Transmission dynamics and baseline epidemiological parameter estimates of Coronavirus disease 2019 pre-vaccination: Davao City, Philippines.

The Coronavirus disease 2019 (COVID-19) has exposed many systemic vulnerabilities in many countries' health system, disaster preparedness, and adequate response capabilities. With the early lack of data and information about the virus and the many differing local-specific factors contributing to its transmission, managing its spread had been challenging. The current work presents a modified Susceptible-Exposed-Infectious-Recovered compartmental model incorporating intervention protocols during different community quarantine periods. The COVID-19 reported cases before the vaccine rollout in Davao City, Philippines, are utilized to obtain baseline values for key epidemiologic model parameters. The probable secondary infections (i.e., time-varying reproduction number) among other epidemiological indicators were computed. Results show that the cases in Davao City were driven by the transmission rates, positivity proportion, latency period, and the number of severely symptomatic patients. This paper provides qualitative insights into the transmission dynamics of COVID-19 along with the government's implemented intervention protocols. Furthermore, this modeling framework could be used for decision support, policy making, and system development for the current and future pandemics.

Toward an optimal contraception dosing strategy.

Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation. The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous estrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. Finally, we show that by combining estrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.

A Model-Based Strategy on COVID-19 Vaccine Roll-out in the Philippines

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. Millions of people have fallen sick, and some have died due to this affliction that has spread across the globe. The current pandemic has disrupted normal day-to-day human life, causing a profound social and economic burden. Vaccination is an important control measure that could significantly reduce the incidence of cases and mortality if properly and efficiently distributed. In this work, an age-structured model of COVID-19 transmission, incorporating an unreported infectious compartment, is developed. Three age groups are considered, namely: young (0-19 years), adult (20-64 years), and elderly (65+ years). The transmission and reporting rates are determined for each group by utilizing the number of COVID-19 cases in the National Capital Region in the Philippines. Optimal control theory is employed to identify the best vaccine allocation to different age groups. Further, three different vaccination periods are considered to reflect phases of vaccination priority groups: the first, second, and third account for the inoculation of the elderly, adult and elderly, and all three age groups, respectively. This study could guide in making informed decisions in mitigating a population-structured disease transmission under limited resources.

Reasons for hospitalization and in-hospital mortality for anti-neutrophil cytoplasmic antibody vasculitides: analysis of the National Inpatient Sample.

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a heterogeneous group of conditions resulting in frequent hospitalizations and high in-hospital mortality (IHM). Our study aimed to use the National Inpatient Sample (NIS) to determine and categorize the main reasons for hospital admission and IHM in patients with AAV. METHODS: We performed a retrospective study of adult AAV hospitalizations in 2016, 2017, and 2018 in acute care hospitals across the USA conducted using the NIS database. We classified the main reasons for hospital admission and IHM into 19 different categories using the principal International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) diagnosis. RESULTS: A total of 41,155 hospitalizations had either a principal or secondary ICD-10 code for AAV (GPA or MPA). Rheumatologic and respiratory diagnoses were the most common reasons for hospitalization, while infectious and respiratory diagnoses were the most common reasons for IHM. Sepsis, unspecified organism A41.9, was the most common specific principal diagnosis for hospitalized and deceased AAV patients. CONCLUSIONS: Our results show that the leading reasons for hospitalization and mortality for AAV patients were rheumatologic, respiratory, and infectious diagnoses. This data suggests that careful monitoring and management of infectious and pulmonary complications in AAV may improve hospital outcomes. Key points • AAV is a heterogeneous group of conditions resulting in frequent hospitalizations and high IHM. In our study, AAV hospitalizations ended in IHM 4.5% of the time, substantially greater than non-ANCA patients. • The leading reasons for hospital admission for AAV patients were rheumatologic and respiratory diagnoses, but the main reason for IHM were infectious and respiratory diagnoses. • Sepsis was the most common principal diagnosis for hospitalized and deceased AAV patients. • Our results highlight the importance of close monitoring and timely management of infectious and respiratory complications to improve hospitalization outcomes.

Conducta fumadora en estudiantes de kinesiología y su asociación con actitudes y conocimientos sobre tabaquismo: estudio de corte transversal / Smoking behavior in Chilean physical therapist students and their association with attitudes and knowledge on cigarette smoking: a cross sectional study

INTRODUCCIÓN: El tabaquismo continúa siendo un problema sanitario en población universitaria y profesionales de la salud. Los kinesiólogos participan en la implementación de programas orientados a la prevención y cese del tabaquismo en la comunidad. El objetivo de este estudio fue explorar la prevalencia de tabaquismo y actitudes sobre consumo de tabaco en estudiantes de kinesiología. MÉTODOS: Estudio de corte transversal realizado en estudiantes de Kinesiología de Concepción (Chile), durante los años 2017 y 2018. Se determinó la conducta y actitudes sobre tabaquismo. Mediante regresión logística se determinó la asociación entre la conducta fumadora y las actitudes sobre tabaquismo. Se consideró un valor de p < 0,05 como estadísticamente significativo. RESULTADOS: Se contestaron 554 cuestionarios. El 57,8% de los estudiantes encuestados declaró no haber fumado nunca, 13 % no haber fumado los últimos 6 meses y 29,4% declaró ser fumador actual. Por su parte, el 99,5% expresó algún grado de acuerdo con que fumar es perjudicial para la salud, lo cual se relacionó con la conducta fumadora (p < 0,0002). En relación a actitudes sobre tabaquismo, comparado a los no fumadores, los fumadores actuales presentan mayor probabilidad de mostrar desacuerdo o indiferencia respecto a actitudes positivas sobre tabaquismo. Principalmente en aquellas acciones que restringen su consumo, venta y divulgación (OR ponderado = 2,43; 95%IC 2,02 - 2,92). CONCLUSIONES: La prevalencia de tabaquismo en estudiantes de Kinesiología de Concepción es del 29,2%. Los estudiantes fumadores expresan una menor aprobación relacionada a intervenciones, actitudes y consecuencias del tabaquismo para la salud comparada con los no fumadores.

INTRODUCTION: Notwithstanding control policies, smoking continues to be a health problem in university students and health professionals, who are responsible for implementing programs oriented to prevention and cessation of smoking in the community. The objective of this study was to explore the prevalence of smoking and attitudes about smoking in physical therapy students. METHODS: Cross-sectional study carried out in students of physical therapy from three universities of Concepción city (Chile), during the years 2017 and 2018. Behavior and attitudes about smoking were evaluated. Association between smoking behavior and attitudes about smoking was determined by logistic regression. A p value < 0.05 was considered statistically significant. RESULTS: 554 questionnaires were answered. 57.8% of respondents had never smoked, 13.0% had not smoked in the last 6 months and 29.4% were current smokers. Moreover 99.5% of respondents stated some degree of agreement that smoking is harmful to health, which was related to smoking behavior (p < 0.0002). In relation to attitudes about smoking, compared to non-smokers, current smokers have a greater chance of showing disagreement or indifference regarding positive attitudes about smoking. Mainly in those actions that restrict tobacco consumption, sale and disclosure (weighted OR = 2.43, 95% CI 2.02 - 2.92). CONCLUSIONS: The prevalence of current smoking in physical therapy students from Concepcion city is 29.2%. Smoking students express lower approval related to interventions, attitudes and consequences of smoking for health compared with non-smokers.

Trait mindfulness and the mental and physical health of caregivers for individuals with cancer.

BACKGROUND: Mindfulness plays a role in moderating the negative mental and physical health outcomes associated with caregiving. The aims of this study were to examine the relationship between trait mindfulness and the (1) psychological functioning, (2) health behaviors, (3) and physical health of caregivers for individuals diagnosed with cancer. METHODS: Caregivers completed a battery of questionnaires and examinations assessing sociodemographic characteristics, trait mindfulness, depression, perceived stress, caregiver stress, sleep, diet, physical activity, tobacco use, alcohol use, blood pressure, and BMI. Demographics and cancer diagnostics were collected for the individuals whom caregivers supported. Linear regression, multivariate analyses, and moderator analyses were performed. RESULTS: Of the 78 caregivers, the mean age was 63.9 (S.D.=13.1); 59% identified as female; 97% identified as White. Regression analyses indicated that caregivers who reported higher levels of trait mindfulness reported significantly less perceived stress (b= -4.38, SE= 0.88, p <.001), lower levels of depression (b= -3.74, SE= 1.10, p = .001), greater caregiver quality of life (b= -9.05, SE=2.12, p < .001), better sleep quality (b= -0.98, SE=0.44, p = 0.03), and lower rates of tobacco use (b= -10.12, SE= 3.43, p =.003). Trait mindfulness was not significantly related to diet, alcohol use, blood pressure, or BMI. CONCLUSIONS: Higher levels of trait mindfulness are associated with positive mental and physical health measure for caregivers. Future research would benefit from further examining mindfulness-based interventions and their impacts in mitigating the negative toll of caregiving in the context of cancer.

Polytherapeutic strategies with oncolytic virus-bortezomib and adjuvant NK cells in cancer treatment.

Proteasome inhibition and oncolytic virotherapy are two emerging targeted cancer therapies. Bortezomib, a proteasome inhibitor, disrupts the degradation of proteins in the cell leading to accumulation of unfolded proteins inducing apoptosis. On the other hand, oncolytic virotherapy uses genetically modified oncolytic viruses (OV) to infect cancer cells, induce cell lysis, and activate an antitumour response. In this work, optimal control theory is used to minimize the cancer cell population by identifying strategic infusion protocols of bortezomib, OV and natural killer (NK) cells. Three different therapeutic protocols are explored: (i) periodic bortezomib and single administrations of both OV and NK cells therapy; (ii) alternating sequential combination therapy; and (iii) NK cell depletion and infusion therapy. In the first treatment scheme, early OV administration followed by well-timed adjuvant NK cell infusion maximizes antitumour efficacy. The second strategy supports timely OV infusion. The last treatment scheme indicates that transient NK cell depletion followed by appropriate NK cell adjuvant therapy yields the maximal benefits. Relative doses and administrative costs of the three anticancer agents for each approach are qualitatively presented. This study provides potential polytherapeutic strategies in cancer treatment.

Milk yield and composition and body weight of offsprings of mixed-breed goats on semi-arid rangelands with different rainfall.

The objective was to characterize milk yield and composition from mixed-breed goats kidding in winter and grazing rangelands with 221 (n = 15), 334 (n = 20), or 441 (n = 12) mm of annual rainfall in northern Mexico (22-25°N). Weekly milk yield and composition were recorded and progeny growth performance assessed. Body weight loss during lactation was the highest (6.4 kg) for goats on rangeland with 441 mm of rainfall than goats on 221 mm (1.6 kg), or 334 mm (1.8 kg; P < 0.01). The highest daily milk yield was for goats on 221 mm (498 mL; P < 0.01). There was not an evident peak of lactation and milk yield increased uninterruptedly at the end of lactation. Milk fat was negatively related to milk yield and goats on rangeland with 334 mm had the greatest milk fat content (P < 0.001). Milk protein and lactose content were higher in goats on rangeland with 221 mm (P < 0.01). Goat kids on rangelands with 221 and 441 mm grew faster and were heavier (P < 0.001) at weaning than kids reared in other rangelands. Weaning weight was positively related to milk yield (P < 0.001); but not milk components (P > 0.05). In conclusion, moderate milk yield of mixed-breed goats on rangeland is feasible with parturitions in winter, and milk yield is not affected by reduced annual precipitation in rangelands of northern Mexico. Offspring growth performance depends on maternal milk yield, but not milk composition. Nevertheless, slow growth to weaning of offspring had adverse effects on time to reach adequate market weight.

An Edge-Based Model of SEIR Epidemics on Static Random Networks.

Studies have been done using networks to represent the spread of infectious diseases in populations. For diseases with exposed individuals corresponding to a latent period, an SEIR model is formulated using an edge-based approach described by a probability generating function. The basic reproduction number is computed using the next generation matrix method and the final size of the epidemic is derived analytically. The SEIR model in this study is used to investigate the stochasticity of the SEIR dynamics. The stochastic simulations are performed applying continuous-time Gillespie's algorithm given Poisson and power law with exponential cut-off degree distributions. The resulting predictions of the SEIR model given the initial conditions match well with the stochastic simulations, validating the accuracy of the SEIR model. We varied the contribution of the disease parameters and the average degree of the network in order to investigate their effects on the spread of disease. We verified that the infection and the recovery rates show significant effects on the dynamics of the disease transmission. While the exposed rate delays the spread of the disease, increasing it towards infinity would lead to almost the same dynamics as that of an SIR case. A network with high average degree results to an early and higher peak of the epidemic compared to a network with low average degree. The results in this paper can be used as an alternative way of explaining the spread of disease and it provides implications on the control strategies applied to mitigate the disease transmission.

Country-specific intervention strategies for top three TB burden countries using mathematical model.

Tuberculosis (TB) is one of the top 10 causes of death globally and the leading cause of death by a single infectious pathogen. The World Health Organization (WHO) has declared the End TB Strategy, which targets a 90% reduction in the incidence rate by the year 2035 compared to the level in the year 2015. In this work, a TB model is considered to understand the transmission dynamics in the top three TB burden countries-India, China, and Indonesia. Country-specific epidemiological parameters were identified using data reported by the WHO. If India and Indonesia succeed in enhancing their treatment protocols and increase treatment and treatment success rate to that of China, the incidence rate could be reduced by 65.99% and 68.49%, respectively, by the end of 2035. Evidently, complementary interventions are essential to achieve the WHO target. Our analytical approach utilizes optimal control theory to obtain time-dependent nonpharmaceutical and latent case finding controls. The objective functional of the optimal control problem includes a payoff term reflecting the goal set by WHO. Appropriate combinations of control strategies are investigated. Based on the results, gradual enhancement and continuous implementation of intervention measures are recommended in each country.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Experiencia del Policlínico De Medicina Complementaria Hospital-CRS El Pino, USACH / Experience of the Complementary Medicine Polyclinic Hospital-CRS El Pino, USACH

Durante el año 2013 comienza a funcionar el Policlínico de Medicina Complementaria en el Campus Hospital y CRS El Pino - USACH con la implementación de la terapia de SP.

Statistical mechanics of the self-gravitating gas in the Tsallis framework.

The statistical mechanics of a cloud of particles interacting via their gravitational potentials encounters some issues when the Boltzmann-Gibbs statistics is applied. In this work, we consider the alternative statistical framework of Tsallis and analyze the statistical and thermodynamical implications for a self-gravitating gas, obtaining analytical and convergent expressions for the equation of state and specific heat in the ensembles of constant temperature and constant energy. Although our results are comparable in both ensembles, it turns out that only in the ensemble of constant temperature do the thermodynamic quantities depend explicitly on the Tsallis parameter, indicating that the question of ensemble equivalence for Tsallis statistics must be further reviewed.

Strategies in regulating glioblastoma signaling pathways and anti-invasion therapy.

Glioblastoma multiforme is one of the most invasive type of glial tumors, which rapidly grows and commonly spreads into nearby brain tissue. It is a devastating brain cancer that often results in death within approximately 12 to 15 months after diagnosis. In this work, optimal control theory was applied to regulate intracellular signaling pathways of miR-451-AMPK-mTOR-cell cycle dynamics via glucose and drug intravenous administration infusions. Glucose level is controlled to activate miR-451 in the up-stream pathway of the model. A potential drug blocking the inhibitory pathway of mTOR by AMPK complex is incorporated to explore regulation of the down-stream pathway to the cell cycle. Both miR-451 and mTOR levels are up-regulated inducing cell proliferation and reducing invasion in the neighboring tissues. Concomitant and alternating glucose and drug infusions are explored under various circumstances to predict best clinical outcomes with least administration costs.

Outbreak of Systemic Avian Pox in Canaries (Serinus canaria domestica) Associated with the B1 Subgroup of Avian Pox Viruses.

This study reports an outbreak of avian pox in a quarantine of canaries imported from Europe, with a mortality of 30% and clinical signs of dyspnea and blepharoconjunctivitis. During necropsy, beak cyanosis, serous blepharitis, caseous sinusitis, oropharyngitis, tracheitis, pulmonary edema, pneumonia, fibrinous airsacculitis, and splenomegaly were observed. Microscopically, edema, epithelial hyperplasia, hydropic degeneration, and vacuolated eosinophilic intracytoplasmic inclusion bodies were found; similar lesions were observed in the thymus, spleen, and other organs. The virus was isolated in chicken embryos, and it was identified and characterized using a sequence of 913 nucleotides of the DNA polymerase gene. Pathologic characteristics and molecular biology indicate the systemic presence of avian pox associated with an avipoxvirus of the B1 subgroup. Additionally, other lesions associated with Aspergillus sp., Macrorhabdus ornithogaster, and Isospora sp. were found, which could contribute to the high mortality. Canarypox virus should be considered a differential diagnosis in cases of dyspnea and high mortality in canary flocks.

Reporte de caso- Brote de viruela aviar sistémica en canarios (Serinus canaria domestica) asociado con el virus de la viruela aviar subgrupo B1. En este estudio se reporta un brote de viruela aviar en unos canarios importados de Europa que estaban bajo cuarentena, con una mortalidad del 30% y signos clínicos de disnea y blefaroconjuntivitis. Durante la necropsia, se observó cianosis de pico, blefaritis serosa, sinusitis caseosa, orofaringitis, traqueítis, edema pulmonar, neumonía, fibrinosa respiratoria y esplenomegalia. Microscópicamente, se encontró edema, hiperplasia epitelial, degeneración hidrópica y cuerpos de inclusión intracitoplásmicos eosinófilos vacuolados; Se observaron lesiones similares en el timo, el bazo y otros órganos. El virus se aisló en embriones de pollo, se identificó y caracterizó analizando una secuencia de 913 nucleótidos del gene de la polimerasa de ADN. Las características patológicas y la biología molecular indican la presentación sistémica de la viruela aviar asociada a un avipoxvirus del subgrupo B1. Además, se encontraron otras lesiones asociadas con Aspergillus sp., Macrorhabdus ornithogaster y Isopora sp., lo que pudo contribuir a la alta mortalidad. El virus de la viruela del canario debe considerarse un diagnóstico diferencial en casos de disnea y alta mortalidad en parvadas de canarios.

Dengue in the Philippines: model and analysis of parameters affecting transmission.

Dengue is endemic in the Philippines and poses a substantial economic burden in the country. In this work, a compartmentalized model which includes healthcare-seeking class is developed. The reproduction number is determined to investigate critical parameters influencing transmission. Partial rank correlation coefficient (PRCC) technique is performed to address how the model output is affected by changes in a specific parameter disregarding the uncertainty over the rest of the parameters. Results show that mosquito biting rate, transmission probability from mosquito to human, respectively, from human to mosquito, and fraction of individuals who seek healthcare at the onset of the disease, posted high PRCC values. In order to obtain the values for the desired parameters, the reported dengue cases by morbidity week in the Philippines for the year 2014 and 2015 are used. The reliability of parameters is then verified via parametric bootstrap.

Porfiria eritropoyética congénita: reporte de un caso y recomendaciones de manejo / Congenital erythropoietic porphyria: case report and management recommendations

La porfiria eritropoyética congènita es una porfiria cutánea no aguda, extremadamente poco frecuente, autosómica recesiva, producida por la deficiencia de la enzima uroporfirinógeno III sintetasa codificada en el gen UROS, en el cromosoma 10q26.2. Esto genera el depósito y la acumulación de porfirinas en las córneas, los huesos y los dientes. Se presenta desde los primeros meses de vida con intensa fotosensibilidad, que se manifiesta con fragilidad cutánea con formación de vesículas, bulas y costras. El curso grave lleva a la mutilación de tejidos acrales, compromiso ocular, anemia hemolítica e hiperesplenismo. El manejo es complejo, basado, sobre todo, en la fotoprotección. Un correcto diagnóstico y enfrentamiento puede mejorar notablemente la calidad y expectativas de vida de estos pacientes. Se presenta el caso de un lactante con porfiria eritropoyética congénita confirmada con el estudio genético.

Congenital erythropoietic porphyria is an extremely rare, autosomal recessive, non-acute cutaneous porphyria, caused by uroporphyrinogen III synthase deficiency, codificated by UROS gene on the chromosome 10q26.2. Porphyrins deposit in cornea, bones and teeth. The first symptoms could be manifested in early childhood, with skin fragility, vesicles and bullae. Severe course produces acral tissues mutilation, eye involvement, hemolytic anemia and hypersplenism. The treatment is complex and it is based in the photoprotection. A correct diagnosis can significantly improve the quality and life expectancy of these patients. We present the case of a child with congenital erythropoietic porphyria confirmed by genetic analysis.

[Congenital erythropoietic porphyria: case report and management recommendations]. / Porfiria eritropoyética congénita: reporte de un caso y recomendaciones de manejo.

Congenital erythropoietic porphyria is an extremely rare, autosomal recessive, non-acute cutaneous porphyria, caused by uroporphyrinogen III synthase deficiency, codificated by UROS gene on the chromosome 10q26.2. Porphyrins deposit in cornea, bones and teeth. The first symptoms could be manifested in early childhood, with skin fragility, vesicles and bullae. Severe course produces acral tissues mutilation, eye involvement, hemolytic anemia and hypersplenism. The treatment is complex and it is based in the photoprotection. A correct diagnosis can significantly improve the quality and life expectancy of these patients. We present the case of a child with congenital erythropoietic porphyria confirmed by genetic analysis.

La porfiria eritropoyética congènita es una porfiria cutánea no aguda, extremadamente poco frecuente, autosómica recesiva, producida por la deficiencia de la enzima uroporfirinógeno III sintetasa codificada en el gen UROS, en el cromosoma 10q26.2. Esto genera el depósito y la acumulación de porfirinas en las córneas, los huesos y los dientes. Se presenta desde los primeros meses de vida con intensa fotosensibilidad, que se manifiesta con fragilidad cutánea con formación de vesículas, bulas y costras. El curso grave lleva a la mutilación de tejidos acrales, compromiso ocular, anemia hemolítica e hiperesplenismo. El manejo es complejo, basado, sobre todo, en la fotoprotección. Un correcto diagnóstico y enfrentamiento puede mejorar notablemente la calidad y expectativas de vida de estos pacientes. Se presenta el caso de un lactante con porfiria eritropoyética congénita confirmada con el estudio genético.

MeHg affects the activation of FAK, Src, Rac1 and Cdc42, critical proteins for cell movement in PDGF-stimulated SH-SY5Y neuroblastoma cells.

Methylmercury (MeHg) is an environmental neurotoxicant that inhibits neuronal migration. This process requires several cyclic steps involving the formation of membrane protrusions (lamellipodia and filopodia) and focal adhesion turnover. FAK and Src are critical proteins that regulate both processes. The FAK-Src complex promotes the activation of Rac1 and Cdc42, two GTPases involved in the remodeling of the actin cytoskeletal network. Here, we studied the effect of MeHg (1, 10, 100, 500 and 1000nM) on cell migration, the formation of cell protrusions, focal adhesion location and the activation of FAK, Src, Rac1 and Cdc42 using the SH-SY5Y neuroblastoma cell line stimulated with PDGF-BB (PDGF). The data show that MeHg (1-500nM) inhibited PDGF-stimulated cell migration. In PDGF-stimulated cells, MeHg (100-1000nM) decreased protrusions and increased the size of the p-FAKY397 clusters. MeHg also inhibited PDGF-induced FAK and Src activation and, at 100nM, MeHg inhibited the activation of Rac1 and Cdc42. Altogether, the findings show that low concentrations of MeHg inhibit SH-SY5Y cell migration by disrupting the activation and disassembly of FAK. This negatively affects the activation of Src, Rac1 and Cdc42, all of which are critical proteins for the regulation of cell movement. These effects could be related to the MeHg-mediated inhibition of PDGF-induced formation of lamellipodia and filopodia, focal adhesion disassembly and PDGF-induced movement.

Management of breast ductal carcinoma in situ in Catalonia, Spain: Results from the Grup Oncologic Calalà-Occità-Catalonia survey with 9-year follow up.

INTRODUCTION: Reliable data on DCIS incidence and management are not available in many countries. The present study describes the management of DCIS in Catalonia, Spain in the year 2005 and compares these findings to data obtained in France. Local recurrence and late toxicity rates from 2005 through the end of 2014 are reported. MATERIALS AND METHODS: Observational survey of patients with pure DCIS (n = 270) diagnosed during 2005. A written questionnaire, the same as used in the French survey, was completed by 14 doctors at 12 cancer centres in Catalonia, Spain. RESULTS: Median patient age was 55 years (range, 29-89). Diagnosis was mammographic in 225 cases (83.3%). Treatment approaches included: mastectomy (10.4% of cases), breast-conserving surgery (BCS) alone (3.7%), and BCS plus radiotherapy (RT) (85.5%). Sentinel node biopsy and axillary dissection were performed in 27.4% and 5.6% of patients, respectively. Hormonotherapy was prescribed in 45.2% of cases. Tumour nuclear grade was as follows: low (16.7% of cases), intermediate (23%), and high (55.6%). Excision was complete (margins ≥1 mm) in 75% of patients treated with BCS alone vs. 95.7% for BCS+RT. The treatment approach varied widely: mastectomy rates ranged from 7.1% to 26.7% of centres, BCS+RT from 55.5% to 87.8%, and hormonotherapy from 3.3% to 83.3%. At a median follow-up of 102.6 months, 14 patients (5.6%) presented ipsilateral breast tumour recurrence. CONCLUSIONS: These findings on DCIS management in Catalonia are consistent with previous international reports. The inter-centre differences observed are similar to those reported in other international surveys during the same period.