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Circadian fluctuations in physiological setpoints are determined by the suprachiasmatic nucleus (SCN) which exerts control over many target structures within and beyond the hypothalamus via projections. The SCN, or central pacemaker, orchestrates synchrony between the external environment and the internal circadian mechanism. The resulting cycles in hormone levels and autonomic nervous system (ANS) activity provide precise messages to specific organs, adjusting, for example, their sensitivity to approaching hormones or metabolites. The SCN responds to both photic (light) and non-photic input. Circadian patterns are found in both heart rate and blood pressure, which are linked to daily variations in activity and autonomic nervous system activity. Variations in blood pressure are of great interest as several cardiovascular diseases such as stroke, arrhythmias, and hypertension are linked to circadian rhythm dysregulation. The disruption of normal day-night cycles, such as in shift work, social jetlag, or eating outside of normal hours leads to desynchronization of the central and peripheral clocks. This desynchronization leads to disorganization of the cellular processes that are normally driven by the interactions of the SCN and photic input. Here, we review autonomic system function and dysfunction due to regulation and interaction between different cardiorespiratory brain centers and the SCN, as well as social, lifestyle, and external factors that may impact the circadian control of blood pressure.

IntroductionHyperiid amphipods of the genus Themisto are a key polar zooplankton group in terms of biomass and play an important role as prey for higher trophic levels. They are prone to undergo changes in abundance and distribution in the course of the ongoing environmental changes. In the Southern Ocean, Themisto gaudichaudii is predicted to expand its distribution poleward. In the Arctic, the boreal-Atlantic T. abyssorum increases in abundance, resulting in an increased competition with a genuine polar congener. It is not known, however, whether T. gaudichaudii and T. abyssorum have the potential to efficiently adapt to changing water temperatures at their current distribution range or whether they will be shifting their ranges poleward.MethodsWe exposed the two Themisto species from different geographic populations to temperature-change experiments, a cold treatment and a heat-shock treatment. After that, we carried out transcriptome sequencing to compare gene expression patterns in the different treatments and species.ResultsWe show that under similar heat conditions, T. gaudichaudii differentially expressed more genes (26-fold change) than T. abyssorum. Furthermore, we observed qualitative differences between genetic clusters in T. gaudichaudii.DiscussionThe differences observed between genetic clusters in T. gaudichaudii suggest that evolutionary divergence can be linked to changes in the regulatory pathways involved in temperature stress. These could influence the capacity of each genetic cluster to cope differently with temperature changes. In contrast to its congeneric species, T. abyssorum showed a pronounced adaptive flexibility to thermal stress; it appears to have the ability to continue its poleward expansion but may also cope with increasing temperatures in its current environments. Our findings contribute to understand the response of two range-shifting Themisto species to thermal stress in view of the environmental gradients they encounter throughout their current or future distribution ranges.

The growing importance of data analytics is leading to a shift in data management strategy at many companies, moving away from simple data storage towards adopting Online Analytical Processing (OLAP) query analysis. Concurrently, NoSQL databases are gaining ground as the preferred choice for storing and querying analytical data. This article presents a comprehensive, systematic mapping, aiming to consolidate research efforts related to the integration of OLAP with NoSQL databases in Big Data environments. After identifying 1646 initial research studies from scientific digital repositories, a thorough examination of their content resulted in the acceptance of 22 studies. Utilizing the snowballing technique, an additional three studies were selected, culminating in a final corpus of twenty-five relevant articles. This review addresses the growing importance of leveraging NoSQL databases for OLAP query analysis in response to increasing data analytics demands. By identifying the most commonly used NoSQL databases with OLAP, such as column-oriented and document-oriented, prevalent OLAP modeling methods, such as Relational Online Analytical Processing (ROLAP) and Multidimensional Online Analytical Processing (MOLAP), and suggested models for batch and real-time processing, among other results, this research provides a roadmap for organizations navigating the integration of OLAP with NoSQL. Additionally, exploring computational resource requirements and performance benchmarks facilitates informed decision making and promotes advancements in Big Data analytics. The main findings of this review provide valuable insights and updated information regarding the integration of OLAP cubes with NoSQL databases to benefit future research, industry practitioners, and academia alike. This consolidation of research efforts not only promotes innovative solutions but also promises reduced operational costs compared to traditional database systems.

Hemarthrosis secondary to heparin use is a scarce event, especially in patients with no underlying thrombophilia or platelet disorders. Although previously associated with thrombophilia, platelet disorders, or secondary to fibrinolytic therapy, to date, there are very few reported cases in contemporary literature for heparin-induced hemarthrosis. In this article, we report a case of left shoulder joint inferior subluxation secondary to heparin-induced hemarthrosis in an 81-year-old male with an extensive cardiac history and multiple comorbidities. This case report depicts a rare event and discusses its clinical implications aiding healthcare professionals in an early diagnosis and timely management.

Abstract Background The COVID‐19 pandemic has disrupted medical care, increased isolation, and exacerbated anxiety in breast cancer patients. Since March 2020, Breastcancer.org experienced a sustained surge in requested pandemic‐related information and support. To characterize the pandemic‐related experiences of breast cancer patients, we surveyed the Breastcancer.org Community early in the COVID‐19 era. Methods Breastcancer.org Community members were invited to complete an online questionnaire regarding their experience during the pandemic. Self‐reported data on demographics, comorbidities, care disruptions, anxiety, coping ability, telemedicine use, and satisfaction with care were collected. Results were analyzed using Stata 16.0 (Stata Corp., Inc). Results Included were 568 current and previous breast cancer patients, primarily with U.S. residence. Overall, 43.8% reported at least one comorbidity associated with severe COVID‐19 illness and 61.9% experienced care delays. Moderate to extreme anxiety about contracting COVID‐19 was reported by 36.5%, increasing with number of comorbidities (33.0% vs. 55.4%, p = 0.021), current breast cancer diagnosis (30.4% vs. 42.5%, p = 0.011), and poorer coping ability (15.5% vs. 53.9%, p

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the landscape for the treatment of hematological malignancies, solid tumors, and, recently, autoimmune disorders. The BTK receptor is expressed in several hematopoietic cells such as macrophages, neutrophils, mast cells, and osteoclasts. Similarly, the BTK receptor is involved in signaling pathways such as chemokine receptor signaling, Toll-like receptor signaling, and Fc receptor signaling. Due to their unique mechanism, these agents provide a diverse utility in a variety of disease states not limited to the field of malignant hematology and are generally well-tolerated.

Traumatic knee dislocation represents a rare event, contributing to less than 0.02 % of all orthopedic trauma and 0.05 % of joint dislocations, respectively. It is critically important to recognize, identify, and appropriately manage such cases as ‘time’ is implicated as an outcome-determining factor. Thus, such cases warrant quick consideration and appropriate management to mitigate the possibility of neurovascular damage and long-term sequelae. We report a case of a 59-year-old man struck by a motor vehicle in a remote rural community in northern Mexico managed with external fixation 16 h after the initial trauma, and later resulting in a supracondylar amputation. The authors of this case report underline the importance of timely intervention strategies when faced with such cases of knee dislocation and promote enhanced training of peripheral trauma-care providers to help improve patient outcomes.

High blood pressure, also known as hypertension, is a major risk factor for cardiovascular disease. Salt intake has been shown to have a significant impact on BP, but the mechanisms by which it influences the blood pressure dipping pattern, and 24-h blood pressure remains controversial. This literature review aims to both summarize the current evidence on high salt diet induced hypertension and discuss the epidemiological aspects including socioeconomic issues in the United States and abroad. Our review indicates that a high salt diet is associated with a blunted nocturnal blood pressure dipping pattern, which is characterized by a reduced decrease in blood pressure during the nighttime hours. The mechanisms by which high salt intake affects blood pressure dipping patterns are not fully understood, but it is suggested that it may be related to changes in the sympathetic nervous system. Further, we looked at the association between major blood pressure and circadian rhythm regulatory centers in the brain, including the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN) and nucleus tractus solitarius (nTS). We also discuss the underlying social and economic issues in the United States and around the world. In conclusion, the evidence suggests that a high salt diet is associated with a blunted, non-dipping, or reverse dipping blood pressure pattern, which has been shown to increase the risk of cardiovascular disease. Further research is needed to better understand the underlying mechanisms by which high salt intake influences changes within the central nervous system.

Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding.

Abstract The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.

The brainstem nucleus tractus solitarii (nTS) processes and modulates the afferent arc of critical peripheral cardiorespiratory reflexes. Sensory afferents release glutamate to initiate the central component of these reflexes, and glutamate concentration is critically controlled by its removal via astrocytic neurotransmitter transporters. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nTS providing tonic and phasic modulation of neuronal activity. GABA is removed from the extracellular space through GABA transporters (GATs), however, the role of GATs in nTS synaptic transmission and their influence on cardiorespiratory function is unknown. We hypothesized that GATs tonically restrain nTS inhibitory signaling and given the considerable nTS GABA-glutamate cross-talk, modify excitatory signaling and thus cardiorespiratory function. Reverse transcription real-time polymerase chain reaction (RT-PCR), immunoblot and immunohistochemistry showed expression of GAT-1 and GAT-3 mRNA and protein within the rat nTS, with GAT-3 greater than GAT-1, and GAT-3 colocalizing with astrocyte S100B. Recordings in rat nTS slices demonstrated GAT-3 block decreased spontaneous inhibitory postsynaptic current (IPSC) frequency and reduced IPSC amplitude evoked from electrical stimulation of the medial nTS. Block of GAT-3 also increased spontaneous excitatory postsynaptic current (EPSC) frequency yet did not alter sensory afferent-evoked EPSC amplitude. Block of GAT-3 in the nTS of anesthetized rats increased mean arterial pressure, heart rate, sympathetic nerve activity, and minute phrenic nerve activity. These results demonstrate inhibitory and excitatory neurotransmission in the nTS is significantly modulated by endogenous GAT-3 to influence basal cardiorespiratory function.

Remdesivir is a leading therapy in patients with moderate to severe coronavirus 2 (SARS-CoV-2) infection; the majority of whom are older individuals. Remdesivir is a nucleoside analog that incorporates into nascent viral RNA, inhibiting RNA-directed RNA polymerases, including that of SARS-CoV-2. Less is known about remdesivir's effects on mitochondria, particularly in older adults where mitochondria are known to be dysfunctional. Furthermore, its effect on age-induced mitochondrial mutations and copy number has not been previously studied. We hypothesized that remdesivir adversely affects mtDNA copy number and deletion mutation frequency in aged rodents. To test this hypothesis, 30-month-old male F333BNF1 rats were treated with remdesivir for three months. To determine if remdesivir adversely affects mtDNA, we measured copy number and mtDNA deletion frequency in rat hearts, kidneys, and skeletal muscles using digital PCR. We found no effects from three months of remdesivir treatment on mtDNA copy number or deletion mutation frequency in 33-month-old rats. These data support the notion that remdesivir does not compromise mtDNA quality or quantity at old age in mammals. Future work should focus on examining additional tissues such as brain and liver, and extend testing to human clinical samples.

In telecommunications, Performance Management (PM) data are collected from network elements to a centralized system, the Network Management System (NMS), which acts as a business intelligence tool specialized in monitoring and reporting network performance. Performance Management files contain the metrics and named counters used to quantify the performance of the network. Current NMS implementations have limitations in scalability and support for volume, variety, and velocity of the collected PM data, especially for 5G and 6G mobile network technologies. To overcome these limitations, we proposed a Big Data framework based on an analysis of the following components: software architecture, ingestion, data lake, processing, reporting, and deployment. Our work analyzed the PM files' format on a real data set from four different vendors and 2G, 3G, 4G, and 5G technologies. Then, we experimentally assessed our proposed framework's feasibility through a case study involving 5G PM files. Test results of the ingestion and reporting components are presented, identifying the hardware and software required to support up to one billion counters per hour. This proposal can help telecommunications operators to have a reference Big Data framework to face the current and future challenges in the NMS, for instance, the support of data analytics in addition to the well-known services.

The eXtensible Markup Language (XML) files are widely used by the industry due to their flexibility in representing numerous kinds of data. Multiple applications such as financial records, social networks, and mobile networks use complex XML schemas with nested types, contents, and/or extension bases on existing complex elements or large real-world files. A great number of these files are generated each day and this has influenced the development of Big Data tools for their parsing and reporting, such as Apache Hive and Apache Spark. For these reasons, multiple studies have proposed new techniques and evaluated the processing of XML files with Big Data systems. However, a more usual approach in such works involves the simplest XML schemas, even though, real data sets are composed of complex schemas. Therefore, to shed light on complex XML schema processing for real-life applications with Big Data tools, we present an approach that combines three techniques. This comprises three main methods for parsing XML files: cataloging, deserialization, and positional explode. For cataloging, the elements of the XML schema are mapped into root, arrays, structures, values, and attributes. Based on these elements, the deserialization and positional explode are straightforwardly implemented. To demonstrate the validity of our proposal, we develop a case study by implementing a test environment to illustrate the methods using real data sets provided from performance management of two mobile network vendors. Our main results state the validity of the proposed method for different versions of Apache Hive and Apache Spark, obtain the query execution times for Apache Hive internal and external tables and Apache Spark data frames, and compare the query performance in Apache Hive with that of Apache Spark. Another contribution made is a case study in which a novel solution is proposed for data analysis in the performance management systems of mobile networks.

This article describes researches regarding Big Data integration in e‑government decision‑making, for instance, in areas like solar energy provisioning, environmental protection, agricultural and natural resources exploitation, health and social care, education, housing and transportation management, among others. These studies refer to regions that have integrated Big Data in e‑government, where South America is still in the early adoption stages. Hence, this study proposes three steppingstones for Big Data integration in e‑government decision‑making, production, management and application. The proposed framework aims to be a reference in South America for Big Data adoption in e‑government and thus help to mitigate the technology delay regarding other regions. Finally, a case study with open data obtained from the Instituto Nacional de Estadística y Censos of Ecuador (Ecuadorian Statistics and Census Agency) is presented.

Chronic wasting disease (CWD) is a contagious, fatal, neurodegenerative prion disease of cervids. The expanding geographical range and rising prevalence of CWD are increasing the risk of pathogen transfer and spillover of CWD to non-cervid sympatric species. As beavers have close contact with environmental and food sources of CWD infectivity, we hypothesized that they may be susceptible to CWD prions. We evaluated the susceptibility of beavers to prion diseases by challenging transgenic mice expressing beaver prion protein (tgBeaver) with five strains of CWD, four isolates of rodent-adapted prions and one strain of Creutzfeldt–Jakob disease. All CWD strains transmitted to the tgBeaver mice, with attack rates highest from moose CWD and the 116AG and H95+ strains of deer CWD. Mouse-, rat-, and especially hamster-adapted prions were also transmitted with complete attack rates and short incubation periods. We conclude that the beaver prion protein is an excellent substrate for sustaining prion replication and that beavers are at risk for CWD pathogen transfer and spillover.

Introduction: Glutamate (Glu) is the primary excitatory amino acid neurotransmitter released from visceral afferents in the nTS. Glu binds to postsynaptic ionotropic glutamate receptors (iGluRs, AMPA or NMDA) to induce rapid phasic synaptic currents and depolarization. Glu also binds to metabotropic glutamate receptors (mGluRs), including postsynaptic Grp I receptors to induce a slower depolarization, or alternatively presynaptic Grp II or III receptors to limit terminal activity and attenuate release of Glu via autoreceptor mechanisms. The timing and effect of iGluR and/or mGluR activation is guided not only by the concentration and spatial distribution of these receptors in the synaptic and extrasynaptic space, but also their position relative to uptake transporters that remove extracellular Glu and thus limit receptor activation. Thus excitatory amino acid transporters (EAATs) are critical to preventing over-excitation and maintaining synaptic efficacy. Objective: To examine the contribution of EAATs on nTS activity induced by iGluRs and mGluRs. Methods: We recorded synaptic currents and membrane activity in rat nTS slices before and after antagonism of iGluRs and mGluRs. Results: We showed that EAAT1 and EAAT2 are localized to nTS astrocytes. EAAT block with TBOA increases the static and afferent-induced, phasic release of nTS Glu. The increase in Glu depolarized neuronal membrane potential, induced inward currents and enhanced action potential discharge that are dependent on AMPARs and NMDARs, with a moderate contribution of Grp I mGluRs. Enhanced nTS discharge amplified network-induced spontaneous excitatory synaptic currents (EPSCs). Conversely, antagonism of EAAT and resulting Glu attenuated the amplitude of afferent (TS)-driven EPSCs. The latter reduction was due to activation of mGluR II/III and reduction in presynaptic calcium. Conclusion: Taken together, our data demonstrate EAATs critically limit activation of ionotropic and metabotropic GluRs, and thus neuronal and synaptic activity. These effects likely influence cardiorespiratory homeostasis and reflex responses to a variety of stimuli.

La helada es el estrés abiótico caracterizado por la disminución de la temperatura del aire por debajo de cero grados centígrados, es uno de los problemas de mayor incidencia e impacto en la agricultura andina. Por otro lado, estudios morfológicos y fisiológicos señalan a las papas nativas como fuentes de tolerancia genética al estrés por helada. Sin embargo, las bases moleculares de los mecanismos de tolerancia en papa, aún son desconocidas. La tecnología del secuenciamiento de ARN (RNA-seq) es una excelente herramienta que permite identificar cambios en los perfiles de expresión génica tras el estrés por helada. En este trabajo, el transcriptoma de una variedad de papa tolerante y otra variedad susceptible a helada fueron secuenciados y comparados después de la exposición al estrés por helada (-8 °C) durante una hora, utilizando la técnica del RNA-seq para identificar diferencias en la expresión de genes entre ambas variedades. Se observó que más de 199 millones de lecturas de RNA-seq fueron alineadas al genoma de referencia (Solanum tuberosum Grupo Phureja), lo que corresponde al 82.1% del total de las lecturas obtenidas tras el secuenciamiento. En cuanto a la modulación en la expresión de genes, la variedad tolerante presentó el mayor número de genes expresados diferencialmente (Differentially Expressed Genes, DEGS) sobreexpresados (262 DEGs) y la variedad susceptible presentó el mayor número de DEGs reprimidos (37 DEGs) tras el estrés por helada.

The mental and physical human costs of social isolation and loneliness—and their possible amelioration through human–animal interaction (HAI)—have both received intense attention since the onset of the COVID-19 pandemic, and its lockdowns, quarantines, and related mitigation measures. Concern about society’s “loneliness epidemic”, however, predates the pandemic, as does serious inquiry into HAI as a positive intervention. Recognizing the potential of companion animals to make a difference on an important public health issue, the Consortium on Social Isolation and Companion Animals—a novel partnership of the Human Animal Bond Research Institute (HABRI) and Mars Petcare—launched a joint initiative in 2019 to advance HAI research, address barriers to HAI, and support best practices in bringing together animals and people to ease loneliness. Beginning with a first-ever summit of multidisciplinary thought leaders, this collaboration has already yielded actionable insights and research projects. As a novel partnership initiative in the HAI field, it offers a promising model for future cross-disciplinary forward thinking to elevate HAI for the mutual benefit of companion animals and their welfare, as well as vulnerable human populations.

Since 2002, West Nile virus (WNV) has been detected every year in Houston and the surrounding Harris County, Texas. In 2014, the largest WNV outbreak to date occurred, comprising 139 cases and causing 2 deaths. Additionally, 1,286 WNV-positive mosquito pools were confirmed, the most reported in a single mosquito season.

In oscillatory systems, neuronal activity phase is often independent of network frequency. Such phase maintenance requires adjustment of synaptic input with network frequency, a relationship that we explored using the crab, Cancer borealis, pyloric network. The burst phase of pyloric neurons is relatively constant despite a > two fold variation in network frequency. We used noise input to characterize how input shape influences burst delay of a pyloric neuron, and then used dynamic clamp to examine how burst phase depends on the period, amplitude, duration, and shape of rhythmic synaptic input. Phase constancy across a range of periods required a proportional increase of synaptic duration with period. However, phase maintenance was also promoted by an increase of amplitude and peak phase of synaptic input with period. Mathematical analysis shows how short-term synaptic plasticity can coordinately change amplitude and peak phase to maximize the range of periods over which phase constancy is achieved.

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach.

BackgroundPrevious studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD.MethodsVolunteers with CUD were admitted to an inpatient unit for the entire study and assigned to one of three rTMS groups: high frequency (10 Hz), low frequency (1 Hz), and sham. Six participants were included in each group and the rTMS was delivered on weekdays for 3 weeks. The cocaine self-administration sessions were performed at three time points: at baseline (pre-TMS, session 1), after 4 days of rTMS (session 2), and after 13 days of rTMS (session 3). During each self-administration session, the outcome measure was the number of choices for cocaine.ResultsThe results showed a significant group by time effect (p = 0.02), where the choices for cocaine decreased between sessions 2 and 3 in the high frequency group. There was no effect of rTMS on cocaine self-administration in the low frequency or sham groups.ConclusionTaken in the context of the existing literature, these results contribute to the data showing that high frequency rTMS to the prefrontal cortex may serve as a potential treatment for CUD.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT2) receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21), a selective AT2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol, BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition), and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT2 receptor by C21 attenuates bleomycin-induced lung injury and associated cardiopulmonary pathology, which needs to be further explored as a promising approach for the clinical treatment of IPF and Group III PH.

Cell phone usage may impair a driver’s decision-making at a dilemma zone. This research seeks to identify the impact of cell phone usage on different dilemma zone driver behaviors. Participants were exposed to different driving situations in a simulator where they had a phone call while driving through signalized intersections. A combination of variables was collected; therefore, this research estimates Classification and Regression Tree (CART) and stepwise logistic regression models to describe the factors influencing dilemma zone driver behavior. While the logistic regression models focus on the overall impact of the variables, the CART model develops subpopulations based on the variables’ impact. Cell phone usage, especially incoming calls on a handheld device, and the overall experiment appear to encourage conservative behavior where the drivers opt to stop even when they are “expected” to go. Unfortunately, when the drivers decide to go, they tend to make the wrong choice and run the red light. Using hands-free devices on outgoing calls appears to reduce the likelihood of performing an illegal maneuver. This represents a potential opportunity for future policy and technological advancements to improve intersection safety by only permitting outgoing hands-free calls on arterials.

The association of cocaine use disorder (CUD) and comorbid major depressive disorder (MDD; CUD/MDD) is characterized by high prevalence and poor treatment outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced MDD). Specific biomarkers are needed to improve diagnoses and therapeutic approaches in this dual pathology. Platelet biomarkers [5-HT2A receptor and imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western blot in subjects with CUD and primary MDD (n = 16) or CUD-induced MDD (n = 9; antidepressant free, AD−; antidepressant treated, AD+) and controls (n = 10) at basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT2A receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%) compared to healthy controls, and this down-regulation was independent of AD medication (decreases in AD−: 47%, and in AD+: 40%). No basal differences were found for IRAS/nischarin contents in AD+ and AD− comorbid CUD/MDD subjects. The comparison of IRAS/nischarin in the different subject groups during/after ATD showed opposite modulations (i.e., increases and decreases) in response to low plasma tryptophan levels with significant differences discriminating between the subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations suggested that platelet IRAS/nischarin might be useful as a biomarker to discriminate between primary and CUD-induced MDD in this dual pathology.

In 2012, we witnessed a resurgence of West Nile virus (WNV) in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection.

In light of the current challenges in addressing the achievement gap between minority and non-minority students, the persistent problems of disproportionality in special education, and the dismal post-school outcomes for culturally and linguistically diverse (CLD) students and those living in poverty, it is critical that successful models of teacher recruitment and retention are developed and implemented. In this article we review current literature on multicultural issues in special education that underscore the need for a more diverse teaching workforce and look at the recruitment trends described in the retention of teachers who are prepared to effectively serve PK-12 students and their families from diverse backgrounds. We also share preliminary data on our efforts to recruit and retain graduate students in an advanced special education program at a Hispanic-serving institution of higher education. To further guide the efforts of others, we provide recommendations for program development and future research.

The purpose of this study was to determine what instructional practices that enhance outcomes for diverse learners do kindergarten teachers see as desirable and feasible to implement and which do they report implementing in their general education classroom. Ninety-five kindergarten teachers were asked about their perceptions and use of instructional practices. A subgroup of 18 teachers also participated in a follow-up interview. Teachers rated the desirability of all practices high indicating their awareness and the importance of each. The most desirable practices reported by teachers primarily focused on practices surrounding the social-emotional domain of students. Although teachers rated the ease of doing most of the practices relatively high, this rating was lower in all cases from the desirability rating. (Contains 2 tables.)