Finding Well-Coupled Optical Fiber Locations for Railway Monitoring Using Distributed Acoustic Sensing.

Distributed acoustic sensors (DAS) utilize optical fibers to monitor vibrations across thousands of independent locations. However, the measured acoustic waveforms experience significant variations along the sensing fiber. These differences primarily arise from changes in coupling between the fiber and its surrounding medium as well as acoustic interferences. Here, a correlation-based method is proposed to automatically find the spatial locations of DAS where temporal waveforms are repeatable. Signal repeatability is directly associated with spatial monitoring locations with both good coupling and low acoustic interference. The DAS interrogator employed is connected to an over 30-year-old optical fiber installed alongside a railway track. Thus, the optical fiber exhibits large coupling changes and different installation types along its path. The results indicate that spatial monitoring locations with good temporal waveform repeatability can be automatically discriminated using the proposed method. The correlation between the temporal waveforms acquired at locations selected by the algorithm proved to be very high considering measurements taken for three days, the first two on consecutive days and the third one a month after the first measurement.

Proliferation in the developing intestine is regulated by the endosomal protein Endotubin.

During postnatal intestinal development, the intestinal epithelium is highly proliferative, and this proliferation is regulated by signaling in the intervillous and crypt regions. This signaling is primarily mediated by Wnt, and requires membrane trafficking. However, the mechanisms by which membrane trafficking regulates signaling during this developmental phase are largely unknown. Endotubin (EDTB, MAMDC4) is an endosomal protein that is highly expressed in the apical endocytic complex (AEC) of villus enterocytes during fetal and postnatal development, and knockout of EDTB results in defective formation of the AEC and giant lysosome. Further, knockout of EDTB in cell lines results in decreased proliferation. However, the role of EDTB in proliferation during the development of the intestine is unknown. Using Villin-CreERT2 in EDTBfl/fl mice, we deleted EDTB in the intestine in the early postnatal period, or in enteroids in vitro after isolation of intervillous cells. Loss of EDTB results in decreased proliferation in the developing intestinal epithelium and decreased ability to form enteroids. EDTB is present in cells that contain the stem cell markers LGR5 and OLFM4, indicating that it is expressed in the proliferative compartment. Further, using immunoblot analysis and TCF/LEF-GFP mice as a reporter of Wnt activity, we find that knockout of EDTB results in decreased Wnt signaling. Our results show that EDTB is essential for normal proliferation during the early stages of intestinal development and suggest that this effect is through modulation of Wnt signaling.

Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment.

More than 50 million people have various forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer's, Parkinson's, and cerebrovascular diseases as well as stroke. Often these conditions coexist and exacerbate one another. The damaged area in post-stroke dementia may lead to neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is implicated in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of cognitive impairment. Dysbiosis may result from obesity; metabolic disorders, cardiovascular disease, and sleep disorders, Lack of physical activity is associated with dysbiosis as well. These may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, it has been reported that several metabolites produced by gut microbiota (e.g., trimethylamine/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids) may be linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier, and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes in combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. This promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that creates new possibilities of pharmacological treatments of many clinical conditions. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.

Design, assembly and validation of a low-cost, high-fidelity simulator for heart exploration.

INTRODUCTION: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. OBJECTIVE: To develop and validate a low-cost, high-fidelity simulator for heart exploration. METHODS: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. RESULTS: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. CONCLUSIONS: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

INTRODUCCIÓN: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. OBJETIVO: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. MÉTODOS: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. RESULTADOS: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. CONCLUSIONES: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells.

Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.

Curcumin: a phytochemical modulator of estrogens and androgens in tumors of the reproductive system.

Curcumin (Cur) is an active derivative extracted from turmeric which exerts a wide range of interactions with biomolecules through complex signaling pathways. Cur has been extensively shown to possess potential antitumor properties. In addition, there is growing body of evidence suggesting that Cur may exert potential anti-estrogen and anti-androgen activity. In vitro and in vivo studies suggest that anticancer properties of Cur against tumors affecting the reproductive system in females and males may be underlied by the Cur-mediated inhibition of androgen and estrogen signaling pathways. In this review we examine various studies assessing the crosstalk between Cur and both androgen and estrogen hormonal activity. Also, we discuss the potential chemopreventive and antitumor role of Cur in the most prevalent cancers affecting the reproductive system in females and males.

Nutritional status of children with cerebral palsy attending rehabilitation centers.

AIM: To describe the nutritional status of children with cerebral palsy (CP) from rehabilitation and therapeutic centers in Argentina, and to analyze their risk of undernutrition based on their Gross Motor Function Classification System (GMFCS) level. METHOD: This was a cross-sectional study with data collected from 321 children (196 males, 125 females) with CP age 2 to 19 years (mean age 9y 3mo, SD 4y 5mo) from 17 rehabilitation and therapeutic centers in five Argentine provinces. Nutritional status was defined by height, weight, and body mass index for age z-scores using World Health Organization growth charts. Odds ratios were used to evaluate the association between GMFCS level and nutritional status. RESULTS: Of the children with CP studied, 52.4% were in GMFCS levels IV and V. Regarding the nutritional status, 41.7% were normal, 19.0% had moderate undernutrition, 33.9% severe undernutrition, 2.5% overweight, and 2.8% obese. When compared to those in GMFCS levels I to III, the odds of children in GMFCS levels IV and V having moderate undernutrition are four times greater and the odds of having severe undernutrition are 14 times greater. INTERPRETATION: There is a high prevalence of undernutrition associated with CP (GMFCS levels IV and V) among children in rehabilitation and therapeutic centers in Argentina. Risk of severe undernutrition increases with increased motor compromises.

The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer.

BACKGROUND: Sleep disorders have emerged as potential cancer risk factors. OBJECTIVE: This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer. RESULTS: Sleep disorders result in abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which is frequently experienced by obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation. DISCUSSION: During short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer was observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated. CONCLUSION: Several factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions.

Novel coronavirus, novel faculty development programs: rapid transition to eLearning during the pandemic.

The novel coronavirus disease 2019 (COVID-19) has caused a rapid and massive transition to online education. We describe the response of our Office of Faculty Development at Texas Tech University Health Sciences Center El Paso (TTUHSC EP) to this unprecedented challenge during and after this post-pandemic crisis. The initiatives for emergency transition to eLearning and faculty development described in this paper may serve as a model for other academic health centers, schools, colleges and universities.

Can miRNAs Be Considered as Diagnostic and Therapeutic Molecules in Ischemic Stroke Pathogenesis?-Current Status.

Ischemic stroke is one of the leading causes of death worldwide. Clinical manifestations of stroke are long-lasting and causing economic burden on the patients and society. Current therapeutic modalities to treat ischemic stroke (IS) are unsatisfactory due to the intricate pathophysiology and poor functional recovery of brain cellular compartment. MicroRNAs (miRNA) are endogenously expressed small non-coding RNA molecules, which can act as translation inhibitors and play a pivotal role in the pathophysiology associated with IS. Moreover, miRNAs may be used as potential diagnostic and therapeutic tools in clinical practice; yet, the complete role of miRNAs is enigmatic during IS. In this review, we explored the role of miRNAs in the regulation of stroke risk factors viz., arterial hypertension, metabolic disorders, and atherosclerosis. Furthermore, the role of miRNAs were reviewed during IS pathogenesis accompanied by excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis, neurogenesis, and Alzheimer's disease. The functional role of miRNAs is a double-edged sword effect in cerebral ischemia as they could modulate pathological mechanisms associated with risk factors of IS. miRNAs pertaining to IS pathogenesis could be potential biomarkers for stroke; they could help researchers to identify a particular stroke type and enable medical professionals to evaluate the severity of brain injury. Thus, ascertaining the role of miRNAs may be useful in deciphering their diagnostic role consequently it is plausible to envisage a suitable therapeutic modality against IS.

Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics.

Parkinson's disease (PD) is the second most frequent age-related neurodegenerative disorder. Sex is an important factor in the development of PD, as reflected by the fact that it is more common in men than in women by an approximate ratio of 2:1. Our hypothesis is that differences in PD among men and women are highly determined by sex-dependent differences in the nigrostriatal dopaminergic system, which arise from environmental, hormonal and genetic influences. Sex hormones, specifically estrogens, influence PD pathogenesis and might play an important role in PD differences between men and women. The objective of this review was to discuss the PD physiopathology and point out sex differences in nigrostriatal degeneration, symptoms, genetics, responsiveness to treatments and biochemical and molecular mechanisms among patients suffering from this disease. Finally, we discuss the role estrogens may have on PD sex differences.

Cardiovascular recurrence of high-grade osteosarcoma presenting as atrial thrombosis and pulmonary embolism: A case report and review of the pediatric literature.

In the era of neoadjuvant and adjuvant chemotherapy, extrapulmonary involvement by high-grade osteosarcoma (HGOS) is rare. Importantly however, HGOS metastasis in the form of cardiovascular tumor thrombus portends a dismal prognosis. Thus, prompt and accurate identification of tumor thrombus is crucial. We report here two unique cases of recurrent HGOS, presenting as thrombotic events, in order to increase awareness and index of suspicion among practitioners regarding this presentation. Additionally, we review 14 previously reported pediatric cases of cardiovascular metastatic HGOS.

Application of Acyzol in the Context of Zinc Deficiency and Perspectives.

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.

The photographic atlas of Spanish food consistency: a new tool for the treatment of dysphagia.

INTRODUCTION: dysphagia requires texture-modified foods and thickened liquids, which is difficult to explain to patients and caregivers. METHODS: an atlas has been developed and validated to explain the consistencies using the Likert scale questionnaire and the Delphi survey. The agreement and reliability of the tool were evaluated, with a minimum of 80%. The atlas was developed in Spanish. RESULTS: an agreement of 93.3% (95% CI: 63.7-100%) was obtained during the evaluation and a value of 97.5% and a Kappa index of 0.96 (95% CI: 0.93-0.99; p = 0.016] were obtained during the validation processes. CONCLUSION: the atlas is a new valid tool that can be used by health professionals.

Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees.

We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.

BLINDNESS RELATED TO PRESUMED RETINAL TOXICITY AFTER USING PERFLUOROCARBON LIQUID DURING VITREORETINAL SURGERY.

PURPOSE: To describe the presumed retinal toxicity after using specific batches of perfluorocarbon liquid ALA OCTA (Alamedics, Dornstadt, Germany) in pars plana vitrectomy. METHODS: This is an observational retrospective consecutive case series analyses of patients operated on pars plana vitrectomy for retinal detachment or intraocular lens subluxation, using the 150141 or 200114 batches of perfluorocarbon liquid ALA OCTA as assistance during the surgery in a single center. Patients were included in this report if they manifested retinal toxicity signs throughout the follow-up, such as retinal and retinal pigment epithelium atrophy, disk paleness, and intensive macular fibrosis. Spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) and Ultra-Wide Field 200° retinal camera (Optos P200Tx; Optos, Scotland, United Kingdom) images, electrophysiological tests, and visual fields were performed to analyze the retinal structure and functionality. RESULTS: Seven of 80 patients showed all the described signs of toxicity, after a mean follow-up of 34.29 days (range: 10-87) since surgery. Four patients needed a second pars plana vitrectomy because of tractional retinal detachment and proliferative vitreoretinopathy, and two of them underwent a third surgery because of redetachment. All patients experienced amaurosis or central scotoma, with a final best-corrected visual acuity ranging from 20/200 to light perception. CONCLUSION: Presumed toxic batches of perfluorocarbon liquid may cause massive retinal toxicity. A rapid suspicion, a correct traceability of surgical products, and informing health authorities are fundamental to prevent further cases of toxicity.

An International Survey of Corticosteroid Use for the Management of Low Cardiac Output Syndrome.

OBJECTIVE: Limited evidence exists on use of corticosteroids in low cardiac output syndrome following cardiac surgery. We sought to determine physicians' practices and beliefs with regard to corticosteroids therapy for low cardiac output syndrome. DESIGN: Multinational internet-based survey. SETTING: Pediatric Cardiac Intensive Care Society member database. SUBJECTS: Pediatric cardiac intensive care physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We received 188 responses from 85 centers throughout the world including 57 U.S. congenital heart centers, eight Canadian centers, and 20 international centers. The majority of respondents (51%) reported performing at least 200 bypass cases per year and had separate dedicated cardiac ICUs (57%). Most physicians (89%) rarely or never prescribe corticosteroids for mild low cardiac output syndrome (single vasoactive agent and mildly decreased perfusion), whereas 94% of those surveyed sometimes or always administer corticosteroids to patients with severe low cardiac output syndrome (two or more vasoactive agents and persistent hypotension). Hydrocortisone was the most commonly used corticosteroids (88%), but there was no consensus on dosage used. There was a variable approach to cortisol level measurement and cortisol stimulation testing to inform therapy with corticosteroids. A majority of respondents (75%) stated that they would be willing to randomize patients with severe low cardiac output syndrome into a trial of corticosteroids efficacy. CONCLUSIONS: Our survey demonstrates considerable practice variability with regard to the type of patients in whom corticosteroids are administered, adrenal axis testing is performed, and dosage of hydrocortisone used. The majority of physicians, however, stated their willingness to randomize patients with severe low cardiac output syndrome in a corticosteroids trial. This survey identified multiple areas for future research on use of corticosteroids for low cardiac output syndrome.

Sodium thiosulphate attenuates brain inflammation induced by systemic lipopolysaccharide administration in C57BL/6J mice.

It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration. STS reduced brain levels of pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), ionized calcium binding adaptor molecule 1 (Iba-1) and 18 kDa translocator protein (TSPO) in an animal model of systemic LPS-induced neuroinflammation. In addition, we demonstrated for the first time elevated TSPO expression in retinal ganglion cells layer after peripheral LPS challenge and inhibition of ocular TSPO expression after treatment with STS. We think that STS may be used as an adjuvant anti-inflammatory therapy for many pathological conditions associated with inflammation in the brain.

A genome-wide quantitative trait locus (QTL) linkage scan of NEO personality factors in Latino families segregating bipolar disorder.

Personality traits have been suggested as potential endophenotypes for Bipolar Disorder (BP), as they can be quantitatively measured and show correlations with BP. The present study utilized data from 2,745 individuals from 686 extended pedigrees originally ascertained for having multiplex cases of BP (963 cases of BPI or schizoaffective BP). Subjects were assessed with the NEO Personality Inventory, Revised (NEO PI-R) and genotyped using the Illumina HumanLinkage-24 Bead Chip, with an average genetic coverage of 0.67 cM. Two point linkage scores were calculated for each trait as a quantitative variable using SOLAR (Sequential Oligogenic Linkage Analysis Routines). Suggestive evidence for linkage was found for neuroticism at 1q32.1 (LOD = 2.52), 6q23.3 (2.32), 16p12 (2.79), extraversion at 4p15.3 (2.33), agreeableness at 4q31.1 (2.37), 5q34 (2.80), 7q31.1 (2.56), 16q22 (2.52), and conscientiousness at 4q31.1 (2.50). Each of the above traits have been shown to be correlated with the broad BP phenotype in this same sample. In addition, for the trait of openness, we found significant evidence of linkage to chromosome 3p24.3 (rs336610, LOD = 4.75) and suggestive evidence at 1q43 (2.74), 5q35.1 (3.03), 11q14.3 (2.61), 11q21 (2.30), and 19q13.1 (2.52). These findings support previous linkage findings of the openness trait to chromosome 19q13 and the agreeableness trait to 4q31 and identify a number of new loci for personality endophenotypes related to bipolar disorder.