustration, we conducted a review of the scientific literature of the studies published to date, whose main designated aim was to demonstrate the relationship between emphysema and LC, and this association's influence on the histology, prognosis and molecular mechanisms responsible. We included over 40 studies (ranging from case-control and cohort studies to systematic reviews and meta-analyses), which highlight the association between emphysema and LC, independently of smoking habit. These studies also report a possible influence on histology, with adenocarcinoma being the most frequent lineage, and an association with poor prognosis, which affects both survival and post-operative complications. Oxidative stress, which generates chronic inflammatory status as well as the presence of certain polymorphisms in various genes (CYP1A1, TERT, CLPTM1L, ERK), gives rise-in the case of patients with emphysema-to alteration of cellular repair mechanisms, which in turn favours the proliferation of neoplastic epithelial cells responsible for the origin of LC.

STAT3 imparts BRCAness by impairing homologous recombination repair in Epstein-Barr virus-transformed B lymphocytes.

Epstein-Barr virus (EBV) causes lymphomas and epithelial cell cancers. Though generally silent in B lymphocytes, this widely prevalent virus can cause endemic Burkitt lymphoma and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. By learning how EBV breaches barriers to cell proliferation, we hope to undermine those strategies to treat EBV lymphomas and potentially other cancers. We had previously found that EBV, through activation of cellular STAT3 prevents phosphorylation of Chk1, and thereby, suppresses activation of the intra-S phase cell-cycle checkpoint, a potent barrier to oncogene-driven proliferation. This observation prompted us to examine the consequences on DNA repair since homologous recombination repair, the most error-free form, requires phosphoChk1. We now report that the defect in Chk1 phosphorylation also curtails RAD51 nucleation, and thereby, homologous recombination repair of DNA double strand breaks. The resulting reliance on error-prone microhomology-mediated end-joining (MMEJ) repair makes EBV-transformed cells susceptible to PARP inhibition and simultaneous accrual of genome-wide deletions and insertions resulting from synthesis-dependent MMEJ. Analysis of transcriptomic and drug susceptibility data from hundreds of cancer lines reveals a STAT3-dependent gene-set predictive of susceptibility of cancers to synthetic lethal PARP inhibition. These findings i) demonstrate how the tumor virus EBV re-shapes cellular DNA repair, ii) provide the first genome-wide evidence for insertions resulting from MMEJ in human cells, and iii) expand the range of cancers (EBV-related and -unrelated) that are likely to respond to synthetic lethal inhibitors given the high prevalence of cancers with constitutively active STAT3.