Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Efficacy of Co-Medications in Patients with Alcoholic Liver Disease.

BACKGROUND: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. METHODS: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the "The Observational Health Data Sciences and Informatics consortium," an open-source, multi-stakeholder, and interdisciplinary collaborative effort. RESULTS: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. ß-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups. CONCLUSION: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and ß-blockers on ALD patient's survival. However, gender and ethnic background lead to diverse efficacy in those patients.

Interactions of circadian clock genes with the hallmarks of cancer.

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets.

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.

Characteristics and outcome of patients with small bowel adenocarcinoma (SBA).

BACKGROUND: Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS: To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS: We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION: SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy.

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual's circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer. Nowadays, there is an increasing interest in understanding how circadian rhythms could be used in the treatment of cancer. Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits and minimize possible adverse effects. Clinical trials so far have confirmed that optimal timing of treatment with chemo or immunotherapies could decrease drug toxicity and increase efficacy. Instead, chronoradiotherapy seems to minimize treatment-related symptoms rather than tumor progression or patient survival. In addition, potential therapeutic targets within the molecular clock have also been identified. Therefore, results of the application of chronotherapy in cancer therapy until now are challenging, feasible, and could be applied to clinical practice to improve cancer treatment without additional costs. However, different limitations and variables such as age, sex, or chronotypes, among others, should be overcome before chronotherapy can really be put into clinical practice.

A high-resolution binocular video-oculography system: assessment of pupillary light reflex and detection of an early incomplete blink and an upward eye movement.

BACKGROUND: The pupillary light reflex characterizes the direct and consensual response of the eye to the perceived brightness of a stimulus. It has been used as indicator of both neurological and optic nerve pathologies. As with other eye reflexes, this reflex constitutes an almost instantaneous movement and is linked to activation of the same midbrain area. The latency of the pupillary light reflex is around 200 ms, although the literature also indicates that the fastest eye reflexes last 20 ms. Therefore, a system with sufficiently high spatial and temporal resolutions is required for accurate assessment. In this study, we analyzed the pupillary light reflex to determine whether any small discrepancy exists between the direct and consensual responses, and to ascertain whether any other eye reflex occurs before the pupillary light reflex. METHODS: We constructed a binocular video-oculography system two high-speed cameras that simultaneously focused on both eyes. This was then employed to assess the direct and consensual responses of each eye using our own algorithm based on Circular Hough Transform to detect and track the pupil. Time parameters describing the pupillary light reflex were obtained from the radius time-variation. Eight healthy subjects (4 women, 4 men, aged 24-45) participated in this experiment. RESULTS: Our system, which has a resolution of 15 microns and 4 ms, obtained time parameters describing the pupillary light reflex that were similar to those reported in previous studies, with no significant differences between direct and consensual reflexes. Moreover, it revealed an incomplete reflex blink and an upward eye movement at around 100 ms that may correspond to Bell's phenomenon. CONCLUSIONS: Direct and consensual pupillary responses do not any significant temporal differences. The system and method described here could prove useful for further assessment of pupillary and blink reflexes. The resolution obtained revealed the existence reported here of an early incomplete blink and an upward eye movement.

Vibration frequency measurement using a local multithreshold technique.

In this paper, we demonstrate the use of a video camera for measuring the frequency of small-amplitude vibration movements. The method is based on image acquisition and multilevel thresholding and it only requires a video camera with high enough acquisition rate, not being necessary the use of targets or auxiliary laser beams. Our proposal is accurate and robust. We demonstrate the technique with a pocket camera recording low-resolution videos with AVI-JPEG compression and measuring different objects that vibrate in parallel or perpendicular direction to the optical sensor. Despite the low resolution and the noise, we are able to measure the main vibration modes of a tuning fork, a loudspeaker and a bridge. Results are successfully compared with design parameters and measurements with alternative devices.

Open-access operating algorithms for commercial videokeratographer and improvement of corneal sampling.

We present an algorithm to process images of reflected Placido rings captured by a commercial videokeratoscope. Raw data are obtained with no Cartesian-to-polar-coordinate conversion, thus avoiding interpolation and associated numerical artifacts. The method provides a characteristic equation for the device and is able to process around 6 times more corneal data than the commercial software. Our proposal allows complete control over the whole process from the capture of corneal images until the computation of curvature radii.

Measurement of wide frequency range structural microvibrations with a pocket digital camera and sub-pixel techniques.

Analysis of vibrations and displacements is a hot topic in structural engineering. Although there is a wide variety of methods for vibration analysis, direct measurement of displacements in the mid and high frequency range is not well solved and accurate devices tend to be very expensive. Low-cost systems can be achieved by applying adequate image processing algorithms. In this paper, we propose the use of a commercial pocket digital camera, which is able to register more than 420 frames per second (fps) at low resolution, for accurate measuring of small vibrations and displacements. The method is based on tracking elliptical targets with sub-pixel accuracy. Our proposal is demonstrated at a 10 m distance with a spatial resolution of 0.15 mm. A practical application over a simple structure is given, and the main parameters of an attenuated movement of a steel column after an impulsive impact are determined with a spatial accuracy of 4 µm.

Doppler fetal y desprendimiento prematuro de placenta / Doppler changes in a pregnancy with abruptio placentae. Case report

Presentamos un caso de desprendimiento prematuro de placenta en semana 34 en un feto pequeño para la edad gestacional. Los estudios Doppler en las arterias umbilical y cerebral media fueron normales. Se quiere destacar la normalidad de estos parámetros de Doppler en esta situación de compromiso vital para el feto. En casos de desprendimiento prematuro de placenta, el Doppler puede ser normal y hay que valorar los hallazgos ecográficos y el resto de las pruebas de bienestar fetal en conjunto. El interés del caso radica en la escasez de descripciones de cambios Doppler asociados al desprendimiento prematuro de placenta. En nuestra opinión, el Doppler fetal no fue útil en el manejo clínico del desprendimiento prematuro de placenta (AU)

We report a pregnancy with a small for gestational age fetus at 34 weeks plus abruptio placentae. The results of Doppler study in the umbilical and middle cerebral artery were normal. We stress that even when the results of Doppler examination are normal, abruptio placentae still poses a risk of fetal anoxia. We suggest that when abruptio placentae is suspected, all tests of fetal well-being, as well as Doppler examination, should be taken into account in order to make an appropriate clinical decision. The interest of this case lies in the scarcity of descriptions of fetal Doppler changes in pregnancies with abruptio placentae. In our opinion, Doppler examination is of no value in decision making in pregnancies with abruptio placentae (AU)

Disminución de respuesta relajante de la vena umbilical de recien nacidos de pacientes preeclampticas al sulfato de magnesio / Relaxant response diminution of umbilical vein in newborn from pre-eclamptic patients to magnesium sulfate

La preeclampsia constituye una fuerte carga de morbi-mortalidad materno-infantil en nuestro medio. Se sabe que la causa del desarrollo de la preeclampsia es una disminución de la irrigación útero placentaria, y que ésta es proporcional a la severidad de la preeclampsia. Recientemente se ha evidenciado la participación del magnesio en la fisiopatología de esta enfermedad, observando que, además de su efecto vasodilatador directo, éste promueve la liberación de prostaglandinas vasodilatadoras desde el endotelio de las venas umbilicales y disminuye el efecto vasopresor de sustancias endógenas; estos efectos son menores en productos de madres preeclámpticas. En el presente estudio se tomaron 24 pacientes con embarazo a término, 12 con preeclampsia y 12 normales; se determinaron los niveles séricos de magnesio antes de la administración de cualquier medicamento; tanto de las madres como de sus productos. Se tomó además una porción de cordon umbilical para evaluar la respuesta vasomotora IN VITRO de la vena umbilical a dosis crecientes de sulfato de magnesio. No se encontro diferencia significativa entre los niveles de magnesio serico de ambos pares de grupo; recien nacidos entre si y maternos entre si. Se observo una respuesta relajante de la vena umbilical de recien nacidos de madres preeclámpticas significativamente menor al administrar sulfato de magnesio. Es posible que la reactividad constrictiva de las venas umbilicales de recién nacidos de preeclámpticos juegue un papel importante en la fisiopatología de esta enfermedad

Potencial farmacológico del magnesio en la crisis asmática: estudio clínico y experimental

El asma es un trastorno caracterizado por una hiperreactividad no específica que causa broncoespasmo en respuesta a una variedad de estímulos. El aumento de la entrada de calcio al interior de la célula es la vía final comúm de la contracción del músculo liso vascular y bronquial; en este sentido los antagonistas del calcio ejercen una protección significativa contra la broncoconstricción. El magnesio es un antagonista débil de la entrada de calcio a las células del músculo liso, e inhibe la liberación de actilcolina, disminuyendo así el efecto broncoconstrictor de este neurotransmisor. En el presente estudio se abarcan dos aspectos: uno clínico y otro experimental. El el primero se toman 42 pacientes, 21 con crisis asmática y 21 voluntarios sanos sin antecedentes asmáticos, con fines de medir los niveles séricos de magnesio en ambas condiciones. Se encontraron niveles séricos de Mgññ disminuidos en los pacientes con crisis asmáticas, 1.52 ñ 0.36 mEq/L(X=DS); en los voluntarios sanos fue de 1.88 ñ 0.49 mEq/L(P=0.011). En el aspecto experimental se determinó in vitro el efecto relajante de concentraciones crecientes y acumulativas de sulfato de magnesio en cadenas de anillos traqueales de cabayos previamente contraídas con acetilcolina. Se obtuvieron respuestas relajantes dosis-dependientes, alcanzándose un promedio máxiom de relajación de 275.5%. Estos hallazgos denotan la posible relación del ión magnesio en la fisiopatología del asma y el efecto relajante que éste ejerce en la musculatura traqueal