Open Access. Powered by Scholars. Published by Universities.®

Physiology Commons

Open Access. Powered by Scholars. Published by Universities.®

Systems and Integrative Physiology

2015

Institution
Keyword
Publication
Publication Type

Articles 1 - 26 of 26

Full-Text Articles in Physiology

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker Dec 2015

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K+ currents. Another pathway that has profound effects on neuronal K+ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …


A New Method For Shear Wave Speed Estimation In Shear Wave Elastography, Aaron J. Engel, Gregory R. Bashford Dec 2015

A New Method For Shear Wave Speed Estimation In Shear Wave Elastography, Aaron J. Engel, Gregory R. Bashford

Biomedical Imaging and Biosignal Analysis Laboratory

Visualization of mechanical properties of tissue can aid in noninvasive pathology diagnosis. Shear wave elastography (SWE) measures the elastic properties of soft tissues by estimation of local shear wave propagation speed. In this paper, a new robust method for estimation of shear wave speed is introduced which has the potential for simplifying continuous filtering and real-time elasticity processing. Shear waves were generated by external mechanical excitation and imaged at a high frame rate. Three homogeneous phantoms of varying elastic moduli and one inclusion phantom were imaged. Waves propagating in separate directions were filtered and shear wave speed was estimated by …


Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu Nov 2015

Brain Injury And Inflammation And Placental Inflammation In Response To Repetitive Umbilical Cord Occlusions In The Near Term Ovine Fetus, Alex Xu

Electronic Thesis and Dissertation Repository

We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and fetal inflammatory response associated with brain injury, which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was2saturation pre-UCOs of >55% and


Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker Nov 2015

Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker

Journal Articles: Cellular & Integrative Physiology

Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …


Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio Oct 2015

Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio

Journal Articles: Cellular & Integrative Physiology

Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of …


Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland Sep 2015

Multi-Stress Proteomics: The Global Protein Response To Multiple Environmental Stressors In The Porcelain Crab Petrolisthes Cinctipes, Michael A. Garland

Master's Theses

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic …


Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman Aug 2015

Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman

Medicine Faculty Publications

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the …


Freeze Tolerance In The Spring Field Cricket, Gryllus Veletis, Alexander H. Mckinnon Jul 2015

Freeze Tolerance In The Spring Field Cricket, Gryllus Veletis, Alexander H. Mckinnon

Electronic Thesis and Dissertation Repository

Many insects are able to survive internal ice formation. However, the mechanisms underlying freeze tolerance are not well-understood, perhaps because of a lack of suitable model organisms. I found that the spring field cricket, Gryllus veletis, seasonally acquires freeze tolerance in the fall when kept outside in London, Ontario. Moreover, individuals acquired freeze tolerance in the laboratory in response to a simulated fall thermophotoperiod. Lab-acclimated G. veletis freeze at -6.1 ± 0.7 ºC and the acquisition of freeze tolerance is accompanied by the accumulation of proline and trehalose. Crickets survived temperatures as low as -12 ºC (1.5 h), and …


The Effects Of Ovarian Hormones And Exercise On Gene Markers Of Cardiac Dysfunction, Anisha S. Patel Jul 2015

The Effects Of Ovarian Hormones And Exercise On Gene Markers Of Cardiac Dysfunction, Anisha S. Patel

Masters Theses

Heart disease is the leading cause of death in women in the United States. Premenopausal women appear to have better cardiac function and lower risk of heart disease compared to male postmenopausal female counterparts. Ovarian hormone loss influences blood pressure homeostasis and causes systemic inflammation, which may result in chronic stress on the heart. Two key physiological changes in cardiac dysfunction are reemergence of the fetal gene pattern and myocardial remodeling. Physical activity has been linked to improved cardiac function. The purpose of this study was to investigate the effects of ovariectomy on early markers of cardiac dysfunction and fibrosis …


Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz Jun 2015

Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz

Journal Articles: Cellular & Integrative Physiology

No abstract provided.


Expressing And Characterizing Mechanosensitive Channels In Xenopus Oocytes, Grigory Maksaev, Elizabeth S. Haswell May 2015

Expressing And Characterizing Mechanosensitive Channels In Xenopus Oocytes, Grigory Maksaev, Elizabeth S. Haswell

Biology Faculty Publications & Presentations

The oocytes of the African clawed frog (Xenopus laevis) comprise one of the most widely used membrane protein expression systems. While frequently used for studies of transporters and ion channels, the application of this system to the study of mechanosensitive ion channels has been overlooked, perhaps due to a relative abundance of native expression systems. Recent advances, however, have illustrated the advantages of the oocyte system for studying plant and bacterial mechanosensitive channels. Here we describe in detail the methods used for heterologous expression and characterization of bacterial and plant mechanosensitive channels in Xenopus oocytes.


Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski May 2015

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …


Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr. May 2015

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …


Effects Of Pre-Release Physical Stressors On Post-Release Success Of Hatchery-Reared Spotted Seatrout, Taylor Westbrook Guest May 2015

Effects Of Pre-Release Physical Stressors On Post-Release Success Of Hatchery-Reared Spotted Seatrout, Taylor Westbrook Guest

Master's Theses

Alteration of habitat associated with coastal development and increased demand for food and recreation can result in the depletion of fisheries resources such as the Spotted Seatrout (Cynoscion nebulosus), the Gulf of Mexico’s most popular recreational fish. Stock enhancement, or the release of cultured fish to supplement wild populations, is one potential tool for managing important fisheries resources. Although much effort has gone into marine stock enhancement, the effectiveness of stocking is not well established, and techniques for ensuring success have not been developed. Although the basic biology of the Spotted Seatrout is well known, comparatively little is known about …


Outline Plan For A Student-Involved Fitness Assessment Program At Western Michigan University, Joanna Gangwisch Apr 2015

Outline Plan For A Student-Involved Fitness Assessment Program At Western Michigan University, Joanna Gangwisch

Honors Theses

This research was aimed at developing a fitness assessment program that would provide undergraduate exercise science students at Western Michigan University (WMU) with hands on experience that would successfully prepare them for their internships and future careers as well as benefiting the campus community at large. Data for this research was obtained by examining the student recreation center websites and sending out an email/phone questionnaire to WMU’s 10 peer institutions. Direct comparisons were made and evaluated. On the basis of the results of this research, it can be concluded that WMU’s exercise science department and student recreation center together could …


Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra Apr 2015

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …


Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra Apr 2015

Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) …


Oxygenation Properties And Isoform Diversity Of Snake Hemoglobins, Jay F. Storz, Chandrasekhar Natarajan, Hideaki Moriyama, Federico G. Hoffmann, Tobias Wang, Angela Fago, Hans Malte, Johannes Overgaard, Roy E. Weber Jan 2015

Oxygenation Properties And Isoform Diversity Of Snake Hemoglobins, Jay F. Storz, Chandrasekhar Natarajan, Hideaki Moriyama, Federico G. Hoffmann, Tobias Wang, Angela Fago, Hans Malte, Johannes Overgaard, Roy E. Weber

Jay F. Storz Publications

Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from …


'In' Or 'As' Space?: A Model Of Complexity, With Philosophical, Simulatory, And Empirical Ramifications, Charles H. Smith Jan 2015

'In' Or 'As' Space?: A Model Of Complexity, With Philosophical, Simulatory, And Empirical Ramifications, Charles H. Smith

DLPS Faculty Publications

A General Systems model based on ideas originating with the writings of Benedict de Spinoza is described, starting with its philosophical underpinnings, and proceeding on to its relation to modern systems concepts, including attempts to simulate the relationships posed, and measure real world structures. Central to the idea is the notion that spatial extension may not have a prior existence, but emerges only through an entropy maximization process in which information and energy exchange is balanced among some limited number of subsystems that in sum comprise any given functioning complex system. Related published empiricism concerning geographical/geological systems – the hypsometry …


Enabling Real-Time Ultrasound Imaging Of Soft Tissue Mechanical Properties By Simplification Of The Shear Wave Motion Equation, Aaron J. Engel, Gregory R. Bashford Jan 2015

Enabling Real-Time Ultrasound Imaging Of Soft Tissue Mechanical Properties By Simplification Of The Shear Wave Motion Equation, Aaron J. Engel, Gregory R. Bashford

Biomedical Imaging and Biosignal Analysis Laboratory

Ultrasound based shear wave elastography (SWE) is a technique used for non-invasive characterization and imaging of soft tissue mechanical properties. Robust estimation of shear wave propagation speed is essential for imaging of soft tissue mechanical properties. In this study we propose to estimate shear wave speed by inversion of the firstorder wave equation following directional filtering. This approach relies on estimation of first-order derivatives which allows for accurate estimations using smaller smoothing filters than when estimating second-order derivatives. The performance was compared to three current methods used to estimate shear wave propagation speed: direct inversion of the wave equation (DIWE), …


Resistant Hypertension: Risk Factors, Subclinical Atherosclerosis, And Comorbidities Among Adults—The Brazilian Longitudinal Study Of Adult Health (Elsa-Brasil), Paulo A. Lotufo Jan 2015

Resistant Hypertension: Risk Factors, Subclinical Atherosclerosis, And Comorbidities Among Adults—The Brazilian Longitudinal Study Of Adult Health (Elsa-Brasil), Paulo A. Lotufo

Paulo A Lotufo

The frequency of resistant hypertension—defined as blood

pressure (BP) ≥140/90 mm Hg with proven use of three

antihypertensive medications, or as the use of four antihypertensive drug classes regardless of BP—is unknown in low-middle–income countries. Using data from the Brazilian Longitudinal Study of Adult Health, a cohort of 15,105 civil servants aged 35 to 74 years, the authors identified 4116 patients taking treatment for hypertension, 11% of who had resistant hypertension. These participants were more likely to be older, black, less educated, poorer, and obese. The adjusted prevalence ratios (95% confidence intervals) were diabetes, 1.44 (1.20–1.72); glomerular filtration rate ( …


Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony Porreca, Robert Colombo, Michael Menze Jan 2015

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony Porreca, Robert Colombo, Michael Menze

Faculty Research & Creative Activity

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown, and understudied due to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can potentially alter the community structure of fishes. We employ this highly tractable system to assess how thermal regimes can alter the physiology and ecology of aquatic species. We documented a significantly reduced lifespan, growth …


The Relationship Between Vagal Tone, A Marker Of Parasympathetic Activity, And Pro-Social Behavior, Emily A. Goodlin Jan 2015

The Relationship Between Vagal Tone, A Marker Of Parasympathetic Activity, And Pro-Social Behavior, Emily A. Goodlin

Scripps Senior Theses

Vagal tone, a measure of parasympathetic activity via the vagus nerve, is known to be associated with positive emotion because it promotes social engagement and self-soothing behavior. Heart rate variability (HRV), especially high frequency oscillation, is a direct measure of vagal tone, and has been used in previous studies to test the correlation between vagal tone and positive emotion. This study aims to determine if the two major oscillations of heart rate variability, high frequency (HF-HRV) and low frequency (LF-HRV) can predict pro-social behavior, which is classified as giving donations to charities. Baseline LF- and HF-HRV levels were recorded, and …


Functional Transcranial Doppler Ultrasound For High Temporal Resolution Measurement Of Lateralization In Visual Memory And Visual Search Cognitive Tasks, B. Hage, M. Alwatban, E. Barney, M. Mills, M. Dodd, E. Truemper, Gregory R. Bashford Jan 2015

Functional Transcranial Doppler Ultrasound For High Temporal Resolution Measurement Of Lateralization In Visual Memory And Visual Search Cognitive Tasks, B. Hage, M. Alwatban, E. Barney, M. Mills, M. Dodd, E. Truemper, Gregory R. Bashford

Biomedical Imaging and Biosignal Analysis Laboratory

Functional transcranial Doppler ultrasound (fTCD) is a noninvasive sensing modality that measures blood flow velocities in cerebral arteries (CBFV) with high temporal resolution. Few studies have examined the relationship of CBFV change during visual search and visual memory cognitive tasks. Here a protocol to compare lateralization between these two similar tasks using fTCD is demonstrated. Thirteen healthy volunteers were shown visual scenes on a computer and performed visual search and visual memory tasks while CBFV in the bilateral middle cerebral arteries was monitored with fTCD. Each subject completed 40 trials, consisting of baseline, calibration, instruction, and task periods. Lateralization was …


Understanding The Physiological Effects Of Suspended Material On Rainbow Trout (Oncorhynchus Mykiss), Tyler J. Weinhardt Jan 2015

Understanding The Physiological Effects Of Suspended Material On Rainbow Trout (Oncorhynchus Mykiss), Tyler J. Weinhardt

Theses and Dissertations (Comprehensive)

The effect of global warming on northern environments is becoming increasingly evident. Melting of underlying permafrost is associated with widespread impacts in these environments. The loss of permafrost results in a destabilizing of underlying sedimentary layers resulting in thermokarst slumping. When this occurs on a large scale (mega-slumping) soil material becomes mobilized and is carried into local streams and rivers. The purpose of this study is to examine the sub-lethal physiological effects that suspended material has on rainbow trout (Oncorhynchus mykiss) in the context of the Peel River Plateau. Juvenile rainbow trout were exposed (following Environment Canada exposure …


Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony P. Porreca, Robert E. Colombo, Michael A. Menze Dec 2014

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony P. Porreca, Robert E. Colombo, Michael A. Menze

Eloy Martinez

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown, and understudied due to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can potentially alter the community structure of fishes. We employ this highly tractable system to assess how thermal regimes can alter the physiology and ecology of aquatic species. We documented a significantly reduced lifespan, growth …