[Evaluation of the application of hyaluronic acid in postoperative arthroscopy patients with grade II-III gonarthrosis using the WOMAC scale]. / Evaluación en la aplicación de ácido hialurónico en pacientes postoperados de artroscopía con gonartrosis grado II-III mediante la escala de womac.

INTRODUCTION: gonarthrosis is a degenerative disease, whose loss of cartilage causes changes in the adjacent bone and its response produces deformations and attempts at regeneration. In 1934 Meyer and Palmer isolated bovine vitreous humor, a polysaccharide called hyaluronic acid, which has the property of visco-elasticity. Today, multiple procedures performed in orthopedics are known, in order to limit the degenerative process that this entails. OBJECTIVE: to know the use and efficacy of hyaluronic acid in the patient requiring knee arthroscopy, evaluating the evolution of the patient using the WOMAC scale; as well as the ideal time of application of hyaluronic acid in this study group. MATERIAL AND METHODS: clinical, non-randomized, prospective, analytical trial. 48 patients from 45 to 60 years of age, divided into 3 groups with a diagnosis of gonarthrosis grade II-III, who underwent arthroscopy with subsequent hyaluronic acid application, were evaluated; in the postoperative period (group 1), one month after the postoperative period (group 2) and without application (group 3) in a period from September 2015 to June 2016 at the ISSSTE Hospital "Dr. Darío Fernández Fierro". RESULTS: the treatment showed differences in patients regarding reduction of pain and stiffness; and improvement in functional capacity. CONCLUSION: despite, there are no conclusive results if the treatment is better than the other, certain data suggests that using hyaluronic acid in the postoperative improves rigidity and function, however, it was not statistically significant.

INTRODUCCIÓN: la gonartrosis es una enfermedad degenerativa, cuya pérdida de cartílago origina cambios en el hueso adyacente y su respuesta produce deformaciones e intentos de regeneración. En 1934 Meyer y Palmer aislaron el humor vítreo bovino, polisacárido denominado ácido hialurónico, que tiene la propiedad de visco elasticidad. Hoy en día se conocen múltiples procedimientos realizados en ortopedia, con la finalidad de limitar el proceso degenerativo que este conlleva. OBJETIVO: conocer el uso y la eficacia del ácido hialurónico, en el paciente que requiere artroscopía de rodilla, valorando la evolución del paciente mediante escala de WOMAC; así como el tiempo ideal de aplicación del ácido hialurónico en este grupo de estudio. MATERIAL Y MÉTODOS: ensayo clínico, no aleatorizado longitudinal, prospectivo, analítico. Se valoraron 48 pacientes de 45 a 60 años de edad, divididos en tres grupos con diagnóstico de gonartrosis grado II-III, en quienes se realizaron artroscopía con posterior aplicación ácido hialurónico; en el transquirúrgico (grupo 1), al mes del postquirúrgico (grupo 2) y sin aplicación (grupo 3) en un período de Septiembre de 2015 a Junio de 2016 en el Hospital del ISSSTE "Dr. Darío Fernández Fierro". RESULTADOS: el tratamiento mostró diferencias en los pacientes en cuanto a reducción de dolor y rigidez; y mejoría en capacidad funcional. CONCLUSIÓN: a pesar de que no es concluyente si algún tratamiento es mejor que otro, ciertos datos sugieren que el utilizar ácido hialurónico en el transquirúrgico mejora la rigidez y la función, sin embargo, no logró ser estadísticamente significativo.

Non-scarring alopecia of lupus erythematosus: A comprehensive review.

BACKGROUND: Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature. It is considered a nonspecific sign in the current classification of skin lesions of LE. The aim of this study was to give an updated overview of the spectrum of NSA in LE patients, with emphasis on the clinical significance thereof. METHOD: We conducted a review of the English literature using the PubMed-Medline database using the keywords "Alopecia" + "Lupus erythematosus". Publications describing LE patients with NSA were included. RESULTS: Data for 237 patients from 27 publications were analyzed. Ninety-one patients had diffuse NSA, 43 had patchy NSA, 83 had lupus hair, 3 had alopecia of dermal cutaneous LE, and 17 had alopecia of linear and annular lupus panniculitis of the scalp. Patients with diffuse/patchy NSA and lupus hair shared the following features: strong association with systemic activity of LE, subtle clinical/trichoscopic signs of inflammation, histological aspect consistent with lesions specific to cutaneous LE, high likelihood of response to SLE therapy, and absence of progression to scarring alopecia. Association with SLE was rare in patients with dermal cutaneous LE or linear and annular lupus panniculitis of the scalp, and skin-directed therapies were most often effective. One patient of each subtype progressed to scarring alopecia. DISCUSSION: Diffuse/patchy NSA and lupus hair may represent a topographic variation of a single entity specific for LE. Prospective studies are warranted to further document the clinical significance of this manifestation.

A Photoactivated Protein Degrader for Optical Control of Synaptic Function.

Hundreds of proteins determine the function of synapses, and synapses define the neuronal circuits that subserve myriad brain, cognitive, and behavioral functions. It is thus necessary to precisely manipulate specific proteins at specific sub-cellular locations and times to elucidate the roles of particular proteins and synapses in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy to optically degrade specific proteins with high spatial and temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze ubiquitylation and degradation of target proteins through endogenous proteasomes. Here we describe the design and chemical properties of a PHOTAC that targets Ca 2+ /calmodulin-dependent protein kinase II alpha (CaMKIIα), which is abundant and crucial for baseline synaptic function of excitatory neurons. We validate the PHOTAC strategy, showing that the CaMKIIα-PHOTAC is effective in mouse brain tissue. Light activation of CaMKIIα-PHOTAC removed CaMKIIα from regions of the mouse hippocampus only within 25 µm of the illuminated brain surface. The optically-controlled degradation decreases synaptic function within minutes of light activation, measured by the light-initiated attenuation of evoked field excitatory postsynaptic potential (fEPSP) responses to physiological stimulation. The PHOTACs methodology should be broadly applicable to other key proteins implicated in synaptic function, especially for evaluating their precise roles in the maintenance of long-term potentiation and memory within subcellular dendritic domains.

Unraveling the Diagnosis of Kiwifruit Allergy: Usefulness of Current Diagnostic Tests.

OBJECTIVES: To determine the usefulness of the in vitro and in vivo methods used in the diagnosis of kiwifruit allergy and to specifically assess the impact of seed proteins on sensitivity. METHODS: We performed skin prick tests (SPTs) using various commercial extracts, homemade pulp, and seed extracts and prick-prick tests with kiwifruit on 36 allergic patients. The presence of specific IgE (sIgE) was assessed using the ImmunoCAP (kiwifruit extract), ELISA (Act d 1, Act d 2), ISAC, and FABER assays. Immunoblotting of seed extract was carried out, and a single-blind oral food challenge was performed with whole seeds in seed-sensitized individuals. RESULTS: The prick prick test with kiwifruit demonstrated the highest diagnostic capacity (81.8% sensitivity and 94.1% specificity) among the in vivo tests. The sIgE levels measured using ImmunoCAP (kiwifruit extract) showed a similar sensitivity to that of global ISAC and FABER (63.9%, 59.5%, and 58.3%, respectively). Act d 1 was the major allergen. Sensitization to Act d 1 was associated with positive sIgE results to whole kiwifruit extract detected by ImmunoCAP (P<.000). A positive SPT result to kiwifruit seeds was associated with severe symptoms induced by kiwifruit (P=.019) as a marker of advanced disease, but not with clinically relevant sensitization. Challenge testing with kiwifruit seeds performed on 8 seed-sensitized patients yielded negative results. CONCLUSION: Sensitization to Act d 1 is associated with a positive result in conventional diagnostic techniques, whereas kiwifruit seed sensitization does not increase the sensitivity of the diagnostic techniques evaluated.

Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation.

The standard rapid approach for the diagnosis of coronavirus disease 2019 (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The detection of specific anti-SARS-CoV-2 immunoglobulins is crucial for screening people who have been exposed to the virus, whether or not they presented symptoms. Recent publications report different methods for the detection of specific IgGs, IgMs, and IgAs against SARS-CoV-2; these methods mainly detect immunoglobulins in the serum using conventional techniques such as rapid lateral flow tests or enzyme-linked immunosorbent assay (ELISA). In this article, we report the production of recombinant SARS-CoV-2 spike protein and the development of a rapid, reliable, cost-effective test, capable of detecting immunoglobulins in serum and saliva samples. This method is based on interferometric optical detection. The results obtained using this method and those obtained using ELISA were compared. Owing to its low cost and simplicity, this test can be used periodically for the early detection, surveillance, detection of immunity, and control of the spread of COVID-19.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

A new optical interferometric-based in vitro detection system for the specific IgE detection in serum of the main peach allergen.

Food allergens cause worldwide chronic diseases with a great impact on public health. Immunoglobulins E (IgEs) trigger allergic reactions by specifically binding the allergens to which the allergic patients are sensitized. In this scientific work we report for the first time a new optical interferometric in vitro system for the detection of specific IgEs (sIgEs) to the principal peach allergen (Pru p 3) in real serum samples. Interferometric Optical Detection Method (IODM) was employed for reading out the signal of Fabry-Perot based interferometers acting as biotransducers. Pru p 3 was immobilized as bioreceptor onto the sensing surface for detecting the target biomolecules, sIgEs to Pru p 3. Moreover, the demanding low concentration of IgE, compared to other analytes in real serum samples, made it necessary to use nanoparticles (NPs) for two reasons: to collect only the IgEs from the serum sample and to enhance the optical interferometric read-out signal. The methodology was validated in advance by scanning electron microscopy (SEM). Consequently, we report in this article a novel high-performance in vitro detection method to recognize sIgE to molecular allergens by means of silicon dioxide (SiO2) NPs. Finally, this scientific work provides the basis for the in vitro component resolved diagnosis (CRD) of sIgEs to molecular allergens.

The auditory context-dependent attenuation of taste neophobia depends on D1 dopamine receptor activity in mice.

Taste recognition memory in rodents is evident as taste neophobia disappears upon repeated taste exposures without aversive consequences, thus increasing the consumption of familiar edibles. The attenuation of taste neophobia (AN) induced by taste familiarity is auditory context-dependent in mice since neophobia to a familiar taste reappears with a novel auditory background. This effect depends on the integrity of the dorsal hippocampus but the potential role of dopamine has remained unexplored. In order to explore the involvement of dopamine through D1 dopamine receptors in AN, C57BL/6 mice were exposed to a 3% vinegar taste solution for 10 min throughout several consecutive days. An experimentally-controlled auditory background was used to define a context, which could either change or remain constant throughout all the drinking sessions. Systemic administration of the D1 dopamine receptor antagonist SCH-23390 induced a similar effect to that of an auditory context change while it was kept constant and systemic administration of SKF-81297 prevented the contextual modulation of AN when the auditory context changed. Additionally, SCH-23390 injection on the following day to the auditory context change further impaired AN, thus suggesting the relevance of dopamine in the consolidation of the context dependency of taste recognition memory. We conclude that the context dependency of the AN involves dopaminergic activity mediated by D1 receptors which might be responsible for proper acquisition of safe taste recognition memory.

Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy.

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 ± 4.3% and 76.2 ± 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.

Impact of age on the use of adjuvant treatments in patients undergoing surgery for colorectal cancer: patients with stage III colon or stage II/III rectal cancer.

BACKGROUND: Many older patients don't receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer. METHODS: A prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics. RESULTS: In colon cancer 92% of patients aged under 65 years, 77% of those aged 65 to 80 years and 27% of those aged over 80 years received adjuvant chemotherapy (χ2trends < 0.001). In rectal cancer preoperative radiotherapy was used in 68% of patients aged under 65 years, 60% of those aged 65 to 80 years, and 42% of those aged over 80 years (χ2trends < 0.001). Adjusting by comorbidity level, tumour characteristics and socioeconomic level, the odds ratio of use of chemotherapy compared with those under age 65, was 0.3 (0.1-0.6) and 0.04 (0.02-0.09) for those aged 65 to 80 and those aged over 80, respectively; similarly, the odds ratio of use of preoperative radiotherapy was 0.9 (0.6-1.4) and 0.5 (0.3-0.8) compared with those under 65 years of age. CONCLUSIONS: The probability of older patients with colorectal cancer receiving adjuvant chemotherapy and preoperative radiotherapy is lower than that of younger patients; many of them are not receiving the treatments recommended by clinical practice guidelines. Differences in comorbidity, tumour characteristics, curative resection, and socioeconomic factors do not explain this lower probability of treatment. Research is needed to identify the role of physical and cognitive functional status, doctors' attitudes, and preferences of patients and their relatives, in the use of adjuvant therapies.

Differential activity pattern of c-Fos in the nucleus accumbens between adult and aged rats during flavor recognition memory.

Previous studies have addressed the role of the nucleus accumbens core (NAcbC) and shell (NAcbSh) in taste aversion learning and in the processing of taste palatability which is affected by aging. However, little is known about its implication in safe taste memory and the aging impact. To explore the role of the NAcb in flavor neophobia and its attenuation during aging, we applied c-Fos immunohistochemistry as an index of neural activity of the NAcbC and NAcbSh. Twenty one adult (5-month-old) and 24 aged (24-month-old) male Wistar rats were exposed to a 3% cider vinegar solution for 1, 2 or 6 consecutive days (n = 7 adult and n = 8 aged rats per group). Aged rats exhibited slower attenuation of flavor neophobia than adult rats. Adult rats showed increased NAcbSh c-Fos activity on day 2 compared to days 1 and 6, while this increase was delayed to day 6 in aged rats. There were no differences in the number of NAcbC c-Fos positive cells. This suggests that changes in the activity of neural circuits of palatability processing during normal aging could contribute to the slower attenuation of flavor neophobia in aged rats.

Flavor recognition memory related activity of the posterior piriform cortex in adult and aged rats.

The relationship between the piriform cortex and flavor recognition memory was investigated in adult and aged rats. By using c-Fos immunohistochemistry, we assessed the piriform cortex activity induced by flavor familiarity. The results indicated increased activity in the rostral region of the posterior piriform cortex elicited by the most familiar cider vinegar solution after six exposures. Aged rats exhibited overall increased activity in the posterior, but not the anterior piriform cortex, which was not related to flavor familiarity. This suggests that the posterior piriform cortex is related to flavor recognition memory and that aging modifies its activity pattern which might underlie their slower attenuation of flavor neophobia.

Dorsal hippocampal damage disrupts the auditory context-dependent attenuation of taste neophobia in mice.

Rodents exhibit neophobia for novel tastes, demonstrated by an initial reluctance to drink novel-tasting, potentially-aversive solutions. Taste neophobia attenuates across days if the solution is not aversive, demonstrated by increased consumption as the solution becomes familiar. This attenuation of taste neophobia is context dependent, which has been demonstrated by maintained reluctance to drink the novel tasting solution if the subject has to drink it after being brought to a novel environment. This spatial context-dependent attenuation of taste neophobia has been described and likely depends on the integrity of the dorsal hippocampus because this brain area is crucial for representing space and spatial context associations, but is unnecessary for processing taste memories per se. Whether changing the non-spatial auditory context causes a similar effect on attenuation of taste neophobia and the potential role of the dorsal hippocampus in processing this decidedly non-spatial information has not been determined. Here we demonstrate that changing the non-spatial auditory context affects the attenuation of taste neophobia in mice, and investigate the consequence of hippocampal lesion. The results demonstrate that the non-spatial auditory context-dependent attenuation of taste neophobia in mice is lost following NMDA excitotoxic lesions of the CA1 region of the dorsal hippocampus. These findings demonstrate that the dorsal hippocampus is crucial for the modulation non-associative taste learning by auditory context, neither of which provide information about space.

Electrohysterography in the diagnosis of preterm birth: a review.

Preterm birth (PTB) is one of the most common and serious complications in pregnancy. About 15 million preterm neonates are born every year, with ratios of 10-15% of total births. In industrialized countries, preterm delivery is responsible for 70% of mortality and 75% of morbidity in the neonatal period. Diagnostic means for its timely risk assessment are lacking and the underlying physiological mechanisms are unclear. Surface recording of the uterine myoelectrical activity (electrohysterogram, EHG) has emerged as a better uterine dynamics monitoring technique than traditional surface pressure recordings and provides information on the condition of uterine muscle in different obstetrical scenarios with emphasis on predicting preterm deliveries. OBJECTIVE: A comprehensive review of the literature was performed on studies related to the use of the electrohysterogram in the PTB context. APPROACH: This review presents and discusses the results according to the different types of parameter (temporal and spectral, non-linear and bivariate) used for EHG characterization. MAIN RESULTS: Electrohysterogram analysis reveals that the uterine electrophysiological changes that precede spontaneous preterm labor are associated with contractions of more intensity, higher frequency content, faster and more organized propagated activity and stronger coupling of different uterine areas. Temporal, spectral, non-linear and bivariate EHG analyses therefore provide useful and complementary information. Classificatory techniques of different types and varying complexity have been developed to diagnose PTB. The information derived from these different types of EHG parameters, either individually or in combination, is able to provide more accurate predictions of PTB than current clinical methods. However, in order to extend EHG to clinical applications, the recording set-up should be simplified, be less intrusive and more robust-and signal analysis should be automated without requiring much supervision and yield physiologically interpretable results. SIGNIFICANCE: This review provides a general background to PTB and describes how EHG can be used to better understand its underlying physiological mechanisms and improve its prediction. The findings will help future research workers to decide the most appropriate EHG features to be used in their analyses and facilitate future clinical EHG applications in order to improve PTB prediction.

Profilin, a Change in the Paradigm.

Profilin is a protein that is present in all eukaryotic cells and is responsible for cross-reactivity between pollen, latex, and plant foods. It has been classically acknowledged as a minor or nearly irrelevant allergen, although recent data are changing this conception. The objective of this manuscript is to provide a comprehensive review of published data on the role of this ubiquitous allergen in pollen, latex, and plant food allergy. The patterns of recognition of this minor allergen follow a north-south gradient. Although present in all pollens and vegetables, profilin is significantly associated with allergy to grass pollen and to Cucurbitaceae fruits. Heb v 8, the latex profilin, is usually a marker of profilin allergy in plant food-allergic patients, although it has no clinical relevance in latex allergy. Sensitization to profilin jeopardizes the diagnosis of pollen allergy and selection of immunotherapy, and although component-resolved diagnosis can identify its impact, there are no tailored treatments available. In recent years, several new publications have shown how profilin should be taken into account and, under certain circumstances, considered a marker of severity, an allergen capable of inducing respiratory symptoms, and, in its natural purified form, a potential candidate for etiological treatment of food allergy. Current data on profilin strongly support the need for a shift in the previously accepted paradigm for this allergen. More research should be done to assess the real clinical impact of sensitization in specific populations and to develop therapeutic strategies.