Indiana University Fort Wayne

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.

The sacroiliac joint (SIJ) is a putative source of low back pain. The objective of this article is to provide clinicians with a concise review of SIJ structure and function, diagnostic indicators of SIJ-mediated pain, and therapeutic considerations. The SIJ is a true diarthrodial joint with unique characteristics not typically found in other diarthrodial joints. The joint differs with others in that it has fibrocartilage in addition to hyaline cartilage, there is discontinuity of the posterior capsule, and articular surfaces have many ridges and depressions. The sacroiliac joint is well innervated. Histological analysis of the sacroiliac joint has verified the presence of nerve fibers within the joint capsule and adjoining ligaments. It has been variously described that the sacroiliac joint receives its innervation from the ventral rami of L4 and L5, the superior gluteal nerve, and the dorsal rami of L5, S1, and S2, or that it is almost exclusively derived from the sacral dorsal rami. Even though the sacroiliac joint is a known putative source of low back and lower extremity pain, there are few findings that are pathognomonic of sacroiliac joint pain. The controlled diagnostic blocks utilizing the International Association for the Study of Pain (IASP) criteria demonstrated the prevalence of pain of sacroiliac joint origin in 19% to 30% of the patients suspected to have sacroiliac joint pain. Conservative management includes manual medicine techniques, pelvic stabilization exercises to allow dynamic postural control, and muscle balancing of the trunk and lower extremities. Interventional treatments include sacroiliac joint, intra-articular joint injections, radiofrequency neurotomy, prolotherapy, cryotherapy, and surgical treatment. The evidence for intra-articular injections and radiofrequency neurotomy has been shown to be limited in managing sacroiliac joint pain.

In addition to functionalities, business process management (BPM) involves several key indicators such as openness, security, flexibility, and scalability. Optimizing system performance is becoming a great challenge for an ever-increasing large-scale distributed application system in the digital economy on the Internet of Things (IoT) era. In a centralized BPM, many indicators, such as security and openness, or cost and flexibility, are conflicting with each other. For example, inviting new partners across enterprises, domains, and regions to form a service workflow exposes new risks and needs additional security mechanisms for scrutiny; enhancing the flexibility of business workflow compositions increases the cost of security assurance. Blockchain technology (BCT) has thrown the light on the development of vital solutions to various BPM problems. BCT has to be integrated with other BPM system components that often involve IoT devices to implement specified functionalities related to the application. Currently, the potentials of using BCT have been explored although still at an early stage. In this paper, the states of the art are presented to identify emerging research topics, challenges, and promising applications in integrating BCT into the development of BPM.

The attitude of the public toward physicians and medical services is an issue of current concern and debate. To address this problem, an instrument was developed using Thurstone scaling methods in conjunction with a Likert format and a modified scoring technique. Following pretesting of the instrument among both patient and population samples, a survey was conducted among the residents of a probability sample of households in a city of 200,000 people. The attitude questionnaire was completed by 1,713 adults in 1,112 households. Overall, attitudes were favorable toward the professional competency and the personal qualities of physicians. Accessibility, including costs and convenience, were less highly regarded. Men were less satisfied than women and blacks less satisfied than whites. Particularly negative attitudes were expressed toward the personal qualities of physicians by young blacks, whereas among blacks over 60 the negative effect was toward cost and convenience. Having a regular physician and long attendance with that physician were correlated with positive attitudes. The most negative sentiment was expressed by women without regular source of care. Medical services are being sought and obtained by a large segment of society, but problems of costs and acceptability for the elderly, low social class persons, members of large families, and for blacks still remain.

The authors review the principles of operation of pyroelectric detectors. The equations for current responsivity, voltage responsivity, noise, noise equivalent power, and detectivity are derived from the fundamental thermodynamic model of a pyroelectric detector. The frequency-dependent current and voltage responsivities are explained. Factors influencing the choice of pyroelectric material for various applications are summarized. The possibilities of various new applications and the developments of pyroelectric detectors are discussed. A laboratory prototype demonstration system has been built using an ELTEC detector type 5192. For a high signal-to-noise ratio, an electric charge integration technique is applied. High-precision operational amplifiers are used for high-quality signal conditioning. The pyroelectric detector consists of two parallel opposed dual lithium tantalate pyroelectric single crystals with a junction FET source follower sealed in a standard TO-5 housing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

BACKGROUND AND PURPOSE: Despite ongoing clinical suspicion regarding the relationship between sacroiliac joint (SIJ) dysfunction and lower extremity symptoms, there is a paucity of scientific literature addressing this topic. The purpose of this study was to describe patterns of contrast extravasation during SIJ arthrography and postarthrography CT in patients with lower back pain and to determine whether there are pathways of communication between the SIJ and nearby neural structures. METHODS: Fluoroscopically guided SIJ arthrography was performed on 76 SIJs. After the injection of contrast medium, anteroposterior, lateral, and oblique radiographs as well as 5-mm contiguous axial and direct coronal CT images were obtained. Contrast extravasation patterns were recorded for each joint. These observations included a search for contrast extravasation from the SIJ that contacted nearby lumbosacral nerve roots or structures of the plexus. RESULTS: Sixty-one percent of all joints studied revealed one of five contrast extravasation patterns. Three of these observed patterns show a pathway of communication between the SIJ and nearby neural structures. These included posterior extravasation into the dorsal sacral foramina, superior recess extravasation at the sacral alar level to the fifth lumbar epiradicular sheath, and ventral extravasation to the lumbosacral plexus. CONCLUSION: Three pathways between the SIJ and neural structures exist.

Proteins that have sequence homology with known RNA m(5)C methyltransferases contain two conserved cysteines, each of which lies within a sequence that bears similarity to a methyltransferase active site. Other enzymes that transfer a methyl group to carbon 5 of a pyrimidine nucleotide, such as the bacterial DNA m(5)C methyltransferases, utilize their single conserved cysteine residue to form a covalent Michael adduct with carbon 6 of the pyrimidine ring during catalysis. We present a model for the utilization of two cysteines in catalysis by RNA m(5)C methyltransferases. It is proposed that one thiol acts in a classical fashion by forming a covalent link to carbon 6 of the pyrimidine base, while the other cysteine assists breakdown of the covalent adduct. Therefore, alteration of the assisting cysteine is anticipated to stabilize the covalent enzyme-RNA intermediate. The model was conceived as a possible explanation for the effects of mutations that change the conserved cysteines in Nop2p, an apparent RNA m(5)C methyltransferase that is essential for ribosome assembly and yeast viability. Evidence for the predicted accumulation of protein-RNA complexes following mutation of the assisting cysteine has been obtained with Nop2p and a known tRNA m(5)C methyltransferase called Ncl1p (Trm4).

Infectious diseases (ID) specialists have played a major role in patient care, infection control, and antibiotic management for many years. With the rapidly changing nature of health care, it has become necessary for ID specialists to articulate their value to multiple audiences. This article summarizes the versatile attributes possessed by ID specialists and delineates their value to patients, hospitals, and other integral groups in the health care continuum.

This study examined the long-term impact of retention/promotion decisions on the academic achievement of primary grade students. First-, second-, and third-grade retainees were matched on several variables with same-age students who were not retained. Results of same-year comparisons indicated that retained students significantly improve their relative class standing by the end of the retained year, and in some cases they maintain this advantage over a 2-year period; however, after 3 years there are no differences between retained and promoted students. Comparisons of same-grade level performance provided some evidence that second- and third-grade retainees experience more sustained benefits from retention, although these benefits are delayed one year.

We tested whether vasorelaxation of coronary arteries is altered after overnight (18-22 h) exposure to physiological levels of 17 beta-estradiol. Ring segments of left circumflex coronary artery from six female and six castrated male pigs were incubated in vials of sterile Dulbecco's modified Eagle's medium with 1 nM 17 beta-estradiol, 1 nM 17 beta-estradiol + 10 nM tamoxifen, 1 nM 17 alpha-estradiol, or estrogen vehicle (ethanol) under normoxic conditions in an O2-CO2 incubator at 37 degrees C for 18-22 h. Coronary rings, with and without endothelium, were then suspended in vessel baths for measurement of isometric force. Vasorelaxation responses to the calcium ionophore A-23187, ADP, and nitroglycerin were examined in the rings after prostaglandin synthesis blockade and precontraction with U-46619. Sensitivity to A-23187 (-log M concentration required for 50% of maximal relaxation) was significantly enhanced in coronary rings with endothelium from females and castrated males when rings were incubated with 17 beta-estradiol but not when they were incubated with 17 alpha-estradiol or 17 beta-estradiol+tamoxifen. Acute (2h) exposure of coronary arteries to 1 nM 17 beta-estradiol did not alter responses to A-23187. 17 beta-Estradiol (1 nM) was not itself directly vasoactive in coronary arteries with or without prior incubation with the steroid. Vasorelaxation of rings with and without endothelium to ADP and nitroglycerin was not significantly different among the treatment groups. Relaxation to A-23187, but not ADP, was abolished by removal of the endothelium or exposure to 100 microM NO2-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Vacuum phenomenon (VP) is an anatomical entity of potential confusion in the diagnosis and evaluation of joint pathology. Observation of this phenomenon has been demonstrated on basic radiographs, computed tomography, and magnetic resonance imaging. Although VP is most often associated with degenerative joint disease, it is observed with other pathologies. Two problematic scenarios can occur: a false-positive diagnosis of serious pathology instead of benign VP and a false-negative diagnosis of benign VP with a more serious underlying process Despite this potential for confusion, criteria for distinguishing VP from other causes of joint pain and for evaluating a suspected case of VP have not been fully established. We reviewed the literature to determine underlying mechanism, symptomology, associated pathologies, and clinical importance of VP. The formation of VP can be explained by gas solubility, pressure-volume relationships, and human physiology. CT, GRE-MRI, and multipositional views are the best imaging studies to view VP. Although most cases of VP are benign, it can be associated with clinical signs and symptoms. VP outside the spine is an underreported finding on imaging studies. VP should be on the differential diagnosis for joint pain, especially in the elderly. We have proposed criteria for diagnosing VP and generated a basic algorithm for its workup. Underreporting of this phenomenon shows a lack of awareness of VP on the part of physicians. By identifying true anatomic VP, we can prevent harm from suboptimal treatment of patients.

The use of a symmetry to reduce the order of an nth-order differential equation is treated by considering the symmetry of an associated vector field. A particular choice of associated vector field leads to the usual extension of the Lie symmetry method. The possibility of other choices leads to a powerful generalisation. An algebraic classification of transformations arises naturally from the theory. It is shown to be equivalent to the geometric classification of transformations as contact and non-contact.

Transection of the anterior cruciate ligament in the dog leads to osteoarthritis. This study defines the kinematic changes in the unstable knee after transection of the cruciate ligament (six dogs) and after a sham operation (four dogs). In the dogs that were anterior cruciate ligament-deficient (ACL-D), the duration of stance 1 week postoperatively decreased 38% from the preoperative value, but only a 4% decrease was seen at 6 weeks. The duration of double hindlimb support increased from 6 to 19% of the entire cycle 1 week after surgery but returned to the baseline value by 18 weeks. As the unstable limb contacted the treadmill belt, the initial flexion (yield) and subsequent extension (propulsive) phases were not evident or were markedly attenuated in every ACL-D dog throughout the 26-week period of observation. The angular velocity patterns were characterized by a slight extension velocity at touchdown (compared with a zero value preoperatively) and a decrease in the peak velocities (both flexion and extension) during the remainder of the stance phase. None of these changes was observed in the animals that had a sham operation. These data indicate that, in the dog, the nervous system compensates for instability of the knee by altering angular, but not temporal, parameters. The extension velocity at touchdown and the reduction in peak flexion velocity during the yield component of the stance phase may reduce the ability of the limb to absorb impact forces and lead to the development of osteoarthritis of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Telemental health (TMH) resources are plentiful; however, we know little about college students' opinions about such resources. We aimed to examine students' previous use of and willingness to use several types of TMH resources. Participants: Students ( N = 662) from two U.S. Midwestern colleges participated. Methods: Using an online survey in spring 2017, we measured students' depression, anxiety, stress, and suicidal thoughts, preferences for care options during distress, and use and interest in anonymous chats with trained nonprofessionals, online therapy, and self-help resources. Results: Overall, 10.1–13.8% had experience with these TMH resources; however, 24.6–40.1% expressed willingness to try them. At-risk students, especially those higher in depression/anxiety scores, showed greater use of and willingness to use some applications. Conclusions: Counseling centers might consider endorsing TMH resources as potential pathways to care. TMH resources might help broaden reach with minimal cost, reduce mental health help-seeking barriers, and provide support to at-risk populations.

Systemic inflammation is associated with increased cognitive decline and risk for Alzheimer’s disease. Microglia (MG) activated during systemic inflammation can cause exaggerated neuroinflammatory responses and trigger progressive neurodegeneration. Dimethyl fumarate (DMF) is a FDA-approved therapy for multiple sclerosis. The immunomodulatory and anti-oxidant properties of DMF prompted us to investigate whether DMF has translational potential for the treatment of cognitive impairment associated with systemic inflammation. Primary murine MG cultures were stimulated with lipopolysaccharide (LPS) in the absence or presence of DMF. MG cultured from nuclear factor (erythroid-derived 2)-like 2-deficient (Nrf2 −/− ) mice were used to examine mechanisms of DMF actions. Conditioned media generated from LPS-primed MG were used to treat hippocampal neuron cultures. Adult C57BL/6 and Nrf2 −/− mice were subjected to peripheral LPS challenge. Acute neuroinflammation, long-term memory function, and reactive astrogliosis were examined to assess therapeutic effects of DMF. DMF suppressed inflammatory activation of MG induced by LPS. DMF suppressed NF-κB activity through Nrf2-depedent and Nrf2-independent mechanisms in MG. DMF treatment reduced MG-mediated toxicity towards neurons. DMF suppressed brain-derived inflammatory cytokines in mice following peripheral LPS challenge. The suppressive effect of DMF on neuroinflammation was blunted in Nrf2 −/− mice. Importantly, DMF treatment alleviated long-term memory deficits and sustained reactive astrogliosis induced by peripheral LPS challenge. DMF might mitigate neurotoxic astrocytes associated with neuroinflammation. DMF treatment might protect neurons against toxic microenvironments produced by reactive MG and astrocytes associated with systemic inflammation.

Three synchronization measures are applied to scalp electroencephalogram (EEG) data collected from 20 patients diagnosed to have either: (1) no dementia, (2) mild cognitive impairment (MCI), or (3) Alzheimer's disease (AD). We apply the three synchronization measures--the phase synchronization, and two measures of nonlinear interdependency--to the data collected from awake patients resting with eyes closed. We show that the synchronization in potential between electrodes near the left and right occipital lobes provides a statistically significant discriminant between the healthy and AD subjects, and the MCI and AD subjects. None of the three measures appears able to distinguish between the healthy and MCI subjects, although MCI subjects show synchronization values intermediate between healthy subjects (with high synchronization values) and AD subjects (with low synchronization values) on average.

OBJECTIVES: To determine the impact of tethered personal health record (PHR) use on patient engagement and intermediate health outcomes among patients with coronary artery disease (CAD). METHODS: Adult CAD patients (N = 200) were enrolled in this prospective, quasi-experimental observational study. Each patient received a PHR account and training on its use. PHRs were populated with information from patient electronic medical records, hosted by a Health Information Exchange. Intermediate health outcomes including blood pressure, body mass index, and hemoglobin A1c (HbA1c) were evaluated through electronic medical record review or laboratory tests. Trends in patient activation measure® (PAM) were determined through three surveys conducted at baseline, 6 and 12 months. Frequency of PHR use data was collected and used to classify participants into groups for analysis: Low, Active, and Super users. RESULTS: There was no statistically significant improvement in patient engagement as measured by PAM scores during the study period. HbA1c levels improved significantly in the Active and Super user groups at 6 months; however, no other health outcome measures improved significantly. Higher PAM scores were associated with lower body mass index and lower HbA1c, but there was no association between changes in PAM scores and changes in health outcomes. Use of the PHR health diary increased significantly following PHR education offered at the 6-month study visit and an elective group refresher course. CONCLUSIONS: The study findings show that PHR use had minimal impact on intermediate health outcomes and no significant impact on patient engagement among CAD patients.

Significant advances in Internet and computer technology have made it possible to develop an Internet-based control, monitoring, and operation scheduling system for heating, ventilation, and air-conditioning (HVAC) systems. The proposed system architecture includes such features as control, measurement, networking, and reporting. This article addresses issues in architecture selection, electronics, embedded processors and software, and Internet technologies. This article also proposes an Internet-based HVAC system architecture that combines Web technology, networking, and functions of direct digital control. The proposed system also includes technologies needed for supporting real-time digital thermostat control, data gathering, remote access and occupancy control, light sensing control, and views of the history of HVAC utilization. This system enables users to make cost-effective energy decisions and quickly identify trouble spots of HVAC systems to minimize system down time.

The locomotor development of three vervet infants across approximately the first 2 months of life is described. Fairly normal-looking walking movements (as compared to adults) were seen in all the animals by approximately 1 month of age and galloping was observed by 2 months. Early locomotor footfall patterns were often aberrant and bounding-type gaits were sometimes exhibited. Most of the symmetrical gaits observed were classifiable as lateral sequence. Across the 2-month period the animals showed decreased three- and four-foot support and improvements in joint angular displacement patterns. From their earliest locomotor movements the infants showed significant linear relationship between both cycle duration and swing and stance durations of the limbs. We suggest that locomotor control mechanisms are probably fairly mature at birth but that weight support and postural control problems explain the initial locomotor difficulties exhibited by these infants.

Anterior cervical discectomy and fusion procedures are one of the most common procedures performed in spinal surgery. Increasingly they are being performed on an outpatient basis. The primary impetus for performing procedures as an outpatient is potential cost savings. However, there are few studies discussing the safety of performing the procedure in an ambulatory setting. This is a retrospective review of our initial experience in performing anterior cervical discectomy and fusion procedures with instrumentation (ACDFI) in an ambulatory surgery center dedicated to spine surgery. Patients were selected for outpatient surgery if they had limited co-morbidities and the surgery involved only 1 or 2 levels. One hundred fifty-two patients underwent outpatient ACDFI during the study period (2007-2009). Six patients returned to the hospital emergency room after discharge. The reasons for evaluation included 2 for neck pain, 1 for dysphagia, 1 for vocal cord paralysis and dysphagia, 1 for nausea, and 1 for cervical swelling. Only 1 of the 6 patients required admission to the hospital. None of the 6 suffered any long-term sequelae. The overall complication rate was 3.9%. A self-reported survey was completed by 75 patients within 6 months of surgery, and there was a 100% satisfaction rate among responders. ACDFI can be performed safely on an outpatient in selected patients with a high degree of patient satisfaction. Our experience is consistent with those of previous investigators.